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CORK Bibliography: Drugs and the Cardiovascular System

79 citations. January 2007 to present

Prepared: March 2008

Agirbasli M; Tanrikulu B; Arikan S; Izci E; Ozguven S; Besimoglu B et al. Trends in body mass index, blood pressure and parental smoking habits in middle socio-economic level Turkish adolescents. Journal of Human Hypertension 22(1): 12-17, 2008. (39 refs.)

Patterns of cardiovascular risk factors in populations are not static over time. We examined trends in body mass index (BMI), parental smoking and blood pressure over a 15-year period in Turkish children aged 15-17 years. Two cross-sectional studies were performed in secondary schools in Turkey in 1989-1990 and 2004-2005. Study participants were 673 children in 1989-1990 and 640 adolescents in 2004-2005. Main outcome measures were weight, height, BMI, presence and amount of parental smoking, systolic and diastolic blood pressure. Age and sex matched comparisons were performed to assess temporal trends in these measures. Children in 2004-2005 had increased weight, height, BMI and decreased systolic and diastolic blood pressure in all age groups compared with children in 1989-1990. According to the international criteria, 3.4% of children were obese and 15.8% were overweight in 2005, compared to 0.7% obese and 4.2% overweight in 1990 (P<0.001). However, a decrease was noted in blood pressure; 16% were classified as hypertensive in 1989-1990 versus 8% in 2004-2005 (P<0.001). The prevalence and amount of parental smoking also decreased over the last 15 years. We observed significant changes in BMI and blood pressure in Turkish children over the last 15 years. Temporal trends in these parameters may indicate a change in the pattern of cardiovascular disease in this population.

Al-Numair K; Barber-Heidal K; At-Assaf A; Ei-Desoky G. Water-pipe (shisha) smoking influences total antioxidant capacity and oxidative stress of healthy Saudi males. Journal of Food, Agriculture and the Environment 5(3-4): 17-22, 2007. (74 refs.)

Water-pipe smoking has been practiced extensively for about 400 years. Water-pipe smoking is common in the Arabian Peninsula, Turkey, India, Pakistan and other countries. Previous studies have confirmed water-pipe smoking has negative health effects similar to those of cigarette smoking. The aim of the present research was to study the effect of water-pipe smoking on the risk factors for cardiovascular diseases as well as oxidative stress and total antioxidant capacity of healthy Saudi males. Two hundred healthy Saudi males (100 non-smokers and 100 smokers) ranging in age 19-50 years old from Riyadh, the capital of Saudi Arabia were selected for this study. Subjects in the smoker group smoked tobacco (Ma'ssel) using a water-pipe (shisha) at least two times per day (two heads of Ma'ssel per day). Each subject was interviewed and asked to provide demographic information and their typical smoking habits. Blood pressure and anthropometric measurements (weight and height) were measured by well-trained staff. Fasting blood samples were collected, and serum samples were analyzed for low density lipoprotein cholesterol (LDL-cholesterol), high density lipoprotein cholesterol (HDL-cholesterol), triglycerides (TG), apolipoprotein A-1 and B (apo A-1 and apo B), malondialdehyde, vitamin C and total antioxidant capacity. The statistical method of t-test was used to compare the mean values obtained between the smoker and non-smoker groups. The chi-square statistical test was used to compare marital and education status of study subjects by groups. Serum concentrations of HDL-cholesterol and apo AI were significantly (p<0.05) lower in smokers than in non-smokers. However, LDL-cholesterol, apo B, triglycerides and malondialdehyde were significantly (p<0.05) higher in smokers than in non-smokers. Total antioxidant capacity and vitamin C were significantly (p<0.05) lower in smokers than in non-smokers. This study provided limited data to suggest that water-pipe smoke is at least as toxic as cigarette smoke.

Aryana A; Williams MA. Marijuana as a trigger of cardiovascular events: Speculation or scientific certainty? (review). International Journal of Cardiology 118(2): 141-144, 2007. (43 refs.)

Marijuana is the most widely used illicit substance in the United States. Cardiovascular complications in association with marijuana use have been reported during the past three decades. In view of the elevated public interest in this drug's role in pharmacotherapy in the recent years and the aging population of long-term marijuana users from the late 1960s, encounters with marijuana-related cardiovascular adversities may be silently on the rise. The purpose of this article is to increase awareness of the potential of marijuana to lead to cardiovascular disease. Here, we will discuss the physiologic effects of marijuana and include a comprehensive review of the studies and case reports that provide supportive evidence for marijuana as a trigger of adverse cardiovascular events, including tachyarrhythmias, acute coronary syndrome, vascular complications, and even congenital heart defects.

Ashton JC; Smith PF. Cannabinoids and cardiovascular disease: The outlook for clinical treatments. (review). Current Vascular Pharmacology 5(3): 175-184, 2007. (107 refs.)

Cannabinoid drugs exert their effects primarily through activation of cannabinoid CB1 and CB2 receptors. Both CB1 and CB2 receptors have been implicated in a number of cardiovascular processes, including vasodilation, cardiac protection, modulation of the baroreceptor reflex in the control of systolic blood pressure, and inhibition of endothelial inflammation and the progress of atherosclerosis in a murine model. These effects are mainly mediated through central and peripheral nervous system CB1 receptors, vascular CB1 receptors and immune cell CB2 receptors. Relevant cellular effects include: the inhibition of neurotransmitter release in the nucleus tractus solitarius and in peripheral adrenergic neurons regulation of NOS activity in vascular beds; inhibition of vascular smooth muscle cell excitability; regulation of endothelial cell migration and proliferation; and effects on immune cell proliferation, activation, and inflammatory functions.

Bansal D; Eigenbrodt M; Gupta E; Mehta JL. Traditional risk factors and acute myocardial infarction in patients hospitalized with cocaine-associated chest pain. Clinical Cardiology 30(6): 290-294, 2007. (25 refs.)

Background: Cocaine causes coronary artery constriction and may cause acute myocardial infarction (AMI). The role of traditional coronary risk factors in cocaine-associated myocardial infarction is unclear. Hypothesis: We hypothesized that traditional risk factors play a major role in predicting AMI in patients admitted with cocaine-associated chest pain Methods: After reviewing, 165 admissions for chest pain in patients with a history of recent cocaine use and/or a positive drug screen from January 2001 to December 2004, we identified 151 patients with information available on at least 6 of the following, 7 risk factors: gender, hypertension, hyperlipidemia, diabetes, smoking, family history of coronary artery disease (CAD) and known CAD. AMI was diagnosed using WHO criteria. A risk score was calculated on the basis of the number of risk factors, gender and age. Association of AMI was evaluated with the individual risk factors and with the risk score. Results: AMI was identified in 21 patients (14%). All patients diagnosed with AMI were smokers. Continuous risk score (p < 0.0001), highest vs. lowest quartile of risk score (p = 0.007), known CAD, age, hyperlipidemia and family history of CAD were individually associated with the diagnosis of AMI (p <= 0.05). Each quartile of risk score was associated with increased odds of the diagnosis of AMI and score of 8 or higher was statistically significant. Conclusion: Several traditional risk factors are associated with the diagnosis of AMI among patients hospitalized with cocaine-associated chest pain and increasing risk factor score was associated with increasing odds of AMI diagnosis.

Barnhart J; Lewis V; Houghton JL; Charney P. Physician knowledge levels and barriers to coronary risk prevention in women: Survey results from the women and heart disease physician education initiative. Women's Health Issues 17(2): 93-100, 2007. (53 refs.)

Background. Few studies have examined whether physician knowledge, attitudes, or practice patterns might contribute to gender disparities in the primary prevention of coronary heart disease (CHD), including among physicians caring for the largest number of reproductive-age women, obstetricians and gynecologists (OB/GYNs). We sought to identify barriers affecting the provision of recommended coronary risk factor therapies in women. Methods. We surveyed internists and OB/GYNs who attended Grand Rounds presentations developed for the New York State Women and Heart Disease Physician Education Initiative. This program was designed to improve screening and management of coronary risk factors in women. Attendees were asked to complete a 7-minute questionnaire. Results. The mean age of the 529 respondents was 40.3 years (standard deviation = 12.3), 75.1% were internists (n = 378), and 42.7% (n = 226) were women. Physicians correctly responded to 71.5% of the 13 questions assessing knowledge of coronary risk prevention (range, 4-13). Almost one third of internists and half of the OB/GYNs did not know that tobacco use was the leading cause of myocardial infarction in young women. For patients who smoked tobacco, only two thirds of internists and 55.4% of OB/GYNs reported suggesting a quit date (p =.007). After controlling for covariates, physicians who did not perceive time as a barrier were more likely to discuss smoking cessation (odds ratio = 1.7 [1.1-2.7]). Conclusions. Among the internists and OB/GYNs surveyed, time was perceived as a barrier to implementing risk prevention. These physicians also underestimated the impact of tobacco use as a risk factor for CHD in young women. To lessen gender disparities in CHD prevention, both specialties need time-efficient educational programs that reflect specialty differences.

Berry JD; Dyer A; Carnethon M; Tian L; Greenland P; Lloyd-Jones DM. Association of traditional risk factors with cardiovascular death across 0 to 10, 10 to 20, and > 20 years follow-up in men and women. American Journal of Cardiology 101(1): 89-94, 2008. (28 refs.)

Previous studies have evaluated the strength of the association between traditional risk factors and cardiovascular disease (CVD) across varying lengths of follow-up in men. However, to our knowledge, little is known regarding the behavior of these risk factors across time in women. Thus, we sought to determine the association between traditional risk factors in men and women across follow-up periods of 0 to 10, 10 to 20, and > 20 years. We studied 9,033 men and 7,575 women (ages 40 to 59 years) from 1967 to 1973 from the Chicago Heart Association Detection Project in Industry. Multivariable-adjusted Cox proportional hazard models were constructed to compare the hazard ratios (HRs) and 95% confidence intervals (CI) for CVD risk factors measured at baseline across different periods of follow-up (0 to 10, 10 to 20, and >20 years). In women, the HRs for smoking and diabetes mellitus were strongest at 0 to 10 years (HR 5.38, 95% CI 2.99 to 9.67 and 3.84, 95% CI 1.82 to 8.13, respectively) but decreased at >20 years (HR 1.71, 95% CI 1.48 to 1.97 and 1.60, 95% CI 1.10 to 2.32, respectively). In men, the HR (per 4 kg/m(2)) for body mass index appeared to increase (0 to 10 years, 1.01, 95% CI 0.90 to 1.14; >20 years, 1.20, 95% CI 1.13 to 1.28). In women, the association was similar across all follow-up periods. For both men and women, the HR for total serum cholesterol remained unchanged across the follow-up. In conclusion, we found gender differences in the patterns of association between risk factors measured at baseline and CVD death across different periods of follow-up. In women, the increased risk associated with both diabetes mellitus and smoking was most prominent in the early follow-up periods.

Biederman J; Spencer TJ; Wilens TE; Prince JB; Faraone SV. Treatment of ADHD with stimulant medications: Response to Nissen perspective in The New England Journal of Medicine. (editorial). Journal of the American Academy of Child and Adolescent Psychiatry 45(10): 1147-1150, 2006

This editorial is a response to an article in the New England Journal of Medicine (SE Nissen, ADHD drugs and cardiovascular risk, 354(14): 1445-1448, 2006) written by a consultant to the Food and Drug and Administration (FDA) Committee that recommended a "black-box" warning describing the cardiovascular risks associated with stimulant drugs used to treat attention deficit-hyperactivity disorder (ADHD).

Bonita JS; Mandarano M; Shuta D; Vinson J. Coffee and cardiovascular disease: In vitro, cellular, animal, and human studies. (review). Pharmacological Research 55(3): 187-198, 2007. (102 refs.)

Coffee is a commonly consumed beverage with potential health benefits. This review will focus on cardiovascular disease. There are three preparations of coffee that are commonly consumed and thus worthy of examination; boiled unfiltered coffee, filtered coffee, and decaffeinated coffee. Coffee has over a thousand chemicals, many formed during the roasting process. From a physiological point of view, the potential bioactives are caffeine, the diterpenes cafestol and kahweol found in the oil, and the polyphenols, most notably chlorogenic acid. We will examine coffee and its bioactives and their connection with and effect on the risk factors which are associated with heart disease such as lipids, blood pressure, inflammation, endothelial function, metabolic syndrome and potentially protective in vivo antioxidant activity. These will be critically examined by means of in vitro studies, cell experiments, animal supplementation, epidemiology, and the most definitive evidence, human trials.

Brunelle C; Barrett SP; Pihl RO. Psychostimulant users are sensitive to the stimulant properties of alcohol as indexed by alcohol-induced cardiac reactivity. Psychology of Addictive Behaviors 20(4): 478-483, 2006. (48 refs.)

One indicator of increased sensitivity to alcohol-induced reward is a heightened heart rate (HR) increase following alcohol intoxication, I characteristic associated with increased alcohol-induced dopamine (DA) release. The goal of this study was to determine whether users of drugs known to induce DA release have higher HR increases after alcohol intoxication than never users have. Sixty-four men with known drug-use histories participated in an alcohol challenge in which HR was measured. Stimulant users had significantly higher ethanol-induced HR increases than never users had, although use of marijuana or hallucinogens was not associated with this marker. Stimulant users obtained superior Sensitivity to Reward scores (R. Torrubia, C. Avila, J. Molto, & X. Caseras, 2001) compared with never users. Stimulant drug users may be more sensitive to the stimulating properties of alcohol, and this appears to be mediated by superior activity in the Behavioral Approach System (J. A. Gray, 1991).

Cecchi E; Imazio M; Tidu M; Forno D; De Rosa FG; Dal Conte I et al. Infective endocarditis in drug addicts: Role of HIV infection and the diagnostic accuracy of Duke criteria. Journal of Cardiovascular Medicine 8(3): 169-175, 2007. (32 refs.)

Background: Intravenous drug users (IVDUs) are at increased risk of infective endocarditis. Moreover, HIV infection is common in IVDUs, with a reported prevalence of 40-90%. The clinical features of IVDUs with infective endocarditis and HIV infection may be peculiar. Few data have been reported on the diagnostic accuracy of Duke criteria in IVDUs with or without HIV infection, and a comparison of these two populations is lacking. Methods The present study aimed to compare prospectively the clinical features of patients with infective endocarditis with or without HIV infection and to evaluate the diagnostic accuracy of Duke criteria in these patients. The study population consisted of 201 consecutive adult IVDUs with a suspected infective endocarditis (102 patients with HIV infection and 99 patients without HIV infection). Results Infective endocarditis was the final diagnosis in 40 of 102 patients (38.2%) with HIV infection and in 55 of 99 HIV-negative patients (55.6%). Despite similar baseline features, longer vegetations were recorded in infective endocarditis without HIV infection (23.7 +/- 7.1 mm versus 13.6 +/- 6.8 mm; P = 0.001). Patients with infective endocarditis and HIV infection had a higher total mortality at 2 months (respectively 12.5% versus 1.8%; P = 0.09); almost all the deaths were recorded in patients with AIDS or a CD4 cell count below 200 per mu l, and no deaths were recorded in patients with HIV infection and a CD4 cell count >500 per mu l. Conclusions: Despite no identical clinical features, Duke criteria had a similar sensitivity, specificity and diagnostic accuracy in IVDUs with and without HIV infection.

Chin KM; Channick RN; Rubin LJ. Is methamphetamine use associated with idiopathic pulmonary arterial hypertension? Chest 130(6): 1657-1663, 2006. (25 refs.)

Background: Amphetamine, methamphetamine, and cocaine are suspected of being pulmonary hypertension risk factors based on a small number of case reports along with pharmacologic similarities to fenfluramine, a diet drug associated with pulmonary arterial hypertension (PAH). We sought to determine whether rates of stimulant use are increased in patients believed to have idiopathic PAH compared with patients with PAH and known risk factors and patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: In this retrospective study, rates of stimulant use were determined for 340 patients with idiopathic PAH, PAH and known risk factors, or CTEPH seen between November 2002 and April 2004. "Stimulant" use was defined as any reported use of amphetamine, methamphetamine, or cocaine. Odds of stimulant use were calculated using a polychotomous logistic regression model. Results: A history of stimulant use was found in 28.9% of patients with a diagnosis of idiopathic PAH, compared with 3.8% of patients with PAH and a known risk factor, and 4.3% of patients with CTEPH. After adjustment for differences in age, patients with idiopathic PAH were 10.14 times (95% confidence interval, 3.39 to 30.3; p < 0.0001) more likely to have used stimulants than patients with PAH and known risk factors, and 7.63 times (95% confidence interval, 2.99 to 19.5; p < 0.0001) more likely to have used stimulants than patients with CTEPH. Conclusions: Patients with idiopathic PAH are significantly more likely to have used stimulants than patients with other forms of pulmonary hypertension.

Chugh SS; Socoteanu C; Reinier K; Waltz J; Jui J; Gunson K. A community-based evaluation of sudden death associated with therapeutic levels of methadone. American Journal of Medicine 121(1): 66-71, 2008. (33 refs.)

BACKGROUND: Published case reports have associated the therapeutic use of methadone with the occasional occurrence of sudden cardiac death. Because of the established utility of this drug and with the eventual goal of enhancing safety of use, we performed a community- based study to evaluate this association. METHODS: During a 4-year period, we prospectively evaluated all patients who consecutively had sudden cardiac death and underwent investigation by the medical examiner in the metropolitan area of Portland, Ore. Case subjects of interest were those with a therapeutic blood level of methadone (< 1 mg/L), and case comparison subjects were those with no methadone identified. Patients with recreational drug use or any drug overdose were excluded from either group. Detailed autopsies were conducted, including the detection and quantification of all substances in the blood. RESULTS: A total of 22 sudden cardiac death cases with therapeutic levels of methadone ( mean 0.48 +/- 0.22 mg/L; range 0.1-0.9 mg/L) were identified (mean age 37.0 +/- 10 years, 68% were male) and compared with 106 consecutive sudden cardiac death cases without evidence of methadone ( mean age 42 +/- 13 years, 69% were male). The most common indication for methadone use was pain control (n = 12, 55%). Among cases receiving methadone therapy, sudden death-associated cardiac abnormalities were identified in only 23% (n = 5), with no clear cause of sudden cardiac death in the remaining 77% (n = 17). Among cases with no methadone, sudden death-associated cardiac abnormalities were identified in 60% (n = 64, P = .002). CONCLUSION: The significantly lower prevalence of cardiac disease in the case group implicates methadone, even at therapeutic levels, as a likely cause of sudden death. These findings point toward an association between methadone and occurrence of sudden death in the community. Clinical safeguards and further prospective studies specifically designed to enhance safety of methadone use are warranted.

Cornelis MC; El-Sohemy A. Coffee, caffeine, and coronary heart disease. Current Opinion in Clinical Nutrition and Metabolic Care 10(6): 745-751, 2007. (62 refs.)

Disterpenes present in unfiltered coffee and caffeine each appear to increase risk of coronary heart disease. A lower risk of coronary heart disease among moderate coffee drinkers might be due to antioxidants found coffee.

Cunningham R; Walton MA; Tripathi SP; Weber JE; Maio RF; Booth BM. Past-year violence typologies among patients with cocaine-related chest pain. American Journal of Drug and Alcohol Abuse 33(4): 571-582, 2007. (23 refs.)

This study examines a consecutive cohort of patients ( n 219) presenting to an urban Emergency Department (ED) for cocaine- related chest pain ( June 2002 to February 2005). Patients were interviewed regarding violence, substance use, and psychosocial factors. Significant markers of violence were increases in: past- year medical service use, binge drinking, marijuana use, cocaine diagnosis, but not cocaine use days. Rates and correlates of violence differed by relationship type (intimate partner, nonpartner) and role context (victimization, perpetration). Understanding these correlates has public health implications, both for preventing future violence and its associated ED service utilization, and for future interventions in cocaine users presenting to the ED.

D'Andrea A; Caso P; Salerno G; Scarafile R; De Corato G; Mita C et al. Left ventricular early myocardial dysfunction after chronic misuse of anabolic androgenic steroids: A Doppler myocardial and strain imaging analysis. British Journal of Sports Medicine 41(3): 149-155, 2007. (38 refs.)

Background: Anabolic androgenic steroids (AAS) are sometimes used by power athletes to improve performance by increasing muscle mass and strength. Recent bioptical data have shown that in athletes under the pharmacological effects of AAS, a focal increase in myocardial collagen content might occur as a repair mechanism against myocardial damage. Objective: To investigate the potential underlying left ventricular myocardial dysfunction after chronic misuse of AAS in athletes by use of Doppler myocardial imaging (DMI) and strain rate imaging (SRI). Methods: Standard Doppler echocardiography, DMI, SRI and ECG treadmill test were undertaken by 45 bodybuilders, including 20 athletes misusing AAS for at least 5 years ( users), by 25 anabolic-free bodybuilders (non-users) and by 25 age-matched healthy sedentary controls, all men. The mean (SD) number of weeks of AAS use per year was 31.3 (6.4) in users, compared with 8.9 (3.8) years in non-users, and the mean weekly dosage of AAS was 525.4 (90.7) mg. Results: The groups were matched for age. Systolic blood pressure was higher in athletes ( 145 ( 9) vs 130 ( 5) mm Hg) than in controls. Left ventricular mass index did not significantly differ between the two groups of athletes. In particular, both users and non-users showed increased wall thickness and relative wall thickness compared with controls, whereas left ventricular ejection fraction, left ventricular end-diastolic diameter and transmitral Doppler indexes were comparable for the three groups. Colour DMI analysis showed significantly lower myocardial early: myocardial atrial diastolic wave ratios in users at the level of the basal interventricular septum (IVS) and left ventricular lateral wall ( p< 0.01), in comparison with both non-users and controls. In addition, in users, peak systolic left ventricular strain rate and strain were both reduced in the middle IVS ( both p< 0.001) and in the left ventricular lateral free wall ( both p< 0.01). By stepwise forward multivariate analyses, the sum of the left ventricular wall thickness (beta coefficient = 20.32, p<0.01), the number of weeks of AAS use per year (beta = -0.42, p< 0.001) and the weekly dosage of AAS (beta = -0.48, p, 0.001) were the only independent determinants of middle IVS strain rate. In addition, impaired left ventricular strain in users was associated with a reduced performance during physical effort ( p, 0.001). Conclusions: Several years after chronic misuse of AAS, power athletes show a subclinical impairment of both systolic and diastolic myocardial function, strongly associated with mean dosage and duration of AAS use. The combined use of DMI and SRI may therefore be useful for the early identification of patients with more diffused cardiac involvement, and eventually for investigation of the reversibility of such myocardial effects after discontinuation of the drug.

Darke S; Kaye S; Duflou J. Comparative cardiac pathology among deaths due to cocaine toxicity, opioid toxicity and non-drug-related causes. Addiction 101(12): 1771-1777, 2006. (36 refs.)

Aim: To compare cardiac and cerebrovascular pathology among deaths due to cocaine toxicity, deaths due to opioid toxicity and deaths from hanging that were toxicologically negative for cocaine/opioids. Design: Case-control. Findings: The cocaine group had significantly higher proportions of left ventricular hypertrophy and ischaemic heart disease than either comparison group. Coronary artery atherosclerosis was also detected in significantly higher proportions of cocaine cases than in either comparison group. The cocaine group was more likely than either comparison group to have atherosclerosis of the left anterior descending coronary artery, right coronary artery and circumflex artery. Only in the left anterior descending coronary artery did the cocaine group exhibit higher levels of moderate-severe atherosclerosis. Cocaine cases also had significantly higher levels of cerebrovascular atherosclerosis than either comparison group. Conclusions: Levels of cardiac and cerebrovascular pathology were higher among cocaine users than either comparison group. The high levels of cardiac and cerebrovascular pathology seen among cocaine cases do not appear to be artefacts of a drug-dependent life-style, but relate specifically to cocaine.

De Giorgio F; Vetrugno G; Fucci N; Rainio J; Tartaglione T; Di Lazzaro V et al. Fatal stroke in a young cocaine drug addict: Chemical hair analysis and cervical artery examination twenty months after death. Folia Neuropathologica 45(3): 149-152, 2007. (12 refs.)

We present a case of a 26-year-old female who died of acute cerebral infarction after thrombosis of the left internal carotid artery, conceivably related to cocaine use. The forensic examination was performed only twenty months post-mortem. Revaluation of clinical data was carried out after exhumation and forensic autopsy examination were done, including anatomic dissection of cervical vessels and histological and toxicological analyses. Interestingly, comparative histological examination of cervical arteries was more useful in determining the putative site of vascular damage than gross and histological examination of the brain itself, although the state of preservation of tissues was poor In conclusion, when a vascular accident is suspected or has to be demonstrated, we suggest performing comparative histological examinations of selected artery samples, even several months after death.

De Rosa FG; Cicalini S; Canta F; Audagnotto S; Cecchi E; Di Perri G. Infective endocarditis in intravenous drug users from Italy: The increasing importance in HIV-infected patients. Infection 35(3): 154-160, 2007. (33 refs.)

Background: Intravenous drug users (IDUs) are at increased risk of infective endocarditis (IE). Patients and Methods: Episodes of IE in IDUs were retrospectively analyzed in this multicenter study. Cases were collected between 1986 and 1999. Only definite diagnosis according to the Duke criteria were analyzed. Results: Two hundred and sixty-three cases, including 100 cases in HIV-positive patients, were observed in IDUs. Any right-sided involvement was detected in 167 out of 263 cases (63.5%) and any left-sided involvement in 115 out of 263 cases (43.7%). The tricuspid valve (TV) alone was affected in 135 cases (51.3%), the mitral valve alone in 32 patients (12.1%), the aortic valve alone in 41 cases (15.6%) and the pulmonic valve alone in 3 cases. Staphylococcus aureus was isolated in 156 cases (59.3%) and Streptococcus spp. in 33 cases (12.5%). No major differences were observed between HIV-negative and HIV-positive patients. Any TV valve involvement was significantly associated with female rather than male gender (p = 0.02). There was a significant association between S. aureus etiology and TV involvement (p < 0.0001). The mortality rate was 16%. On multivariate analysis, only left-side IE (p = 0.0006; OR 5.2; 95% CI 2.0-13.5) and age greater than 35 years (p = 0.0068; OR 3.6; 95% CI 1.4-9.0) were independently associated with mortality. Conclusions: Infective endocarditis in IDUs is significantly associated with right-side localization (63.5% for any rightsided heart involvement vs 43.7% for any left-sided heart involvement; OR 2.24; 95% CI 1.55-3.23; p < 0.001). S. aureus is the microorganism most frequently isolated and is significantly associated with TV involvement. Any left-side involvement and age greater than 35 years are independently associated with mortality. HIV infection does not appear to have a significant effect on mortality.

Doolan DM; Stotts NA; Benowitz NL; Covinsky KE; Froelicher ES. The Women's Initiative for Nonsmoking (WINS) XI: Age-related differences in smoking cessation responses among women with cardiovascular disease. American Journal of Geriatric Cardiology 17(1): 37-47, 2008. (24 refs.)

Smoking cessation has immediate health benefits; however, the efficacy of smoking cessation interventions among older adults and women has received limited research attention. The original Women's Initiative for Nonsmoking (WINS) study was a randomized controlled trial that tested the efficacy of a smoking cessation intervention for Bay Area women hospitalized with cardiovascular disease. The current study, which used the WINS dataset, compares participants 62 and older with those younger than 62 years. The sample (n =277) contained 136 older smokers and 141 younger smokers. At the 6-month, follow-up, 52.1% of older smokers had quit smoking compared with 40.6% of younger smokers. At the 12-month follow-up, 52.0% of older smokers had quit smoking compared with 38.1% of younger smokers. The difference at 12 months was statistically significant, and a Kaplan-Meier survival analysis further supported these findings. Clinicians should be sure to also include older smokers in smoking assessments and smoking cessation interventions.

Droogmans S; Cosyns B; D'haenen H; Creeten E; Weytjens C; Franken PR et al. Possible association between 3,4-methylenedioxymethamphetamine abuse and valvular heart disease. American Journal of Cardiology 100(9): 1442-1445, 2007. (12 refs.)

Valvular heart disease, inducing valvular regurgitation, has been described in users of drugs such as anorectic agents and ergot derivates. 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") also leads in vitro to the proliferation of cardiac valvular interstitial cells by activation of the 5-hydroxytryptamine 2B receptor. The aim of this study was to determine the occurrence of valvulopathy in young adults taking MDMA. Twenty-nine subjects using or having used MDMA and 29 gender- and age-matched controls were blindly evaluated with echocardiography. Eight subjects (28%) who took MDMA had abnormal echocardiographic results using the United States Food and Drug Administration's criteria for appetite suppressant-induced valvular heart disease, compared with none in the control group (p = 0.0045). Six (21%) subjects had mitral regurgitation of 1/4 and 4 (14%) of >= 2/4, compared with none in the control group (p = 0.002). The mean mitral regurgitant area ratios (jet/atrium) were 12 +/- 9.8% and 5 +/- 1.3%, respectively (p = 0.007). Tricuspid regurgitation >= 2/4 was present in 13 MDMA users (45%) and absent in controls (p < 0.001). The mean tricuspid regurgitant area ratios were 19 +/- 9.5 % and 9 +/- 4.5 %, respectively (p <0.001). Four MDMA users (14%) had mild aortic regurgitation (p = 0.11). Valvular "strands" were present in 6 MDMA users (21%) and in none of the controls (p = 0.02). In conclusion, MDMA may lead to mild to moderate valvular heart disease and valvular strands.

Ehret GB; Desmeules JA; Broers B. Methadone-associated long QT syndrome: improving pharmacotherapy for dependence on illegal opioids and lessons learned for pharmacology. (review). Expert Opinion on Drug Safety 6(3): 289-303, 2007. (129 refs.)

Methadone is used as the pharmacologic mainstay for substitution for illegal opiates and as analgesic for chronic or cancer-related pain. Given the benefits of methadone substitution for illicit opioids, the finding of an association between methadone and prolongation of cardiac depolarization (QT prolongation) and torsades de pointes is of great concern. QT prolongation can occur with many drugs and is a potentially lethal adverse drug reaction, necessitating risk monitoring and therapeutic alternatives in some patients. Recent studies suggest that QT prolongation with methadone is context dependent: occurrence is more frequent with high doses of methadone, concomitant administration of CYP3A4 inhibitors, hypokalemia, hepatic failure, administration of other QT prolonging drugs and pre-existing heart disease. The valued benefit of methadone substitution therapy on the one hand and the increased cardiovascular risk in particular situations on the other illustrate the difficulties in dealing with drug-induced QT prolongation in general.

Epstein AE. Baseball, crackers, green dust, nose candy, and snow cones: Cocaine, defibrillation, and ICDs (editorial). Journal of Cardiovascular Electrophysiology 18(7): 726-727, 2007. (17 refs.)

This editorial provides a commentary on an article in this issu by Chen et al. which identifies a heretofore unrecognized cardiovascular problem associated with cocaine use, elevation of the defibrillation threshhold.

Fingerhood MI. Co-morbid medical disorders. IN: Strain EC; Stitzer ML, eds. The Treatment of Opioid Dependence. Baltimore: Johns Hopkins University Press, 2006. pp. 398-420. (65 refs.)

This chapter focuses on the provision of medical care to individuals receiving opioid agonist medications. It considers the issues related to health maintenance, and the multiple medical complications. Among those with a history of intravenous use, there are special concerns related to the route of administration -- including viruses from needle sharing as well as the soft tissue infections from injecting technique. These problems are not restricted to those involved with opiates, but also common in cocaine users. The chapter begins with an overview of basic primary care, with attention to medical history and physical exam. It then turns of matters related to prescribing, pain management, and drug interactions with methadone, that may have an impact on blood levels or alter methadone's effects. Also specifically addressed are skin and soft tissue infections, HIV/AIDS, sexually transmitted disease, hepatitis, as well as cardiac, pulmonary, renal, neurological, and immunologic complications, and for women concerns related to domestic violence.

Gan Q; Smith KR; Hammond SK; Hu TW. Disease burden of adult lung cancer and ischaemic heart disease from passive tobacco smoking in China. Tobacco Control 16(6): 417-422, 2007. (41 refs.)

Objective: To address the health hazards tobacco smoking imposes upon non-smokers in China, this paper estimates the burden of diseases in adults from passive tobacco smoking for two major diseases-lung cancer and ischaemic heart disease (IHD). Methods: The disease burden was estimated in terms of both premature mortality and disability adjusted life years (DALYs), a measure that accounts for both the age at death and the severity of the morbidity. Results: Passive smoking caused more than 22 000 lung cancer deaths in 2002 according to these estimates. When the toll of disability is added to that of mortality, passive smoking was responsible for the loss of nearly 230 000 years of healthy life from lung cancer. Using the evidence from other countries that links IHD to passive smoking, we estimated that approximately 33 800 IHD deaths could be attributable to passive smoking in China in 2002. Passive smoking is also responsible for the loss of more than one quarter of a million years of healthy life from IHD. Although most of the disease burden caused by active smoking occurs among men, women bear nearly 80% of the total burden from passive smoking. The number of deaths among women caused by passive smoking is about two-thirds of that caused by smoking for the two diseases we examined. Conclusion: Even without considering the passive smoking risks for other diseases and among children that have been documented in other countries, passive smoking poses serious health hazards for non-smokers, especially for adult female non-smokers in China, adding more urgency to the need for measures to be taken immediately to protect the health of non-smokers and curb the nation's tobacco epidemic.

Greenberg JA; Dunbar CC; Schnoll R; Kokolis R; Kokolis S; Kassotis J. Caffeinated beverage intake and the risk of heart disease mortality in the elderly: A prospective analysis. American Journal of Clinical Nutrition 85(2): 392-398, 2007. (33 refs.)

Background: Motivated by the possibility that caffeine could ameliorate the effect of postprandial hypotension on a high risk of coronary events and mortality in aging, we hypothesized that caffeinated beverage consumption decreases the risk of cardiovascular disease (CVD) mortality in the elderly. Objective: The objective of the study was to use prospective cohort study data to test whether the consumption of caffeinated beverages exhibits this protective effect. Design: Cox regression analyses were conducted for 426 CVD deaths that occurred during an 8.8-y follow-up in the prospective first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. The analysis involved 6594 participants aged 32-86 y with no history of CVD at baseline. Results: Participants aged >= 65 y with higher caffeinated beverage intake exhibited lower relative risk of CVD and heart disease mortality than did participants with lower caffeinated beverage intake. It was a dose-response protective effect: the relative risk (95% CI) for heart disease mortality was 1.00 (referent), 0.77 (0.54, 1.10), 0.68 (0.49, 0.94), and 0.47 (0.32, 0.69) for < 0.5, 0.5-2, 2-4, and >= 4 servings/d, respectively (P for trend = 0.003). A similar protective effect was found for caffeine intake in mg/d. The protective effective was found only in participants who were not severely hypertensive. No significant protective effect was found in participants aged < 65 y or in cerebrovascular disease mortality for those aged 65 y. Conclusion: Habitual intake of caffeinated beverages provided protection against the risk of heart disease mortality among elderly participants in this prospective epidemiologic analysis.

Hamer M; Williams ED; Vuononvirta R; Gibson EL; Steptoe A. Association between coffee consumption and markers of inflammation and cardiovascular function during mental stress. Journal of Hypertension 24(11): 2191-2197, 2006. (42 refs.)

Background: Coffee is widely consumed in the Western diet and therefore has important implications for public health. Research findings pertaining to the effects of coffee consumption on cardiovascular health are conflicting, and the role of caffeine is not clear. Objective: To examine the relationship between coffee intake, inflammation and cardiovascular function at baseline and during mental stress, both cross-sectionally and after a 4-week period of withdrawal of coffee during which intake of caffeine was maintained. Methods: Eighty-five healthy, non-smoking men with varying coffee-drinking habits were recruited. Blood pressure, heart rate, and markers of inflammation [C-reactive protein (CRP), von Willebrand factor antigen (vWF)], were measured at baseline and during mental stress. These measures were repeated after a 4-week period of withdrawal of coffee, during which intake of caffeine was maintained. Habitual levels of coffee and caffeine consumption were assessed from a self-reported questionnaire, and saliva samples for the analysis of caffeine concentrations were collected regularly throughout the period of withdrawal, to confirm compliance. Results: Multiple linear regression analysis of prewithdrawal data, adjusted for age, body mass index and intake of tea, red wine, fruit, vegetables, oily fish and dietary supplements revealed that coffee consumption was positively related to baseline systolic blood pressure, and increased heart rate and vWF responses to mental stress. Four weeks after withdrawal of coffee, the heightened vWF and heart rate responses to stress in habitual coffee drinkers persisted, whereas baseline systolic blood pressure had decreased. Total caffeine intake was unrelated to any measures of physiological function. Conclusions Habitual coffee consumption is associated with heightened acute vascular inflammatory responses to mental stress, although these effects are not affected by short-term abstinence from coffee. These findings suggest that the relationship between coffee and markers of cardiovascular risk may be explained by residual or unmeasured confounding factors.

Haning W; Goebert D. Electrocardiographic abnormalities in methamphetamine abusers. Addiction 102(Supplement 1): 70-75, 2007. (46 refs.)

Aims: Although many adverse cardiovascular outcomes are mentioned in conjunction with methamphetamine use, a causal relationship between methamphetamine use and arrhythmia or cardiomyopathy has not been demonstrated in man. Clinical experience with methamphetamine users suggested a higher incidence of electrocardiographic abnormalities. This study seeks to quantify that incidence, among subjects enrolled in a study of adults with methamphetamine dependence. Methods: Electrocardiograms obtained during screening in a previous clinical trial were examined. The study population (n = 158) of adults with methamphetamine dependence [Diagnostic and Statistical Manual version IV (DSM IV-TR)] was drawn from five sites across the United States, recruited in the interval 2002-03. Results A significant variance from the normal population was noted in the electrocardiograms of the study cohort. Among the abnormalities was a prolongation of the QTc beyond 440 ms in 27.2% of the group. QTc prolongation to this extent poses a particular risk for ventricular arrhythmias, most notably torsades de pointes. Conclusions: We believe that this is the first demonstration of clinically significant QTc prolongation in a methamphetamine-using population, and that this has implications for the types of arrhythmias for which this population is at risk. It may further provide a marker for risk of cardiomyopathy. The fact of electrocardiographic changes with potential cardiac risks may be useful in a motivational interviewing approach, in challenging the methamphetamine user's basis for continuing use.

Herbst S; Pietrzak RH; Wagner J; White WB; Petry NM. Lifetime major depression is associated with coronary heart disease in older adults: Results from the national epidemiologic survey on alcohol and related conditions. Psychosomatic Medicine 69(8): 729-734, 2007. (37 refs.)

Objective: To examine the association between mood and anxiety disorders and coronary heart disease (CHD) in a nationally representative sample of older adults. Methods: Data from the National Epidemiologic Survey on Alcohol and Related Conditions were analyzed with 10,573 adults aged >= 60 years surveyed. Results: A total of 13.30% of older adults reported diagnoses of CHD. Age (odds ratio (OR) = 1.04), morbid obesity (OR = 1.60), hypertension (OR = 2.29), lifetime nicotine dependence (OR = 1.41), and lifetime drug use disorders (OR = 2.19) were all significantly related to CHD. Being female (OR = 0.73) relative to male and a lifetime social drinker (OR = 0.71) compared with alcohol abstainers decreased the odds of CHD. After controlling for these characteristics, the presence of a lifetime major depressive episode was significantly associated with increased risk of CHD (OR = 2.05), but the lifetime anxiety disorders assessed were not. The association between lifetime mood disorders and CHD was similar for both genders, and single versus multiple depressive episodes conferred equal risk of CHD. Conclusions: These data demonstrate that a lifetime major depressive episode increases the risk of CHD in older adults.

Hsue PY; McManus D; Selby V; Ren XS; Pillutla P; Younes N et al. Cardiac arrest in patients who smoke crack cocaine. American Journal of Cardiology 99(6): 822-824, 2007. (15 refs.)

The aim of the study is to determine the clinical features and outcomes of cocaine users admitted to the hospital after cardiac arrest and compare them with nonusers. Cocaine is associated with cardiovascular complications, including ventricular arrhythmias; however, resuscitated cardiac arrest in relation to cocaine use is not a well-defined clinical entity. We reviewed available hospital charts at San Francisco General Hospital with the International Classification of Diseases, Ninth Revision diagnosis of cardiac arrest and cocaine use from 1994 to 2006. Clinical features and outcomes of cocaine users were compared with those of randomly selected control patients and age-matched controls with resuscitated cardiac arrest without cocaine use. We identified 22 patients with resuscitated cardiac arrest in the setting of cocaine use. Their average age was 42 +/- 10 years, > 20 years younger than nonusers (68 +/- 16 years, p < 0.01). After cardiac arrest, 12 of 22 patients (55%) who used cocaine had complete neurologic recovery in contrast to only 3 of 20 unmatched controls (15%, p < 0.01) and 7 of 41 age-matched controls (17%, p < 0.01). Only 10 of 22 cocaine users (46%) died compared with 15 of 20 unmatched controls (75%, p = 0.05) and 32 of 41 age-matched controls (78%, p < 0.01). In a combined analysis of all patients, cocaine use was the only significant predictor of neurologic recovery (p < 0.01) and survival (p < 0.01). In conclusion, cocaine use is associated with cardiac arrest. In patients with cardiac arrest, cocaine users are younger than nonusers and more likely to survive with neurologic recovery, even compared with age-matched controls with cardiac arrest.

Huisman TAGM; Kubat SH; Eckhardt BP. The "dark cerebellar sign". Neuropediatrics 38(3): 160-163, 2007. (14 refs.)

We present and discuss the "dark cerebellar sign" in contrast to the well known "white cerebellar sign". The "white cerebellar sign" relates to a normal cerebellum which appears hyperdense in contrast to a pathological hypodense cerebrum on computer tomography (CT). We present a child with a "dark cerebellar sign" characterized by an ischemic or edematous cerebellum which appears hypodense in contrast to a normal relatively dense cerebrum. Isolated infarction of the cerebellum is a rare finding in premature neonates. Even rarer, cerebellar infarction may be observed in children and young adults due to an overdose of tricyclic antidepressants (TCA). The reason for the selective cerebellar infarction with TCA intoxication is still unknown. Our case shows that TCA intoxication should be included in the differential diagnosis of children with a "dark cerebellar sign".

Hussain T; Ewer AK. Maternal methadone may cause arrhythmias in neonates. (editorial). Acta Paediatrica 96(5): 768-769, 2007. (11 refs.)

Methadone treatment is a well recognised cause of QT interval lengthening in adults. In this case report, we present for the first time, clinically significant QT interval lengthening in a neonate secondary to maternal methadone treatment. Neonatal paediatricians should be aware of this important and potentially serious clinical phenomenon. Conclusion: Bradycardia, tachycardia or an irregular heart rate in an infant born to a mother on methadone treatment should not be ignored and a 12-lead electrocardiogram should be performed. Furthermore, there is also a need for a prospective study of QTc intervals in infants born to mothers receiving methadone.

Jansson LM; Dipietro JA; Elko A; Velez M. Maternal vagal tone change in response to methadone is associated with neonatal abstinence syndrome severity in exposed neonates. Journal of Maternal-Fetal & Neonatal Medicine 20(9): 677-685, 2007. (48 refs.)

Objective. Though methadone pharmacotherapy is the treatment of choice for opiate-dependence during pregnancy in the USA, most methadone-exposed neonates develop neonatal abstinence syndrome (NAS). NAS expression is widely variable among methadone-exposed neonates and only a subset requires pharmacotherapy. This study explores the potential predictors of NAS severity, including aspects of maternal substance use and methadone maintenance histories, concomitant exposure to other licit substances, and individual differences in intrinsic maternal or infant factors that may affect the infant's vulnerability to NAS expression. Methods. Fifty methadone-maintained pregnant women attending a comprehensive substance abuse treatment facility, received electrocardiogram monitoring at 36 weeks of gestation at the times of trough and peak maternal methadone levels. Vagal tone, an estimate of the magnitude of an individual's respiratory sinus arrhythmia and an indicator of autonomic control, was derived. Results. NAS expression was unrelated to maternal substance abuse history, methadone maintenance history, or psychotropic medication exposure. Male infants displayed more profound NAS symptoms and received more pharmacotherapy to treat NAS (all p < 0.05). NAS expression was related to maternal vagal reactivity; both suppression and activation of maternal vagal tone in response to methadone administration were positively and significantly associated with NAS symptomatology (F (2,44) = 4.15, p < 0.05) and treatment (F (2,44) = 3.39, p < 0.05). Infants of vagal non-responder mothers showed substantially lower NAS expression. Conclusions. NAS severity is associated with maternal vagal tone change in response to methadone administration.

Jee SH; Park J; Jo I; Lee J; Yun S; Yun JE et al. Smoking and atherosclerotic cardiovascular disease in women with lower levels of serum cholesterol. Atherosclerosis 190(2): 306-312, 2007. (26 refs.)

This cohort study of Koreans examines the relationship between smoking on atherosclerotic cardiovascular disease (ASCVD) and whether serum levels of total cholesterol modify the impact of smoking on ASCVD. A 10-year prospective cohort study was carried out on 234,399 Korean women, ranging 40-69 years of age who received health insurance from the National Health Insurance Corporation and had a medical evaluation in 1993. The main outcome measures were hospital admissions and deaths from ischemic heart disease (IHD), cerebrovascular disease (CVD), and total ASCVD. At baseline, 13,696 (5.8%) were current smokers and 105,755 (45.1%) had a total cholesterol < 200 mg/dl. Between 1994 and 2003, 4534 IHD (176/100,000 person year), 7961 CVD (310/100,000 person year), and 2418 other ASCVD events (94/100,000 person year) occurred. In multivariate Cox proportional hazard models controlling for age, hypertension, hypercholesterolemia, diabetes and alcohol drinking, current smoking increased the risk of IHD [hazard ratio (HR) = 1.7 (95% CI: 1.5-1.9)], CVD [HR = 1.6 (95% CI: 1.5-1.6)], and total ASCVD events [HR = 1.6 (95% CI: 1.5-1.7)]. Throughout the range of serum cholesterol levels, current smoking significantly increased the risk of myocardial infarction and CVD, but not angina pectoris. There was no evidence of an interaction between smoking and serum cholesterol (P for interaction = 0.469, 0.612, and 0.905 for IHD, CVD, and total ASCVD, respectively). This study demonstrated that smoking was a major independent risk factor for IHD, CVD and ASCVD in Korean women. A low cholesterol level confers no protective benefit against smoking-related ASCVD.

Karisson G; Rehman J; Kalaria V; Breall JA. Increased incidence of stent thrombosis in patients with cocaine use. Catherization and Cardiovascular Interventions 69(7): 955-958, 2007. (27 refs.)

Introduction: Coronary stent thrombosis is a rare occurrence in the era of dual-antiplatelet therapy. It is not known whether patients who use cocaine have a higher risk of thrombosis following coronary stent placement. Methods: We studied 247 consecutive patients who underwent coronary stent placement at an inner-city hospital. Results: Twelve patients (4.9%) were actively using cocaine at the time of PCI. Of these twelve patients, four patients presented with stent thrombosis (33%) at a mean of 51 +/- 40 days (median 45 days), after the index revascularization procedure. Only 2 of the 235 patients without documented cocaine use (0.85%) had stent thrombosis during the same period (P < 0.0001). Conclusion: The patients who actively use cocaine have a markedly higher risk of stent thrombosis when compared with patients without a documented history of cocaine use. We discuss various factors that potentially predispose cocaine users to stent thrombosis.

Kashani J; Ruha AM. Isolated atomoxetine overdose resulting in seizure. Journal of Emergency Medicine 32(2): 175-178, 2007. (6 refs.)

Background: Atomoxetine (Strattera (TM)), has recently been approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adolescents and adults. Atomoxetine acts by inhibiting the reuptake of norepinephrine. There are limited reports of the effects of atomoxetine in overdose. We report a case of isolated atomoxetine overdose resulting in seizure and mild cardiac toxicity. Case Report: A 17-year-old female ingested 2840 mg of atomoxetine in an attempt to kill herself. She presented to an Emergency Department 2-3 hours after ingestion and soon after arrival had a tonic clonic seizure that lasted one minute. An initial electrocardiogram (ECG) revealed a sinus tachycardia with a rate of 110 beats per minute (bpm) and a QRS interval of 93 ms. She was transferred to a pediatric toxicology referral center and had progressive improvement in her symptoms. Gas chromatography and mass spectometry of the urine detected the following drugs: atomoxetine, naproxen, and nicotine. A quantitative serum atomoxetine level of 1995 ng/ml and a quantitative serum naproxen level of 12 mcg/L (30-90 mcg/L anti-inflammatory or analgesic range) were obtained. The patient had no further complications and was without symptoms within 24 hours of hospitalization. Repeat ECG 14 hours following ingestion revealed QRS interval of 79 ms. Conclusion: We report a case of atomoxetine overdose resulting in seizure and mild widening of the QRS interval on ECG. It is important to be aware of the potential for atomoxetine to cause central nervous system and cardiac toxicity.

Knight M. Stimulant-drug therapy for attention-deficit disorder (with or without hyperactivity) and sudden cardiac death. (editorial). Pediatrics 119(1): 154-155, 2007. (6 refs.)

Korantzopoulos P; Liu T; Papaioannides D; Li G; Goudevenos JA. Atrial fibrillation and marijuana smoking. (review). International Journal of Clinical Practice 62(2): 308-313, 2008. (30 refs.)

Marijuana is the most commonly used illicit drug while its abuse and dependence has an increasing prevalence among the young population. Marijuana smoking affects the circulatory system triggering various cardiovascular events. Of note, recent case reports indicate a possible association with atrial fibrillation (AF). In this article, we provide a brief systematic review of all reported cases implicating marijuana smoking in AF development and we concisely discuss the potential underlying mechanisms as well as the clinical implications of this emerging association.

Le Page L; Lion-Daolio S; Guillaumont MP; Grignon P; Small A; Ducroix JP. An abnormal electrocardiogram in a drug addict patient. (editorial). Revue de Medecine Internel 28(10): 709-710, 2007. (5 refs.)

Lemos PA. Hidden drugs, hidden risks - Is cocaine use a new risk factor for stent thrombosis? (editorial). Catherization and Cardiovascular Interventions 69(7): 959-960, 2007. (8 refs.)

Madsen C; Nafstad P; Eikvar L; Schwarze PE; Ronningen KS; Haaheim LL. Association between tobacco smoke exposure and levels of C-reactive protein in the Oslo II Study. European Journal of Epidemiology 22(5): 311-317, 2007. (37 refs.)

It is well known that tobacco smoke exposure is related to the risk of developing cardiovascular diseases and events. One mechanism could be that tobacco smoke acts on the cardiovascular system by altering the autonomic function and/or inducing inflammatory responses. We used data from 3,744 men aged 67-77 years from the city of Oslo that participated in the health screening for the Oslo II Health Study in 2000, to explore associations between C-reactive protein and environmental exposures including exposure to tobacco smoke products. Levels of C-reactive protein were higher in current smokers (2.05 mg/l, IQR, 1.11-4.17 mg/l), compared to former-smokers (1.58 mg/l, IQR, 0.83-3.03 mg/l) and non-smokers (1.26 mg/l, IQR, 0.65-2.40 mg/l). The risk of elevated C-reactive protein increased with both numbers of current cigarettes smoked per day and numbers of pack-years of smoking, when other factors were adjusted for (P < 0.001). We found a positive dose-response relationship between amount of current cigarette smoking and elevated C-reactive protein levels. These findings support the idea that the induction or exacerbation of inflammation could be a mechanism by which smoking promotes atherosclerotic cardiovascular diseases.

Mayorov DN. Does coffee reinforce the vascular inflammatory response to mental stress? (editorial). Journal of Hypertension 24(11): 2149-2151, 2006. (36 refs.)

Mazzone A; Giani L; Faggioli P; Pichini S; Pacifici R. Cocaine-related peripheral vascular occlusive disease treated with iloprost in addition to anticoagulants and antibiotics. Clinical Toxicology 45(1): 65-66, 2007. (14 refs.)

We describe a case of acute ischemia of the 2(nd), 3(rd) and 4(th) fingers of the right hand secondary to peripheral vascular occlusive disease induced by repeated intra-arterial cocaine injections. The complete occlusion of the distal arteries resolved following treatment with iloprost, a synthetic stable analogue of prostacyclin PG12, in addition to anticoagulants and antibiotics.

McNamara R; Maginn M; Harkin A. Caffeine induces a profound and persistent tachycardia in response to MDMA ("Ecstasy") administration. European Journal of Pharmacology 555(2-3): 194-198, 2007. (16 refs.)

Caffeine promotes hyperthermia and lethality when co-administered with the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") to rats. In the present study, co-administration of caffeine (10 mg/kg, s.c.) with MDMA (10 mg/kg, s.c.) induced a profound tachycardic response compared to rats treated with either drug alone. However, neither caffeine (30 mu M) nor MDMA, (1-30 mu M), alone or in combination, affected the electrocardiogram of the isolated heart suggesting that central and sympathomimetic actions, rather than direct actions of these drugs on the heart, are responsible for the tachycardia. observed in vivo. This is a serious drug interaction, which could have important health consequences for recreational drug users.

Mendizabal VE; Adler-Graschinsky E. Cannabinoids as therapeutic agents in cardiovascular disease: A tale of passions and illusions. (review). British Journal of Pharmacology 151(4): 427-440, 2007. (133 refs.)

In addition to their classical known effects, such as analgesia, impairment of cognition and learning and appetite enhancement, cannabinoids have also been related to the regulation of cardiovascular responses and implicated in cardiovascular pathology. Elevated levels of endocannabinoids have been related to the extreme hypotension associated with various forms of shock as well as to the cardiovascular abnormalities that accompany cirrhosis. In contrast, cannabinoids have also been associated with beneficial effects on the cardiovascular system, such as a protective role in atherosclerosis progression and in cerebral and myocardial ischaemia. In addition, it has also been suggested that the pharmacological manipulation of the endocannabinoid system may offer a novel approach to antihypertensive therapy. During the last decades, the tremendous increase in the understanding of the molecular basis of cannabinoid activity has encouraged many pharmaceutical companies to develop more potent synthetic cannabinoid analogues and antagonists, leading to an explosion of basic research and clinical trials. Consequently. not only the synthetic THC dronabinol (Marinol) and the synthetic THC analogue nabilone ( esamet) have been approved in the United States, but also the standardized cannabis extract (Sativex) in Canada. At least three strategies can be foreseen in the future clinical use of cannabinoid-based drugs: (a) the use of CB1 receptor antagonists, such as the recently approved rimonabant (b) the use of CB2-selective agonists, and (c) the use of inhibitors of endocannabinoid degradation. In this context, the present review examines the effects of cannabinoids and of the pharmacological manipulation of the endocannabinoid system, in cardiovascular pathophysiology.

Mukamal KJ. The effects of smoking and drinking on cardiovascular disease and risk factors. Alcohol Research and Health 29(3): 199-202, 2006. (23 refs.)

Research on how tobacco and alcohol use interact to influence risk for cardiovascular disease is limited. Alcohol consumption of three or more drinks per day and cigarette smoking share similar, and probably additive, effects on some forms of cardiovascular disease. There is relatively little evidence, however, that the effects are worse when smoking and drinking occur together than would be expected from their independent effects. In most cases, moderate drinking does not share these risks and even has opposite effects of cigarette smoking on some risk factors. Ongoing public health efforts to minimize tobacco use and harmful drinking should result in clear and important gains to the nation's cardiovascular well-being.

Public Domain

Naya T; Hosomi N; Ohyama H; Ichihara SI; Ban CR; Takahashi T et al. Smoking, fasting serum insulin, and obesity are the predictors of carotid atherosclerosis in relatively young subjects. Angiology 58(6): 677-684, 2007. (26 refs.)

The purpose of this study was to identify predictors of atherosclerosis in a healthy young cohort comprised of 241 subjects who underwent a regular employee medical check-up at Ohshima National Sanatorium over a 9-month period. All subjects underwent carotid ultrasound examinations to determine maximal common carotid artery intima media thickness. In addition, serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, blood urea nitrogen, creatinine, glucose, and insulin were evaluated. The subjects were relatively young (mean age, 44 years; range, 18 to 62 years), with 130 females (54%) and 111 males (46%). Maximal common carotid artery intima media thickness was predicted by smoking habit, body mass index, fasting blood sugar, fasting serum insulin, and systolic blood pressure (F-5,F-235 = 52.8, P < 10(-5)). There was clear separation in common carotid artery intima media thickness values based on body mass index, smoking, and fasting serum insulin, and somewhat more overlap with systolic blood pressure and fasting blood sugar. These findings suggest that smoking and high values of body mass index, fasting serum insulin, systolic blood pressure, and fasting blood sugar are warning factors for early atherosclerosis development, and could conceivably serve as the basis of diagnostic screening. Smoking is particularly deleterious, as smokers with high body mass index, high fasting serum insulin, or high systolic blood pressure tend to have larger common carotid artery intima media thickness values than would have been predicted by consideration solely of the individual risk factors.

O'Leary DS; Block RI; Koeppel JA; Schultz SK; Magnotta VA; Ponto LB et al. Effects of smoking marijuana on focal attention and brain blood flow. Human Psychopharmacology: Clinical and Experimental 22(3): 135-148, 2007. (44 refs.)

Using an attention task to control cognitive state, we previously found that smoking marijuana changes regional cerebral blood flow (rCBF). The present study measured rCBF during tasks requiring attention to left and right ears in different conditions. Twelve occasional marijuana users (mean age 23.5 years) were imaged with PET using [150]water after smoking marijuana or placebo cigarettes as they performed a reaction time (RT) baseline task, and a dichotic listening task with attend-right- and attend-left-ear instructions. Smoking marijuana, but not placebo, resulted in increased normalized rCBF in orbital frontal cortex, anterior cingulate, temporal pole, insula, and cerebellum. RCBF was reduced in visual and auditory cortices. These changes occurred in all three tasks and replicated our earlier studies. They appear to reflect the direct effects of marijuana on the brain. Smoking marijuana lowered rCBF in auditory cortices compared to placebo but did not alter the normal pattern of attention-related rCBF asymmetry (i.e., greater rCBF in the temporal lobe contralateral to the direction of attention) that was also observed after placebo. These data indicate that marijuana has dramatic direct effects on rCBF, but causes relatively little change in the normal pattern of task-related rCBF on this auditory focused attention task.

Panagiotakos DB; Pitsavos C; Stefanadis C; GREECS Study Investigators. Short-term prognosis of patients with acute coronary syndromes through the evaluation of physical activity status, the adoption of Mediterranean diet and smoking habits: the Greek Acute Coronary Syndromes (GREECS) study. European Journal of Cardiovascular Prevention & Rehabilitation 13(6): 901-908, 2006. (33 refs.)

Purpose Our aim was to evaluate whether healthy dietary habits, physical activity and non-smoking are associated with less severe acute coronary syndromes and better short-term prognosis. Subjects and methods From October 2003 to September 2004, 2172 patients (1649 males), hospitalized for severe acute coronary syndromes in six major hospitals in Greece were included in the study. The severity of severe acute coronary syndromes was assessed through troponin-I and maximum creatinine kinase MB levels, while 30-day recurrent event rate (death or rehospitalization for cardiovascular disease, angioplasty or coronary artery bypass surgery) was used to evaluate the prognosis of the patients. A 'healthy index' that assessed adherence to the Mediterranean diet, moderate alcohol intake, physical activity and abstinence from smoking was developed (range 0-4). Results One unit increment in the healthy index was associated with -12.4 +/- 2.4 ng/ml decrease in troponin I levels (P = 0.001) and -9.7 +/- 2.5ng/ml decrease in maximum creatinine kinase MB levels (P = 0.001). The in-hospital mortality rate was 3.2% in males and 5.7% in females (i.e. overall 82 deaths, P = 0.009); during the first 30 days following hospitalization the event rate was 15.7% in males and 16.3% in females (P = 0.001). Values of the healthy index above one (i.e. presence of two or more protective factors) seemed to be associated with 44-84% lower risk of having recurrent events (P < 0.001), even after various adjustments were made. Conclusion: Among patients who had had severe acute coronary syndromes, a healthy lifestyle seemed to be associated with less severe cardiac events and lower risk of death or rehospitalization 30 days after the event.

Peles E; Bodner G; Kreek MJ; Rados V; Adelson M. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients: A cross-sectional study. Addiction 102(2): 289-300, 2007. (43 refs.)

Aims: To determine and evaluate OTc intervals in electrocardiograms (ECGs) of former heroin addicts, currently in methadone maintenance treatment (MMT), as previous reports suggest that methadone may prolong QTc intervals, thus possibly increasing the risk for Torsade de pointes (TdP). Design: Cross-sectional study. Setting Between January 2003 and September 2004, patients on a steady dose of methadone for at least 2 weeks were studied. Participants This study is a subset of 15 3 patients, of whom 15 1 patients participated in a study of high methadone doses and serum levels. A total of 138 patients in MMT for a minimum of 100 days up to 10.7 years, receiving 40-290 mg/day methadone dose, participated. Measurements Patients had an ECG at the time when blood was drawn for determination of serum methadone levels at around 24 hours after the last oral methadone dose. Corrected-QT intervals (QTc) were calculated using the Bazett formula. Findings Of 13 8 patients studied, 9 8 (71%) were male. Mean OTc interval was 418.3 +/- 32.8 milliseconds (ms). Mean methadone dose was 170.9 +/- 50.3 mg/day and mean serum methadone level was 708.2 +/- 363.1 ng/ml. Methadone dose and serum levels did not correlate with QTc. Three patients had QTC intervals above 500 ms ('prolonged'). After 2 +/- 0.4 years of follow-up, two patients died; they were two of three patients with very prolonged QTc. Causes of death were not attributed to cardiac origin. An additional 19 patients had QTc intervals of between 450 and 499 ms ('possibly prolonged'). None of these QTc >= 450 ms patients had any cardiac problems. Methadone doses of all 22 patients were > 120 mg/day. Conclusions: Methadone maintenance is generally safe; however, the possible toxicity of high dose I(> 120 mg/day) should be monitored for QTc.

Perez GH; Nicolau JC; Romano BW; Laranjeira R. Smoking-associated factors in myocardial infarction and unstable angina: Do gender differences exist? Addictive Behaviors 32(6): 1295-1301, 2007. (12 refs.)

The aim of this study was to investigate demographic and psychological characteristics associated with smoking in patients with acute coronary syndrome (myocardial infarction or unstable angina). Interviews were conducted with 348 consecutive hospitalized patients with acute coronary syndrome and included questions about demographic characteristics, coffee consumption, heart disease risk perception, economic status, alcohol consumption, depression, anxiety, and stress. Female group multivariate analysis showed that smoking in females was significantly and negatively associated with age, heart disease risk perception, and positively associated with coffee consumption. Male group multivariate analysis showed that for males, smoking was significantly and negatively associated with age, heart disease risk perception, and positively associated with coffee and alcohol consumption. Unlike studies conducted with non-heart disease patients, our results do not show an association between smoking and depression. Compared with nonsmokers, smokers with acute coronary syndrome are younger, more likely to drink coffee, and less likely to perceive smoking as a heart disease risk. Male smokers are also more likely to drink alcohol, indicating that they use more psycho-stimulants than do nonsmoking men and women who smoke.

Peyrot I; Garsaud AM; Saint-Cyr I; Quitman O; Sanchez B; Quist D. Cannabis arteritis: A new case report and a review of literature. (review). Journal of the European Academy of Dermatology and Venerology 21(3): 388-391, 2007. (10 refs.)

Cannabis arteritis manifests in cannabis users, independently of tobacco consumption. Around 50 cases were reported in the literature since the first description of this entity in 1960. We report the case of a 36-year-old man, cannabis user, without vascular risk factor who developed digital necrosis on the right foot. The pedal pulses were not palpable. He had no abnormal laboratory findings. Arteriography revealed distal segmental lesions and occlusion of popliteal artery. This arteritis was linked to cannabis use, but the patient did not stop cannabis consumption. His symptoms became even worse and he eventually developed sub-acute ischaemia in his left leg despite vascular treatments. Amputation of the right second toe and of the left leg finally became necessary. Cannabis arteritis is relatively similar to thromboangiitis obliterans in its clinical and arteriographical presentation. A parallelism can be made between the role of tobacco in thromboangiitis obliterans pathogenesis and the role of cannabis in cannabis arteritis. Cannabis use must be searched in young patients presenting with arteriopathy. Cannabis arteritis may indeed represent a frequent cause of juvenile peripheral obstructive arterial disease, but is probably under-diagnosed.

Pieper B; Templin TN; Birk TJ; Kirsner RS. Effects of injection-drug injury on ankle mobility and chronic venous disorders. Journal of Nursing Scholarship 39(4): 312-318, 2007. (18 refs.)

Purpose: To identify potential confounders and test a causal model of injection-site risk, chronic venous disorders (CVD), and ankle mobility. The reliability and validity of goniometry measurements of ankle mobility were also of interest because they are seldom performed in people with a history of injection-drug use. Design: The study was a test-retest design, consisting of 104 participants from a methadone maintenance treatment center. Methods: Each participant provided demographic information, health and drug histories, and underwent bilateral ankle goniometric measures of dorsiflexion, plantar flexion, inversion, and eversion. The clinical portion of the Clinical-Etiology-Anatomy-Pathophysiology (CEAP)was used to classify CVD severity. Findings: Reliability of goniometry measurements ranged from .70 to .90. Causal modeling supported hypotheses of increased risk from leg injection and reciprocal effects involving ankle mobility and disease progression. Ankle inversion mobility was the strongest indicator of ankle mobility. Conclusions: Injury to the lower extremities from IDU affected CVD and mobility. Further research should include assessment of comorbidity and other potential confounders. Ankle inversion should remain part of the goniometry assessment.

Randhawa K; Mendes E; Wanner A. Acute effect of cigarette smoke and nicotine on airway blood flow and airflow in healthy smokers. Lung 184(6): 363-368, 2006. (39 refs.)

Cigarette smoke contains irritants and vasoactive substances. We wanted to determine the effect of smoking a cigarette and of nasally or orally inhaled nicotine on airway blood flow (Q(aw)) and airflow in smokers. In ten healthy current smokers, Q(aw), FEV1, and FEF25-75 were measured before and at 5, 30, and 180 min after smoking a cigarette. The effects of systemic nicotine using a nicotine nasal spray and local nicotine using a nicotine inhaler were also studied. Mean (+/- SE) Q(aw) increased by 81% +/- 16% (p = 0.03) 5 min after smoking a cigarette and was no longer different from baseline at 30 and 180 min. Nicotine nasal spray and nicotine oral inhaler had no effect on Q(aw.) FEV1 and FEF25-75 remained unchanged after smoking a cigarette and after local or systemic nicotine administration. Smoking a cigarette is followed by a transient increase in airway blood flow but no changes in airflow. Nicotine, at the rate and dose provided by the nasal spray (systemic action) and oral inhaler (local and systemic action), does not appear to be involved in the Q(aw) change, suggesting a pharmacologic or nonspecific irritant effect of other cigarette smoke constituents.

Rao H; Wang J; Giannetta J; Korczykowski M; Shera D; Avants BB et al. Altered resting cerebral blood flow in adolescents with in utero cocaine exposure revealed by perfusion functional MRI. Pediatrics 120(5): E1245-E1254, 2007. (54 refs.)

OBJECTIVES. Animal studies have clearly demonstrated the effects of in utero cocaine exposure on neural ontogeny, especially in dopamine-rich areas of cerebral cortex; however, less is known about how in utero cocaine exposure affects longitudinal neurocognitive development of the human brain. We used continuous arterial spin-labeling perfusion functional MRI to measure the effect of in utero cocaine exposure on resting brain function by comparing resting cerebral blood flow of cocaine-exposed adolescents with non-cocaine-exposed control subjects. PATIENTS AND METHODS. Twenty-four cocaine-exposed adolescents and 25 matched non-cocaine-exposed control subjects underwent structural and perfusion functional MRI during resting states. Direct subtraction, voxel-wise general linear modeling, and region-of-interest analyses were performed on the cerebral blood flow images to compare the resting cerebral blood flow between the 2 groups. RESULTS. Compared with control subjects, cocaine-exposed adolescents showed significantly reduced global cerebral blood flow. The decrease of cerebral blood flow in cocaine-exposed adolescents was observed mainly in posterior and inferior brain regions, including the occipital cortex and thalamus. After adjusting for global cerebral blood flow, however, a significant increase in relative cerebral blood flow in cocaine-exposed adolescents was found in anterior and superior brain regions, including the prefrontal, cingulate, insular, amygdala, and superior parietal cortex. Furthermore, the functional modulations by in utero cocaine exposure on all of these regions except amygdala cannot be accounted for by the variation in brain anatomy. CONCLUSIONS. In utero cocaine exposure may reduce global cerebral blood flow, and this reduction may persist into adolescence. The relative increase of cerebral blood flow in anterior and superior brain regions in cocaine-exposed adolescent participants suggests that compensatory mechanisms for reduced global cerebral blood flow may develop during neural ontogeny. Arterial spin-labeling perfusion MRI may be a valuable tool for investigating the long-term effects of in utero drug exposure.

Rhee MY; Na SH; Kim YK; Lee MM; Kim HY. Acute effects of cigarette smoking on arterial stiffness and blood pressure in male smokers with hypertension. American Journal of Hypertension 20(6): 637-641, 2007. (30 refs.)

Background: Although the acute increase of arterial stiffness and blood pressure (BP) after cigarette smoking in healthy smokers is considered a possible mechanism of increased cardiovascular risk, the acute effect of smoking on arterial stiffness in hypertensive smokers is unknown. We investigated the acute effects of cigarette smoking on arterial stiffness and BP in hypertensive male smokers. Methods: Heart rate (HR), brachial and ankle BP, and pulse-wave velocity (PWV) were measured in 22 hypertensive male smokers (HTs) and in 30 normotensive male smokers (NTs) before and 5, 10, and 15 min after smoking one cigarette (nicotine content, 0.9 mg). Results: Smoking induced acute increases of HR, brachial BP, and heart-femoral PWV (hfPWV) in NTs and HTs (P < .05). Ankle systolic BP and femoral-ankle PWV were acutely increased in HTs (P < .05), but not in NTs. In HTs, brachial systolic BP and hfPWV at 15 min were higher than at baseline (P < .05). An acute increase of hfPWV in the HTs was significant (P =.025) after adjustment for total cholesterol, time-dependent HR, and brachial mean arterial pressure, but acute changes of other PWVs lost statistical significance. Conclusions: Cigarette smoking acutely increases aortic stiffness and BP in male smokers with hypertension, and the effects persist longer than in male smokers without hypertension.

Rigotti NA; Thorndike AN; Regan S; McKool K; Pasternak RC; Chang YC et al. Bupropion for smokers hospitalized with acute cardiovascutar disease. American Journal of Medicine 119(12): 1080-1087, 2006. (37 refs.)

PURPOSE: Smoking cessation after myocardial infarction reduces cardiovascular mortality, but many smokers cannot quit despite state-of-the-art counseling intervention. Bupropion is effective for smoking cessation, but its safety and efficacy in hospitalized smokers with acute cardiovascular disease is unknown. METHODS: A five-hospital randomized double-blind placebo-controlled trial assessed the safety and efficacy of 12 weeks of sustained-release bupropion (300 mg) or placebo in 248 smokers admitted for acute cardiovascular disease, primarily myocardial infarction and unstable angina. All subjects had smoking counseling in the hospital and for 12 weeks after discharge. Cotinine-validated 7-day tobacco abstinence, cardiovascular mortality, and new cardiovascular events were assessed at 3 months (end-of-treatment) and 1 year. RESULTS: Validated tobacco abstinence rates in bupropion and placebo groups were 37.1% vs 26.8% (OR 1.61, 95% CI, 0.94-2.76; P = .08) at 3 months and 25.0% vs 21.3% (OR, 1.23, 95% CI, 0.68-2.23, P = .49) at I year. The adjusted odds ratio, after controlling for cigarettes per day, depression symptoms, prior bupropion use, hypertension, and length of stay, was 1.91 (95% CI, 1.06-3.40, P = .03) at 3 months and 1.51 (95% CI, 0.81-2.83) at 1 year. Bupropion and placebo groups did not differ in cardiovascular mortality at 1 year (0% vs 2%), in blood pressure at follow-up, or in cardiovascular events at end-of-treatment (16% vs 14%, incidence rate ratio [IRR]1.22 (95% CI: 0.64-2.33) or 1 year (26% vs 18%, IRR 1.56, 95% CI 0.91-2.69). CONCLUSIONS: Bupropion improved short-term but not long-term smoking cessation rates over intensive counseling and appeared to be safe in hospitalized smokers with acute cardiovascular disease.

Rosner SA; Akesson A; Stampfer MJ; Wolk A. Coffee consumption and risk of myocardial infarction among older Swedish women. American Journal of Epidemiology 165(3): 288-293, 2007. (34 refs.)

Numerous studies have examined the association between coffee consumption and risk of myocardial infarction (MI), but results have been inconsistent. Case-control studies generally suggest a harmful effect of coffee drinking, whereas cohort studies have mostly shown no association. Recent studies found that coffee may lower the risk of diabetes, a major coronary risk factor. The authors prospectively examined the effect of coffee consumption on MI risk in 32,650 older Swedish women, aged 40-74 years, participating in the Swedish Mammography Cohort; 459 cases of MI developed during 165,896 person-years of follow-up from 1997 to 2002. After adjustment for age, coronary heart disease risk factors, and dietary variables, the relative risk of MI associated with drinking >= 5 cups/week versus 0-4 cups/week was 0.68 (95% confidence interval (CI): 0.43, 1.07). The authors observed a nonsignificant trend toward lower risk with higher consumption levels. Compared with that for 0-4 cups/week, the relative risks of MI were 0.84 ( 95% CI: 0.51, 1.38) for 5-7 cups/week, 0.65 ( 95% CI: 0.41, 1.03) for 2-3 cups/day, 0.64 ( 95% CI: 0.39, 1.04) for 4-5 cups/day, and 0.65 ( 95% CI: 0.37, 1.12) for >= 6 cups/day (p-trend = 0.07). Contrary to previous case-control studies, the authors concluded that coffee consumption does not increase MI risk. Coffee consumption of >= 5 cups/week was nonsignificantly inversely associated with MI risk among older Swedish women.

Rott D; Salameh S Weiss AT; Chajek-Shaul T; Leibowitz D. Smoking cessation does not alter ST deviation pattern of recurrent myocardial infarctions. International Journal of Cardiology 123(3): 343-345, 2008. (14 refs.)

Background: Myocardial infarction (MI) may be classified as ST elevation MI (STEMI) or non ST elevation MI (NSTEMI). We used the term recurrent MI (RMI's) to denote repeated MI episodes, in a particular patient, in which a different coronary site is responsible for each episode. Recently we reported that most patients with recurrent MI episodes will have either STEMI's or NSTEMI's but not both. A history of smoking was associated with recurrent STEMI's. Objective: To determine whether smoking cessation will alter the type of RMI in patients with an index MI of STE type. Methods: The analysis included 128 patients who underwent at least 2 MI episodes. We attempted to include only MI's of native vessels, without the presence of extra cardiac conditions that intensify myocardial ischemia. All 128 patients were active smokers who presented with an index MI of the STE type. Of these patients 94 had recurrent STEMI and 34 had recurrent NSTEMI (STE/NSTE group). Results: We identified all patients who were no longer active smokers at the time of the recurrent MI: there were 31 (33%) such patients in the STEMI group and 13 (38%) in the STE/NSTE group (p=NS). Conclusion: Smoking cessation did not influence the type of recurrent MI in these patients.

Routhier DD; Katz KD; Brooks DE. QTc prolongation and Torsades de Pointes associated with methadone therapy. Journal of Emergency Medicine 32(3): 275-278, 2007. (11 refs.)

Oral methadone therapy is an effective and increasingly popular treatment for opioid dependency and chronic pain. Although it is not typically considered pro-dysrhythmic, we present the unique case of a 52-year-old HIV-positive woman without underlying cardiac disease who developed QTc prolongation and pulseless Torsades secondary to high dose methadone therapy.

Saavedra LE. Endocannabinoid system and cardiometabolic risk. Clinical Pharmacology & Therapeutics 82(5): 591-594, 2007. (31 refs.)

The increasing prevalence of overweight and obesity counteracts the favorable advances of risk factor management achieved for cardiovascular disease (CVD) prevention. Obese and overweight individuals are at increased risk for CVDs and diabetes mellitus, a risk pattern called "cardiometabolic risk.'' There is a growing interest concerning the role of the endocannabinoid system in energy metabolism and how blockade of cannabinoid receptors (CB1) may optimize fat distribution, insulin sensitivity, and blood lipids to improve cardiovascular risk profile.

Salimi J; Shojaeefar A; Khashayar P. Management of infected femoral pseudoaneurysms in intravenous drug abusers: A review of 57 cases. Archives of Medical Research 39(1): 120-124, 2008. (15 refs.)

Background. The present study was carried out to evaluate the clinical characteristics and surgical methods used for the management of infected femoral pseudoaneurysms secondary to illegal drug injections. Methods. Fifty seven consecutive patients who presented with infected pseudoaneurysm of the lower limb and were admitted to the emergency department of Sina Hospital during a 5-year period were enrolled in this study. Surgical methods performed consisted of vein angioplasty, simple ligation of femoral artery, and emergent or delayed revascularization. Results. All participating patients were males with a mean age of 36.7 years. Three (5.3%) and two (3.5%) patients underwent primary repair and emergent vascular bypass, respectively; whereas delayed revascularization was performed in only eight (14%) cases. Forty four (77.2%) patients achieved a normal lifestyle without any vascular bypass. Early critical ischemia and late claudication was reported in two (3.5%) and eight (14%) patients, respectively. Other complications such as amputation and mortality were rarely reported. Conclusions. In our study, simple ligation of the external iliac or femoral artery was the most frequent management method for treating infected femoral pseudoaneurysms. Simple ligation of the external iliac or femoral artery seems to be a safe procedure in drug abusers presenting with infected femoral pseudoaneurysms.

Sekine R; Obbens EAMT; Coyle N; Inturrisi CE. The successful use of parenteral methadone in a patient with a prolonged QTc interval. (review). Journal of Pain and Symptom Management 34(5): 566-569, 2007. (23 refs.)

Recent case reports have raised concerns about the potential for methadone to prolong the QTc interval (QT corrected for heart rate) and predispose patients to torsade de pointes (TdP), a lift threatening arrhythmia. We present a case report that describes the successful use of parenteral and oral methadone in a patient with uncontrolled cancer pain and a history of QTc prolongation. We describe an approach to the use of methadone in this Patient and review both case reports and recent prospective studies that have evaluated the risk of TdP and the long-term outcome with respect to the development of TdP in patients receiving methadone for chronic pain or addiction.

Seo DC; Torabi MR. Reduced admissions for acute myocardial infarction associated with a public smoking ban: Matched controlled study. Journal of Drug Education 37(3): 217-226, 2007. (21 refs.)

There has been no research linking implementation of a public smoking ban and reduced incidence of acute myocardial infarction (AMI) among nonsmoking patients. An ex post facto matched control group study was conducted to determine whether there was a change in hospital admissions for AMI among nonsmoking patients after a public smoking ban was implemented in Monroe County compared with Delaware County, Indiana without such a ban. Poisson analysis was conducted for 44 months of hospital admissions. A significant drop occurred in the number of admissions among nonsmoking patients in Monroe County after the ban whereas a nonsignificant decrease in the number of admissions occurred in Delaware County. The changes in the number of smoking-patient admissions before and after the ban were not significant.

Shea KJ; Sopko NA; Ludrosky K; Hoercher K; Smedira NG; Taylor DO et al. The effect of a donor's history of active substance on outcomes following orthotopic heart transplantation. European Journal of Cardio-Thoracic Surgery 31(3): 452-456, 2007. (18 refs.)

Objective: To review the short-term and tong-term outcomes of using heart donors with a history of substance abuse. Methods: Retrospective chart review was performed of heart recipients over an 8-year span. Charts provided demographics, mechanisms of donor death, and history of substance abuse. Additionally, charts were quarried for post-operative echocardiography and coronary angiogram results, serologic tests, and survival. Results: Between January 1997 and December 2005, 689 heart transplants were performed, 150 (21.8%) had a history positive for substance abuse. The mean donor age was 34.5 years (range 16-62 years); most common cause of death was traumatic head injury in 87 donors (58.0%). Most patients (76.0%) had a history of 1 ppd smoking for >= 5 years, 89 (59.3%) had a history of inhaled drug use, 75 (50.0%) alcohol abuse, and 12 (8.0%) intravenous drug use. At a mean follow-up of 8.3 days, 68 hearts (45.3%) had normal, 36 (24.0%) mild, 23 (15.3%) moderate, and 10 (6.7%) severe ventricular dysfunction by echocardiography. Furthermore, 110 hearts (73.3%) had normal coronaries, 20 (13.3%) had mild, and 2 (1.3%) had evidence of moderate coronary artery disease (CAD) on coronary angiogram at a mean follow-up of 9.8 months (range 0.1-43.7 months). All recipients who received organs from known hepatitis B, or C positive, donors converted to positive serologies. Overall post-transplant survival for the group was 89.8% at a mean follow up of 43.3 months (range 5.8-108.6 months). Conclusions: A history of donor substance abuse does not have a negative impact on overall survival, cardiac function, risk of transplant associated coronary artery disease (TCAD). In patients who receive organs from virus positive donors, the risk of viral conversion is high, but survival seems not to be influenced.

Sheinkopf SJ; Lagasse LL; Lester BM; Liu J; Seifer R; Bauer CR et al. Prenatal cocaine exposure: Cardiorespiratory function and resilience. Annals of the New York Academy of Sciences: Resilience in Children 1094: 354-358, 2006. (8 refs.)

Cardiac vagal tone (VT) was studied as a resilience factor in children prenatally exposed to cocaine and nonexposed controls (n = 550). A cumulative risk index was derived and used to classify children as high versus low risk. VT was measured during mildly stressful observations at 1 and 36 months of age. Children were classified as having consistently high, consistently low, or fluctuating VT. Risk and VT interacted to predict adaptive behaviors. For high-risk children, low VT was related to higher ratings of adaptive behaviors. This finding suggests that regulatory functioning, as indexed by VT, may be a protective factor in prenatal CE.

Singh S; Arora R; Khraisat A; Handa K; Bahekar A; Trivedi A et al. Increased incidence of in-stent thrombosis related to cocaine use: Case series and review of literature. Journal of Cardiovascular Pharmacology and Therapeutics 12(4): 298-303, 2007. (24 refs.)

The purpose of this article was to determine the incidence of in-stent thrombosis (IST) after coronary stent implantation in patients with cocaine abuse. A retrospective review was done of medical records of consecutive patients who underwent coronary stent implantation for obstructive coronary artery disease at a single inner-city institution from January 1997 to October 2006. Patients with temporal cocaine use were identified by positive urine drug screen. IST was confirmed angiographically Of the 81 patients with active cocaine use that underwent coronary stent implantation, 4 (5%) suffered IST (mean period from stent implantation, 28.5 +/- 14 days). All procedures were performed successfully and received intravenous IIb/IIIa antagonist intraprocedurally. All patients were prescribed dual antiplatelet therapy with aspirin and clopidogrel at discharge; however, all 4 patients that suffered from IST continued cocaine abuse were noncompliant with the prescribed dual antiplatelet therapy. Of these 4 patients, 2 presented with ST segment elevation myocardial infarction (50%), whereas 2 presented with non-ST-segment elevation myocardial infarction (50%). One was managed medically. Two received repeat percutancous coronary intervention, and 1 underwent coronary artery bypass surgery. The patient that underwent surgery died in the postoperative period. The remaining 3 patients survived. Patients with active cocaine abuse who undergo successful coronary stent revascularization have a high (5%) incidence of stent thrombosis. A majority of patients that suffer stent thrombosis continue cocaine abuse and are noncompliant with antiplatelet therapy.

Singh S; Trivedi A; Adhikari T; Molnar J; Arora R; Khosla S. Cocaine-related acute aortic dissection: Patient demographics and clinical outcomes. Canadian Journal of Cardiology 23(14): 1131-1134, 2007. (23 refs.)

BACKGROUND: To compare the demographics, inpatient mortality and short-term survival following hospital discharge between cocaine-using and non-cocaine-using patients presenting with acute aortic dissection. METHODS: Retrospective analysis of 46 consecutive patients admitted with the diagnosis of acute aortic dissection at the Mount Sinai Hospital (Chicago, USA) between 1996 and 2005. Among these 46 patients, cocaine use was temporally related to the presenting symptom in 13 patients (28%, group 1). Patients who were not cocaine users were grouped into group 2 (33 patients [72%]. RESULTS: Patients in group I were younger than those in group 2 (mean age 38 +/- 9 years versus 63 +/- 17 years, P=0.001), more likely to be smokers (13 of 13 patients [100%] versus 15 of 33 patients [45%], P=0.001) and had a higher prevalence of accelerated hypertension (mean blood pressure 210/130 mmHg) compared with group 2 (10 of 13 patients [77%] versus 11 of 33 patients [33%] (P=0.01). Group 1 patients had a higher prevalence of type B dissection than group 2 (nine of 13 patients [69%] versus one of 33 patients [3%]. After hos, pital discharge, eight of 13 patients (62%) in the cocaine group continued to use cocaine. Mortality following hospital discharge was significantly higher in cocaine users (nine of 13 patients [69%]) compared with the non-cocaine users (four of 33 patients [12%] P=0.01). Recurrent dissection was the cause of death in five of the 13 deaths (42%) in the cocaine group. CONCLUSIONS: Patients presenting with acute aortic dissection temporally related to cocaine use are more likely to be younger, smokers, have higher prevalence of hypertensive crises, more likely to have type B aortic dissection and may have a higher mortality following hospital discharge, possibly due to continued cocaine use and recurrent aortic dissection.

Sneider JT; Pope HG; Silveri MM; Simpson NS; Gruber SA; Yurgelun-Todd DA. Altered regional blood volume in chronic cannabis smokers. Experimental and Clinical Psychopharmacology 14(4): 422-428, 2006. (39 refs.)

The quantitative measurement of cerebral perfusion is crucial for the study of both normal and impaired human brain function. Although cannabis is the most commonly abused illicit substance in the United States, its effects on cerebral blood volume (CBV) have not been fully examined. The objective of the present study was to examine differences in relative regional blood volume in focal regions of interest-including the frontal lobe, the temporal lobe, and the cerebellum-during a period of supervised abstinence from cannabis. Dynamic susceptibility contrast MRI data were collected on 12 current, long-term daily cannabis users between 6 and 36 hr after the subjects' last reported cannabis use. Resting-state CBV images were also acquired in 17 healthy comparison subjects. Data were acquired in the axial plane with a 1.5-Tesla GE Signa scanner following a bolus of gadolinium contrast agent. Cannabis users demonstrated significantly increased blood volumes in the right frontal area (p < .05), in the left temporal area (p < .005), and in the cerebellum (p < .005) relative to comparison subjects. Among the cannabis users, there were no significant correlations between regional blood volumes and either total lifetime episodes of smoking or urinary tetrahydrocannabinol concentrations. These findings have important implications for understanding the effects of chronic heavy cannabis use on brain function. It would be of interest to extend the investigation beyond 6-36 hr of abstinence from cannabis to determine whether increased CBV values persist for several weeks or eventually normalize.

Sofi F; Conti AA; Gori AM; Luisi MLE; Casini A; Abbate R et al. Coffee consumption and risk of coronary heart disease: A meta-analysis. Nutrition Metabolism and Cardiovascular Diseases 17(3): 209-223, 2007. (73 refs.)

Background and aims: During the past three decades the relationship between habitual coffee drinking and coronary heart disease (CHD) has been assessed in numerous studies, with conflicting results. The aim of this study was to systematically examine the data published on the association between habitual coffee consumption and risk of CHID. Methods and results: Thirteen case-control and 10 cohort studies were included. Case-control studies incorporated 9487 cases of CHID and 27,747 controls, and cohort studies included a total of 403,631 participants that were followed for between 3 and 44 years. The summary of odds ratios (OR) for the case-control studies showed statistically significant associations between coffee consumption and CHID for the highest intake group (>4 cups/day), OR 1.83 (95% Cl 1.49-2.24; P < 0.0001), and for the second highest category (3-4 cups/day), OR 1.33 (95% Cl 1.04-1.71; P < 0.0001), white no significant association emerged for low daily coffee intake (<= 2 cups/day), OR 1.03 (95% CI 0.87-1.21; P = 0.45). The analysis of tong-term follow-up cohort studies did not show any association between the consumption of coffee and CHID, with a relative risk (RR) of 1.16 (95% CI 0.95-1.41; P = 0. 14) for the highest category, and 1.05 (95% C1 0.90-1.22; P = 0.57) and 1.04 (95% CI 0.90-1.19; P = 0.60) for the second and third highest categories, respectively. These results did not differ substantially when controlling for region of origin, fatal and non-fatal events, year of publication, and number of years of follow-up. Conclusions: Despite a significant association between high consumption of coffee and CHD reported among case-control. studies, no significant association between daily coffee consumption and CHD emerged from tong-term follow-up prospective cohort studies.

Srikanth S; Barua R; Ambrose J. Methamphetamine-associated acute left ventricular dysfunction: A variant of stress-induced cardiomyopathy. Cardiology 109(3): 188-192, 2008. (18 refs.)

This brief report describes a case of transient left ventricular dysfunction in a 42-year-old woman associated with methamphetamine abuse. Transient (stress-induced) left ventricular dysfunction has been described previously, usually in postmenopausal women following emotional stress and also severe medical illness. This is the first reported case associated with methamphetamine abuse.

Swan GE; Lessov-Schlaggar CN; Krasnow RE; Wilhelmsen KC; Jacob P; Benowitz NL. Genetic and environmental sources of variation in heart rate response to infused nicotine in twins. Cancer Epidemiology, Biomarkers & Prevention 16(6): 1057-1064, 2007. (39 refs.)

The heart rate response to nicotine may be an important component of the process leading to dependence. The present study is the first to determine the extent to which genetic and environmental sources play a role in various components of the heart rate response. One hundred and ten monozygotic and 29 dizygotic twin pairs received an i.v. infusion of nicotine and cotinine over 30 min. Before, during, and for 30 min after infusion, heart rate was measured via an electronic monitor. The clearance of nicotine was determined as a measure of the rate of nicotine metabolism. Average resting heart rate before infusion was 64.7 beats per minutes (bpm), and at the termination of infusion, heart rate had increased to an average of 72.7 bpm. At 30 min after infusion, heart rate had decreased to 67.5 bpm. Age, current smoking status, body mass index, and nicotine clearance were associated significantly with heart rate levels over the full 60 min of measurement. After adjustment for several covariates, including dose of administered nicotine and rate of nicotine clearance, the variance in several characteristics of the heart rate response curve was examined for the relative contribution from genetic and environmental sources. In the total sample, as much as 30.3% of the variance in the acceleration of heart rate was due to additive genetic sources. In nonsmokers, 34.8% and 31.0% of variance in the acceleration and deceleration of heart rate, respectively, was due to genetic sources. Heart rate acceleration and deceleration may be a reflection of central nervous system responsiveness to nicotine. The contribution from genetic sources to heart rate response characteristics should be investigated further as a potential endophenotype for use in genetic studies of nicotine dependence.

Tatli E; Yilmaztepe M; Altun G; Altun A. Cannabis-induced coronary artery thrombosis and acute anterior myocardial infarction in a young man. International Journal of Cardiology 120(3): 420-422, 2007. (14 refs.)

Information concerning acute myocardial infarction after cannabis usage is limited and the actual mechanism of cannabis-induced myocardial infarction is not well known. In the report, we described a young man with an acute myocardial infarction and cannabis-induced coronary thrombosis.

Thalme A; Westling K; Julander I. In-hospital and long-term mortality in infective endocarditis in injecting drug users compared to non-drug users: A retrospective study of 192 episodes. Scandinavian Journal of Infectious Diseases 39(3): 197-204, 2007. (26 refs.)

In a retrospective study, in-hospital and long-term mortality for patients with infective endocarditis (IE) was analysed. The study was conducted at a department of infectious diseases in Stockholm, Sweden. Mortality was compared between injecting drug users (IDUs) and patients without drug abuse (non-IDUs). 192 episodes of IE from 1995 to 2000 were analysed, 60 in IDUs and 135 in non-IDUs, median follow-up 4.4 y. Episodes were classified using the Duke criteria: 145 definite and 47 possible. Of 53 definite episodes in IDUs, 55% were right-sided IE and 43% left-sided IE (including combined left- and right-sided). Surgical treatment was used in 34/145 definite episodes, all being left- sided IE. The in-hospital mortality was 14/145 (9.6%). There was no difference in in-hospital mortality between patient groups with left-sided IE. The IDU patients with left-sided IE had a higher long-term mortality with the increased mortality rate explained by late deaths in the surgically treated IDUs. Treatment results for IDUs with right-sided IE were good with no in-hospital mortality, no relapses and no increase in long-term mortality. This difference in prognosis between left- sided and right-sided IE in IDUs makes high quality echocardiography important to identify patients with left- sided IE and worse prognosis.

Treadwell SD; Robinson TG. Cocaine use and stroke. (review). Postgraduate Medical Journal 83(980): 389-394, 2007. (104 refs.)

Stroke is the third most common cause of death in developed countries. In England and Wales, 1000 people under the age of 30 have a stroke each year. Cocaine is the most commonly used class A drug, and the first report of cocaine-induced stroke was in 1977. Since the development of alkaloidal "crack'' cocaine in the 1980s, there has been a significant rise in the number of case reports describing both ischaemic and haemorrhagic stroke associated with cocaine use. Cocaine is a potent central nervous system stimulant, and acts by binding to specific receptors at pre-synaptic sites preventing the reuptake of neurotransmitters. The exact mechanism of cocaine-induced stroke remains unclear and there are likely to be a number of factors involved including vasospasm, cerebral vasculitis, enhanced platelet aggregation, cardioembolism, and hypertensive surges associated with altered cerebral autoregulation. The evidence surrounding each of these factors will be considered here.

van Amelsvoort LGPM; Jansen NWH; Kant I. Smoking among shift workers: More than a confounding factor. Chronobiology International 23(6): 1105-1113, 2006. (21 refs.)

In studies on the cardiovascular disease risk among shift workers, smoking is considered to be a confounding factor. In a study of 239 shift and 157 daytime workers, it was found that shift work was prospectively related to increased cigarette consumption, indicating that smoking might be in the causative pathway; however, the number of study subjects was too low to warrant sound conclusions. Therefore, data from the Maastricht Cohort study were used to investigate the longitudinal relation between smoking and shift work in a much larger population. In this study, a total of 12,140 employees were followed for two years by means of self-administered questionnaires. The authors compared workers who normally worked during daytime hours only (74%) with those who worked other than day shifts (26%). Logistic regression analyses were performed, adjusting for demographic factors of age, gender, and educational level to evaluate the risk of starting to smoke (n=25) in the group of non-smoking workers and the risk of quitting (n=318) in the group of smoking workers. Logistic regression analysis showed a significant association between shift work and taking up smoking during the two-year follow-up (odds ratio: 1.46, p =0.03). The risk to stop smoking was somewhat lower in shift workers (odds ratio: 0.91) but not statistically significant (p =0.5). To conclude, this study showed that, independent of educational level, shift workers are more prone to start smoking. This finding might have important implications for studies on the health effects of shift workers and for possible interventions aimed at the reduction of the excess health risk among shift workers.

Wiggers LCW; Smets EMA; Oort FJ; Peters RJG; Storm-Versloot MN; Vermeulen H et al. The effect of a minimal intervention strategy in addition to nicotine replacement therapy to support smoking cessation in cardiovascular outpatients: A randomized clinical trial. European Journal of Cardiovascular Prevention & Rehabilitation 13(6): 931-937, 2006. (30 refs.)

Background Smoking is an important risk factor for recurrent events in cardiovascular patients. Evidence exists that nicotine replacement therapy (NRT) approximately doubles smoking cessation rates. The minimal intervention strategy (MIS) has been used successfully to assist patients to quit smoking in general practice, and was recently adapted for cardiology inpatients (C-MIS). It is hypothesized that in cardiovascular outpatients the combination of C-MIS and NRT significantly increases the number of quitters compared to NRT alone. Methods A randomized clinical trial in 385 smoking patients who attended the cardiovascular outpatient departments in the Academic Medical Centre, Amsterdam for the treatment of atherosclerotic disease. Patients were allocated to either NRT+C-MIS or NRT alone. Self-reported and biochemically validated abstinence rates were measured at 12 months' follow-up. Results: Including patients with incomplete follow-up as smokers, abstinence was reported by 19% of the NRT+C-MIS group and 14% of the NRT group [absolute risk reduction (ARR)=0.05; 95% confidence interval (CI)= -0.02; 0.12]. According to biochemical markers, abstinence rates were 28 and 24%, respectively (ARR=0.04, 95% CI= -0.06; 0.14). Hence, no significant differences between groups were found. The number of cigarettes smoked a day decreased significantly at 12 months: from 21 to 15 a day in the experimental group, and from 21 to 14 in the control group (P < 0.001), but did not differ between groups (P = 0.32). Conclusions: The effectiveness of a minimal contact intervention was investigated in order to reach as many cardiovascular patients as possible in the setting of outpatient departments. This intervention was not found to be effective.

Wong DR; Willett WC; Rimm EB. Smoking, hypertension, alcohol consumption, and risk of abdominal aortic aneurysm in men. American Journal of Epidemiology 165(7): 838-845, 2007. (40 refs.)

Despite the known protective association between moderate alcohol consumption and ischemic heart disease, little is known about the effects of alcohol consumption on abdominal aortic aneurysms (AAA). The authors analyzed prospective, biennially updated data for a cohort of 39,352 US men from 1986 to 2002. The association of incident AAA diagnosis with alcohol consumption in grams per day was assessed at baseline and by using alcohol consumption data updated every 4 years, controlling for previously reported cardiovascular risk factors. During 576,374 person-years of follow-up, 376 newly diagnosed cases of AAA were demonstrated. After adjustment for other risk factors for AAA, including smoking, hypertension, and body mass index, alcohol consumption at baseline was independently associated with AAA diagnosis (p for trend = 0.03), with a maximum hazard ratio of 1.21 (95% confidence interval: 0.78, 1.87) for >= 30.0 g (approximately >= 2 standard drinks) of daily alcohol consumption. This association was stronger when the updated alcohol consumption data were assessed rather than simply baseline exposure (p for trend = 0.02); the hazard ratio for the highest level of intake (>= 30.0 g/day) was 1.65 (95% confidence interval: 1.03, 2.64). Small numbers limited analyses by beverage type, but liquor demonstrated the strongest positive association with AAA.

Xiao DL; Huang XH; Yang SM; Zhang LB. Direct effects of nicotine on contractility of the uterine artery in pregnancy. Journal of Pharmacology and Experimental Therapeutics 322(1): 180-185, 2007. (43 refs.)

Recent studies indicate that smoking/ nicotine increases maternal blood pressure and decrease in uterine blood flow in pregnancy. However, the mechanisms are not fully understood. The present study was designed to test the hypothesis that nicotine exposure decreases endothelium- dependent relaxation and increases vascular contractility of the uterine artery in pregnancy. Uterine arteries were isolated from near- term ( similar to 140 days gestation) pregnant ewes. Arteries were subjected to acute ( 20 min) or chronic ( 48 h) nicotine treatment, and agonist- induced contractions and relaxations were measured in tissue bath. Endothelial eNOS was detected by immunohistochemistry in situ in arteries and by Western blotting in isolated endothelial cells. Chronic nicotine treatment produced a concentration-dependent increase in alpha(1)-adrenoceptor agonist phenylephrine- induced contractions. In contrast, the acute treatment showed no effect. Inhibition of eNOS with N-G-nitro-L-arginine (L-NNA) significantly increased phenylephrine- induced contractions, which was abolished in uterine arteries after chronic nicotine treatment. In the presence of L-NNA, there was no significant difference in phenylephrine- induced contractions between control and nicotine- treated vessels. Chronic, but not acute, nicotine treatment significantly attenuated the calcium ionophore A23187- induced relaxations. Unlike A23187, the endothelium-independent relaxation mediated by sodium nitroprusside was not affected by nicotine. Endothelial eNOS protein levels and the phosphorylation levels of eNOSSer1179 were significantly decreased in nicotine- treated uterine arteries. The results suggest that nicotine impairs uterine vascular function in pregnancy, which may lead to an increased vascular resistance and a decrease in uterine blood flow.