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CORK Bibliography: Alcohol's Effects on Cardiovascular System

126 citations. January 2009 to present

Prepared: March 2010

Adabag AS; Peterson G; Apple FS; Titus J; King R; Luepker RV. Etiology of sudden death in the community: Results of anatomical, metabolic, and genetic evaluation. American Heart Journal 159(1): 33-39, 2010. (43 refs.)

Background: Identifying persons at risk for sudden cardiac death (SCD) is challenging. A comprehensive evaluation may reveal clues about the clinical, anatomical, genetic, and metabolic risk factors for SCD. Methods: Seventy-one patients who had SCD (25-60 years old) without an initially apparent cause of death were evaluated at the Hennepin County Medical Examiner's office (Minneapolis, MN) from August 2001 to July 2004. We reviewed their clinic records conducted next-of-kin interviews and performed autopsy, laboratory testing, and genetic analysis for mutations in genes associated with the long QT syndrome. Results: Mean age was 49.5 +/- 7 years, 86% were male, and 2 subjects had history of coronary heart disease (CHD). Coronary risk factors were highly prevalent in comparison to individuals of the same age group in this community (eg, smoking 61%, hypertension 27%, hyperlipidemia 25%) but inadequately treated. On autopsy, 80% of the subjects had high-grade coronary stenoses. Acute coronary lesions and previous silent myocardial infarction (MI) were found in 27% and 34%, respectively. Furthermore, 32% of the subjects had recently smoked cigarettes, and 50% had ingested analgesics. Possible deleterious mutations of the ion channel genes were detected in 5 subjects (7%). Of these, 4 were in the sodium channel gene SCN5A. Conclusions: Most of the persons who had SCD in the community had severe subclinical CHD, including undetected previous MI. Traditional coronary risk factors were prevalent and undertreated. Mutations in the long QT syndrome genes were detected in a few subjects. These findings imply that improvements in the detection and treatment of subclinical CHD in the community are needed to prevent SCD.

Adamopoulos D; Argacha JF; Gujic M; Preumont N; Degaute JP; van de Borne P. Acute effects of nicotine on arterial stiffness and wave reflection in health young non-smokers. Clinical and Experimental Pharmacology & Physiology 36(8): 784-789, 2009. (32 refs.)

Recently, we have demonstrated that cigarette smoke exposure proportionally increases plasma nicotine levels and arterial wave reflection to the aorta. However, the exact contribution of nicotine to the smoke-induced enhancement of wave reflection and the potential underlying mechanisms have not been fully investigated. The present study was a prospective study in 15 healthy male non-smokers. All received a placebo and a 2 mg nicotine tablet, according to a randomized double-blind cross-over study design. Each subject underwent repeated measurements at baseline and for 1 h after nicotine or placebo intake, using carotid-femoral pulse wave velocity (PWV) to assess arterial compliance. Concurrently, aortic pressures and the augmentation index were evaluated using applanation tonometry. Plasma nicotine concentrations achieved 1 h after intake of the nicotine tablet reached comparable levels to those achieved after 1 h exposure to passive smoke (3.6 +/- 0.4 vs 3.2 +/- 0.4 ng/mL, respectively; P = 0.4). Nicotine enhanced arterial wave reflection to the aorta, as assessed by the augmentation index corrected for heart rate (4.2 +/- 1.3 vs -0.7 +/- 0.8% with placebo; P = 0.001). In addition, a progressive increase in carotid-femoral PWV was noted after nicotine administration (0.3 +/- 0.1 vs -0.02 +/- 0.1 m/s with placebo; P = 0.04). This remained significant even after adjustment for changes in mean blood pressure and heart rate (P = 0.01). Plasma nicotine concentrations comparable to those achieved after exposure to passive smoke enhance arterial wave reflection to the aorta. This is accompanied by an increase in carotid-femoral PWV, denoting a deterioration of arterial compliance by nicotine.

Ahmed HN; Levitan EB; Wolk A; Mittleman MA. Coffee consumption and risk of heart failure in men: An analysis from the Cohort of Swedish Men. American Heart Journal 158(4): 667-672, 2009. (38 refs.)

Background: A previous study found that consuming 5 or more cups of coffee per day was associated with increased incidence of heart failure (HF). We sought to evaluate this association in a larger population. Methods: We measured coffee consumption using food frequency questionnaires among 37,315 men without history of myocardial infarction, diabetes, or HF. They were observed for HF hospitalization or mortality from January 1, 1998, until December 31, 2006, using record linkage to the Swedish inpatient and cause of death registries. Cox proportional hazards models adjusted for age, dietary, and demographic factors were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CIs). Results: For 9 years of follow-up, 784 men experienced an HF event. Compared to men who drank l cup of coffee per day (unadjusted rate 29.9 HF events/ 10,000 person-years), RR were 0.87 (95% CI 0.69-1.11, unadjusted rate 29.2/10,000 person-years) for 2 cups/d, 0.89 (95% CI 0.70-1.14, unadjusted rate 25.1/10,000 person-years) for 3 cups/d, 0.89 (95% CI 0.69-1.15, unadjusted rate 25.0/10,000 person-years) for 4 cups/d, and 0.89 (95% CI 0.69-1.15, unadjusted rate 18.1/10,000 person-years) for >= 5 cups/d (P for trend in RR = .61). Conclusions This study did not support the hypothesis that high coffee consumption is associated with increased rates of HF hospitalization or mortality.

Ammar KA; Samee S; Colligan R; Morse R; Faheem O; Shapiro M et al. Is self-reported "moderate" drinking in the cardiovascular benefit range associated with alcoholic behavior? A population based study. Journal of Addictive Diseases 28(3): 243-249, 2009. (19 refs.)

This article aims at identifying a threshold number of drinks per day beyond which there is a high risk of developing alcoholic behavior that would enable physicians to more confidently support the use of alcohol for cardiovascular risk prevention. In a randomly selected, population-based sample of 2,042 adults 45 years or older, we graded alcohol drinking behavior using the Self-Administered Alcoholism Screening Test, quantified alcohol amount by questionnaire, and assessed the prevalence of cardiovascular disease (coronary, peripheral, or cerebrovascular disease) by medical record review. Although optimal alcohol use (<= 2 drinks/day) was associated with reduced odds of cardiovascular disease, 43% of alcoholics and 82% of problem drinkers reported alcohol use in the optimal range as well. The association of alcohol use in the optimal range with alcohol-related behavioral problems supports the reluctance in physicians from recommending alcohol use for cardiovascular benefit, not withstanding the underreporting of alcohol use by alcoholics.

Anchersen K; Clausen T; Gossop M; Hansteen V; Waal H. Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: A mortality assessment study. Addiction 104(6): 993-999, 2009. (38 refs.)

To determine the prevalence of corrected QT interval (QTc) prolongation among patients in opioid maintenance treatment (OMT) and to investigate mortality potentially attributable to QTc prolongation in the Norwegian OMT programme. Two hundred OMT patients in Oslo were recruited to the QTc assessment study between October 2006 and August 2007. The Norwegian register of all patients receiving OMT in Norway (January 1997-December 2003) and the national death certificate register were used to assess mortality. Mortality records were examined for the 90 deaths that had occurred among 2382 patients with 6450 total years in OMT. The QTc interval was assessed by electrocardiography (ECG). All ECGs were examined by the same cardiologist, who was blind to patient history and medication. Mortality was calculated by cross-matching the OMT register and the national death certificate register: deaths that were possibly attributable to QTc prolongation were divided by the number of patient-years in OMT. In the QTc assessment sample (n = 200), 173 patients (86.5%) received methadone and 27 (13.5%) received buprenorphine. In the methadone group, 4.6% (n = 8) had a QTc above 500 milliseconds; 15% (n = 26) had a QTc interval above 470 milliseconds; and 28.9% (n = 50) had a QTc above 450 milliseconds. All patients receiving buprenorphine (n = 27) had QTc results < 450 milliseconds. A positive dose-dependent association was identified between QTc length and dose of methadone, and all patients with a QTc above 500 milliseconds were taking methadone doses of 120 mg or more. OMT patient mortality, where QTc prolongation could not be excluded as the cause of death, was 0.06/100 patient-years. Only one death among 3850 OMT initiations occurred within the first month of treatment. Of the methadone patients, 4.6% had QTc intervals above 500 milliseconds. The maximum mortality attributable to QTc prolongation was low: 0.06 per 100 patient-years.

Andrews CM; Krantz MJ; Wedam EF; Marcuson MJ; Capacchione JF; Haigney MC. Methadone-induced mortality in the treatment of chronic pain: Role of QT prolongation. (review). Cardiology Journal 16(3): 210-217, 2009. (73 refs.)

Methadone is increasingly prescribed for chronic pain, yet the associated mortality appears to be rising disproportionately relative to other opioid analgesics. We review the available evidence on methadone-associated mortality, and explore potential pharmacokinetic and pharmacodynamic explanations for its greater apparent lethality. While methadone shares properties of central nervous system and respiratory depression with other opioids, methadone is unique as a potent blocker of the delayed rectifier potassium ion channel (IKr). This results in QT-prolongation and torsade de pointes (TdP) in susceptible individuals. In some individuals with low serum protein binding of methadone, the extent of blockade is roughly comparable to that of sotalol, a potent QT-prolonging drug. Predicting an individual's propensity for methadone-induced TdP is difficult at present given the inherent limitations of the QT interval as a risk-stratifier combined with the multifactorial nature of the arrhythmia. Consensus recommendations have recently been published to mitigate the risk of TdP until further studies better define the arrhythmia risk factors for methadone. Studies are needed to provide insights into the clinical covariates most likely to result in methadone-associated arrhythmia and to assess the feasibility of current risk mitigation strategies.

Arora S; Aukrust P; Andreassen A; Simonsen S; Gude E; Grov I et al. The prognostic importance of modifiable risk factors after heart transplantation. American Heart Journal 158(3): 431-436, 2009. (18 refs.)

Background: It is well established that the treatment of modifiable risk factors can reduce cardiovascular mortality in the general population. However, there is limited data evaluating the importance of modifiable risk factors for survival following heart transplantation (HTx). Hence, we evaluated the prognostic importance of smoking, obesity, hyperglycemia and hyperlipidemia at 1 year after HTx for all-cause and cardiac mortality. Methods We evaluated 38 +/- 1 patients attending their first annual visit post-HTx. Data regarding modifiable risk factors was collected together with other clinical variables. Median follow-up time was 7.4 years. Results: In total, there were 122 (32%) deaths and smoking and elevated total cholesterol were independent risk factors for all-cause mortality (adjusted HR 1.6 [P = .02] and 1.8 [P = .003], respectively). A significantly higher incidence of cardiac death was noted amongst smokers and patients with elevated total cholesterol. Elevated body mass index and hemoglobin A(1c) did not affect prognosis and elevated total cholesterol was not a risk factor once statin therapy commenced at the time of HTx was instituted as protocol. Conclusions Smoking is a risk factor for all-cause and cardiac mortality, but elevated total cholesterol is a risk factor only in the absence of statin therapy being commenced at the time of HTx.

Azarasa M; Azarfarin R; Changizi A; Alizadehasl A. Substance use among Iranian cardiac surgery patients and its effects on short-term outcome. Anesthesia and Analgesia 109(5): 1553-1559, 2009. (19 refs.)

BACKGROUND: We assessed the prevalence of substance use among patients undergoing coronary artery bypass graft and valve surgery in northwest Iran. We evaluated the postoperative complications and in-hospital mortality of patients with substance dependence and abuse. METHODS: In this prospective, observational study, we interviewed 600 patients during the preoperative visit in a tertiary referral educational hospital in northwest Iran. The definition of substance abuse and dependence was according to DSM-IV criteria. Postoperative complications and in-hospital mortality of patients with substance (cigarette, opium, and alcohol) dependence and abuse were compared with those in control patients who did not use these substances. RESULTS: In 600 studied patients, the prevalence of cigarette smoking was 42.1% (ex-smokers 26.0% and current smokers 16.1%,), prevalence of opium use was 12.0% (opium abuse 7.0% and opium dependence 5.0%), and alcohol consumption was 8.1% (alcohol abuse 7.4% and alcohol dependence 0.7%). The prevalence of cigarette smoking was 58.9% in men and 7.6% in women (P = 0.001). Postoperative cardiac complications in current smokers (21.5%) and ex-smokers (20.5%) were not significantly different from the control group (28.2%). Also, pulmonary complications were not different in current smokers (24.7%) and ex-smokers (17.9%) from the control group (26.8%; P = 0.196). However, in men, pulmonary complications in current smokers were more prevalent than in the control group (P = 0.044). In opium and alcohol dependents and abusers, postoperative complications were not statistically different from the control group (all P values >0.05). No increase was observed regarding in-hospital mortality in patients with substance use. CONCLUSIONS: In cardiac surgery patients in northwest Iran, the prevalence of cigarette smoking is relatively low (very low in women), as is alcohol use, compared with Western countries; however, opium use is twice as prevalent. We found higher pulmonary complication rates in men who smoked, but no increase in postoperative cardiopulmonary complications and in-hospital mortality rates in patients who abused opium and consumed alcohol.

Aziz O; Skapinakis P; Rahman S; Rao C; Ashrafian H; Panesar SS et al. Behavioural interventions for smoking cessation in patients hospitalised for a major cardiovascular event. International Journal of Cardiology 137(2): 171-174, 2009. (27 refs.)

The impact of cigarette smoking on progression of atherosclerosis in patients with known cardiovascular disease suggests a strong need for effective cessation interventions in this group. This letter compares and discusses smoking cessation outcomes following behavioural smoking cessation interventions versus usual care in hospitalised cardiovascular patients using meta-analysis of randomised controlled peer-reviewed publications. It particularly focuses on the impact of intensity and duration of intervention on outcome.

Baker A; Richmond R; Castle D; Kulkarni J; Kay-Lambkin F; Sakrouge R et al. Coronary heart disease risk reduction intervention among overweight smokers with a psychotic disorder: Pilot trial. Australian and New Zealand Journal of Psychiatry 43(2): 129-135, 2009. (26 refs.)

Objective: The aim of the present pilot study was to test the feasibility and short-term impact of a multi-component risk factor intervention for reducing (i) coronary heart disease (CHD) risk; (ii) smoking; and (iii) weight among smokers with psychosis. Secondary dependent variables included physical activity, unhealthy eating, substance use, psychiatric symptomatology, treatment retention, general functioning, and quality of life. Method: This was a feasibility study utilizing a pre-post-treatment design with no control group (n=43). All participants provided written informed consent and were assessed before treatment and again a mean of 19.6 weeks later. The treatment consisted of nine individual 1 h sessions of motivational interviewing and cognitive behaviour therapy plus nicotine replacement therapy, in addition to treatment as usual. Research assistants who had not been involved in the delivery of the treatment programme conducted post-treatment assessments. Results: The intervention was associated with significant reductions in CHD risk scores, smoking and weight. A significant improvement was also reported in level of moderate physical activity, and a small change in the unhealthy eating index was reported. No improvement in biological measures (cholesterol and blood pressure) was evident. Conclusions: A multi-component CHD risk factor intervention among smokers with psychosis appears to be feasible and effective in the short-term. A randomized controlled trial replicating and extending these findings is warranted.

Balakumar P; Kaur J. Is nicotine a key player or spectator in the induction and progression of cardiovascular disorders? (review). Pharmacological Research 60(5): 361-368, 2009. (141 refs.)

Cigarette smoking is common in societies worldwide and a growing body of evidence suggests that chronic cigarette smoking may affect the structure and function of cardiovascular system. The chronic exposure to high levels of nicotine, a major component of cigarette smoking, has been observed to play a pathogenic role in the induction and progression of cardiovascular disorders including cardiomyopathy and peripheral vascular disease. Nicotine alters the function of vascular endothelium, initiates the adhesion cascade and stimulates the vascular inflammatory events to induce atherosclerosis and hypertension. Moreover, nicotine has been noted to induce direct coronary spasm and ischemia, which develop coronary artery disease and myocardial infarction. In addition, nicotine stimulates the excessive release of impulses from sinoatrial node that may account for the induction of cardiac arrhythmia. The present review critically discussed the possible detrimental role of chronic nicotine exposure in cardiac and vascular endothelial dysfunction. Moreover, the signaling mechanisms involved in the pathogenesis of nicotine exposure-induced cardiovascular dysfunction have been discussed. In addition, the pharmacological interventions to ameliorate chronic nicotine exposure-induced cardiovascular abnormalities have been delineated.

Barnes DE; Haight TJ; Mehta KM; Carlson MC; Kuller LH; Tager IB. Secondhand smoke, vascular disease, and dementia incidence: Findings from the Cardiovascular Health Cognition Study. American Journal of Epidemiology 171(3): 292-302, 2010. (49 refs.)

Recent studies have found that smoking is associated with an increased risk of dementia, but the effects of secondhand smoke (SHS) on dementia risk are not known to have previously been studied. The authors used Cox proportional hazards marginal structural models to examine the association between self-reported lifetime household SHS exposure and risk of incident dementia over 6 years among 970 US participants in the Cardiovascular Health Cognition Study (performed from 1991 to 1999) who were never smokers and were free of clinical cardiovascular disease (CVD), dementia, and mild cognitive impairment at baseline. In addition, because prior studies have found that SHS is associated with increased risk of CVD and that CVD is associated with increased risk of dementia, the authors tested for interactions between SHS and measures of clinical and subclinical CVD on dementia risk. Moderate (16-25 years) and high (> 25 years) SHS exposure levels were not independently associated with dementia risk; however, subjects with > 25 years of SHS exposure and > 25% carotid artery stenosis had a 3-fold increase (hazard ratio = 3.00, 95% confidence interval: 1.03, 9.72) in dementia risk compared with subjects with no/low (0-15 years) SHS exposure and < 25% carotid artery stenosis. High lifetime SHS exposure may increase the risk of dementia in elderly with undiagnosed CVD.

Bart G. Concerns about consensus guidelines for QTc interval screening in methadone treatment. Annals of Internal Medicine 151(3): 218-218, 2009. (4 refs.)

Behar JM; Lindsay AC; McEwan JR. Cocaine-induced myocardial infarction: Not your average acute coronary syndrome. British Journal of Hospital Medicine 70(2): 108-109, 2009. (13 refs.)

This is a case report of a 31 year old woman who presented to an ER complaining of chest pains. Only 15 hours post-admission did she acknowledge being a regular cocaine user, who had smoked cocaine as well as injecting cocaine into the femeral artery the previous night, after which she experienced severe chest pain. Coronary angiopgraphy revelaed a thrombus in the proximal left anterior descending artery. The discussion summarizes the basis for cardiovascular problems in response to cocaine use, diagnostic issues, and clinical management and how cocaine-induced myocardial infarction requires different management than other acute coronary syndromes.

Berger AJ; Alford K. Cardiac arrest in a young man following excess consumption of caffeinated "energy drinks". Medical Journal of Australia 190(1): 41-43, 2009. (16 refs.)

An otherwise healthy 28-year-old man had a cardiac arrest after a day of motocross racing. He had consumed excessive amounts of a caffeinated "energy drink" throughout the day. We postulate that a combination of excessive ingestion of caffeine- and taurine-containing energy drinks and strenuous physical activity can produce myocardial ischaemia by inducing coronary vasospasm.

Bertelli AAA; Das DK. Grapes, wines, resveratrol, and heart health. (review). Journal of Cardiovascular Pharmacology 54(6): 468-476, 2009. (70 refs.)

Epidemiological and experimental studies have revealed that a mild to moderate drinking of wine, particularly red wine, attenuates the cardiovascular, cerebrovascular, and peripheral vascular risk. However, the experimental basis for such health benefits is not fully understood. The cardioprotective effect of wine has been attributed to both components of wine: the alcoholic portion and, more importantly, the alcohol-free portion containing antioxidants. Wines are manufactured from grapes, which also contain a large variety of antioxidants, including resveratrol, catechin, epicatechin, and proanthocyanidins. Resveratrol is mainly found in the grape skin, whereas proanthocyanidins are found only in the seeds. Recent studies have demonstrated that resveratrol and proanthocyanidin are the major compounds present in grapes and wines responsible for cardioprotection. The purpose of this review is to provide evidence that grapes, wines, and resveratrol are equally important in reducing the risk of morbidity and mortality due to cardiovascular complications. Both wines and grapes can attenuate cardiac diseases such as atherosclerosis and ischemic heart disease. Recently, wine was also found to increase life span by inducing longevity genes. It appears that resveratrol and proanthocyanidins, especially resveratrol, present in grapes and wines play a crucial role in cardioprotective abilities of grapes and wines.

Boffetta P; Straif K. Use of smokeless tobacco and risk of myocardial infarction and stroke: Systematic review with meta-analysis. British Medical Journal 339(article b3060), 2009. (28 refs.)

Objective: To assess whether people who use smokeless tobacco products are at increased risk of myocardial infarction and stroke. Design: Meta-analysis of observational studies from Sweden and the United States. Data sources Electronic databases and reference lists. Data extraction: Quantitative estimates of the association between use of smokeless tobacco products and risk of myocardial infarction and stroke among never smokers. Review methods Both authors independently abstracted risk estimates and study characteristics. Summary relative risks were estimated on the basis of random effects models. Results 11 studies, mainly in men, were included. Eight risk estimates were available for fatal myocardial infarction: the relative risk for ever use of smokeless tobacco products was 1.13 (95% confidence 1.06 to 1.21) and the excess risk was restricted to current users. The relative risk of fatal stroke, on the basis of five risk estimates, was 1.40 (1.28 to 1.54). The studies from both the United States and Sweden showed an increased risk of death from myocardial infarction and stroke. The inclusion of non-fatal myocardial infarction and non-fatal stroke lowered the summary risk estimates. Data on dose-response were limited but did not suggest a strong relation between risk of dying from either disease and frequency or duration of use of smokeless tobacco products. Conclusion: An association was detected between use of smokeless tobacco products and risk of fatal myocardial infarction and stroke, which does not seem to be explained by chance.

Bowen ME. Coronary heart disease from a life-course approach: Findings from the Health and Retirement Study, 1998-2004. Journal of Aging and Health 22(2): 219-241, 2010. (75 refs.)

Objective: Guided by a life-course approach to chronic disease, this study examined the ways in which childhood deprivation (low parental education and father's manual occupation) may be associated with coronary heart disease (CHD). Method: Multilevel modeling techniques and a nationally representative sample of Americans above age 50 from the Health and Retirement Study (HRS; N = 18,465) were used to examine childhood and CHD relationships over the course of 6 years (1998-2004). Results: Having a father with <= 8 years of education was associated with 11% higher odds of CHD, accounting for demographic characteristics, adult socioeconomic status (SES; education, income, and wealth), CHD risks (diabetes, hypertension, cigarette smoking, and obesity), and other factors (childhood health, exercise, stroke, and marital status). Discussion: Policies and programs aimed at improving the conditions of poor children and their families may effectively reduce the prevalence of CHD in later life.

Britton KA; Gaziano JM; Sesso HD; Djousse L. Relation of alcohol consumption and coronary heart disease in hypertensive male physicians (from the Physicians' Health Study). American Journal of Cardiology 104(7): 932-935, 2009. (18 refs.)

Alcohol has diverse effects on the cardiovascular system. Moderate drinking is associated with a decreased risk of cardiovascular disease, yet increasing amounts of alcohol consumption are known to increase blood pressure. These opposing effects have led to interest in the effect of moderate alcohol consumption on the risk of coronary heart disease (CHD) in patients with hypertension. To test the hypothesis that moderate alcohol consumption decreases the risk of myocardial infarction (MI) in patients with hypertension, we used data on 5,164 participants in the Physicians' Health Study who were apparently healthy and free of CHD at baseline. Incident MI was ascertained by annual follow-up questionnaires and validated through review of medical records. Cox proportional hazard model was used to compute multivariable-adjusted hazard ratios with corresponding 95% confidence intervals. From 1982 to 2008, 623 cases of MI occurred. Compared to subjects consuming <1 drink per week, hazard ratios for MI were 1.05 (95% confidence interval 0.85 to 1.28), 0.78 (95% confidence interval 0.64 to 0.97), and 0.57 (95% confidence interval 0.35 to 0.95) for alcohol consumption of I to 4, 5 to 7, and >8 drinks per week adjusted for age, body mass index, smoking, exercise, diabetes, multivitamin use, vegetable intake, breakfast cereal intake, and cholesterol, (p for trend <0.0022). Similar inferences could be made for the secondary outcomes of angina pectoris and any CHD (which included MI, angina pectoris, and previous revascularization). In conclusion, our data demonstrated an inverse relation between moderate alcohol consumption and CHD in hypertensive men.

Burra P; Senzolo M; Adam R; Delvart V; Karam V. Liver transplantation for alcoholic liver disease in Europe: A study from the ELTR (European Liver Transplant Registry). American Journal of Transplantation 10(1): 138-148, 2010. (25 refs.)

Alcohol-related liver disease (ALD) is one of the most common indications for liver transplantation (LT). Long-term outcome after LT for ALD versus other etiologies is still under debate. The aim of this study was to compare outcome after LT of patients with ALD, viral (VIR), and cryptogenic cirrhosis. Donor, graft and recipient ELTR variables were analysed in transplants for alcoholic and nonalcoholic cirrhosis (1988-2005) and were correlated with patient survival. Causes of death and/or graft failure were compared between groups. Nine thousand eight hundred eighty ALD, 10 943 VIR, 1478 ALD + VIR and 2410 cryptogenic (CRYP) liver transplants were evaluated. One, 3, 5 and 10 years graft survival rates after LT in ALD patients were 84%, 78%, 73%, 58%, significantly higher than in VIR and CRYP (p = 0.04, p = 0.05). By multivariate analysis, ALD + VIR (RR 1.14) and viral alone (RR 1.06) were significant risk factors for mortality. De novo tumors, cardiovascular and social causes were causes of death/graft failure in higher percentage in ALD groups versus other etiologies. LT for ALD cirrhosis has a favorable outcome, however, hepatitis C virus co-infection seems to eliminate this advantage. Screening for de novo tumors and prevention of cardiovascular complications are essential to provide better long-term results.

Buscemi S; Verga S; Batsis JA; Tranchina MR; Belmonte S; Mattina A et al. Dose-dependent effects of decaffeinated coffee on endothelial function in healthy subjects. European Journal of Clinical Nutrition 63(10): 1200-1205, 2009. (31 refs.)

Background/Objectives: Coffee is known to contain antioxidant substances whose effects may be blunted because of caffeine that may unfavorably affect the cardiovascular system. This study was designed to investigate the acute dose-dependent effects of decaffeinated coffee (DC) on endothelial function measured by the brachial artery flow-mediated dilation (FMD). Subjects/Methods: A total of 15 (8 men and 7 women) healthy nonobese subjects underwent a single-blind, crossover study. Subjects ingested one and two cups of decaffeinated Italian espresso coffee in random order at 5- to 7-day intervals. Results: In the hour following the ingestion of two cups of DC, FMD increased (mean +/- s.e.m.): 0 min, 7.4 +/- 0.7%; 30 min, 8.0 +/- 0.6%; 60 min, 10.8 +/- 0.8%; P < 0.001) as compared to consumption of one cup of DC (0 min, 6.9 < 0.7%; 30 min, 8.4 +/- 1.2%; 60 min, 8.5 +/- 1.1%; 3 x 2 repeated-measures analysis of variance: P = 0.037 for time x treatment effect). Blood pressure did not differ between groups, and basal heart rate was lower in the two-cup group at baseline and 60 min. Conclusions: The present study demonstrated a significant acute favorable dose-dependent effect of decaffeinated espresso coffee on endothelial function. Further studies are needed to investigate the effects of chronic use of DC especially with respect to caffeinated coffee and in subjects with cardiovascular diseases.

Buyukhatipoglu H; Tiryaki O; Usalan C. Impaired fibrinolytic and blunted nitric oxide response to phlebotomy in cigarette smoking healthy blood donors. Journal of International Medical Research 37(3): 674-679, 2009. (25 refs.)

This study was designed to investigate the effects of smoking on endothelial function in 88 healthy blood donors: 48 smokers and 40 non-smokers. Two markers of endothelial dysfunction, plasminogen activator inhibitor-1 (PAI-1) and nitric oxide (NO) levels, were measured at baseline and after phlebotomy. It has been proposed that phlebotomy acutely activates the renin-angiotensin-aldosterone system, thereby activating endothelial activity and increasing PAI-1 and NO expression. At baseline there were no significant differences between smokers and non-smokers in terms of PAI-1 expression and NO levels. After phlebotomy, both PAI-1 and NO levels were significantly increased in both groups. The increase in PAI-1 was more pronounced in smokers and the increase in NO was more pronounced in nonsmokers. These findings suggest that smoking causes endothelial dysfunction, even in healthy smokers, which may remain silent until a clinically evident disorder develops.

Byrne A. Concerns about consensus guidelines for QTc interval screening in methadone treatment. (letter). Annals of Internal Medicine 151(3): 216-216, 2009. (3 refs.)

Cagirci G; Cay S; Karakurt O; Eryasar N; Kaya V; Canga A et al. Influence of heavy cigarette smoking on heart rate variability and heart rate turbulence parameters. Annals of Noninvasive Electrocardiology 14(4): 327-332, 2009. (23 refs.)

Methods: Heavy cigarette smoking was defined as more than 20 cigarettes smoked per day. Heavy cigarette smokers, 69 subjects and nonsmokers 74 subjects (control group) were enrolled in this study. HRV and HRT analyses [turbulence onset (TO) and turbulence slope (TS)] were assessed from 24-hour Holter recordings. Results: The values of TO were significantly higher in heavy cigarette smokers than control group (-1.150 +/- 4.007 vs -2.454 +/- 2.796, P = 0.025, respectively), but values of TS were not statistically different between two groups (10.352 +/- 7.670 vs 9.613 +/- 7.245, P = 0.555, respectively). Also, the number of patients who had abnormal TO was significantly higher in heavy cigarette smokers than control group (23 vs 10, P = 0.006). TO was correlated with the number of cigarettes smoked per day (r = 0.235, P = 0.004). While LF and LF/HF ratio were significantly higher, standard deviation of all NN intervals (SDNN), standard deviation of the 5-minute mean RR intervals (SDANN), root mean square of successive differences (RMSSD), and high-frequency (HF) values were significantly lower in heavy smokers. While, there was significant correlation between TO and SDNN, SDANN, RMSSD, LF, and high frequency (HF), only HF was correlated with TS. Conclusion: Heavy cigarette smoking has negative effect on autonomic function. HRT is an appropriate noninvasive method to evaluate the effect of cigarette on autonomic function. Simultaneous abnormal HRT and HRV values may explain increased cardiovascular event risk in heavy cigarette smokers.

Caldarola P; Cuonzo M. QT Interval. Heroin Addiction and Related Clinical Problems 11(4): 5-9, 2009. (15 refs.)

The electrocardiogram records the electrical activity of the heart, the depolarization and repolarization of the atria and ventricles. Deflections are all shown by the single features of the electrocardiogram: the P wave, the QRS complex, the T wave, the U wave, the PR interval and the QT. The QT interval represents the entire electrical activity of the left ventricle: it begins with the onset of ventricular depolarization (start of the Q wave) and is completed when ventricular repolarization ends at the end of the T wave). Measurement of the QT interval is important because of the useful information it provides on the electrical activity of the heart; the length of the interval depends on various pathophysiological conditions, changes in electrolyte concentration, and the pharmacological action of toxic substances.

Cappelli F; Valente S; Gensini GF. Is it time to consider cannabis smoking a cardiovascular risk factor? (editorial). Journal of Cardiovascular Medicine 10(10): 745-746, 2009. (16 refs.)

Chikritzhs T; Fillmore K; Stockwell T. A healthy dose of scepticism: Four good reasons to think again about protective effects of alcohol on coronary heart disease. (editorial). Drug and Alcohol Review 28(4): 441-444, 2009. (16 refs.)

Issues. Alcohol has been implicated in both the popular press and scientific literature as having a protective effect for at least a dozen conditions including coronary heart disease (CHD). Approach. Epidemiological evidence for an apparent protective effect of alcohol on CHD is now being challenged on a number of fronts. This paper is a synopsis of those various challenges as they currently stand. Key Findings. The argument that systematic misclassification of ex-drinkers and occasional drinkers to 'abstainer' categories among epidemiological studies might explain apparent protective effects of moderate alcohol consumption on CHD has recently been supported by new meta-analyses and independent research. The influence of uncontrolled or unknown factors on the relationship between alcohol and disease cannot be ruled out. Exclusion of participants on the basis of ill-health severely reduces study sample size and new analyses suggest that doing so might artificially create the appearance of protective effects. The ability of respondents to accurately recall their own alcohol consumption is in serious doubt and very few individuals maintain one single drinking level or style throughout life. The relationship between alcohol and some conditions might be a function of drinking patterns but few studies have addressed the issue. Implications. Popular perceptions regarding the strength of evidence for alcohol's protective effect on a growing number of conditions might be misguided. Conclusion. It is time for the wider research, health and medical community to seriously reflect on the quality of current evidence for apparent protective effects of alcohol on human disease.

Chong E; Poh KK; Shen L; Yeh IB; Chai P. Infective endocarditis secondary to intravenous Subutex abuse. Singapore Medical Journal 50(1): 34-42, 2009. (16 refs.)

Introduction: Subutex (buprenophine) was approved by the Health Science Authority of Singapore for heroin detoxification in 2002. The number of heroin addicts has decreased in Singapore since the introduction of Subutex. However, Subutex abuse and its associated complications became arising medical problems. We report the management of a series of infective endocarditis cases secondary to Subutex abuse. Methods: We identified 12 cases of infective endocarditis in former heroin addicts treated with Subutex from August 2005 to April 2006. All patients were interviewed by the research coordinator and prospectively followed-up for two years. Results: The treatment period of Subutex endocarditis was often prolonged with a mean hospitalisation stay of 48 days, with 3.8 days in the intensive care unit. Multiple medical complications were noted. Staphylococcus aureus septicaemia accounted for 92 percent of cases. Mortality rate was 42 percent. Failure rate of medical therapy alone was common. 25 percent underwent open heart valve surgery. All patients were subsidised. Mean hospitalisation expenses was S$31,218. Conclusion: Subutex endocarditis causes significant morbidity and mortality. It imposes a heavy medical and financial burden to the patient and society. Multidisciplinary treatment involving cardiologists, infectious disease physicians, psychiatrists, surgeons, medical counsellors and social workers is required to manage these patients.

Chow CK; Jolly S; Rao-Melacini P; Fox KAA; Anand SS; Yusuf S. Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes. Circulation 121(6): 750-758, 2010. (20 refs.)

Background-Although preventive drug therapy is a priority after acute coronary syndrome, less is known about adherence to behavioral recommendations. The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events. Methods and Results: The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS) 5 randomized clinical trial. At the 30-day follow-up, patients reported adherence to diet, physical activity, and smoking cessation. Cardiovascular events (myocardial infarction, stroke, cardiovascular death) and all-cause mortality were documented to 6 months. About one third of smokers persisted in smoking. Adherence to neither diet nor exercise recommendations was reported by 28.5%, adherence to either diet or exercise by 41.6%, and adherence to both by 29.9%. In contrast, 96.1% of subjects reported antiplatelet use, 78.9% reported statin use, and 72.4% reported angiotensin-converting enzyme/angiotensin receptor blocker use. Quitting smoking was associated with a decreased risk of myocardial infarction compared with persistent smoking (odds ratio, 0.57; 95% confidence interval, 0.36 to 0.89). Diet and exercise adherence was associated with a decreased risk of myocardial infarction compared with nonadherence (odds ratio, 0.52; 95% confidence interval, 0.4 to 0.69). Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold (95% confidence interval, 2.5 to 5.9) increased risk of myocardial infarction/stroke/death compared with never smokers who modified diet and exercise. Conclusions-Adherence to behavioral advice (diet, exercise, and smoking cessation) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events. These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary syndrome.

Ciftci O; Caliskan M; Guilu H; Erdogan D; Topcu S; Guler O et al. Acute effects of smoking light cigarettes on coronary microvascular functions. Clinical Cardiology 32(4): 210-214, 2009. (21 refs.)

Background: To date, there has been no study comparing the possible acute effects on coronary microvascular functions of smoking light cigarettes (those with low tar and nicotine yield) and regular cigarettes. Methods: Twenty healthy volunteers (8 women and 12 men; mean age, 25.8 +/- 5.8 years) were included in a single-blind, open-label, cross-over study to compare the effects of smoking light cigarettes (containing 0.6 mg nicotine, 8 mg tar, 9 mg carbon monoxide) and smoking regular cigarettes (containing 0.9 mg nicotine, 12 mg tar, 12 Mg carbon monoxide) on coronary flow reserve (CFR). For each participant, CFR values were measured at baseline, after smoking 2 regular or light cigarettes, and 15 days later after smoking 2 cigarettes of the other kind. Results: After smoking 2 cigarettes, CFR values declined from 2.8 +/- 0.56 (baseline) to 2.31 +/- 0.51 after smoking tight cigarettes (P = .003), and from 2.8 +/- 0.56 (baseline) to 2.21 +/- 0.45 after smoking regular cigarettes (P < .001). After smoking light and regular cigarettes, CFR values were similar (P = .678). Conclusions: Light cigarette smoking has similar acute detrimental effects on coronary microvascular function and CFR as does regular cigarette smoking.

Cohen SP; Mao JR. Concerns about consensus guidelines for QTc interval screening in methadone treatment. (letter). Annals of Internal Medicine 151(3): 216-217, 2009. (5 refs.)

Collins MA; Neafsey EJ; Mukamal KJ; Gray MO; Parks DA; Das DK et al. Alcohol in moderation, cardioprotection, and neuroprotection: Epidemiological considerations and mechanistic studies. (review). Alcoholism: Clinical and Experimental Research 33(2): 206-219, 2009. (120 refs.)

In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions-pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, beta-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol-dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress-associated, anti-inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways.

Cop-Blazic N; Zavoreo I. There is no healthy level of smoking. Acta Clinica Croatica 48(3): 371-376, 2009. (28 refs.)

Cigarette smoking is the leading preventable cause of death in the world. Nicotine is a highly addictive substance. Nicotine dependence is a major barrier to successful smoking cessation. Smoking is a risk factor for 30 diseases with a high rate of morbidity and mortality. There is no safe level of smoking. Help and support to smoking cessation should be ail integral part of treatment, particularly for cardiovascular and cerebrovascular diseases. Prevention of smoking and effective treatment for nicotine dependence can significantly decrease the risk of vascular and malignant diseases.

Cruickshank CC; Dyer KR. A review of the clinical pharmacology of methamphetamine. (review). Addiction 104(7): 1085-1099, 2009. (182 refs.)

To examine the literature regarding clinical pharmacokinetics, direct effects and adverse clinical outcomes associated with methamphetamine use. Relevant literature was identified through a PubMed search. Additional literature was obtained from relevant books and monographs. The mean elimination half-life for methamphetamine is approximately 10 hours, with considerable inter-individual variability in pharmacokinetics. Direct effects at low-to-moderate methamphetamine doses (5-30 mg) include arousal, positive mood, cardiac stimulation and acute improvement in cognitive domains such as attention and psychomotor coordination. At higher doses used typically by illicit users (>= 50 mg), methamphetamine can produce psychosis. Its hypertensive effect can produce a number of acute and chronic cardiovascular complications. Repeated use may induce neurotoxicity, associated with prolonged psychiatric symptoms, cognitive impairment and an increased risk of developing Parkinson's disease. Abrupt cessation of repeated methamphetamine use leads to a withdrawal syndrome consisting of depressed mood, anxiety and sleep disturbance. Acute withdrawal lasts typically for 7-10 days, and residual symptoms associated with neurotoxicity may persist for several months.

Darke S; Duflou J; Torok M. The comparative toxicology and major organ pathology of fatal methadone and heroin toxicity cases. Drug and Alcohol Dependence 106(1): 1-6, 2010. (23 refs.)

In order to determine the comparative toxicology and systemic disease of cases of death due to methadone and heroin toxicity, 1193 coronial cases of opioid overdose that occurred in New South Wales, Australia between I January 1998 and 31 December 2007 were inspected. These comprised 193 cases in which cause of death involved methadone toxicity (METH) and 1000 cases in which cause of death involved heroin toxicity in the absence of methadone (HER). METH cases were significantly more likely to have benzodiazepines (63.7% vs. 32.2%), and less likely to have alcohol (23.6% vs. 42.7%) detected. METH cases were significantly more likely to be diagnosed with pre-existing systemic pathology (94.3% vs. 79.9%), and Multiple organ system pathology (68.8% vs. 41.4%). Specifically, METH cases were more likely to have cardiac (58.9% vs. 34.5%), pulmonary (53.6% vs. 30.9%), hepatic (80.7% vs. 62.8%) and renal (25.0% vs. 9.5%) disease. Given the notable differences in toxicology and disease patterns, great caution appears warranted in prescribing benzodiazepines to methadone users, and regular physical examinations of methadone treatment patients would appear clinically warranted.

de Leone A; Giaquinto S; Riegler G. Suspension of smoking is a risk factor for ulcerative colitis diagnosed after an acute myocardial infarction. (letter). Journal of Crohn's & Colitis 3(3): 215-215, 2009. (4 refs.)

Deruvo G; Vendramin A; Di Sciascio G. Psychoactive drugs and prolongation of the QT interval. Heroin Addiction and Related Clinical Problems 11(4): 11-19, 2009. (25 refs.)

The links between psychiatry and cardiology that are pertinent to potential cardiovascular risks associated with the use of psychotropic drugs, especially antipsychotics, cannot be viewed as entirely new. In Italy, however, an important innovation wag made when, on 28 February 2007, the Italian Medicines Agency (AIFA), issued a directive laying down provisions for the amendment of the printed papers that accompany various medicines, including haloperidol: that initiative has revived the relevance of the whole question. In particular, contraindications to the use of these drugs have been redefined. The primary ones are now listed as acute myocardial infarction, decompensated heart failure, arrhythmias treated with antiarrhythmic drugs be longing to special classes, the prolongation of the QT interval corrected for heart rate (QTc), the family history for arrhythmia or torsades de pointes, hypokalaemia and the concomitant use of drugs that prolong the QTc.

Desai NR; Mega JL; Jiang ST; Cannon CP; Sabatine MS. Interaction between cigarette smoking and clinical benefit of clopidogrel. Journal of the American College of Cardiology 53(15): 1273-1278, 2009. (28 refs.)

Objectives: The aim of this study was to examine the interaction between cigarette smoking and the clinical efficacy of clopidogrel in ST-segment elevation myocardial infarction (STEMI). Background: Cigarette smoking induces cytochrome P450 (CYP)1A2, which converts clopidogrel into its active metabolite, and prior studies suggest greater inhibition of platelet aggregation by clopidogrel in smokers of >= 10 cigarettes/day. Methods The effect of clopidogrel compared with placebo on angiographic and clinical outcomes was examined in 3,429 STEMI patients in the CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28) randomized trial stratified by smoking intensity as follows: not current smokers (n = 1,732), and smokers of 1 to 9 (n = 206), 10 to 19 (n = 354), 20 to 29 (n = 715), and >= 30 cigarettes/day (n = 422). Logistic regression was used to adjust for other baseline characteristics and interaction terms to test for effect modification. Results: Although clopidogrel reduced the rate of the primary end point of a closed infarct-related artery or death/myocardial infarction before angiography in the CLARITY-TIMI 28 trial, the benefit was especially marked among those who smoked >= 10 cigarettes/day (adjusted odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.37 to 0.66; p < 0.0001) compared with those who did not (adjusted OR: 0.72, 95% CI: 0.57 to 0.91; p = 0.006; p(interaction) = 0.04). Similarly, clopidogrel was significantly more effective at reducing the rate of cardiovascular death, myocardial infarction, or urgent revascularization through 30 days among those who smoked >= 10 cigarettes/ day (adjusted OR: 0.54, 95% CI: 0.38 to 0.76; p = 0.0004) compared with those who did not (adjusted OR: 0.98; 95% CI: 0.75 to 1.28; p = 0.87; p(interaction) = 0.006). Conclusions: Cigarette smoking seems to positively modify the beneficial effect of clopidogrel on angiographic and clinical outcomes. This study demonstrates that common clinical factors that influence the metabolism of clopidogrel might impact its clinical effectiveness.

Dhaliwal SS; Welborn TA. Central obesity and cigarette smoking are key determinants of cardiovascular disease deaths in Australia: A public health perspective. Preventive Medicine 49(2-3): 153-157, 2009. (31 refs.)

Background. our objective is to develop a parsimonious model to predict coronary heart disease (CHD) and cardiovascular disease (CVD) deaths using individual components of the Framingham risk score plus measures of central obesity. Methods. 15 year mortality follow-up of 8662 representative Australian adults in the National Heart Foundation Risk Factor Prevalence Survey of 1989, excluding those with a baseline history of heart disease, stroke or diabetes. Measures included blood pressure, fasting lipids, smoking history, body mass index (BMI), waist circumference (WC) and waist to hip ratio (WHIR). Multivariable logistic regression was used to assess the effects of the Framingham risk variables and central obesity variables on cardiovascular disease mortality. Results . Smoking status, high density lipoprotein cholesterol (HDL-C) and the total cholesterol (TC) to HDL-C ratio were significant univariate predictors of CHD deaths. These together with systolic blood pressure were significant predictors of CVD deaths. The obesity measures of WC and WHR were significant univariate predictors but BMI was not. In multivariable analyses, only smoking status and waist to hip ratio were identified as key independent risk factors for CHD and CVD deaths, although TC to HDL-C ratio contributed minimally to CHD deaths. Receiver operator characteristic (ROC) curves for the Framingham risk score in comparison to the WHIR plus smoking model were virtually identical, with no added effect of the lipid ratio. Conclusion. The preferred model for predicting CHD and CVD deaths uses central obesity plus smoking with no added influence of measured lipids or blood pressure. A public health focus on identifying and modifying central obesity is at least as important as the measurement and treatment of lipids and hypertension.

Ding D; Fung JWH; Zhang Q; Yip GWK; Chan CK; Yu CM. Effect of household passive smoking exposure on the risk of ischaemic heart disease in never-smoke female patients in Hong Kong. Tobacco Control 18(5): 354-357, 2009. (21 refs.)

Objective: To investigate the relation between household passive smoking exposure and risk of ischaemic heart disease (IHD) among never-smoke female patients by a retrospective case-control analysis. Methods: This study recruited 314 patients with IHD who had never smoked and 319 controls who were admitted for other reasons in the same hospital during the same period. Subjects were interviewed about their exposure to household passive smoking. The dose metrics of passive smoking exposure were evaluated by using "pack years'' and "hour years'', which indicated the cumulative amount and duration of exposure. The ORs and 95% CIs were computed by unconditional logistic regression, adjusted for other risk factors. Results: Subjects with passive smoking exposure were associated with higher risk of IHD (OR 1.51, 95% CI 1.01 to 2.27, p = 0.043) when compared to non-exposed subjects. Subjects exposed to an average of >= 1 pack of cigarette per day had an OR of 1.69 (95% CI 1.07 to 2.68, p = 0.025). The OR was 1.52 for those exposed for >= 5 years (95% CI 1.01 to 2.29, p = 0.043) and was 1.82 for those exposed >= 4 h per day (95% CI 1.05 to 3.15, p = 0.032). Similarly, the risk of IHD increased with cumulative exposure duration, with an OR of 1.53 (95% CI 1.01 to 2.32, p = 0.043) at the exposure level >= 5 pack years, and an OR of 1.61 (95% CI 1.03 to 2.52, p = 0.037) at the exposure level >= 20 hour years. There was a significant dose-response association between the exposure measures and risk of IHD (p < 0.01 for trend). Conclusion: Our data suggested an increased risk of IHD from passive household smoking in female never-smoke subjects, and demonstrated a dose-response association.

Djousse L; Driver JA; Gaziano JM. Relation between modifiable lifestyle factors and lifetime risk of heart failure. Journal of the American Medical Association 302(4): 394-400, 2009. (46 refs.)

Context: The lifetime risk of heart failure at age 40 years is approximately 1 in 5 in the general population; however, little is known about the association between modifiable lifestyle factors and the remaining lifetime risk of heart failure. Objective To examine the association between modifiable lifestyle factors and the lifetime risk of heart failure in a large cohort of men. Design, Setting, and Participant: Prospective cohort study using data from 20 900 men (mean age at baseline, 53.6 years) from the Physicians' Health Study I (19822008) who were apparently healthy at baseline. Six modifiable lifestyle factors were assessed: body weight, smoking, exercise, alcohol intake, consumption of breakfast cereals, and consumption of fruits and vegetables. Main Outcome Measure: Lifetime risk of heart failure. Results: During a mean follow-up of 22.4 years, 1200 men developed heart failure. Overall, the lifetime risk of heart failure was 13.8% (95% confidence interval [CI], 12.9%-14.7%) at age 40 years. Lifetime risk remained constant in men who survived free of heart failure through age 70 years and reached 10.6% (95% CI, 9.4%-11.7%) at age 80 years. Lifetime risk of heart failure was higher in men with hypertension than in those without hypertension. Healthy lifestyle habits (normal body weight, not smoking, regular exercise, moderate alcohol intake, consumption of breakfast cereals, and consumption of fruits and vegetables) were individually and jointly associated with a lower lifetime risk of heart failure, with the highest risk in men adhering to none of the 6 lifestyle factors (21.2%; 95% CI, 16.8%-25.6%) and the lowest risk in men adhering to 4 or more desirable factors (10.1%; 95% CI, 7.9%-12.3%). Conclusion: In this cohort of apparently healthy men, adherence to healthy lifestyle factors is associated with a lower lifetime risk of heart failure.

Djousse L; Lee IM; Buring JE; Gaziano JM. Alcohol consumption and risk of cardiovascular disease and death in women: Potential mediating mechanisms. Circulation 120(3): 237-244, 2009. (48 refs.)

Background-Although an association between moderate alcohol consumption and decreased cardiovascular disease (CVD) and death has been reported, limited data are available on potential mediating mechanisms. We examined the association between alcohol and CVD and death in 26 399 women and estimated the proportion of reduced risk of CVD/death explained by a series of intermediate factors. Methods and Results-Alcohol consumption was self-reported at baseline, and CVD events and deaths were ascertained via follow-up questionnaires and medical records. Baseline levels of hemoglobin A1c, inflammatory markers, hemostatic factors, and lipids were measured. Blood pressure and hypercholesterolemia and treatment for lipids were self-reported. During a mean follow up of 12.2 years, 1039 CVD events and 785 deaths (153 CVD deaths) occurred. There was a J-shaped relation between alcohol consumption and incident CVD and total and CVD deaths in a multivariable model. Compared with abstainers, alcohol intake of 5 to 14.9 g/d was associated with 26%, 35%, and 51% lower risk of CVD, total death, and CVD death, respectively, in a multivariable model. For CVD risk reduction, lipids made the largest contribution to the lower risk of CVD (28.7%), followed by hemoglobin A1c/diabetes (25.3%), inflammatory/hemostatic factors (5%), and blood pressure factors (4.6%). All these mediating factors together explained 86.3%, 18.7%, and 21.8% of the observed lower risk of CVD, total death, and CVD death, respectively. Conclusions-These data suggest that alcohol effects on lipids and insulin sensitivity may account for a large proportion of the lower risk of CVD/death observed with moderate drinking under the assumption that the alcohol-CVD association is causal.

Eisenberg MJ; Blum LM; Filion KB; Rinfret S; Pilote L; Paradis G et al. The efficacy of smoking cessation therapies in cardiac patients: A meta-analysis of randomized controlled trials. Canadian Journal of Cardiology 26(2): 73-79, 2010. (42 refs.)

INTRODUCTION: Several meta-analyses have examined the efficacy of smoking cessation therapies in the general population. However, little is known about the efficacy of these therapies in cardiac patients. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to determine the efficacy of behavioural therapy and pharmacotherapy for smoking cessation in cardiac patients. METHODS: The medical literature was systematically reviewed to identify smoking cessation RCT in cardiac patients. Only RCTs that reported smoking abstinence at six or 12 months were included. Smoking abstinence was examined based on the 'most rigorous criterion', defined as the most conservative outcome reported in any given RCT. RESULTS: Eleven behavioural therapy RCTs that enrolled 2105 patients and four pharmacotherapy RCTs chat enrolled 1542 patients were identified. RCTs differed in the type of behavioural therapy administered as well as the total length and duration of the intervention. RCTs differed in the type of pharmacotherapy administered (one nicotine patch RCT one nicotine guru RCT and two bupropion RCTs). Behavioural therapy was associated with a significantly higher proportion of smoking abstinence than usual care (OR 1.97 [95% CI 1.37 to 2.851). Pharmacotherapies were more efficacious than placebo (pooled OR 1.72 195% CI 1.15 to 2.571). CONCLUSIONS: Both behavioural therapy and pharmacotherapy are more efficacious than usual care for smoking cessation in cardiac patients. The present meta-analysis highlights the need for head-to-head RCTs to identify which smoking cessation therapy is preferred in cardiac patients as well as RCT, examining the efficacy of combined behavioural and pharmacotherapies.

Erhardt L. Cigarette smoking: An undertreated risk factor for cardiovascular disease. (review). Atherosclerosis 205(1): 23-32, 2009. (97 refs.)

Smoking and other forms of tobacco use are major risk factors for cardiovascular disease. The effect of cigarette smoking on cardiovascular health is evident even at the lowest levels of exposure. Yet, the adverse effects of smoking are reversible, with cardiovascular risk decreasing substantially within the first 2 years of smoking cessation. Significantly, the mortality from coronary heart disease is reduced more through smoking cessation than by other secondary preventive therapies such as cholesterol lowering. Smoking cessation is a highly effective way to improve cardiovascular health in smokers and extremely cost-effective. However, smoking cessation therapies are not implemented maximally if they are implemented at all, perhaps because smoking is seen as a lifestyle choice or because smokers frequently relapse, as indicated by very low long-term quit rates. Too often, healthcare professionals, including lipidologists and cardiologists, do little to address their patients' smoking status, in spite of its impact on cardiovascular health. With the advent of new therapies to treat the nicotine addiction that results from smoking and other tobacco use, it is hoped that physicians will be more proactive in encouraging and implementing smoking cessation programs for their patients, with the goal of increasing long-term quit rates, and reducing the morbidity and mortality associated with cardiovascular disease.

Foerster M; Marques-Vidal P; Gmel G; Daeppen JB; Cornuz J; Hayoz D et al. Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption. American Journal of Cardiology 103(3): 361-368, 2009. (30 refs.)

Moderate alcohol consumption has been associated with lower coronary artery disease (CAD) risk. However, data on the CAD risk associated with high alcohol consumption are conflicting. The aim of this study was to examine the impact of heavier drinking on 10-year CAD risk in a population with high mean alcohol consumption. In a population-based study of 5,769 adults (aged 35 to 75 years) without cardiovascular disease in Switzerland, 1-week alcohol consumption was categorized as 0, 1 to 6, 7 to 13, 14 to 20, 21 to 27, 28 to 34, and >= 35 drinks/week or as nondrinkers. (0 drinks/week), moderate (1 to 13 drinks/week), high (14 to 34 drinks/week), and very high (>= 35 drinks/week). Blood pressure and lipids were measured, and 10-year CAD risk was calculated according to the Framingham risk score. Seventy-three percent (n = 4,214) of the participants consumed alcohol; 16% (n = 909) were high drinkers and 2% (n = 119) very high drinkers. In multivariate analysis, increasing alcohol consumption was associated with higher high-density lipoprotein cholesterol (from a mean +/- SE of 1.57 +/- 0.01 mmol/L in nondrinkers to 1.88 +/- 0.03 mmo/L in very high drinkers); triglycerides (1.17 +/- 1.01 to 1.32 +/- 1.05 mmol/L), and systolic and diastolic blood pressure (127.4 +/- 0.4 to 132.2 +/- 1.4 mm Hg and 78.7 +/- 0.3 to 81.7 +/- 0.9 mm Hg, respectively) (all p values for trend <0.001). Ten-year CAD risk increased from 4.31 +/- 0.10% to 4.90 +/- 0.37% (p = 0.03) with alcohol use, with a J-shaped relation. Increasing wine consumption was more related to high-density lipoprotein cholesterol levels, whereas beer and spirits were related to increased triglyceride levels. In conclusion, as measured by 10-year CAD risk, the protective effect of alcohol consumption disappears in very high drinkers, because the beneficial increase in high-density lipoprotein cholesterol is offset by the increases in blood pressure levels.

Fonseca F; Marti-Almor J; Pastor A; Cladellas M; Farre M; de la Torre R et al. Prevalence of long QTc interval in methadone maintenance patients. Drug and Alcohol Dependence 99(1-3): 327-332, 2009. (33 refs.)

Background: There is a concern about cardiac rhythm disorders related to QTc interval prolongation induced by methadone. A cross-sectional study was designed to evaluate the prevalence of long QTc (LQTc) interval in patients in methadone maintenance treatment (MMT) and risk factors for LQTc. Methods: The study population included 109 Subjects (74 males, median age 43 years). Socio-demographic and toxicological variables were recorded, as well as concomitant use of drugs related with QT prolongation, history of heart diseases, and corrected QT interval by heart rate (QTc) in the ECG. Plasma concentrations of(R)-methadone and (S)-methadone enantiomers were determined in 69 Subjects. Results: Ten patients (9.2%) presented a QTc above 440 ms but a QTc above 500 ins was observed in only 2 Patients with QTc above 440 ms compared with the remaining subjects were older (median [25th-75th percentile range]: 49 [39-56] years vs. 37 [33-43]; Wilcoxon's W = 217.5, p = 0.002) and took a higher daily dose of methadone (median [25th-75th percentile range]: 120 [66-228] mg/day vs. 60 [40-110] mg/day: W = 298.5, p = 0.037). Methadone dose correlated with QTc interval (Pearson's r(2) = 0.291, p = 0.002). Patients with and without long QTc showed no differences in plasma concentrations of (R)-methadone and (S)-methadone enantiomers. Conclusions: The prevalence of LQTc was 9.2%. An association between LQTc and methadone doses was observed but the relationship with plasma concentrations of methadone enantiomers; is unclear.

Fuster M; Estrada V; Fernandez-Pinilla MC; Fuentes-Ferrer ME; Tellez MJ; Vergas J et al. Smoking cessation in HIV patients: Rate of success and associated factors. HIV Medicine 10(10): 614-619, 2009. (24 refs.)

Background: Smoking is the modifiable cardiovascular (CV) risk factor that contributes most to causing premature CV disease. Prevalence of smoking in patients with HIV infection is double that of the general population. Objectives: To determine the rate of patients succeeding in quitting smoking after 12 months, factors associated with this success, and the characteristics of tobacco consumption and nicotine dependence. Methods: Longitudinal descriptive study. Three hundred and sixty-eight HIV-infected patients were interviewed. Smokers in Prochaska's stage of action began a programme to quit smoking. We registered the variables related to tobacco consumption and the level of success of cessation. Results: 63.9% of the patients were active smokers and 14% of them began the cessation programme. Average motivation for cessation was 7.8 +/- 1.4 (Richmond) and nicotine dependence rate 5.5 +/- 3.0 (Fagerstrom). After 1 year, 25% had quit smoking. Those patients who stopped smoking presented a higher motivation level (8.8 +/- 1.3 vs. 7.5 +/- 1.5, P=0.048). Cessation significantly reduced their CV risk at 12 months {2.5 [interquartile range (IQR) 2.0-5.2] vs. 1.7 [IQR 1.0-3.5], P=0.026}. Conclusions The prevalence of smokers in our population of HIV-infected patients was 63.9%. Only 14% began a smoking cessation programme. Twelve months after a programme to quit smoking, cessation rate was 25%; this was influenced mostly by the level of motivation of the patient.

Gambarana C. Cardiovascular complications of cocaine use. Heroin Addiction and Related Clinical Problems 11(4): 35-39, 2009. (16 refs.)

As cocaine use has become prevalent, an increasing number of reports of cocaine-associated morbidity and mortality, largely because of central nervous system and cardiovascular toxicity, appeared. Cardiovascular toxicity is broad, and it may also lead to neurological, psychiatric and other organ-specific symptoms. Cocaine may induce myocardial ischemia by increasing myocardial oxygen demand while simultaneously decreasing myocardial Oxygen Supply. Most of the cardiovascular toxic effects elicited by cocaine are likely related to its ability to selectively bind to the L-type calcium channels and the potassium channels that modulate the Ikr current. In addition, cocaine may promote intracoronary thrombosis in the absence of corona y atherosclerosis. This article briefly reviews the current knowledge regarding the cardiovascular effects of cocaine, providing insight into some of the underpinning mechanisms.

Gasparrini A; Gorini G; Barchielli A. On the relationship between smoking bans and incidence of acute myocardial infarction. European Journal of Epidemiology 24(10): 597-602, 2009. (40 refs.)

During the last few years several studies have reported a substantial reduction of acute myocardial infarction (AMI) in the general population few months after the enforcement of comprehensive smoking bans. We reviewed the consistency and plausibility of this association, investigating the effect of the Italian law, entered into force on January 10, 2005. We compared the AMI incidence on the first year after the ban with the period before (2000-2004) in the Tuscany population aged 30-64 years. The analysis was performed with a Poisson model of the monthly time-series, adjusting for seasonality and comparing different models with linear and non-linear long-term trends. While the model with linear time trend estimated a decrease of 5.4% (RR 0.95; 95% CI: 0.89-1.00), this effect completely disappeared once the linearity assumption was relaxed (RR 1.01; 95% CI: 0.93-1.10). The model with non-linear terms showed a significantly improved fit (P-value = 0.01). The estimate of the effect of the ban seems to be highly sensitive to the model specification and to the effects of unaccounted factors which could modify the trend of AMI incidence, such as changes in the prevalence of other risk factors or the modification of diagnostic criteria. Several arguments which are put forward to inspect the causal relation between smoking bans and AMI indicate that the plausible effects could be lower than the estimates reported so far.

Gerber Y; Rosen LJ; Goldbourt U; Benyamini Y; Drory Y. Smoking status and long-term survival after first acute myocardial infarction: A population-based cohort study. Journal of the American College Of Cardiology 54(25): 2382-2387, 2009. (30 refs.)

Objectives We compared long-term survival after acute myocardial infarction (AMI) of never-smokers, pre-AMI quitters, post-AMI quitters, and persistent smokers and assessed whether cigarette reduction among persistent smokers is associated with lower mortality. Background: Quitting smoking has been shown to improve outcome after AMI. However, longitudinal cohort data with repeated assessments of smoking and information on multiple confounders are lacking. Moreover, little is known about the importance, if any, of reductions in the amount smoked. Methods Consecutive patients <= 65 years of age, discharged from 8 hospitals in central Israel after first AMI in 1992 to 1993, were followed through 2005. Extensive data, including self-reported smoking habits, were obtained at baseline and 4 times during follow-up. Cox proportional hazards regressions were used to assess the hazard ratios (HRs) for death associated with smoking categories modeled as time-dependent variables. Results: At baseline, smokers were younger, more likely to be male, and had a lower prevalence of hypertension and diabetes than nonsmokers. Over a median follow-up of 13.2 years, 427 deaths occurred in 1,521 patients. The multivariable-adjusted HRs for mortality were 0.57 (95% confidence interval [CI]: 0.43 to 0.76) for never-smokers, 0.50 (95% CI: 0.36 to 0.68) for pre-AMI quitters, and 0.63 (95% CI: 0.48 to 0.82) for post-AMI quitters, compared with persistent smokers. Among persistent smokers, upon multivariable adjustment including pre-AMI intensity, each reduction of 5 cigarettes smoked daily after AMI was associated with an 18% decline in mortality risk (p < 0.001). Conclusions: Smoking cessation either before or after AMI is associated with improved survival. Among persistent smokers, reducing intensity after AMI appears to be beneficial.

Gerlich MG; Kramer A; Gmel G; Maggiorini M; Luscher TF; Rickli H et al. Patterns of alcohol consumption and acute myocardial infarction: A case-crossover analysis. European Addiction Research 15(3): 143-149, 2009. (46 refs.)

Background: Alcohol consumption has been causally related to the incidence of coronary heart disease, but the role of alcohol before the event has not been explored in depth. This study tested the hypothesis that heavy drinking (binge drinking) increases the risk of subsequent acute myocardial infarctions (AMI), whereas light to moderate drinking occasions decrease the risk. Methods: Case-crossover design of 250 incident AMI cases in Switzerland, with main hypotheses tested by conditional logistic regression. Results: Alcohol consumption 12 h before the event significantly increased the risk of AMI (OR 3.1;95% CI 1.4-6.9). Separately, the effects of moderate and binge drinking before the event on AMI were of similar size but did not reach significance. In addition, AMI patients showed more binge drinking than comparable control subjects from the Swiss general population. Conclusions: We found no evidence that alcohol consumption before the event had protective effects on AMI. Instead, alcohol consumption increased the risk.

Girgis G. Concerns about consensus guidelines for QTc interval screening in methadone treatment. (letter). Annals of Internal Medicine 151(3): 217-218, 2009. (9 refs.)

Hall W; Degenhardt L. Adverse health effects of non-medical cannabis use. (review). Lancet 374(9698): 1383-1391, 2009. (97 refs.)

For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest --that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.

Hewitt S; Graff-Iversen S. Risk factors for cardiovascular diseases and diabetes in disability pensioners aged 40-42 years: A cross-sectional study in Norway. Scandinavian Journal of Public Health 37(3): 280-286, 2009. (28 refs.)

Aims: Few disability pensions at the age of 40 in Norway are granted due to cardiovascular diseases (CVD) or diabetes, but disability pensioners have an excess mortality of these diseases. In this study, we aim to present risk factors for CVD and diabetes in young disability pensioners, compared with persons able to work. Methods: A population-based survey of Norwegian men and women aged 40-42 years was conducted in 1997-1999, with 62,778 participants. Disability pensioners (n = 2636) and other non-working persons (n = 5105) were compared with persons able to work. Risk factors were compared in persons without CVD and diabetes. Results: Prevalence of self-reported CVD and diabetes was markedly higher in disability pensioners than in persons able to work. In persons without these diseases, we found elevations of all measured risk factors were more prevalent in disabled men and women. Myocardial infarction risk was about 50% higher in disability pensioners. Disability pensioners were more physically inactive and obese; they smoked more and had lipid disorders with elevated total cholesterol, low high-density lipoprotein (hdl)-cholesterol and elevated triglycerides. Other non-working persons had less pronounced elevations of most of the risk factors. Conclusions: A high proportion of disability pensioners and others not working at the age of 40 had an elevated risk for CVD and diabetes.

Ho EL; Josephson SA; Lee HS; Smith WS. Cerebrovascular complications of methamphetamine abuse. Neurocritical Care 10(3): 295-305, 2009. (44 refs.)

Methamphetamine is a stimulant widely abused in the United States. The objective of this study was to demonstrate an association of methamphetamine use and ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage and to further reveal the underlying vascular pathology using neuroimaging and pathology. This was a retrospective study based on medical chart review of admissions to the neurovascular service of a tertiary care medical center from January 2003 to July 2007. Cases included patients who used methamphetamine as documented by history or urine toxicology screening. From 1,574 records, 30 cases were identified. The mean age of patients was 43 years and the discharge diagnoses included ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. All subarachnoid hemorrhages were aneurysmal with the majority of the aneurysms located in the anterior circulation. The majority of strokes were located in the anterior circulation. In many cases, radiologic imaging confirmed arterial stenoses in the vascular distribution of the stroke. One patient who presented with ischemic stroke had severe atherosclerosis of bilateral common, internal, and external carotid arteries. On pathology, there was no evidence of inflammation or necrosis to suggest vasculitis as a possible etiology. Methamphetamine use is associated with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, especially among young patients. We showed no evidence that the ischemic stroke associated with methamphetamine use is due to an inflammatory etiology but may be due to a process of accelerated atherosclerosis.

Ho RCM; Ho ECL; Tan CH; Mak A. Pulmonary hypertension in first episode infective endocarditis among intravenous buprenorphine users: Case Report. American Journal of Drug and Alcohol Abuse 35(3): 199-202, 2009. (6 refs.)

Background: Since the Food and Drug Administration (FDA) approved the use of buprenorphine hydrochloride (Subutex) for the treatment of opiate dependence in 2002, there has been a global trend of its IV abuse which led to life-threatening medical complications such as infective endocarditis (IE), cardiac failure, and death. Methods: First episode IE were identified in 14 patients (prevalence of 10.8%) among 130 IV buprenorphine abusers who presented to the National University Hospital, Singapore between 2004 to 2006. The variables that were examined in the present study included age, gender, ethnicities, duration of symptoms, types of valves, laboratory, microbiology, echocardiographic features, types of antibiotics given, duration of hospitalization, and the mortality rate. Results: While the majority of these patients presented predominantly with pleuropneumonic symptoms and had tricuspid-valve vegetations with Staphylococcus aureus being the commonest causative organism as reported in other IV drug abusers, pulmonary arterial hypertension (PHT) seemed peculiarly common (79%), and the mortality (21%) was higher in our patients compared to previously reported series (5-10%). Univariate linear regression revealed no relationship between PHT and the presence of septic pulmonary emboli (p =.284) and pulmonary embolism (p =.777). Conclusion and Scientific Significance: PHT may contribute to morbidity and mortality amongst IV buprenorphine abusers. A high index of suspicion of PHT is required in treating IV buprenorphine abusers who presented with pleuropneumonic symptoms. The absence of a relationship between PHT and pulmonary embolism underscores the possibility of the contribution of buprenorphine to PHT, which have been demonstrated in a number of animal studies.

Honjo K; Iso H; Tsugane S; Tamakoshi A; Satoh H; Tajima K et al. The effects of smoking and smoking cessation on mortality from cardiovascular disease among Japanese: Pooled analysis of three large-scale cohort studies in Japan. Tobacco Control 19(1): 50-57, 2010. (37 refs.)

Objectives: To estimate the gender-specific risk of mortality from cardiovascular disease according to smoking status and time since smoking cessation among former smokers in Japan. Design: Prospective study. Setting 140 026 males and 156 810 females aged 40-79 years who participated in one of three cohort studies conducted in Japan between 1980 and 1990. Outcome: The gender-specific hazard ratios (HRs) for cardiovascular disease mortality were calculated after adjustment for age and cohort. Results: The age-adjusted and cohort-adjusted HRs for current smokers compared with lifelong non-smokers were 1.51 (95% CI 1.38 to 1.64) for total cardiovascular diseases, 2.19 (95% CI 1.79 to 2.67) for coronary heart disease and 1.24 (95% CI 1.10 to 1.41) for total stroke in males, and were 1.85 (95% CI 1.65 to 2.06), 2.84 (95% CI 2.24 to 3.60) and 1.70 (95% CI 1.44 to 2.01), respectively, in females. The age-adjusted and cohort-adjusted HRs for former smokers compared with current smokers according to the time period since smoking cessation decreased by approximately 5 years after smoking cessation and reached the same level as lifelong non-smokers approximately 10 years after smoking cessation among both males and females. Conclusions: The present study confirmed the association between smoking and mortality from cardiovascular disease in both males and females. Smoking cessation is a crucial preventive measure against death from cardiovascular disease.

Hossain M; Sathe T; Fazio V; Mazzone P; Weksler B; Janigro D et al. Tobacco smoke: A critical etiological factor for vascular impairment at the blood-brain barrier. Brain Research 1287: 192-205, 2009. (62 refs.)

Active and passive tobacco smoke are associated with the dysfunction of endothelial physiology and vascular impairment. Studies correlating the effects of smoking and the brain microvasculature at the blood-brain barrier (BBB) level have been largely limited to few selective compounds that are present in the tobacco smoke (TS) yet the pathophysiology of smoking has not been unveiled. For this purpose, we characterized the physiological response of isolated human brain microvascular endothelial cells (HBMEC) and monocytes to the exposure of whole soluble TS extract. With the use of a well established humanized flow-based in vitro blood-brain barrier model (DIV-BBB) we have also investigated the BBB physiological response to TS under both normal and impaired hemodynamic conditions simulating ischemia. Our results showed that TS selectively decreased endothelial viability only at very high concentrations while not significantly affecting that of astrocytes and monocytes. At lower concentrations, despite the absence of cytotoxicity, TS induced a strong vascular pro-inflammatory response. This included the upregulation of endothelial pro-inflammatory genes, a significant increase of the levels of pro-inflammatory cytokines, activated matrix metalloproteinase, and the differentiation of monocytes into macrophages. When flow-cessation/reperfusion was paired with TS exposure, the inflammatory response and the loss of BBB viability were significantly increased in comparison to sham-smoke condition. in conclusion, TS is a strong vascular inflammatory primer that can facilitate the loss of BBB function and viability in pathological settings involving a local transient loss of cerebral blood flow such as during ischemic insults.

Ikehara S; Iso H; Yamagishi K; Yamamoto S; Inoue M; Tsugane S. Alcohol consumption, social support, and risk of stroke and coronary heart disease among Japanese men: The JPHC Study. Alcoholism: Clinical and Experimental Research 33(6): 1025-1032, 2009. (35 refs.)

It is unclear whether the association between alcohol consumption and risk of cardiovascular disease is affected by social support. The prospective data for 19,356 men aged 40 to 69 years who participated in the Japan Public Health Center-Based Prospective Study. Alcohol consumption was classified into 7 categories: never, past, occasional, 1 to 149, 150 to 299, 300 to 449, or >= 450 g ethanol/wk. Associations between alcohol consumption and risk of cardiovascular disease were stratified by the median level of social support score, which was measured in emotional support score of this cohort study. During an average follow-up of 9.9 years, 629 total strokes and 207 coronary heart diseases were documented. Light-to-moderate alcohol consumption was associated with reduced risks of coronary heart disease and total cardiovascular disease, while heavy alcohol consumption was associated with increased risk of total stroke, in particular hemorrhagic stroke. When stratified by social support score, the multivariable hazard ratios of total cardiovascular disease associated with light-to-moderate alcohol consumption (1 to 299 g/wk) were 0.99 (0.72 to 1.37) in the low social support group and 0.56 (0.44 to 0.70) in the high social support group (p for interaction = 0.002), while the multivariable hazard ratios of hemorrhagic stroke associated with heavy alcohol consumption (>= 300 g/wk) were 2.09 (1.03 to 4.27) in the low social support group and 1.25 (0.72 to 2.15) in the high social support group (p for interaction = 0.44). There was no interaction between alcohol consumption and social support in relation to risk of coronary heart disease. Social support may enhance the beneficial effect of light-to-moderate alcohol consumption on risk of cardiovascular disease.

Innasimuthu AL; Sankarnarayanan R; Rao GKB; Hornung RS. An unusual cause of breathlessness in a young man. (editorial). Canadian Journal of Cardiology 25(6): 369-371, 2009. (5 refs.)

Amphetamine abuse is a common problem in the developed world. Cardiomyopathy secondary to amphetamine abuse is rare in the general population. The present report describes a 34,year-old mail who presented with shortness of breath. Following further investigations, the cause of his breathlessness was determined to be amphetamine abuse. The incidence Of amphetamine abuse and its cardiac sequelae are reviewed. The mechanism of amphetamine-induced dilated cardiomyopathy is analyzed, with further review of its complications and treatment.

Janzon E; Hedblad B. Swedish snuff and incidence of cardiovascular disease. A population-based cohort study. BMC Cardiovascular Disorders 9: article 21, 2009. (33 refs.)

Background: The relationship between smoking and an increased incidence of cardiovascular diseases is well known. Whether smokeless tobacco (snuff) is related to myocardial infarction (MI) or stroke is still controversial. Aim of this study was to explore whether snuff users have an increased incidence of MI or stroke. Methods: A total of 16 754 women and 10 473 men (aged 45-73 years), without history of cardiovascular disease (CVD), belonging to the population-based "Malmo Diet and Cancer" study were examined. Incidence of MI and stroke were monitored over 10.3 years. Results: Snuff was used by 737 (7.0%) men and 75 (0.4%) women, respectively. Among men, snuff was significantly associated with low occupation level, single civil status, high BMI and with current and former smoking. In women, snuff was associated with lower systolic blood pressure. A total of 964 individuals (3.5%), i.e. 544 men (5.3%) and 420 (2.5%) women suffered a MI during the follow-up period. The corresponding numbers of incident stroke cases were 1048, i.e. 553 men (5.3%) and 495 (3.0%) women, respectively. Snuff was not associated with any statistically significant increased risk of MI or stroke in men or women. The relative risks (RR) in male snuff users compared to non-users were 1.05 (95% confidence interval (CI): 0.8-1.4, p = 0.740) for incident MI and 0.97 (0.7-1.4, p = 0.878) for stroke, after taking age and potential confounders into account. In women none of the 420 (2.5%) women who were snuff users had a MI and only one suffered a stroke during the follow-up. Conclusion: Several life-style risk factors were more prevalent in snuff-users than in non-users. However, the present study does not support any relationship between snuff and incidence of cardiovascular disease in men.

Jayanthi S; Buie S; Moore S; Herning RI; Better W; Wilson NM et al. Heavy marijuana users show increased serum apolipoprotein C-III levels: evidence from proteomic analyses. Molecular Psychiatry 15(1): 101-112, 2010. (68 refs.)

Marijuana (MJ) is the most commonly used illicit drug in the United States. Its abuse is associated with cognitive dysfunctions and increased resistance to blood flow in the cerebral vasculature. In addition, MJ abuse is associated with increased risks of potentially serious cardiovascular disorders. In the present study, we used the protein chip platform based on surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) to test the possibility that MJ abuse might be associated with changes in serum protein levels. Indeed, MJ users showed significant increases in three protein peaks, which were identified as three isoforms of apolipoprotein (apo) C-III. Immunoprecipitation using an apoC-III antibody also validated the identification of the proteins. Marijuana-induced increases in apoC-III levels might occur through chronic stimulation of hepatic cannabinoid receptors (CB1 and/or CB2) by its active ingredient, Delta(9)tetrahydrocannibol (THC). Thus, chronic MJ abuse might cause increased transcription and/or translation of apoC-III in the liver with corresponding changes reflected in the plasma of these patients. In any case, because apoC-III is a cardiovascular risk factor, the increased levels observed in MJ users might explain, in part, the cardiac and cerebral abnormalities reported in these patients.

Jia EZ; Liang J; Yang ZJ; Zhu TB; Wang LS; Chen B et al. Smoking and coronary atherosclerosis: Follow-up study in China. Clinical and Experimental Pharmacology & Physiology 36(7): 690-695, 2009. (10 refs.)

The aim of the present study was to explore the association between the total number of cigarettes smoked in life and the severity of and mortality due to coronary atherosclerosis. The study population comprised 1096 consecutive patients (820 men and 276 women) who underwent coronary angiography for suspected or known coronary atherosclerosis. Anthropometric and plasma measurements (body mass index, blood pressure and blood lipid, blood glucose and pro-insulin levels) were made. The number of cigarettes smoked during previous years was estimated. The severity of coronary atherosclerosis was defined by the Gensini score system. At baseline, a significant positive association was observed between the number of cigarettes smoked and Gensini score (r = 0.213; P = 0.000), pro-insulin (r = 0.072; P = 0.017), total leucocyte count (r = 0.179; P = 0.000) and neutrophil count (r = 0.164; P = 0.000), whereas an inverse correlation was found between the number of cigarettes smoked and High-density lipoprotein-cholesterol (r = -0.150; P = 0.000). When participants were divided into five categories based on the baseline number of cigarettes smoked, an independent association between baseline number of cigarettes smoked and all-cause mortality was observed in a multivariate analysis of Cox proportional hazards models, with a hazard ratio (95% confidence interval) of 1.328 (1.086-1.623; P = 0.006) during a median follow up of 2.86 years. The number of cigarettes smoked was a highly significant predictor of coronary atherosclerosis and an independent risk factor for mortality in subjects with atherosclerosis in this Chinese population.

Jockel KH; Lehmann N; Jaeger BR; Moebus S; Moehlenkamp S; Schmermund A et al. Smoking cessation and subclinical atherosclerosis: Results from the Heinz Nixdorf Recall Study. Atherosclerosis 203(1): 221-227, 2009. (40 refs.)

Background: Smoking accounts for more than 5 million years of potential life lost per year in the US alone. Leading causes of smoking attributable mortality are acute atherothrombotic complications of coronary heart disease (CHID). Smoking cessation is a key issue in preventive medicine, but quantitative data on its benefit for the coronary arteries are sparse. Methods: The Heinz Nixdorf Recall Study is an ongoing population-based, prospective cohort study, with 4814 participants aged 45-74 years (49.8% men). Baseline data of 4078 participants without history of established coronary heart disease or stroke are included in this report. Electron beam-computed tomography allows for non-invasive quantification of coronary artery calcium (CAC). We estimate the risk-related ageing of coronary arteries from multivariable regression of CAC on smoking behavior, sex, age and risk factors. Results: Smoking 20 cigarettes per day since the age of 16 is associated with a CAC burden which is found in a person 10 years older who has never smoked (both sexes). Smoking cessation at 45, 55 or 65 leads to CAC at the age of 75 that would have been reached 9, 6 or 3 years earlier, respectively, had smoking been continued. Conclusion.,: In individuals without overt CHID, present smokers are about 10 years older in 'coronary artery age' than never smokers. The accumulation of CAC is accelerated by smoking and slows down after smoking cessation, but advanced CAC is persistent for a long period. These quantitative findings strongly support smoking cessation measures as early as possible, to prevent accelerated arterial ageing.

Katz DA; Graber M; Birrer E; Lounsbury P; Baldwin A; Hillis SL et al. Health beliefs toward cardiovascular risk reduction in patients admitted to chest pain observation units. Academic Emergency Medicine 16(5): 379-387, 2009. (47 refs.)

Even after acute coronary syndrome (ACS) is ruled out, observational studies have suggested that many patients with nonspecific chest pain have a high burden of cardiovascular risk factors (CRFs) and are at increased long-term risk of ischemic heart disease (IHD)-related mortality. The aim of this study was to evaluate the premise that evaluation in an observation unit for symptoms of possible ACS is a "teachable moment" with regard to modification of CRFs. The authors conducted a baseline face-to-face interview and a 3-month telephone interview of 83 adult patients with at least one modifiable CRF who presented with symptoms of possible ACS to an academic medical center. Existing questionnaires were adapted to measure Health Belief Model (HBM) constructs for IHD. Stage of change and self-reported CRF-related behaviors (diet, exercise, and smoking) were assessed using previously validated measures. The paired t-test or signed rank test was used to compare baseline and 3-month measures of health behavior within the analysis sample. Of the 83 study patients, 45 and 40% reported having received clinician advice regarding diet and physical activity during the observation unit encounter, respectively; 69% of current smokers received advice to quit smoking. Patients reported lower susceptibility to IHD (13.3 vs. 14.0, p = 0.06) and greater perceived benefit of healthy lifestyles (27.5 vs. 26.4, p = 0.0003) at 3-month follow-up compared to baseline. Patients also reported greater readiness to change and improved self-reported behaviors at follow-up (vs. baseline): decreased intake of saturated fat (10.1% vs. 10.5% of total calories, p = 0.005), increased fruit and vegetable intake (4.0 servings/day vs. 3.6 servings/day, p = 0.01), and fewer cigarettes (13 vs. 18, p = 0.002). Observed changes in IHD health beliefs and CRF-related behaviors during follow-up support the idea that observation unit admission is a teachable moment. Patients with modifiable risk factors may benefit from systematic interventions to deliver CRF-related counseling during observation unit evaluation.

Kinoshita M; Herges RM; Hodge DO; Friedman L; Ammash NM; Bruce CJ et al. Role of smoking in the recurrence of atrial arrhythmias after cardioversion. American Journal of Cardiology 104(5): 678-682, 2009. (24 refs.)

We aimed to determine whether smoking status affects the recurrence of atrial fibrillation or atrial flutter in patients after cardioversion. The clinical data of patients undergoing cardioversion for atrial flutter from January 1, 2000 to December 31, 2005 were prospectively collected. Arrhythmia recurrences were detected by retrospective review of comprehensive medical records and were determined using electrocardiography. The smoking history was prospectively collected through a standardized clinical form and subsequently categorized as lifetime nonsmoker, exsmoker, or current smoker. Univariate and multivariate associations with end points for clinical and lifestyle variables were assessed with Cox proportional hazards models. Women who were current smokers at cardioversion had a greater risk of atrial arrhythmia recurrence than did nonsmokers (hazard ratio 1.71, 95% confidence interval 1.10 to 2.67, p = 0.02). The increased risk of arrhythmia recurrence in female smokers was not seen in male smokers. Compared to lifetime nonsmokers, the mortality hazard ratio among men was 1.18 (95% confidence interval 0.88 to 1.58; p = 0.28) in exsmokers and 1.93 (95 % confidence interval 1.20 to 3.11; p = 0.007) in current smokers. The risk of death after cardioversion was not increased in women. In conclusion, smoking is an independent predictor of atrial arrhythmia recurrence after cardioversion in women; however, an increased mortality risk, but not arrhythmia recurrence risk, was seen in men.

Kocabay G; Yildiz M; Duran NE; Ozkan M. Acute inferior myocardial infarction due to cannabis smoking in a young man. (editorial). Journal of Cardiovascular Medicine 10(9): 669-670, 2009. (8 refs.)

Cannabis smoking, which has euphoric effects, is consistently increasing in Europe. Smoking cannabis is a rare trigger of acute myocardial infarction (MI) by inducing coronary artery spasm. Some cases who have thrombus formation in acute coronary artery and no serious atherosclerotic lesions have been reported in the literature. These cases had involved the left coronary artery. Although some cases were reported with MI after cannabis smoking, only two case reports with inferior MI after cannabis smoking were reported in the literature. The present report is of a young male patient who was affected by acute inferior MI half an hour after cannabis smoking.

Krantz MJ; Martin J; Stimmel B; Haigney MCP. Concerns about consensus guidelines for QTc interval screening in methadone treatment response. (letter, response). Annals of Internal Medicine 151(3): 218-219, 2009. (7 refs.)

Krishnamoorthy S; Lip GYH; Lane DA. Alcohol and illicit drug use as precipitants of atrial fibrillation in young adults: A case series and literature review. American Journal of Medicine 122(9): 851-U83, 2009. (37 refs.)

BACKGROUND: Atrial fibrillation in young patients (<= 45 years) is uncommon. There is the perception that the precipitant in such cases is alcohol, but we also have noted cases related to illicit drug abuse. There are no clear guidelines on the treatment of atrial fibrillation in patients presenting with "lone atrial fibrillation" precipitated by alcohol or illicit drugs. METHODS: We retrospectively analyzed young (defined as <= 45 years) patients with "lone" atrial fibrillation who were admitted to the hospital with electrocardiographically confirmed diagnosis of atrial fibrillation or atrial flutter, precipitated by either alcohol or illicit drugs, over a 6-year period. RESULTS: Eighty-eight patients aged <= 45 years were admitted with atrial fibrillation or atrial flutter. In 22 patients, (mean [SD] age 33.6 [8.4] years; 20 male), alcohol (n = 19) and/or illicit drugs (n = 3) were found to be the precipitant. One patient required electrical cardioversion, with the remaining patients cardioverting back to sinus rhythm either pharmacologically or spontaneously. Twelve (54.5%) were investigated for atrial fibrillation burden by 24-hour Holter monitoring and the majority also underwent a transthoracic echocardiogram (81.8%). At discharge, 14 (63.6%) patients were treated with anti-arrhythmic drugs and 10 received either antiplatelets or anticoagulants. Most (85%) patients were followed-up for at least 12 months, during which time 6 had further paroxysms; all of whom continued to abuse either alcohol or illicit drugs. CONCLUSIONS: Alcohol and illicit drugs are arrhythmogenic and are associated with atrial fibrillation. Apart from abstinence, the optimal management of such patients and the long-term effects of these substances on the heart and atrial fibrillation recurrences are still unclear.

Lao XQ; Jiang CQ; Sen Zhang W; Adab P; Lam TH; Cheng KK et al. Smoking, smoking cessation and inflammatory markers in older Chinese men: The Guangzhou Biobank Cohort Study. Atherosclerosis 203(1): 304-310, 2009. (30 refs.)

Aims: Smoking increases the risk of cardiovascular disease and inflammation plays a key role in the process of atherosclerosis. We therefore study the role of smoking and smoking cessation on the levels of inflammatory markers, C-reactive protein (CRP) and white blood cell (WBC) count, in older Chinese men. Methods: This cross-sectional analysis included 2999 men aged 50-85 years who received a medical check-up including measurement of fasting plasma vascular risk factors. Information on smoking status, socioeconomic and lifestyle factors was collected by standardized interview. Results: After adjustment for potential confounders, both CRP and WBC increased linearly across never. former and current smokers (both p < 0.01). The odds ratios of elevated CRP and WBC (upper tertiles) were also increased across never, former and current smokers (both p < 0.01). Dose-response relationships were observed among current smokers. Compared to current smokers, the odds ratios of elevated CRP and WBC and means of CRP and WBC declined with longer duration of smoking cessation (all p < 0.01). Conclusions: Smoking is associated with increased CRP and WBC levels, and smoking cessation is associated with the reduction of the increase, confirming the benefits of quitting. Inflammation may be a potential mechanism by which smoking promotes atherosclerotic disease.

Lewis MJ; Balaji G; Dixon H; Syed Y; Lewis KE. Influence of smoking abstinence and nicotine replacement therapy on heart rate and QT time-series. Clinical Physiology and Functional Imaging 30(1): 43-50, 2010. (41 refs.)

Many smokers attempt to quit without using nicotine replacement therapy (NRT) or pharmacotherapy, i.e. 'cold-turkey'. The cardiac implications of this are important but are incompletely understood. Previous studies have associated smoking cessation with improvements in heart rate (HR) and its variability, but its influence on QT time-series is unclear. Furthermore, the relative influence on these parameters of acute nicotine withdrawal and of NRT has not been adequately compared. Additional insight might come from analysing the dynamic (e.g. fractal) properties of electrocardiographic data during different levels of nicotine exposure. We examined the influence of smoking cessation, during cold-turkey and subsequent NRT, on HR and QT time-series during 30 days of smoking abstinence. Seven smokers and sixteen healthy non-smokers received ECG monitoring at baseline (Day 0). Smokers subsequently refrained from smoking without using NRT for 24 h, and then received NRT for 29 days. ECG monitoring was repeated at Days 1, 7, 30. Following smoking cessation we observed that: HR and rate-corrected QT were both reduced, heart rate variability (HRV) increased (improved), and QT variability index (QTVI) showed signs of improvement (trend only). Improvements in HR and QT were maintained throughout NRT use, whilst improvements in HRV and QTVI were sustained for at least the early stages of NRT. The dynamic (multifractal) properties of HR and QT were similar for smokers and non-smokers, and were unchanged by smoking abstinence or NRT. Our results provide tentative evidence that electrocardiographic improvements during a cold-turkey smoking quit attempt (acute nicotine withdrawal) are maintained during NRT pharmacotherapy.

Liang LR; Wong ND; Shi P; Zhao LC; Wu LX; Xie GQ et al. Cross-sectional and longitudinal association of cigarette smoking with carotid atherosclerosis in Chinese adults. Preventive Medicine 49(1): 62-67, 2009. (29 refs.)

Objective. To assess the cross-sectional and longitudinal association of cigarette smoking with carotid atherosclerosis in middle-aged and older Chinese adults. Methods. The study population consisted of 1132 residents in Beijing (748 women and 384 men) aged 35 to 64 years. Information on baseline smoking characteristics, including smoking status and pack-years was collected in 1993-1994. The cohort was resurveyed in 2002 and common carotid artery intima-media thickness (CCA-IMT) and carotid plaques were measured by B-mode ultrasound. Results. The multivariable-adjusted mean CCA-IMT at resurvey was significantly associated with smoking status at both resurvey and baseline, and was 0.72 mm for consistent current smokers, 0.71 mm for former and inconsistent smokers, and 0.70 mm for consistent never smokers at both surveys, respectively (p-trend < 0.01). The multivariable-adjusted odds ratio [OR, 95% confidence interval (CI)] of having carotid plaques was 1.5 (1.0-2.1) for consistent current smokers vs consistent never smokers. In addition, there was a significant dose-response relationship between baseline smoking pack-years and multivariable-adjusted mean CCA-IMT and risk of having carotid plaques at resurvey. Conclusion. Smoking is associated with carotid atherosclerosis in middle-aged and older Chinese adults both cross-sectionally and longitudinally. Smoking cessation may play a significant role in prevention and control of cardiovascular diseases in China.

Lin WY; Pi-Sunyer FX; Liu CS; Li TC; Li CI; Huang CY et al. Betel nut chewing is strongly associated with general and central obesity in Chinese male middle-aged adults. Obesity 17(6): 1247-1254, 2009. (36 refs.)

Betel nut chewing has been reported to increase the risk of cardiovascular disease and all-cause mortality. The reason is unclear. In this study, we investigated the association between betel nut chewing and general obesity (BMI >= 25 kg/m(2)) and central obesity (waist circumference (WC) >= 90 cm). A total of 1,049 male subjects, aged >= 40 years, were recruited from Taichung city in Taiwan in 2004. The relationships between betel nut chewing and general and central obesity were studied by multiple linear and logistic regression analyses. The prevalence of current and former betel nut chewing was 7.0 and 10.5% in our male Taiwanese cohort. Current/former betel nut chewers had a higher prevalence of general and central obesity when compared with individuals who had never chewed betel nut. Adjusted for age, diabetes, hypertension, lipids, smoking, alcohol drinking, physical activity, income, and education level, the odds ratios (ORs; 95% confidence intervals) of general and central obesity among the lower consumption of betel nut chewers were 1.78 (1.07, 2.96) and 1.19 (0.70, 2.02), respectively, compared to 2.01 (1.18, 3.41) and 1.89 (1.10, 3.23), respectively, among higher consumption chewers compared to individuals who had never chewed betel nut. The increasing ORs of general and central obesity with higher betel nut consumption revealed dose-response effects. Using multiple linear regression analyses, after adjusting for potential confounders, betel nut consumption was statistically significantly associated with BMI and WC. In conclusion, betel nut chewing was independently associated with general and central obesity in Taiwanese men. Dose-response effects of the association between betel nut consumption and general obesity as well as central obesity were found.

Linke SE; Rutledge T; Johnson BD; Olson MB; Bittner V; Cornell CE et al. The joint impact of smoking and exercise capacity on clinical outcomes among women with suspected myocardial ischemia: The WISE study. Journal of Women's Health 18(4): 443-450, 2009. (46 refs.)

Background: Although extensive research has been conducted on both smoking and low exercise capacity alone, few studies have examined the joint impact or interaction of these two risk factors. We examined the joint and interactive effects of smoking and self-reported exercise capacity on subsequent clinical events (heart failure, myocardial infarction [MI], stroke, and cardiovascular-related mortality) among women with suspected myocardial ischemia. Methods: At baseline (1996-1999), 789 women completed angiographic testing of coronary artery disease (CAD) severity and provided self-report information about their smoking history and exercise capacity as well as demographic and other risk factor data. Incidence of clinical events among the women was tracked for a median of 5.9 years; this analysis was conducted in 2008. Results: In an adjusted survival analysis, women with a positive smoking history and self-reported low exercise capacity had the greatest risk of experiencing a clinical event (HR = 7.7, 95% CI 2.3, 25.5), followed by women with a positive smoking history and self-reported high exercise capacity (HR = 6.9, 95% CI 2.0, 24.6) and those with a negative smoking history and self-reported low exercise capacity (HR = 4.9, 95% CI 1.5, 15.8), relative to women with a negative smoking history and self-reported high exercise capacity. Additional analyses revealed a significant interaction between smoking history and exercise capacity, such that (1) women with a positive smoking history did not experience an additional significantly greater risk due to low exercise capacity, unlike those with a negative smoking history, and (2) all women experienced a significantly greater risk due to a positive smoking history regardless of their exercise capacity. Conclusions: Among women with suspected myocardial ischemia, the combined protective health effects of self-reported high exercise capacity and a negative smoking history remained significant after controlling for preexisting CAD severity and other established risk factors. These findings highlight the importance of studying behavioral risk factors in combination.

Lucena J; Blanco M; Jurado C; Rico A; Salguero M; Vazquez R et al. Cocaine-related sudden death: A prospective investigation in south-west Spain. European Heart Journal 31(3): 318-329, 2010. (62 refs.)

With an estimated 12 million consumers in Europe, cocaine (COC) is the illicit drug leading to the most emergency department visits. The aim of this study was to examine a consecutive series of sudden deaths (SDs) to focus on the prevalence, the toxicological characteristics, and the causes of death in COC-related fatalities. Prospective case-control study of forensic autopsies was carried out in the time interval November 2003 to June 2006 at the Institute of Legal Medicine, Seville, south-west Spain, with a reference population of 1,875,462 inhabitants. Toxicology included blood ethanol analysis and blood and urine investigation for drugs of abuse and medical drugs. Autopsy was performed according to the European standardized protocol. Ten age- and sex-matched patients who died of violent causes with no antecedents of COC consumption and negative toxicology served as controls. During the study period, 2477 forensic autopsies were performed, including 1114 natural deaths. Among the latter, 668 fulfilled the criteria of SD and 21 (all males, mean age 34.6 +/- 7.3 years) resulted to be COC-related (3.1%). Cocaine was detected in 67.1% of the blood (median 0.17 mg/L, interquartile range 0.08-0.42) and in 83.0% of the urine samples (median 1.15 mg/L, interquartile range 0.37-17.34). A concomitant use of ethanol was found in 76.0% and cigarette smoking in 81.0%. Causes of SD were cardiovascular in 62.0%, cerebrovascular in 14.0%, excited delirium in 14.0%, respiratory and metabolic in 5.0% each. Left ventricular hypertrophy was observed in 57.0%, small vessels disease in 42.9%, severe atherosclerotic coronary artery disease in 28.6%, and coronary thrombosis in 14.3%. Systematic toxicology investigation indicates that 3.1% of SDs are COC-related and are mainly due to cardio-cerebrovascular causes. Left ventricular hypertrophy, small vessel disease, and premature coronary artery atherosclerosis, with or without lumen thrombosis, are frequent findings that may account for myocardial ischaemia at risk of cardiac arrest in COC addicts.

Makaryus JN; Volfson A; Azer V; Bogachuk E; Lee A. Acute stent thrombosis in the setting of cocaine abuse following percutaneous coronary intervention. Journal of Interventional Cardiology 22(1): 77-82, 2009. (40 refs.)

The treatment of acute coronary syndrome (ACS) in patients with documented cocaine abuse has always presented significant challenges. Issues related to medication compliance, the potential risks of beta adrenergic blockade, and possible continued cocaine abuse postmyocardial infarction necessitate a unique, individualized approach to these patients. Recent data in the era of extensive percutaneous coronary interventions (PCI) and intracoronary stent (ICS) implantation have raised questions regarding the safety of ICS in patients who may revert to cocaine abuse postacute coronary syndrome as a result of the potentially higher risk of stent thrombosis in these patients. While the precise reason as to why cocaine use may increase the risk of stent thrombosis is not fully understood, it is likely the result of a confluence of factors, including coronary vessel vasoconstriction, impaired vascular compliance, as well as the platelet-activating effect of cocaine. We present the case a 46-year-old male with a history of cocaine abuse who presented with an acute stent thrombosis 2 days post-PCI likely as a result of cocaine abuse on the day of discharge following initial stent implantation for a non-ST-elevation myocardial infarction (NSTEMI). We also review the literature regarding the safety of PCI in cocaine abusers.

Malatestinic D; Roncevic N; Bencevic-Striehl H; Jankovic S; Micovic V. Smoking is the most frequent risk factor for cardiovascular diseases in Croatian Western region: findings of the Croatian health survey 2003. Medicinski Glasnik {Dartmouth e-journal} 6(2): 218-226, 2009. (30 refs.)

Aim: To estimate the prevalence of selected behavioral risk factors for cardiovascular diseases in the western region of Croatia and to determine the differences based on age and gender. Methods A national survey on health status and health behavior of the adult population has been conducted. The representative sample of 10,766 households for six officially defined regions of Croatia has been determined, and Western region has been included with 1,562 inhabitants, aged 18 years and older. The overall response rate of administered face-to-face questionnaire was 85-61%. Prevalence rates per 100 inhabitants (smoking, eating habits, alcohol, consumption, physical activity, socio-economic characteristics, chronic conditions) have been determined. Results Nearly half (46.3%) of the adults were smokers or had quit smoking less than 10 years ago. Prevalence of high blood pressure was high amounting to 40.6% and it was higher in middle aged males (46.7%, p<0.01) and young males (13.7%), p<0.01). Prevalence of obesity was 38.9%, highest in females aged 35-64 (51.2%, p<0.001) and 65 and older (73.8%, p<0.01). Almost a quarter of respondents (23.3%) has been insufficiently physically active, especially young females 22.5%, p<0.01). Conclusion There was a significant difference in the prevalence of all observed behavioral risk factors according to the gender and age. Moreover, smoking tobacco has been found as the most frequent risk Factor in the observed population.

Masoomi M; Ramezani MA; Shahriari S; Shahesmaeeli A; Mirzaeepour F. Is opium addiction a risk factor for deep vein thrombosis? A case-control study. Blood Coagulation & Fibrinolysis 21(2): 109-112, 2010. (28 refs.)

The objective of the present study was to investigate the association between opioid addiction and deep vein thrombosis (DVT) and whether opioid addiction is a risk factor of DVT. This case-control study was conducted in Kerman, Iran in 2008. The cases were selected among the patients hospitalized because of DVT. The controls were recruited from the same hospital from internal wards. Opioid addiction was investigated by physician's interview based on Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. Logistic regression modeling was carried out for statistical analysis. The crude odds ratio (OR) of opioid addiction for DVT was 4.25 (95% confidence interval=2.6-6.9). However, multivariate logistic regression analysis revealed that opioid addiction was not an independent risk factor for DVT, OR 0.56 (0.1-3). The method of opioid usage - oral or inhaled and injected OR 6.3 (1.41-28.3) and previous surgery in the last 3 months before the study, OR 3.1 (1.36-7), were significant independent risk factors for incidence of DVT. Opiod addiction per se was not a risk factor for DVT, whereas the method of its use especially injection was found to be independent risk factor for DVT. Our results suggested the prophylactic treatment of anticoagulant for intravenous drug abuser is considerable.

Mayhan WG; Arrick DM; Sharpe GM; Sun H. Nitric oxide synthase-dependent responses of the basilar artery during acute infusion of nicotine. Nicotine & Tobacco Research 11(3): 270-277, 2009. (70 refs.)

Our goals were to determine whether acute exposure to nicotine alters nitric oxide synthase (NOS)-dependent responses of the basilar artery and to identify a potential role for activation of NAD(P)H oxidase in nicotine-induced impairment in NOS-dependent responses of the basilar artery. We measured in vivo diameter of the basilar artery in response to NOS-dependent (acetylcholine) and NOS-independent (nitroglycerin) agonists before and during an acute infusion of nicotine (2 mu g/kg/min intravenously for 30 min followed by a maintenance dose of 0.35 mu g/kg/min). In addition, we measured superoxide anion production (lucigenin chemiluminescence) by the basilar artery in response to nicotine in the absence or presence of apocynin. We found that NOS-dependent, but not NOS-independent, vasodilation was impaired during infusion of nicotine. In addition, treatment of the basilar artery with apocynin (100 mu M, 30 min prior to infusion of nicotine) prevented nicotine-induced impairment in NOS-dependent vasodilation. Further, the production of superoxide anion was increased in the basilar artery by nicotine, and this increase could be inhibited by apocynin. Our findings suggest that acute exposure to nicotine impairs NOS-dependent dilation of the basilar artery by a mechanism that appears to be related to the release of superoxide anion. A possible source of superoxide may be via the activation of NAD(P)H oxidase.

McGuinness TM. Update on marijuana. Journal of Psychosocial Nursing and Mental Health Services 47(10): 19-22, 2009. (17 refs.)

Marijuana, the illicit drug most widely used by adolescents, is not a benign substance. Inhalation of marijuana smoke is more harmful than tobacco smoke; cannabis smoke delivers 50% to 70% more carcinogens. Other physiological effects include decreased immune function, higher rates of cardiac arrhythmias, and documented cases of cerebellar infarction. Mood and cognitive effects of marijuana include exacerbation of depression and anxiety (including panic attacks), as well as memory problems that may persist for a month after last use. Cannabis abuse is a risk factor for psychosis in genetically predisposed people and may lead to a worse outcome of schizophrenia. The cumulative respiratory, cardiovascular, metabolic, and mental health risks of marijuana are significant and should be emphasized by nurses who work with adolescents.

Najafi K; Zarrabi H; Shirazi M; Fekri F; Mohseni R. Prevalence of substance use among Iranian high school students in 2005-2006. Kuwait Medical Journal 41(1): 20-25, 2009. (34 refs.)

Objectives: To determine the prevalence of substance use among high-school students in Guilan province, Iran Design: Cross-sectional study conducted from September 2004 to June 2005 Settings: Guilan province high-schools, Iran Subjects: A representative sample of 1927 students Interventions: A self-report questionnaire that included socio-demographic data, type of substance used, history of lifetime and past month substance use, first motivation, first place and first provider of substance was applied. Main Outcome Measure(s): Frequency of substance use in high-school students and some associated factors. Results: About 24% of subjects had substance use during their lifetime. 24% of the sample used tobacco and 10.5%, alcohol. Substance use was significantly higher in males(p < 0.001). The highest frequency of substance use was among 3(rd) and 4(th) grade students (28.8% and 23.7% respectively). Substance use was related with higher educational grades in boys (p < 0.001) and significantly associated with smoker parents(p < 0.001). First experience with substances most commonly happened at home (26.6%), friends' parties (26.3%) and park / street (20.4%). 55.68% had obtained drugs, first time, from friends. Curiosity was the most common reason for drug use in 42.61% of the sample. Although substance use was higher in public schools and students with illiterate parents, it was not related with the type of school and parents' educational levels. Conclusion: A large number of high-school students had the experience of substance use, mostly tobacco and alcohol. Effective solutions and preventive programs should be applied to reduce substance use in Iranian youth population.

Nakamura K; Barzi F; Huxley R; Lam TH; Suh I; Woo J et al. Does cigarette smoking exacerbate the effect of total cholesterol and high-density lipoprotein cholesterol on the risk of cardiovascular diseases? Heart 95(11): 909-916, 2009. (32 refs.)

Objective: To explore whether an interaction between smoking and serum total cholesterol (TC) and/or decreased levels of serum high-density lipoprotein cholesterol (HDLC) exists for any major subtype of cardiovascular disease. Design: An individual participant overview of 34 cohort studies. Setting: The Asia-Pacific region. Participants: People aged >= 20 years without a particular condition or risk factor. Mean outcome measures: Hazard ratios (HRs) and 95% confidence intervals (CIs) for both TC and HDLC by smoking status were estimated using Cox proportional hazard models adjusted for age and systolic blood pressure and stratified by study and sex. Results: During follow-up (median 4.0 years), 3298 coronary heart disease (CHD) and 4318 stroke events were recorded. For CHD, the HR (95% CI) for an additional 1.06 mmol/l increment in TC was greater in current smokers than in non-smokers: 1.54 (1.43 to 1.66) versus 1.38 (1.30 to 1.47); p= 0.02. Similarly, the HR (95% CI) for an additional 0.40 mmol/l decrement in HDLC was greater in current smokers than in non-smokers: 1.67 (1.35 to 2.07) versus 1.28 (1.10 to 1.49); p= 0.04. The positive association of TC with ischaemic stroke, and the negative association of TC with haemorrhagic stroke, were broadly similar for current smokers and nonsmokers. Similarly, the risks of both the subtypes of stroke remained broadly unchanged as HDLC decreased in both current smokers and non-smokers. Conclusions: Smoking exacerbated the effects of both TC and HDLC on CHD, although no interaction between smoking and TC or HDLC existed for either of the subtypes of stroke.

Namdar M; Schepis T; Koepfli P; Gaemperli O; Siegrist PT; Grathwohl R et al. Caffeine impairs myocardial blood flow response to physical exercise in patients with coronary artery disease as well as in age-matched controls. PLoS one 4(5): e-5665, 2009. (27 refs.)

Background: Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). Methodology/Principal Findings: MBF was measured with O-15-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58 +/- 13 years) and in CAD patients (n = 15, mean age 61 +/- 9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26 +/- 0.56 vs. 2.02 +/- 0.56, P<0.005), remote (2.40 +/- 0.70 vs. 1.78 +/- 0.46, P<0.001) and in stenotic segments (1.90 +/- 0.41 vs. 1.38 +/- 0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). Conclusions: We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls.

Nelson MR; Alkhateeb AN; Ryan P; Willson K; Gartlan JG; Reid CM. Physical activity, alcohol and tobacco use and associated cardiovascular morbidity and mortality in the Second Australian National Blood Pressure study cohort. Age and Ageing 39(1): 112-116, 2010. (32 refs.)

Physical inactivity and smoking are modifiable risk factors for cardiovascular disease. High alcohol consumption and a sedentary lifestyle contribute to the risk of hypertension in the elderly and thus mortality from its associated disease outcomes. This study seeks to ascertain the prevalence rate at baseline and the changes over time of alcohol intake, cigarette smoking and physical activity among 6,083 Australian hypertensive elderly who participated in the Second Australian National Blood Pressure study. The risk of cardiovascular events or death from any cause as a result of these lifestyle factors was also assessed. It was found that adverse lifestyle factors (especially physical inactivity) are prevalent in the hypertensive elderly, and there is a significant increase in relative risk of CVD or death from any cause in these patients who continued to smoke or were physically inactive.

Nilsson PM; Cederholm J; Eeg-Olofsson K; Eliasson B; Zethelius B; Fagard R et al. Smoking as an independent risk factor for myocardial infarction or stroke in type 2 diabetes: A report from the Swedish National Diabetes Register. European Journal of Cardiovascular Prevention & Rehabilitation 16(4): 506-512, 2009. (36 refs.)

Background Few earlier studies have analysed smoking as a risk factor for myocardial infarction NO or stroke in type 2 diabetic patients. Design and methods A longitudinal study involved 13087 female and male patients with type 2 diabetes from the Swedish National Diabetes Register with no previous M I or stroke at baseline, aged 30-74 years, and with data available for all analysed variables, followed up for mean 5.7 years. Results Adjusted hazard ratios (HRs) for smoking and first-incident fatal/nonfatal MI, stroke and total mortality were 1.7 [95% confidence interval (CI): 1.4-2.0; P<0.001], 1.3 (95% CI: 1.1-1.6; P=0.006) and 1.8 (95% CI: 1.5-2.2; P<0.001), respectively, by Cox regression analysis, adjusted for age, sex, diabetes duration, hypoglycaemic treatment, haemoglobin A(1c), blood pressure, body mass index, microalbuminuria, antihypertensive and lipid-lowering drugs. Adjusted HR was higher for fatal MI, 2.1 (95% CI: 1.7-2.7; P<0.001), than for nonfatal MI, 1.4 (95% CI: 1.2-1.7; P<0.001). The highest HRs were observed in more frequently smoking (22%), middle-aged patients (age <60 years) for fatal/nonfatal MI, 2.3 (95% CI: 1.8-3.1; P<0.001) and for total mortality, 2.5 (95% CI: 1.6-3.8, P<0.001), whereas lower HRs were observed in older and less smoking patients. With predicted cessation of smoking in patients aged below 60 years, 24% (95% CI: 15-33%) of cases of fatal/nonfatal MI and 24% (11-37%) of cases of total mortality may have been prevented. Conclusion The risk for MI and total mortality associated with smoking is high in type 2 diabetes, especially in more frequently smoking, middle-aged patients, and was higher for MI than for stroke, and also higher for fatal than for nonfatal events. Smoking cessation would strongly affect risk reduction.

Nusselder WJ; Franco OH; Peeters A; Mackenbach JP. Living healthier for longer: Comparative effects of three heart-healthy behaviors on life expectancy with and without cardiovascular disease. BMC Public Health 9: e-487, 2009. (32 refs.)

Background: Non-smoking, having a normal weight and increased levels of physical activity are perhaps the three key factors for preventing cardiovascular disease (CVD). However, the relative effects of these factors on healthy longevity have not been well described. We aimed to calculate and compare the effects of non-smoking, normal weight and physical activity in middle-aged populations on life expectancy with and without cardiovascular disease. Methods: Using multi-state life tables and data from the Framingham Heart Study (n = 4634) we calculated the effects of three heart healthy behaviours among populations aged 50 years and over on life expectancy with and without cardiovascular disease. For the life table calculations, we used hazard ratios for 3 transitions (No CVD to CVD, no CVD to death, and CVD to death) by health behaviour category, and adjusted for age, sex, and potential confounders. Results: High levels of physical activity, never smoking (men), and normal weight were each associated with 20-40% lower risks of developing CVD as compared to low physical activity, current smoking and obesity, respectively. Never smoking and high levels of physical activity reduced the risks of dying in those with and without a history of CVD, but normal weight did not. Never-smoking was associated with the largest gains in total life expectancy (4.3 years, men, 4.1 years, women) and CVD-free life expectancy (3.8 and 3.4 years, respectively). High levels of physical activity and normal weight were associated with lesser gains in total life expectancy (3.5 years, men and 3.4 years, women, and 1.3 years, men and 1.0 year women, respectively), and slightly lesser gains in CVD-free life expectancy (3.0 years, men and 3.1 years, women, and 3.1 years men and 2.9 years women, respectively). Normal weight was the only behaviour associated with a reduction in the number of years lived with CVD (1.8 years, men and 1.9 years, women). Conclusions: Achieving high levels of physical activity, normal weight, and never smoking, are effective ways to prevent cardiovascular disease and to extend total life expectancy and the number of years lived free of CVD. Increasing the prevalence of normal weight could further reduce the time spent with CVD in the population.

Ohira T; Tanigawa T; Tabata M; Imano H; Kitamura A; Kiyama M et al. Effects of habitual alcohol intake on ambulatory blood pressure, heart rate, and its variability among Japanese men. Hypertension 53(1): 13-U29, 2009. (29 refs.)

We sought to examine effects of habitual alcohol intake on ambulatory blood pressure (BP), heart rate (HR), and HR variability among Japanese men. Subjects were 539 men aged 35 to 65 years from rural and urban communities. Ambulatory BP and HR were monitored with an automated, portable, noninvasive multibiomedical recorder. Power spectral analysis of the RR intervals on the ECG was performed every 5 minutes. Compared with nondrinkers, moderate drinkers (alcohol intake 23 to 45 g/d) and heavy drinkers (alcohol intake >= 46 g/d) showed higher age- and field-adjusted mean values of systolic and diastolic BPs during the morning and while awake, but there were no differences in BPs over 24-hour periods and while asleep among the alcohol intake categories. Alcohol intake was positively associated with mean values of sleep-morning differences and daytime variability in BPs, HRs while awake and asleep, and low frequency: high frequency ratio while asleep. The results were virtually unchanged after adjustment for body mass index, smoking, and diabetes mellitus. Compared with the nondrinkers, age- and field-adjusted odds ratios of the morning BP surge (excess elevation of BP in the morning: morning systolic BP minus sleep systolic BP >= 37 mm Hg) for light (alcohol intake 0 to 22 g/d), moderate, and heavy drinkers were 0.96 (95% CI: 0.34 to 2.78), 1.68 (95% CI: 0.64 to 4.38), and 2.73 (95% CI: 1.12 to 6.67), respectively. Habitual alcohol intake was associated with increased BP in the morning, HR while awake and asleep, and sympathetic activity while asleep, which may explain some of the mechanisms of the relationship between heavy alcohol intake and risk of cardiovascular diseases.

Otsuka F; Kojima S; Maruyoshi H; Kojima S; Matsuzawa Y; Funahashi T et al. Smoking cessation is associated with increased plasma adiponectin levels in men. Journal of Cardiology 53(2): 219-225, 2009. (28 refs.)

Objectives: Low levels of adiponectin, an adipocytokine with anti-diabetic and anti-atherogenic properties, are associated with increased risk of future myocardial infarction in men. Previous studies have demonstrated that cigarette smoking is involved in the development of insulin resistance, and current smokers have been shown to have reduced plasma adiponectin levels. However, the influence of smoking cessation on adiponectin levels remains unknown. We sought to assess whether smoking cessation is associated with increased plasma adiponectin levels in men. Methods: The study includes 72 men (47 non-smokers and 25 current smokers at baseline) with stable angina pectoris who underwent percutaneous coronary intervention and follow-up coronary angiography 6 months later. During the 6-month follow-up period, all 47 non-smokers remained non-smokers, while 15 men of the 25 baseline current smokers successfully quit smoking. We evaluated plasma adiponectin levels at coronary intervention and 6 months later. Results: Plasma adiponectin levels at coronary intervention were comparable to those after 6 months in non-smokers (4.22 [3.15-6.43] vs. 4.58 [3.03-6.26] mu g/mL, P=0.124) and in persistent smokers (4.77 [4.25-10.53] vs. 5.16 [4.11-8.10] mu g/mL, P=0.721). Meanwhile, an increase in adiponectin level was observed in patients who quit smoking for 6 months (4.24 [3.30-5.70] vs. 5.50 [4.03-8.00] mu g/mL, P=0.002). Univariate analysis revealed that the percent increase in adiponectin levels correlated positively with smoking cessation (P=0.003) and negatively with additional use of beta-blockers (P=0.049). In addition, increases in adiponectin levels were closely associated with increase in high-density lipoprotein cholesterol (P=0.148), decrease in triglycerides (P=0.140), and additional use of renin-angiotensin system inhibitors (P=0.069). Multivariate analysis demonstrated that smoking cessation was an independent determinant of the increase in adiponectin (P=0.036). Conclusions: Smoking cessation is associated with increased plasma adiponectin levels in men with stable angina, suggesting that the significance of smoking cessation may be partly explained by the increase in adiponectin level.

Pacini M; Maremmani AGJ; Dell'Osso L; Maremmani I. Opioid treatment and "Long-QT Syndrome (LQTS)": A critical review of the literature. Heroin Addiction and Related Clinical Problems 11(4): 21-28, 2009. (73 refs.)

The present paper aims to provide a critical survey of the current literature on QT-related cardiac safety in cases of methadone treatment. On the whole, case reports, whether single or Multiple, do not seem to offer it reliable basis for drawing conclusions about the weight of any putative risk factor in QT prolongation. Systematic Studies, on the other hand, do allow certain statements to be made about the extent and the the importance of QT prolongation during methadone maintenance treatment for heroin addiction. There do not seem to be any major concerns about cardiac safety arising from methadone itself in the average addict. Higher risk conditions due to multiple and polydrug treatments deserve more intensive surveillance. From a risk/benefit perspective, there is no clear rationale for applying a dose ceiling.

Pani PP. Management of cardiac risk during methadone treatment: Focus on the QT Interval. Heroin Addiction and Related Clinical Problems 11(4): 29-33, 2009. (30 refs.)

In recent years, methadone, along with various other drugs, has been implicated in the lengthening of the QT interval of the electrocardiogram (ECG) and in the onset of potentially fatal arrhythmias. The risk of prolonged QT in methadone-maintained subjects is estimated at between 2-4%, while the risks of torsades de pointes or sudden death are extremely low. Despite the diversities reported, the guidelines available to date indicate the need to implement preventive measures based on ECG screening. The impact of these recommendations is, however, limited by the lack of a comparative risk/benefit assessment of specific procedures.

Parrino M; AATOD Board Directors. QTc Interval Screening. American Association for the Treatment of Opioid Dependance (AATOD) Policy and Guidance Statement. (letter). Heroin Addiction and Related Clinical Problems 11(2): 59-61, 2009. (22 refs.)

Pell JP; Haw S; Cobbe S; Newby DE; Pell ACH; Fischbacher C et al. Secondhand smoke exposure and survival following acute coronary syndrome: Prospective cohort study of 1261 consecutive admissions among never-smokers. Heart 95(17): 1415-1418, 2009. (23 refs.)

Objective: To determine whether exposure to second-hand smoke is associated with early prognosis following acute coronary syndrome. Design, setting and participants: We interviewed consecutive patients admitted to nine Scottish hospitals over 23 months. Information was obtained, via questionnaire, on age, sex, smoking status, postcode of residence and admission serum cotinine concentration was measured. Follow-up data were obtained from routine hospital admission and death databases. Results: Of the 5815 participants, 1261 were never-smokers. Within 30 days, 50 (4%) had died and 35 (3%) had a non-fatal myocardial infarction. All-cause deaths increased from 10 (2.1%) in those with cotinine <= 0.1 ng/ml to 22 (7.5%) in those with cotinine >0.9 ng/ml (chi(2) test for trend p<0.001). This persisted after adjustment for potential confounders (cotinine >0.9 ng/ml: adjusted OR 4.80, 95% CI 1.95 to 11.83, p = 0.003). The same dose response was observed for cardiovascular deaths and death or myocardial infarction. Conclusions: Secondhand smoke exposure is associated with worse early prognosis following acute coronary syndrome. Non-smokers need to be protected from the harmful effects of secondhand smoke.

Peters A. Air quality and cardiovascular health smoke and pollution matter. Circulation 120(11): 924-927, 2009. (20 refs.)

This commentary considers various aspects of air quality, i.e. particulate matter, ultrafine matter, carbon monoxide, and compares these to cigarettee smoking, in particular drawing upon two articles in this issue -"Cardiovascular mortality and exposure to airborne fine particulate matter and cigarette smoke: shape of the exposure-response relationship," by Pope et al. and "Emergency Hospital Admissions for Cardiovascular Diseases and Ambient Levels of Carbon Monoxide: Results for 126 United States Urban Counties, 1999-2005" by Bell.

Phillips K; Luk A; Soor GS; Abraham JR; Leong S; Butany J. Cocaine cardiotoxicity: A review of the pathophysiology, pathology, and treatment options. (review). American Journal of Cardiovascular Drugs 9(3): 177-196, 2009. (189 refs.)

Cocaine is a powerful stimulant that gives users a temporary sense of euphoria, mental alertness, talkativeness, and a decreased need for food and sleep. Cocaine intoxication is the most frequent cause of drug-related death reported by medical examiners in the US, and these events are most often related to the cardiovascular manifestations of the drug. Once playing a vital role in medicine as a local anesthetic, decades of research have established that cocaine has the ability to cause irreversible structural damage to the heart, greatly accelerate cardiovascular disease, and initiate sudden cardiac death. Although pathologic findings are often reported in the literature, few images are available to support these findings, and reviews of cocaine cardiopathology are rare. We describe the major pathologic findings linked to cocaine abuse in earlier research, their underlying mechanisms, and the treatment approaches currently being used in this patient population. A MEDLINE search was conducted to identify all English language articles from January 2000 to June 2008 with the subject headings and key words 'cocaine', 'heart', 'toxicity', and 'cardiotoxicity'. Epidemiologic, laboratory, and clinical studies on the pathology, pathophysiology, and pharmacology of the effects of cocaine on the heart were reviewed, along with relevant treatment options. Reference lists were used to identify earlier studies on these topics, and related articles from Google Scholar were also included. There is an established connection between cocaine use and myocardial infarction (MI), arrhythmia, heart failure, and sudden cardiac death. Numerous mechanisms have been postulated to explain how cocaine contributes to these conditions. Among these, cocaine may lead to MI by causing coronary artery vasoconstriction and accelerated atherosclerosis, and by initiating thrombus formation. Cocaine has also been shown to block K+ channels, increase L-type Ca2+ channel current, and inhibit Na+ influx during depolarization, all possible causes for arrhythmia. Additionally, cocaine use has been associated with left ventricular hypertrophy, myocarditis, and dilated cardiomyopathy, which can lead to heart failure if drug use is continued. Certain diagnostic tools, including ECG and serial cardiac markers, are not as accurate in identifying MI in cocaine users experiencing chest pain. As a result, clinicians should be suspicious of cocaine use in their differential diagnosis of chest pain, especially in the younger male population, and proceed more cautiously when use is suspected. Treatment for cocaine-related cardiovascular disease is in many ways similar to treatment for traditional cardiovascular disease. However use of beta-receptor antagonists and class Ia and III anti-arrhythmics is strongly discouraged if the patient is likely to continue cocaine use, because of documented adverse effects. The medical community is in urgent need of a pharmacologic adjunct to cocaine-dependence treatment that can deter relapse and reduce the risks associated with cardiovascular disease in these patients.

Polednak AP. Trends in death rates from tobacco-related cardiovascular diseases in selected US states differing in tobacco-control efforts. Epidemiology 20(4): 542-546, 2009. (27 refs.)

Background: Tobacco-control efforts (starting with California in 1989) have been associated with smoking cessation among Young adults in certain US states. The impact on trends in tobacco-related cardiovascular diseases is less clear. Methods: Annual percent change in age-standardized mortality rates for tobacco-related cardiovascular diseases were compared for 1990-2004 in states or groups of states that differed in tobacco-control efforts. Results: Cardiovascular disease mortality rates for age 20-44 years have fallen more rapidly in California and in New Jersey-New York (which had cigarette taxes similar to California but a less comprehensive tobacco control program in the 1990s) than in 6 Southern "tobacco-growing" states (which had low cigarette taxes and limited tobacco-control efforts in the 1990s). Conclusions: The geographic differences in the decline in cardiovascular mortality rates may be related to stronger tobacco-control efforts. These results suggest that expansion of tobacco-control efforts in the US may help reduce cardiovascular disease deaths.

Polonia J; Barbosa L; Silva JA; Rosas M. Improvement of aortic reflection wave responses 6 months after stopping smoking: A prospective study. Blood Pressure Monitoring 14(2): 69-75, 2009. (39 refs.)

Background: Cigarette smoking is one important preventable cause of cardiovascular illness that has been associated with increased stiffness of large arteries and wave reflection, which are independent predictors of cardiovascular disease. Methods We investigated the effect of a 6-month quitting smoking programme on aortic stiffness, central pressure and wave reflections in chronic heavy smokers. Seventy-one (83% normotensives) long-term heavy smokers [>20 cigarettes/day and exhaled carboxy haemoglobin (COHb) ( >= 4% and CO ppm >= 21)] completed a 6-month psychological-based stop-smoking program. Patients were divided into two groups. Thirty-one patients aged 45 +/- 2 years, 71% male, fully quit smoking for 6 months (COHb < 2% and CO ppm < 10 at 1, 3 and 6 months) - group 1, whereas 40 patients aged 45 +/- 1 years, 73% male, did not change their smoking habits - group II. We measured between baseline and changes after 6 months in aortic stiffness assessed as pulse wave velocity (Complior), central-peripheral pulse pressure (PP) amplification ratio (PPAr), wave reflection (augmentation index corrected for heart rate), augmentation pressure and transit time (Sphygmocor). Ambulatory 24 h blood pressure (ABP) data were obtained at baseline and after 6 months in 36 patients (n=19) of group I and 17 of group II. ResultsIn group I, but not in group II, there were significant reductions of peripheral systolic BP (baseline: 131 +/- 4 to after 6 months: 127 +/- 4 mmHg, P<0.04) and of systolic BP (baseline: 121 +/- 4 to after 6 months: 114 +/- 4 mmHg, P<0.03). In group -I from baseline to after 6 months, PPAr increased by 13.1 +/- 4.1% and transit time (ms) by 8.7 +/- 2.9%; augmentation index was reduced by 9.2 +/- 1.6%, augmentation pressure by 5.7 +/- 1.9 mmHg (all P<0.03 vs. baseline and vs. group II); and pulse wave velocity by 2.3 +/- 2.8% (P=0.062). In group I, only daytime ABP was reduced from baseline to after 6 months (1129/82 +/- 2/2 to 123/78 +/- 2/2 mmHg, P<0.03), whereas no change in 24h-ABP was found in group II. Conclusion Six months of smoking cessation is associated with clear improvement of reflected waves, central pressure and aortic stiffness, and with a reduction of daytime BP. This may contribute to the improvement of cardiovascular prognosis attributed to smoking cessation.

Pyrgakis VN. Smoking and cardiovascular disease. (editorial). Hellenic Journal of Cardiology 50(3): 231-234, 2009. (53 refs.)

Ramstedt M. Fluctuations in male ischaemic heart disease mortality in Russia 1959-1998: Assessing the importance of alcohol. Drug and Alcohol Review 28(4): 390-395, 2009. (25 refs.)

Introduction and Aims. The decline in cardiovascular mortality in Russia following the Soviet anti-alcohol campaign of 1985-1988 and the subsequent increase when these extreme alcohol controls were repealed suggested that alcohol consumption is responsible for a substantial number of ischaemic heart disease (IHD) deaths in Russia. To examine whether a similar conclusion can be drawn on the basis of a time-series analysis covering a longer time period, namely 1959-1998. Design and Methods. Using ARIMA time-series analysis, the male IHD mortality rates from 1959 to 1998 were analysed in relation to three indicators of alcohol consumption: estimated per capita consumption, mortality from liver cirrhosis and alcohol poisonings. Cigarette sales and lung cancer mortality were used as indicators of smoking. Results. Each indicator of alcohol consumption had positive and statistically significant relationships with male IHD mortality in bivariate autoregressive integrated moving average models. The association was stronger in models predicting changes in premature male IHD mortality (30-54 years). At least one alcohol indicator was significantly related to IHD mortality in multivariate models, and in the case of premature IHD mortality, both mortality indicators were significant. Discussion and Conclusions. The results provide additional empirical evidence supporting alcohol's conceivable negative effects on IHD in Russia and the idea that binge drinking could be the mechanism through which this effect is mediated. There were no signs of any protective effects from alcohol among Russian men.

Rantakomi SH; Laukkanen JA; Kurl S; Kauhanen J. Binge drinking and the progression of atherosclerosis in middle-aged men: An 11-year follow-up. Atherosclerosis 205(1): 266-271, 2009. (36 refs.)

Objective: There is limited knowledge on drinking patterns and the progression of atherosclerosis. Previous studies have shown conflicting results between alcohol consumption and atherosclerotic progression. We investigated the association between the pattern of binge drinking and the 11-year progression of carotid atherosclerosis in a population-based sample of middle-aged men. Methods and results: This study is a part of the FinDrink Study, based on the Kuopio Ischemic Heart Disease Risk Factor Study. We investigated the effect of drinking patterns on the changes in maximum and mean intima-media thickness, including changes in maximum plaque height in 751 participants as measured by carotid ultrasound. The increased atherosclerosis progression was statistically significant among those men with binge drinking of >= 6 drinks per session (22.4% of total number of participants) using different covariates in different models according to the mean increase in maximum intima-media thickness (Model 1, p=0.008: Model 2, p=0.031, Model 3, p=0.037) and the mean increase in maximum plaque height (Model 1, p=0.002; Model 2, p=0.012, Model 3, p=0.017). Conclusion: Our study shows that binge drinking was associated with an increased atherosclerosis progression during an 11-year follow-up in middle-aged men, independent of the total alcohol consumption.

Reece AS. Chronic toxicology of cannabis. (review). Clinical Toxicology 47(6): 517-524, 2009. (154 refs.)

Introduction. Cannabis is the most widely used illicit drug worldwide. As societies reconsider the legal status of cannabis, policy makers and clinicians require sound knowledge of the acute and chronic effects of cannabis. This review focuses on the latter. Methods. A systematic review of Medline, PubMed, PsychInfo, and Google Scholar using the search terms "cannabis," "marijuana," "marihuana," "toxicity," "complications," and "mechanisms" identified 5,198 papers. This list was screened by hand, and papers describing mechanisms and those published in more recent years were chosen preferentially for inclusion in this review. Findings. There is evidence of psychiatric, respiratory, cardiovascular, and bone toxicity associated with chronic cannabis use. Cannabis has now been implicated in the etiology of many major long-term psychiatric conditions including depression, anxiety, psychosis, bipolar disorder, and an amotivational state. Respiratory conditions linked with cannabis include reduced lung density, lung cysts, and chronic bronchitis. Cannabis has been linked in a dose-dependent manner with elevated rates of myocardial infarction and cardiac arrythmias. It is known to affect bone metabolism and also has teratogenic effects on the developing brain following perinatal exposure. Cannabis has been linked to cancers at eight sites, including children after in utero maternal exposure, and multiple molecular pathways to oncogenesis exist. Conclusion. Chronic cannabis use is associated with psychiatric, respiratory, cardiovascular, and bone effects. It also has oncogenic, teratogenic, and mutagenic effects all of which depend upon dose and duration of use.

Rigotti NA. Helping smokers with cardiac disease to abstain from tobacco after a stay in hospital. (editorial). Canadian Medical Association Journal 180(13): 1283-1284, 2009. (11 refs.)

Russell M; Chu BC; Banerjee A; Fan AZ; Trevisan M; Dorn JM et al. Drinking patterns and myocardial infarction: A linear dose-response model. Alcoholism: Clinical and Experimental Research 33(2): 324-331, 2009. (32 refs.)

The relation of alcohol intake to cardiovascular health is complex, involving both protective and harmful effects, depending on the amount and pattern of consumption. Interpretation of data available on the nature of these relations is limited by lack of well-specified, mathematical models relating drinking patterns to alcohol-related consequences. Here we present such a model and apply it to data on myocardial infarction (MI). The dose-response model derived assumes: (1) each instance of alcohol use has an effect that either increases or decreases the likelihood of an alcohol-related consequence, and (2) greater quantities of alcohol consumed on any drinking day add linearly to these increases or decreases in risk. Risk was reduced algebraically to a function of drinking frequency and dosage (volume minus frequency, a measure of the extent to which drinkers have more than 1 drink on days when they drink). In addition to estimating the joint impact of frequency and dosage, the model provides a method for calculating the point at which risk related to alcohol consumption is equal to background risk from other causes. A bootstrapped logistic regression based on the dose-response model was conducted using data from a case-control study to obtain the predicted probability of MI associated with current drinking patterns, controlling for covariates. MI risk decreased with increasing frequency of drinking, but increased as drinking dosage increased. Rates of increasing MI risk associated with drinking dosage were twice as high among women as they were among men. Relative to controls, lower MI risk was associated with consuming < 4.55 drinks per drinking day for men (95% CI: 2.77 to 7.18) and < 3.08 drinks per drinking day for women (95% CI: 1.35 to 5.16), increasing after these cross-over points were exceeded. Use of a well-specified mathematical dose-response model provided precise estimates for the first time of how drinking frequency and dosage each contribute linearly to the overall impact of a given drinking pattern on MI risk in men and women.

Schroeder SA. Public smoking bans are good for the heart. (editorial). Journal of the American College of Cardiology 54(14): 1256-1257, 2009. (18 refs.)

Scott-Storey K; Wuest J; Ford-Gilboe M. Intimate partner violence and cardiovascular risk: Is there a link? Journal of Advanced Nursing 65(10): 2186-2197, 2009. (50 refs.)

Aim. This paper is a report of a study of the relationship between stress associated with intimate partner violence and smoking and cardiovascular risk. Background. Stress related to intimate partner violence persists after a woman leaves an abusive relationship. Persistent stress is associated with cardiovascular disease, the leading single cause of death among women. Smoking, an established risk factor for cardiovascular disease, is a coping mechanism commonly used to decrease the anxiety and stress of intimate partner violence. However, cardiovascular health is poorly understood in abused women. Method. Secondary analysis of data collected between 2004 and 2005 with a community sample of 309 women who had separated from an abusive partner 3 months to 3 years previously was conducted to create a descriptive profile of cardiovascular risk. Bivariate tests of association and logistic regression analysis were used to test relationships among variables. Results. Of the women, 44 center dot 1% were smokers; 53 center dot 2% had body mass indices classified as overweight or obese; 54 center dot 7% had blood pressures above normal range; and 50 center dot 8% reported cardiovascular symptoms. Neither severity of intimate partner violence nor smoking behaviours were statistically significant in explaining the presence of cardiovascular symptoms. Conclusion. The prevalence of hypertension, obesity and smoking suggests that survivors of intimate partner violence may be at heightened risk for cardiovascular disease and warrant clinical attention. Because cardiac symptoms develop as women get older, the mean age of 39 years in this sample may explain why intimate partner violence severity and smoking did not sufficiently explain the presence of cardiac symptoms.

Skotzko CE; Vrinceanu A; Krueger L; Freudenberger R. Alcohol use and congestive heart failure: Incidence, importance, and approaches to improved history taking. Heart Failure Reviews 14(1): 51-55, 2009. (19 refs.)

Alcohol use, abuse, and dependence have the potential to result in alcoholic cardiomyopathy (ACM). This distinct form of congestive heart failure (CHF) is responsible for 21-36% of all cases of nonischemic dilated cardiomyopathy in Western society. Without complete abstinence, the 4-year mortality for ACM approaches 50%. Therefore, accurate and detailed assessment of alcohol use in congestive heart failure is essential. The prevalence of problematic alcohol use is unrecognized by many clinicians. Clinical assessment of alcohol intake is often reduced to a simple question such as, "Do you drink?" Denial and minimization are hallmarks of alcohol abuse, with many individuals underreporting their use of alcohol. Clinicians can overcome these hurdles by implementing practical history taking measures to improve the accuracy of self-reported alcohol use. The data regarding the dangers of ongoing alcohol use in individuals with ACM make attempts to engage individuals in treatment to support abstinence essential. Suggestions for detailed and accurate assessment are discussed.

Smith PM; Burgess E. Smoking cessation initiated during hospital stay for patients with coronary artery disease: A randomized controlled trial. Canadian Medical Association Journal 180(13): 1297-1303, 2009. (40 refs.)

Background: Programs for smoking cessation for cardiac patients are underused in Canada. We examined the efficacy of an intervention for smoking cessation for patients admitted to hospital for coronary artery bypass graft (CABG) or because of acute myocardial infarction (MI). Methods: Nurses randomly assigned 276 sequential patients admitted because of acute MI or for CABG who met the inclusion criteria. Participants received an intensive or minimal smoking-cessation intervention. The minimal intervention included advice from physicians and nurses and 2 pamphlets. The intensive intervention included the minimal intervention plus 60 minutes of bedside counselling, take-home materials and 7 nurse-initiated counselling calls for 2 months after discharge. The outcomes were point prevalence of abstinence at 3, 6 and 12 months after discharge. Results: The 12-month self-reported rate of abstinence was 62% among patients in the intensive group and 46% among those in the minimal group (odds ratio [ OR] 2.0, 95% confidence interval [ CI] 1.2-3.1). Abstinence was confirmed for 54% of patients in the intensive group and 35% in the minimal group (OR 2.0, 95% CI 1.3-3.6). Abstinence was significantly lower among those who used pharmacotherapy than among those who did not (p < 0.001). Continuous 12-month abstinence was 57% in the intensive group and 39% in the minimal group (p < 0.01). It was significantly higher among patients admitted for CABG than among those admitted because of acute MI (p < 0.05). Interpretation: Providing intensive programs for smoking cessation for patients admitted for CABG or because of acute MI could have a major impact on health and health care costs.

Steinke L; Lanfear DE; Dhanapal V; Kalus JS. Effect of "energy drink" consumption on hemodynamic and electrocardiographic parameters in healthy young adults. Annals of Pharmacotherapy 43(4): 596-602, 2009. (21 refs.)

BACKGROUND: Energy drinks are frequently purported to improve cognitive function and concentration. However, the cardiovascular effects of these drinks have not been adequately studied. OBJECTIVE: component To determine the cardiac effects of a commercially available, multienergy drink in healthy volunteers. METHODS: Fifteen healthy adults were included in this prospective study. Individuals who had chronic medical conditions, were on chronic medication, or were pregnant or breast-feeding were excluded. Subjects abstained from caffeine for 48 hours prior to and during the study. In the morning on Day 1 of the study, while subjects were in a fasted state, baseline blood pressure (BP), heart rate (HR), and electrocardiographic (ECG) parameters were measured. Participants then consumed 500 mL (2 cans) of an energy drink and measurements were repeated 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours later. Participants then drank 500 mL of energy drink daily for the next 5 days. Day 1 protocol was repeated on Day 7. RESULTS: On Days 1 and 7, maximum mean systolic BP (SBP), HR, and QTc interval occurred at 4 hours. Maximum diastolic BP (DBP) occurred at 2 hours on Days 1 and 7. Within 4 hours of energy drink consumption, on Days 1 and 7, respectively, SBP increased by 7.9% (p = 0.006) and 9.6% (p < 0.001), HR increased by 7.8% (p = 0.009) and 11.0% (p < 0.001), and QTc interval increased by 2.4% (p = 0.368) and 5.0% (p = 0.052). DBP increased by 7.0% (p = 0.046) and 7.8% (p = 0.063) within 2 hours of energy drink consumption on Days 1 and 7 respectively. CONCLUSIONS: Although no significant ECG changes were observed, HR increased 5-7 beats/min and SBP increased 10 mm Hg after energy drink consumption.

Streppel MT; Ocke MC; Boshuizen HC; Kok FJ; Kromhout D. Long-term wine consumption is related to cardiovascular mortality and life expectancy independently of moderate alcohol intake: The Zutphen Study. Journal of Epidemiology and Community Health 63(7): 534-540, 2009. (64 refs.)

Background: Light to moderate alcohol intake lowers the risk of cardiovascular mortality, but whether this protective effect can be attributed to a specific type of beverage remains unclear. Moreover, little is known about the effects of long-term alcohol intake on life expectancy. Methods: The impact of long-term alcohol intake and types of alcoholic beverages consumed on cardiovascular mortality and life expectancy at age 50 was investigated in the Zutphen Study, a cohort of 1373 men born between 1900 and 1920 and examined repeatedly between 1960 and 2000. Hazard ratios (HRs) for total alcohol intake and alcohol from wine, beer and spirits were obtained from time-dependent Cox regression models. Life expectancy at age 50 was calculated from areas under survival curves. Results: Long-term light alcohol intake, that is ( 20 g per day, compared with no alcohol, was strongly and inversely associated with cerebrovascular (HR 0.43, 95% CI 0.26 to 0.70), total cardiovascular ( HR 0.70, 95% CI 0.55 to 0.89) and all-cause mortality ( HR 0.75, 95% CI 0.63 to 0.91). Independent of total alcohol intake, long-term wine consumption of, on average, less than half a glass per day was strongly and inversely associated with coronary heart disease ( HR 0.61, 95% CI 0.41 to 0.89), total cardiovascular ( HR 0.68, 95% CI 0.53 to 0.86) and all-cause mortality ( HR 0.73, 95% CI 0.62 to 0.87). These results could not be explained by differences in socioeconomic status. Life expectancy was about 5 years longer in men who consumed wine compared with those who did not use alcoholic beverages. Conclusion: Long-term light alcohol intake lowered cardiovascular and all-cause mortality risk and increased life expectancy. Light wine consumption was associated with 5 years longer life expectancy; however, more studies are needed to verify this result.

Stringer J; Welsh C; Tommasello A. Methadone-associated Q-T interval prolongation and torsades de pointes. American Journal of Health-System Pharmacy 66(9): 825-833, 2009. (70 refs.)

Purpose. The association of methadone with Q-T interval prolongation and torsades de pointes (TdP) is reviewed, and recommendations for preventing Q-T interval prolongation in methadone users are provided. Summary. Abnormalities in voltage-gated potassium channels have been shown to lead to prolonged action potentials that are expressed as long Q-T intervals, and methadone has been found to interact with the voltage-gated potassium channels of the myocardium. While cardiac arrhythmias in methadone users have been reported for several decades, specific reports of methadone-associated Q-T interval prolongation and TdP did not appear in the literature until the early part of the 21st century. Because not every patient experiences Q-T interval prolongation with methadone, recent research has elucidated risk factors that predispose patients to this adverse effect, including female sex, hypokalemia, high-dose methadone, drug interactions, underlying cardiac conditions, unrecognized congenital long Q-T interval syndrome, and predisposing DNA polymorphisms. Given the high mortality rates seen in untreated illicit opioid users and the clear efficacy of methadone in treating opioid addiction, the risk of using methadone, even in a patient with other risk factors for Q-T interval prolongation, may outweigh the alternative of no pharmacologic treatment. A baseline electrocardiogram (ECG), personal and family history of syncope, and a complete medication history should be obtained before a patient begins treatment with methadone. Given the apparent synergistic effects of parenteral methadone and chlorobutanol, oral methadone should be used whenever possible. Conclusion. Q-T interval prolongation and TdP associated with the use of methadone are potentially fatal adverse effects. A thorough patient history and ECG monitoring are essential for patients treated with this agent, and alterations in treatment options may be necessary.

Sull JW; Yi SW; Nam CM; Ohrr H. Binge drinking and mortality from all causes and cerebrovascular diseases in Korean men and women: A Kangwha cohort study. Stroke 40(9): 2953-2958, 2009. (22 refs.)

Background and Purpose-The purpose of this study was to examine the association between binge drinking and risks of mortality due to all causes of death with a focus on cerebrovascular disease in Korean men and women. Methods-This study followed a cohort of 6291 residents in Kangwha County, aged >= 55 years in March 1985, for their cause-specific mortality for 20.8 years up to December 31, 2005. We calculated hazard ratio of mortality by experience or frequency of binge drinking using the Cox proportional hazard model. Binge drinking was defined as having >= 6 drinks on one occasion. Results-In men, binge drinkers who drink daily had an increased risk of mortality from all causes (hazard ratio, 1.33; 95% CI, 1.11 to 1.60) as compared with nondrinkers. They showed much increased risks of mortality from total stroke (hazard ratio, 1.86; 95% CI, 1.16 to 2.99) and hemorrhagic stroke (hazard ratio, 3.39; 95% CI, 1.38 to 8.35). Female binge drinkers also showed an increased risk of mortality from cardiovascular disease as compared with female nondrinkers, but the outcome was not statistically significant. Conclusions-The results of this study suggest that frequent binge drinking has a harmful effect on hemorrhagic stroke in Korean men. These findings need to be confirmed in further studies.

Suzuki K; Elkind MSV; Boden-Albala B; Jin ZZ; Berry G; Di Tullio MR et al. Moderate alcohol consumption is associated with better endothelial function: A cross sectional study. BMC Cardiovascular Disorders 9: article 8, 2009. (27 refs.)

Background: Moderate alcohol consumption is protective against coronary artery disease. Endothelial dysfunction contributes to atherosclerosis and the pathogenesis of cardiovascular disease. The effects of alcohol consumption on endothelial function may be relevant to these cardiovascular outcomes, but very few studies have examined the effect of alcohol consumption on endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery in humans. Methods: In the population-based Northern Manhattan Study (NOMAS), we performed a cross-sectional analysis of lifetime alcohol intake and brachial artery FMD during reactive hyperemia using high-resolution B-mode ultrasound images among 884 stroke-free participants (mean age 66.8 years, women 56.6%, Hispanic 67.4%, black 17.4%, and white 15.2%). Results: The mean brachial FMD was 5.7% and the median was 5.5%. Compared to non-drinkers, those who drank >1 drink/month to 2 drinks/day were more likely to have FMD above the median FMD (5.5%) (unadjusted OR 1.7, 95% CI 1.2-2.4, p = 0.005). In multivariate analysis, the relationship between moderate alcohol consumption and FMD remained significant after adjusting for multiple traditional cardiovascular risk factors, including sex, race-ethnicity, body mass index, diabetes mellitus, coronary artery disease, Framingham risk score, medication use (adjusted OR 1.8, 95% CI 1.1-3.0, p = 0.03). No beneficial effect on FMD was seen for those who drank more than 2 drinks/day. Conclusion: In conclusion, consumption of up to 2 alcoholic beverages per day was independently associated with better FMD compared to no alcohol consumption in this multiethnic population. This effect on FMD may represent an important mechanism in explaining the protective effect of alcohol intake on cardiovascular disease.

Tan KK; Chen K; Chia KH; Lee CW; Nalachandran S. Surgical management of infected pseudoaneurysms in intravenous drug abusers: Single institution experience and a proposed logorithm. World Journal of Surgery 33(9): 1830-1835, 2009. (19 refs.)

Vascular complications from intravenous drug abuse pose significant challenges to vascular surgeons. No formalized polices have been reached on surgical management of the resultant infected pseudoaneurysm. A retrospective review of all patients who underwent surgery for pseudoaneurysms due to chronic intravenous drug abuse from July 2005 to February 2008 was performed. A total of 15 patients with infected pseudoaneurysms from chronic intravenous drug abuse were operated on during the study period. The sites of involvement were restricted to the femoral (86.7%) and brachial (13.3%) areas. The drug involved was buprenorphine (Subutex) in all cases. Pain over the limb swelling (100%), pulsatility (60%), and symptoms suggestive of septicemia (46.7%) were the most common symptoms. Staphylococcus aureus was present in 93.3%. Diagnosis was achieved clinically in 26.7%, by duplex ultrasonography in 60.0%, and by computed tomography (CT) angiography in 13.3%. In the two patients with brachial pseudoaneurysms, the brachial artery was ligated in one, and a basilic vein patch was used in the other. In the 13 patients with femoral pseudoaneurysms, the pseudoaneurysm was ligated and excised in 8 (61.5%), and immediate reconstructive bypass surgery was performed in 5 (38.5%). Two patients had critical ischemia after ligation and required reconstructive bypass surgery a few weeks later. Postoperative complications included claudication, digital gangrene, localized wound infection, and rebleeding. There was no associated mortality. Pseudoaneurysm from intravenous drug abuse continues to pose significant challenges to surgeons worldwide, ranging from an accurate diagnosis to the choice of surgery. The aims of surgery must be to achieve adequate debridement and control infection and hemorrhage. Any associated postoperative complications must be identified and dealt with.

Thompson J; Thompson JR. Acute myocardial infarction related to methylphenidate for adult attention deficit disorder. Journal of Emergency Medicine 38(1): 18-21, 2010. (17 refs.)

Adult Attention Deficit Disorder is increasingly diagnosed and treated. Psychostimulant medications, such as methylphenidate, are commonly prescribed for this condition, but the long-term safety of such medications in an adult population is unknown at present. Because these medications are closely related to amphetamines, it is expected that toxic side effects would be similar. We present the case of a 27-year-old man who suffered an acute myocardial infarction due to coronary vasospasm related to use of methylphenidate complicated by concomitant use of pseudoephedrine.

Thorndike AN; Rigotti NA. A tragic triad: Coronary artery disease, nicotine addiction, and depression. (review). Current Opinion In Cardiology 24(5): 447-453, 2009. (56 refs.)

Purpose of review: Despite the availability of multiple resources for treating smoking in patients with cardiovascular disease (CVD) and the well known risks of continued smoking, a majority of smokers resume smoking after hospitalization for acute CVD. Depression is common among patients with CVD and is associated with failure to follow recommendations to reduce cardiac risk. This review examines the complex relationship between smoking and depression in patients with CVD and current evidence for treating this triad. Recent findings: The prevalence of depressive symptoms among smokers hospitalized with CVD is 22-24%. Smokers with depressive symptoms are more likely to return to smoking after hospital discharge compared with nondepressed smokers. Stronger nicotine withdrawal symptoms among the depressed smokers contribute to relapse. Secondary analyses suggest that bupropion SR and cognitive behavioral therapy may be effective treatments for smokers with depression and CVD. A systematic review of smoking interventions in hospitalized patients found that only intensive counseling interventions with follow-up for more than 1 month were effective for smokers with CVD. Summary: Clinicians should consider screening all smokers with CVD for depression, particularly during hospitalization for an acute event. Smokers hospitalized with CVD need intensive counseling lasting more than 1 month after discharge, and smokers with depressive symptoms need even more prolonged treatment for quitting. The addition of pharmacotherapy to long-term counseling has the potential to further improve cessation rates.

Tonstad S. Smoking cessation: How to advise the patient. Heart 95(19): 1635-1640, 2009. (20 refs.)

Observations show that only one third to one half of patients who smoke at the time of myocardial infarction subsequently manage to quit. This indicates that many smokers do not receive optimal medical support for cessation. There is often a gap between hospital discharge and follow-up by the primary care physician. Cardiologists and hospital physicians potentially play a key role in motivating and supporting quitting behaviour and should not assume that primary care physicians will fill the gap. The 5 A's (ask, assess, advise, assist, arrange) have been adopted by the European Society of Cardiology as an effective strategy to promote smoking cessation. Smokers should be identified systematically by hospital and office operating procedures. All notes should include an up to date record of smoking status. When a patient is identified as a smoker, the consultant physician or cardiologist intervenes by: (1) assessing dependence on cigarettes; (2) personalising benefits of cessation; (3) boosting motivation for a quit attempt; (4) recommending and prescribing medication; (5) discussing behavioural changes and setting a quit date; and (6) arranging follow-up. The combination of support (motivational, social) and pharmacotherapy has been shown to be the most effective treatment for patients with CVD

Wakabayashi I; Araki Y. Influences of gender and age on relationships between alcohol drinking and atherosclerotic risk factors. Alcoholism: Clinical and Experimental Research 34(2, Supplement 1): S54-S60, 2010. (14 refs.)

Background. Alcohol drinking affects atherosclerotic progression mainly through blood pressure and lipid metabolism. The purpose of the present study was to clarify whether effects of alcohol drinking on atherosclerotic risk factors differ by gender and age. Methods. The database of periodic health check-ups for local district workers was used. The subjects were divided into 3 groups according to mean ethanol consumption per day (nondrinkers; light drinkers, less than 30 g per day; moderate-to-heavy drinkers, 30 g or more per day). The mean levels of each atherosclerosis-related variable in the 3 groups were compared. Results. The mean level of body mass index (BMI) was slightly but significantly lower in drinkers than in nondrinkers in the thirties, forties, and fifties age groups in men and in the twenties, thirties, forties, and fifties age groups in women, while this tendency was not found in the sixties age groups of men and women. In men, mean blood pressure was higher in moderate-to-heavy drinkers than in nondrinkers in all age groups and was higher in light drinkers than in nondrinkers only in the age groups after 40 years. Mean blood pressure of women was higher in the moderate-to-heavy drinker group than in the nondrinker group and this difference became higher with advance of age. In women, mean blood pressure was not affected by light drinking in any of the age groups except for the fifties age group. In men, serum total cholesterol was higher in drinkers than in nondrinkers in the twenties age group but was lower in drinkers than in nondrinkers at thirties or older. Serum total cholesterol in women was lower in drinkers than in nondrinkers in the age groups from twenties to forties but tended to be higher in drinkers than in nondrinkers in the sixties age group. Serum HDL cholesterol increased with advance of age from thirties to sixties in men, while it decreased with advance of age from twenties to sixties in women. Serum HDL cholesterol was higher in drinkers than in nondrinkers in all age groups of men and women, and atherogenic index, calculated by using serum total cholesterol and HDL cholesterol concentrations, was lower in drinkers than in nondrinkers in all age groups of men and women. Conclusions. Both in men and women, blood pressure and HDL cholesterol were strongly affected by alcohol drinking: the elevating effect of alcohol drinking on blood pressure was more prominent in the elderly than in the young, while the elevating effect of alcohol drinking on serum HDL cholesterol was not influenced by age. Relationships of drinking with total cholesterol and BMI vary by age and gender.

Wakabayashi I; Groschner K. Modification of the association between alcohol drinking and non-HDL cholesterol by gender. Clinica Chimica Acta 404(2): 154-159, 2009. (33 refs.)

Background: Serum non-HDL cholesterol is a strong predictor of cardiovascular diseases. We studied the relationship between habitual alcohol drinking and non-HDL cholesterol. Methods: Healthy male subjects (n = 27,005) and female subjects (n = 16.805) were divided into 5 groups by average daily ethanol intake. Serum non-HDL cholesterol level and prevalence of serum high non-HDL cholesterol (>= 170 mg/dl) were compared among the groups. Results: Non-HDL cholesterol level and prevalence of high non-HDL cholesterol became lower as alcohol intake increased. The threshold alcohol intake in the drinker groups showing significantly lower non-HDL cholesterol level and significantly lower prevalence of high non-HDL cholesterol, compared with those in non-drinkers, was lower in women (< 10 g/d) than in men (>= 10 and <20 g/d). Odds ratios of each drinker group vs. the non-drinker group for high non-HDL cholesterol became lower as alcohol intake increased. The odds ratio of each drinker group vs. the non-drinker group for high non-HDL cholesterol tended to be lower in women than in men. Conclusions: The results suggest that even light drinking is sufficient to significantly lower serum non-HDL cholesterol and that this effect of alcohol drinking on non-HDL cholesterol is more pronounced in women than in men.

Wiklund U; Karlsson M; Otrom M; Messner T. Influence of energy drinks and alcohol on post-exercise heart rate recovery and heart rate variability. Clinical Physiology and Functional Imaging 29(1): 74-80, 2009. (28 refs.)

Media have anecdotally reported that drinking energy drinks in combination with alcohol and exercise could cause sudden cardiac death. This study investigated changes in the electrocardiogram (ECG) and heart rate variability after intake of an energy drink, taken in combination with alcohol and exercise. Ten healthy volunteers (five men and five women aged 19-30) performed maximal bicycle ergometer exercise for 30 min after: (i) intake of 0.75 l of an energy drink mixed with alcohol; (ii) intake of energy drink; and, (iii) no intake of any drink. ECG was continuously recorded for analysis of heart rate variability and heart rate recovery. No subject developed any clinically significant arrhythmias. Post-exercise recovery in heart rate and heart rate variability was slower after the subjects consumed energy drink and alcohol before exercise, than after exercise alone. The healthy subjects developed blunted cardiac autonomic modulation after exercising when they had consumed energy drinks mixed with alcohol. Although they did not develop any significant arrhythmia, individuals predisposed to arrhythmia by congenital or other rhythm disorders could have an increased risk for malignant cardiac arrhythmia in similar situations.

Winkelmann BR; von Holt K; Unverdorben M. Smoking and atherosclerotic cardiovascular disease: Part II: Role of cigarette smoking in cardiovascular disease development. (review). Biomarkers in Medicine 3(5): 617-653, 2009. (450 refs.)

Potential mechanisms and biomarkers of atherosclerosis related to cigarette smoking - a modifiable risk factor for that disease - are discussed in this article. These include smoking-associated inflammatory markers, such as leukocytes, high-sensitivity C-reactive protein, serum amyloid A, ICAM-1 and IL-6. Other reviewed markers are indicative for smoking-related impairment of arterial endothelial function (transcapillary leakage of albumin, inhibition of endogenous nitric oxide synthase activity and reduced endothelium-dependent vasodilation) or point to oxidative stress caused by various chemicals (cholesterol oxidation, autoantibodies to oxidized low-density lipoprotein, plasma levels of malondialdehyde and F-2-isoprostanes and reduced antioxidant capacity). Smoking enhances platelet aggregability, increases blood viscosity and shifts the pro- and antithrombotic balance towards increased coagulability (e.g., fibrinogen, von Willebrand factor, ICAM-1 and P-selectin). Insulin resistance is higher in smokers compared with nonsmokers, and hemoglobin A1c is dose-dependently elevated, as is homocysteine. Smoke exposure may influence the kinetics of markers with different response to transient or chronic changes in cigarette smoking behavior.

Winkelmann BR; von Holt K; Unverdorben M. Smoking and atherosclerotic cardiovascular disease: Part III: Functional biomarkers influenced by smoking. (review). Biomarkers in Medicine 3(6): 807-823, 2009. (307 refs.)

Smoking cigarettes induces rapidly occuring and reversible functional changes in the cardiovascular system, which precede morphologic changes. These functional changes are also related to atherosclerotic disease development and thus may qualify as prognostic parameters in chronic smokers. As opposed to smoking-induced morphologic changes functional alterations occur and revert within minutes, thus, allowing for the detection of smoking-induced effects on the cardiovascular system within minutes following exposure to mainstream smoke. Some alterations represent 'direct' changes (e.g., endothelial function), others reflect changes in a different organ system (e.g., the autonomous nervous system influencing heart rate variability), while some represent the sum of alterations in many organs and systems (e.g., exercise performance influenced by the autonomous nervous and by endothelial and cardiac function). Since a specific functional parameter usually changes with at least one or several others, caution should be exercised when trying to establish a direct cause relationship between the alteration of a single parameter and a clinical outcome.

Wong OF; Tsui KL; Fung HT. Acute coronary syndrome secondary to methylphenidate overdose. Hong Kong Journal of Emergency Medicine 17(1): 66-70, 2010. (28 refs.)

A 28-year-old lady presented to the emergency department after an overdose of methylphenidate. She complained of chest pain and developed an acute coronary syndrome with marked ST segment depression in the electrocardiogram and elevated troponin I level. She was closely monitored in the cardiac care unit and was treated with the standard therapy for acute coronary syndrome. Echocardiogram showed global left ventricle impairment. The follow-up echocardiogram showed that the left ventricular function normalised and the subsequent coronary angiogram was normal. The clinical use, abuse potential, toxicity and overdose treatment of methylphenidate are discussed.

Woodward M; Fang X; Gu DF; Huxley R; Imai Y; Lam TH et al. Impact of cigarette smoking on the relationship between body mass index and coronary heart disease: A pooled analysis of 3264 stroke and 2706 CHD events in 378,579 individuals in the Asia Pacific region. BMC Public Health 9(article 294), 2009. (28 refs.)

Background: Elevated levels of body mass index (BMI) and smoking are well established lifestyle risk factors for coronary heart disease (CHD) and stroke. If these two risk factors have a synergistic relationship, rigorous lifestyle modification may contribute to greater reduction in cardiovascular burden than previously expected. Methods: A pooled analysis of individual participant data from 38 cohorts, involving 378,579 participants. Hazards ratios (HRs) and 95% confidence intervals (CIs) for BMI by cigarette smoking status were estimated using Cox proportional hazard models. Results: During a mean follow-up of 3.8 years, 2706 CHD and 3264 strokes were recorded. There was a log-linear, positive relationship of BMI with CHD and stroke in both smokers and nonsmokers with evidence of a synergistic effect of smoking on the association between BMI and CHD only: HRs (95% CIs) associated with a 2 kg/m(2) higher BMI were 1.13 (1.10 - 1.17) in current smokers and 1.09 (1.06 - 1.11) in non-smokers (p-value for interaction = 0.04). Conclusion: Smoking amplifies the positive association between BMI and CHD but not stroke. If confirmed, these results suggest that effective strategies that target smoking cessation and weight loss are likely to have a greater impact than anticipated on reducing the burden of CHD.

Xie J; Hu DY; Wang X; Luo YL; Wang JW. Smoking state determined by cotinine and arterial stiffness. Circulation Journal 73(8): 1537-1542, 2009. (44 refs.)

Background: Exposure to active and passive smoking is associated with arterial stiffness and cotinine is an objective biochemical indicator to classify smoking state. The aim of the Study was to Survey participant smoking,; condition with cotinine in North China and discuss its destructive effect on arterial stiffness. Methods and Results: Nine hundred and six people were recruited in this study and were classified into non-smokers, passive smokers and active smokers according to the cotinine level. Brachial-ankle Pulse wave velocity (baPWV) was measured using an automatic device. Active smokers vs non-smokers showed a significantly higher baPWV (P=0.023) after adjusting for covariates. Participants who smoked longer than 10 years had a higher baPWV than non-smokers (P=0.029) although no significant difference existed between those who had a smoking history of less than 10 years and those who had never smoked. In less developed areas, the active and passive smoking rates were hi-her than that in Beijing (P < 0.001) while active smokers vs non-smokers had a hi-her baPWV (P=0.017). Conclusions: Active smokers. as confirmed by the cotinine level have worse arterial stiffness, and long-term smoking can cause marked arterial stiffness. Smoking exposure might bring about more serious effects on arterial function in patients from poor areas than in modernized cities.

Yufu K; Takahashi N; Okada N; Shinohara T; Hara M; Saikawa T et al. Influence of systolic blood pressure and cigarette smoking on endothelial function in young healthy people. Circulation Journal 73(1): 174-178, 2009. (27 refs.)

Background: Flow-mediated dilatation (FMD) of the brachial artery represents systemic endothelial function, the relationship between FMD and blood pressure (BP) profile. in relation to the effects of cigarette smoking, was investigated in young healthy subjects. Methods and Results The 62 healthy Subjects (14 females, 48 males; mean 29.7 +/- 5.5 years old), were divided into a smoking group (n=30) and non-smoking group (n=32). FMD was induced by reactive hyperemia. It was lower in the smoking group than in the non-smoking group (P<0.05). In the non-smoking group, there was an inverse correlation (r=-0.59, P<0.0005) between FMD and systolic BP (SBP), which was not recognized in the smoking group. Multiple stepwise regression analysis revealed that FMD was predicted by either the SBP or the brachial artery diameter in the non-smoking group, whereas it was predicted by the brachial artery diameter in the smoking group. Subdivision by cut-off value of SBP=120 mmHg demonstrated that although FMD with SBP<120mmHg was preserved in subjects in the non-smoking group, it was depressed to a level comparable with SBP >= 120 mmHg in the smoking group. Conclusions: Highly-preserved FMD in subjects with SBP<120 mmHg appears to be impaired by cigarette smoking, resulting in a loss of association between FMD and SBP.

Zhang WL; Lopez-Garcia E; Li TY; Hu FB; van Dam RM. Coffee consumption and risk of cardiovascular events and all-cause mortality among women with type 2 diabetes. Diabetologia 52(5): 810-817, 2009. (46 refs.)

Coffee has been linked to both beneficial and harmful health effects, but data on its relationship with cardiovascular disease and mortality in patients with type 2 diabetes are sparse. This was a prospective cohort study including 7,170 women with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Coffee consumption was assessed in 1980 and then every 2-4 years using validated questionnaires. A total of 658 incident cardiovascular events (434 coronary heart disease and 224 stroke) and 734 deaths from all causes were documented between 1980 and 2004. After adjustment for age, smoking and other cardiovascular risk factors, the relative risks were 0.76 (95% CI 0.50-1.14) for cardiovascular diseases (p trend = 0.09) and 0.80 (95% CI 0.55-1.14) for all-cause mortality (p trend = 0.05) for the consumption of a parts per thousand yen4 cups/day of caffeinated coffee compared with non-drinkers. Similarly, multivariable RRs were 0.96 (95% CI 0.66-1.38) for cardiovascular diseases (p trend = 0.84) and 0.76 (95% CI 0.54-1.07) for all-cause mortality (p trend = 0.08) for the consumption of a parts per thousand yen2 cups/day of decaffeinated coffee compared with non-drinkers. Higher decaffeinated coffee consumption was associated with lower concentrations of HbA(1c) (6.2% for a parts per thousand yen2 cups/day versus 6.7% for < 1 cup/month; p trend = 0.02). These data provide evidence that habitual coffee consumption is not associated with increased risk of cardiovascular diseases or premature mortality among diabetic women.

Zhou KY; Zhang L; Xi JK; Tian W; Xu ZL. Ethanol prevents oxidant-induced mitochondrial permeability transition pore opening in cardiac cells. Alcohol and Alcoholism 44(1): 20-24, 2009. (37 refs.)

Aims: The purpose of this study was to determine if ethanol prevents the mitochondrial permeability transition pore (mPTP) opening via glycogen synthase kinase 3 beta (GSK-3 beta). Methods: Cardiac H9c2 cells were exposed to ethanol (10-1000 mu M) for 20 min. GSK-3 beta activity was determined by measuring its phosphorylation at Ser(9). Mitochondrial membrane potential (Delta Psi(m)) was assessed by imaging (confocal microscopy) H9c2 cells loaded with tetramethylrhodamine ethyl ester (TMRE). To activate GSK-3 beta, cells were transfected with constitutively active GSK-3 beta (GSK-3 beta-S9A-HA) mutant plasmid. Results: Treatment of cardiac cells with low doses of ethanol (10-500 mu M) significantly enhanced GSK-3 beta phosphorylation, indicating that ethanol can inactivate GSK-3 beta in H9c2 cells. The effect of ethanol on GSK-3 beta activity was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and ethanol could enhance Akt phosphorylation, implying that the PI3K/Akt pathway accounts for the action of ethanol. Ethanol prevented oxidant (H2O2)-induced loss Delta Psi(m), an effect that was reversed by LY294002, indicating that ethanol can modulate the mPTP opening caused by oxidant stress through the PI3K/Akt pathway. Ethanol failed to preserve Delta Psi(m) in cells transfected with the constitutively active GSK-3 beta (GSK-3 beta-S9A-HA) mutant, suggesting that ethanol prevents the mPTP opening by inactivating GSK-3 beta. Conclusions: These data suggest that ethanol prevents the mPTP opening through inactivation of GSK-3 beta. The PI3K/Akt signaling pathway is responsible for inactivation of GSK-3 beta by ethanol.