Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study

BACKGROUND: Depression leads to adverse outcomes in patients with coronary heart disease (CHD). Medication nonadherence is a potential mechanism for the increased risk of CHD events associated with depression, but it is not known whether depression is associated with medication nonadherence in outpatients with stable CHD. METHODS: We examined the association between current major depression (assessed using the Diagnostic Interview Schedule) and self-reported medication adherence in a cross-sectional study of 940 outpatients with stable CHD. RESULTS: A total of 204 participants (22%) had major depression. Twenty-eight (14%) of 204 depressed participants reported not taking their medications as prescribed compared with 40 (5%) of 736 nondepressed participants (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.7-4.7; P<.001). Twice as many depressed participants as nondepressed participants (18% vs 9%) reported forgetting to take their medications (OR, 2.4; 95% CI, 1.6-3.8; P<.001). Nine percent of depressed participants and 4% of nondepressed participants reported deciding to skip their medications (OR, 2.2; 95% CI, 1.2-4.2; P = .01). The relationship between depression and nonadherence persisted after adjustment for potential confounding variables, including age, ethnicity, education, social support, and measures of cardiac disease severity (OR, 2.2; 95% CI, 1.2-3.9; P = .009 for not taking medications as prescribed). CONCLUSIONS: Depression is associated with medication nonadherence in outpatients with CHD. Medication nonadherence may contribute to adverse cardiovascular outcomes in depressed patients.     

Hyperuricemia and coronary heart disease: A systematic review and meta‐analysis

Objective

The role of serum uric acid as an independent risk factor for cardiovascular disease remains unclear, although hyperuricemia is associated with cardiovascular disease such as coronary heart disease (CHD), stroke, and hypertension.

Methods

A systematic review and meta‐analysis using a random‐effects model was conducted to determine the risk of CHD associated with hyperuricemia in adults. Studies of hyperuricemia and CHD were identified by searching major electronic databases using the medical subject headings and keywords without language restriction (through February 2009). Only prospective cohort studies were included if they had data on CHD incidences or mortalities related to serum uric acid levels in adults.

Results

Twenty‐six eligible studies of 402,997 adults were identified. Hyperuricemia was associated with an increased risk of CHD incidence (unadjusted risk ratio [RR] 1.34, 95% confidence interval [95% CI] 1.19–1.49) and mortality (unadjusted RR 1.46, 95% CI 1.20–1.73). When adjusted for potential confounding, the pooled RR was 1.09 (95% CI 1.03–1.16) for CHD incidence and 1.16 (95% CI 1.01–1.30) for CHD mortality. For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR for CHD mortality was 1.12 (95% CI 1.05–1.19). Subgroup analyses showed no significant association between hyperuricemia and CHD incidence/mortality in men, but an increased risk for CHD mortality in women (RR 1.67, 95% CI 1.30–2.04).

Conclusion

Hyperuricemia may marginally increase the risk of CHD events, independently of traditional CHD risk factors. A more pronounced increased risk for CHD mortality in women should be investigated in future research.     

Synergistic effects of depressed mood and obesity on long-term cardiovascular risks in 1510 obese men and women: results from the MONICA-KORA Augsburg Cohort Study 1984-1998

OBJECTIVE: To examine the contribution of depressed mood in obese subjects on the prediction of a future coronary heart disease event (CHD). DESIGN: A prospective population-based cohort study of three independent cross-sectional surveys with 6239 subjects, 45-74 years of age and free of diagnosed CHD, stroke and cancer. During a mean follow-up of 7 years, 179 CHD events occurred among men and 50 events among women. SUBJECTS: A total of 737 (23%) male and 773 (26%) female subjects suffering from obesity (BMI >or=30 kg/m2). MEASUREMENTS: Body weight determined by trained medical staff following a standardized protocol; standardized questionnaires to assess subsyndromal depressive mood and other psychosocial features. RESULTS: The main effect of obesity to predict a future CHD (hazard ratio, HR=1.38, 95% CI 1.03-1.84; P=0.031) and the interaction term of obesity by depression (HR=1.73, 95% CI 0.98-3.05; P=0.060) were borderline significant, both covariate adjusted for multiple risk factors. Relative to the male subgroup with normal body weight and no depression, the male obese group with no depression was not at significantly increased risk for CHD events (HR=1.17, 95% CI 0.76-1.80; P=0.473) whereas CHD risk in males with both obesity and depressed mood was substantially increased (HR=2.32, 95% CI 1.45-3.72, P>0.0001). The findings for women were similar, however, not significant probably owing to lack of power associated with low event rates. Combining obesity and depressed mood resulted in a relative risk to suffer from a future CHD event of HR 1.84 (95% CI 0.79-4.26; P=0.158). CONCLUSIONS: Depressed mood substantially amplifies the CHD risk of middle-aged obese, but otherwise apparently healthy men. The impact of depression on the obesity risk in women is less pronounced.     

Depressive symptoms and development of coronary heart disease events: the Italian longitudinal study on aging

BACKGROUND: Studies on the association between depressive symptomatology (DS) and cardiovascular events and mortality in elderly persons have yielded contradictory findings. To address this issue, the authors assessed DS and an extensive array of sociodemographic, behavioral, and biological variables in the largest population-based sample of older Italians ever studied and analyzed their association with coronary heart disease (CHD) morbidity and total number of deaths. METHODS: This prospective, community-based cohort study included a sample of 5632 Italians, 65 years and older, who were recruited from the demographic registries of eight municipalities in Italy. Depressive symptomatology was assessed using the Geriatric Depression Scale, and a score > or =10 was used to indicate the presence of DS. All traditional cardiovascular disease risk factors were assessed at baseline, through questionnaires, blood tests, and physical examinations. The outcomes were CHD fatal and nonfatal events and total number of deaths. The association of the predictive variables with the outcomes was assessed using different Cox models. RESULTS: Baseline DS was associated with a higher incidence of fatal and nonfatal CHD events (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.06-2.60) and with cardiovascular mortality in men (HR, 2.49; 95% CI, 1.60-3.87) and with total mortality in men (HR, 2.02; 95% CI, 1.58-2.58) and women (HR, 1.43; 95% CI, 1.04-1.95) at the 4-year follow-up assessment. This association was observed after adjusting for a vast array of potential confounding variables, including major chronic conditions. CONCLUSIONS: Depressive symptomatology confers an increased risk for CHD in men and for total mortality in men and women but is not explained by health behaviors, social isolation, or biological or clinical determinants.     

Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus: a meta-analysis

BACKGROUND: Most studies suggest that diabetes is a stronger coronary heart disease (CHD) risk factor for women than men, but few have adjusted their results for classic CHD risk factors: age, hypertension, total cholesterol level, and smoking. OBJECTIVE: To establish an accurate estimate of the odds ratio for fatal and nonfatal CHD due to diabetes in both men and women. METHODS: We compared the summary odds ratio for CHD mortality and the absolute rates of CHD mortality in men and women with diabetes. We searched the MEDLINE and Cochrane Collaboration databases and bibliographies of relevant articles and consulted experts. Studies that included a nondiabetic control group and provided sex-specific adjusted results for CHD mortality, nonfatal myocardial infarction, and cardiovascular or all-cause mortality were included. Of 4578 articles identified, 232 contained primary data, and 182 were excluded. Two reviewers recorded data on study characteristics, quality, and outcomes from 50 studies. RESULTS: Sixteen studies met all inclusion criteria. In unadjusted and age-adjusted analyses, odds of CHD death were higher in women than men with diabetes. From 8 prospective studies, the multivariate-adjusted summary odds ratio for CHD mortality due to diabetes was 2.3 (95% confidence interval, 1.9-2.8) for men and 2.9 (95% confidence interval, 2.2-3.8) for women. There were no significant sex differences in the adjusted risk associated with diabetes for CHD mortality, nonfatal myocardial infarction, and cardiovascular or all-cause mortality. Absolute CHD death rates were higher for diabetic men than women in every age strata except the very oldest. CONCLUSIONS: The excess relative risk of CHD mortality in women vs men with diabetes was absent after adjusting for classic CHD risk factors, but men had more CHD deaths attributable to diabetes than women.     

Complement factor H (Y402H) polymorphism and risk of coronary heart disease in US men and women.

AIMS: Complement factor H (CFH) Y402H polymorphism is located in a region that binds C-reactive protein and may affect inflammatory processes and risk of coronary heart disease (CHD). We assessed the association between Y402H and risk of CHD in nested case-control studies among two large prospective cohorts of US male health professionals and female nurses. METHODS AND RESULTS: Among participants who were disease-free at baseline, we confirmed 266 (men) and 249 (women) incident CHD deaths and non-fatal myocardial infarctions (MIs) over 6 and 8 years of follow-up, respectively. Using risk-set sampling, controls were matched 2:1 on the basis of age, smoking, and date of blood draw. Comparing homozygous HH with YY, the relative risk (RR) of CHD was 0.94 [95% confidence interval (CI) 0.59-1.49] among men and 0.51 (95% CI 0.29-0.89) among women (pooled RR 0.73, 95% CI 0.51-1.04). The HH genotype was inversely associated with CHD among those <65 years at onset (men: RR 0.39, 95% CI 0.16-0.95; women: 0.21, 95% CI 0.07-0.65; pooled: 0.30, 95% CI 0.15-0.61), but not among those > or =65 years (pooled RR 1.09, 95% CI 0.71-1.68). CONCLUSION: CFH Y402H was inversely associated with CHD among women, but not men. This inverse association was observed in both populations with earlier age of CHD.     

Persistent depression affects adherence to secondary prevention behaviors after acute coronary syndromes

BACKGROUND: The persistence of depressive symptoms after hospitalization is a strong risk factor for mortality after acute coronary syndromes (ACS). Poor adherence to secondary prevention behaviors may be a mediator of the relationship between depression and increased mortality. OBJECTIVE: To determine whether rates of adherence to risk reducing behaviors were affected by depressive status during hospitalization and 3 months later. DESIGN: Prospective observational cohort study. SETTING: Three university hospitals. PARTICIPANTS: Five hundred and sixty patients were enrolled within 7 days after ACS. Of these, 492 (88%) patients completed 3-month follow-up. MEASUREMENTS: We used the Beck Depression Inventory (BDI) to assess depressive symptoms in the hospital and 3 months after discharge. We assessed adherence to 5 risk-reducing behaviors by patient self-report at 3 months. We used chi2 analysis to compare differences in adherence among 3 groups: persistently nondepressed (BDI < 10 at hospitalization and 3 months); remittent depressed (BDI > or = 10 at hospitalization; < 10 at 3 months); and persistently depressed patients (BDI > or = 10 at hospitalization and 3 months). RESULTS: Compared with persistently nondepressed, persistently depressed patients reported lower rates of adherence to quitting smoking (adjusted odds ratio [OR] 0.23, 95% confidence interval [95% CI] 0.05 to 0.97), taking medications (adjusted OR 0.50, 95% CI 0.27 to 0.95), exercising (adjusted OR 0.57, 95% CI 0.34 to 0.95), and attending cardiac rehabilitation (adjusted OR 0.5, 95% CI 0.27 to 0.91). There were no significant differences between remittent depressed and persistently nondepressed patients. CONCLUSIONS: Persistently depressed patients were less likely to adhere to behaviors that reduce the risk of recurrent ACS. Differences in adherence to these behaviors may explain in part why depression predicts mortality after ACS.     

Sex differences in risk for coronary heart disease mortality associated with diabetes and established coronary heart disease

BACKGROUND: The sex-specific independent effect of diabetes mellitus and established coronary heart disease (CHD) on subsequent CHD mortality is not known. METHODS: This is an analysis of pooled data (n = 5243) from the Framingham Heart Study and the Framingham Offspring Study with follow-up of 20 years. At baseline (1971-1975), 134 men and 95 women had diabetes, while 222 men and 129 women had CHD. Risk for CHD death was analyzed by proportional hazards models, adjusting for age, hypertension, serum cholesterol levels, smoking, and body mass index. The comparative effect of established CHD vs diabetes on the risk of CHD mortality was tested by testing the difference in log hazards. RESULTS: The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for death from CHD were 2.1 (95% CI, 1.3-3.3) in men with diabetes only, and 4.2 (95% CI, 3.2-5.6) in men with CHD only compared with men without diabetes or CHD. The HR for CHD death was 3.8 (95% CI, 2.2-6.6) in women with diabetes, and 1.9 (95% CI, 1.1-3.4) in women with CHD. The difference between the CHD and the diabetes log hazards was +0.73 (95% CI, 0.72-0.75) in men and -0.65 (95% CI, -0.68 to -0.63) in women. CONCLUSIONS: In men, established CHD signifies a higher risk for CHD mortality than diabetes. This is reversed in women, with diabetes being associated with greater risk for CHD mortality. Current treatment recommendations for women with diabetes may need to be more aggressive to match CHD mortality risk.     

Male pattern baldness and coronary heart disease: the Physicians' Health Study

OBJECTIVE: To examine the association between male pattern baldness and the risk of coronary heart disease (CHD) events. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study among 22,071 US male physicians aged 40 to 84 years enrolled in the Physicians' Health Study. Of these, 19,112 were free of CHD at baseline and completed a questionnaire at the 11-year follow-up concerning their pattern of hair loss at age 45 years. Response options included no hair loss, frontal baldness only, or frontal baldness with mild, moderate, or severe vertex baldness. MAIN OUTCOME MEASURES: Coronary heart disease events defined as nonfatal myocardial infarction (MI), angina pectoris, and/or coronary revascularization. RESULTS: During 11 years of follow-up, we documented 1446 CHD events in this cohort. Compared with men with no hair loss, those with frontal baldness had an age-adjusted relative risk (RR) of CHD of 1.09 (95% confidence interval [CI], 0.94-1.25), while those with mild, moderate, or severe vertex baldness had RRs of 1.23 (95% CI, 1.05-1.43), 1.32 (95% CI, 1.10-1.59), and 1.36 (95% CI, 1.11-1.67), respectively (P for trend, <.001). Multivariate adjustment for age, parental history of MI, height, body mass index (weight in kilograms divided by the square of the height in meters as a continuous variable), smoking, history of hypertension, diabetes, high cholesterol level, physical activity, and alcohol intake did not materially alter these associations. Results were similar when nonfatal MI, angina, and coronary revascularization were examined separately, and when events were analyzed among men older and younger than 55 years at baseline. Vertex baldness was more strongly associated with CHD risk among men with hypertension (multivariate RR, 1.79; 95% CI, 1.31-2.44) or high cholesterol levels (multivariate RR, 2.78; 95% CI, 1.09-7.12). CONCLUSION: Vertex pattern baldness appears to be a marker for increased risk of CHD events, especially among men with hypertension or high cholesterol levels.     

Coronary heart disease among diabetic and nondiabetic people - socioeconomic differences in incidence, prognosis and mortality

OBJECTIVE: To investigate coronary heart disease (CHD) morbidity and mortality and their patterning by socioeconomic status among diabetic and nondiabetic individuals in Finland. METHODS: All diabetic persons aged 35-74 years entitled to free anti-diabetic medication were drawn from the 1991-1996 national health insurance files along with nondiabetic referents. Outcome events for up to 6 years of follow-up, corresponding to 418,987 and 867,813 person-years in diabetic and nondiabetic people, respectively, were identified from national health insurance, hospital discharge and causes of death registers using personal identification codes. RESULTS: The annual CHD incidence for diabetic women and men was 2.7% and 3.7%, respectively, corresponding to relative risks of 3.55 (95% CI: 3.43-3.67) and 2.64 (95% CI: 2.56-2.72) compared to nondiabetic persons. The impact of diabetes on CHD mortality was greater, with relative death rates of 6.04 and 3.42 for women and men, respectively. CHD mortality and incidence displayed systematic socioeconomic trends with higher rates among worse-off diabetic and nondiabetic people, although gradients were generally steeper for nondiabetics. In the diabetic population, socioeconomic differences were rather similar for sudden CHD deaths and nonfatal CHD incident cases. For both genders, socioeconomic differences in mortality after CHD diagnosis were small in both diabetic and nondiabetic persons, except for the lowest compared to the highest income quintile. CONCLUSIONS: Socioeconomic CHD mortality differences among diabetic people in Finland were mainly explained by higher CHD incidence and particularly sudden deaths without prior CHD diagnosis. No systematic socioeconomic differences were found in long-term prognosis after CHD diagnosis.     

Hypertension as a risk factor for cardiovascular morbidity and mortality in an elderly German population; the prospective STEPHY II study. Starnberg Study on Epidemiology of Parkinsonism and Hypertension in the Elderly.

AIM: To prospectively study the relationship between blood pressure levels and subsequent cardiovascular morbidity and mortality in a population aged 65 years and older. METHODS: Participants of the 1992 baseline survey of the population-based Starnberg Study on Epidemiology of Parkinsonism and Hypertension in the Elderly (STEPHY, 394 men and 588 women above age 65) were followed up for 3 years. Total mortality was assessed by official death data. Cardiovascular morbidity, that is, the occurrence of non-fatal events (new cases of acute myocardial infarction, angina pectoris, stroke, and heart failure) could be assessed in 681 of the 863 survivors by a second interview and analysis of general practitioners' records. The mortality and morbidity risks were compared for hypertensives (baseline blood pressure > or = 160/95 mmHg or antihypertensive treatment) and non-hypertensives. RESULTS: During follow-up a total of 55 men and 64 women died resulting in a 2.7-year cumulative mortality in this population of 12%. Mortality was higher in men (14%) than in women (11%). Hypertensives had no increased risk of death compared to non-hypertensives (adjusted relative risk (RR)=0. 92; 95% CI: 0.48-1.76 for men and RR=1.36; 95% CI 0.67-2.78 for women). This was confirmed in age-stratified analyses. However, among survivors hypertension was associated with a significantly higher occurrence of non-fatal cardiovascular events. After controlling for potentially confounding baseline conditions, the relative risk for any event (RR=1.44; 95% CI: 1.04-2.0) and, in particular, of acute myocardial infarction (RR=5.5; 95% CI: 1.6-18. 7) was raised among hypertensives. Higher rates for angina pectoris (RR=1.4; 95% CI: 0.9-2.4) and heart failure (RR 1.7; 95% CI: 0.9-2. 9) were of borderline significance. Positive risk associations were confined to the age group 65 to 75 years and not detected at higher ages. CONCLUSION: This study demonstrates for a Central European population older than 65 years the impact of hypertension as a risk factor for cardiovascular and cerebrovascular morbidity. To address the issue that risk of death showed no significant relationship to blood pressure, a longer follow-up period might be necessary.     

Depression as a risk factor for mortality after acute myocardial infarction

The ENRICHD clinical trial, which compared an intervention for depression and social isolation to usual care, failed to decrease the rate of mortality and recurrent acute myocardial infarction (AMI) in post-AMI patients. One explanation for this is that depression was not associated with increased mortality in these patients. The purpose of this study was to determine if depression was associated with an increased risk of mortality in a subsample of the ENRICHD trial's depressed patients compared with a group of nondepressed patients recruited for an ancillary study. Three hundred fifty-eight depressed patients with an acute AMI from the ENRICHD clinical trial and 408 nondepressed patients who met the ENRICHD medical inclusion criteria were followed for up to 30 months. There were 47 deaths (6.1%) and 57 nonfatal AMIs (7.4%). After adjusting for other risk factors, depressed patients were at higher risk for all-cause mortality (hazard ratio 2.4, 95% confidence interval 1.2 to 4.7) but not for nonfatal recurrent infarction (hazard ratio 1.2, 95% confidence interval 0.7 to 2.0) compared with nondepressed patients. In conclusion, depression was an independent risk factor for death after AMI, but it did not have a significant effect on mortality until nearly 12 months after the acute event, nor did it predict nonfatal recurrent infarction.     

Menstrual cycle irregularity and risk for future cardiovascular disease

Cross-sectional studies suggest that women who have irregular menstrual cycles and hyperandrogenism may be at increased risk for cardiovascular disease (CVD). However, prospective data are lacking on the relationship between menstrual cycle irregularity and subsequent CVD risk. The objective of this study was to assess prospectively the risk for coronary heart disease (CHD) and stroke associated with a history of irregular menstrual cycles. The study design was a prospective cohort study of 82,439 female nurses who provided information in 1982 on prior menstrual regularity (at ages 20-35 yr) and were followed through 1996 for cardiovascular events. Incident reports of nonfatal myocardial infarction, fatal CHD, and nonfatal and fatal stroke were made. Medical records were reviewed for confirmation. During 14 yr (1,155,915 person-yr) of follow-up, there were 1417 incident cases of CHD and 838 incident cases of stroke, including 471 cases of ischemic stroke. Compared with women reporting a history of very regular menstrual cycles, women reporting usually irregular or very irregular cycles had an increased risk for nonfatal or fatal CHD [age-adjusted relative risks (RR), 1.25 and 1.67, respectively; 95% confidence intervals (CI), 1.07-1.47 and 1.35-2.06, respectively]. Increased risks for CHD associated with prior cycle irregularity remained significant after adjustment for body mass index and several potential confounders. There was a nonsignificant increase in overall stroke risk (RR, 1.30; 95% CI = 0.97-1.74) and in ischemic stroke risk (RR, 1.40; 95% CI = 0.97-2.04) associated with very irregular cycles. Menstrual cycle irregularity may be a marker of metabolic abnormalities predisposing to increased risk for CVD.     

Smoking and risk of coronary heart disease among women with type 2 diabetes mellitus

BACKGROUND: Although the association between smoking and increased risk of coronary heart disease (CHD) is well established in the general population, this relationship is less well-defined among individuals with diabetes. OBJECTIVE: To assess the relationship between cigarette smoking and risk of CHD among women with type 2 diabetes mellitus in the Nurses' Health Study cohort. METHODS: The Nurses' Health Study, a prospective cohort study of 121,700 US female registered nurses surveyed in 11 states and followed up from July 1, 1976, through July 1, 1996, involved a total of 6547 women diagnosed as having type 2 diabetes mellitus. Incident cases of CHD were our main outcome measure in this study. RESULTS: We documented 458 incident cases of CHD (200 fatal CHD-related cases and 258 nonfatal myocardial infarctions) during 20 years (68,227 person-years) of follow-up. We found a dose-response relationship between current smoking status and risk of CHD among diabetic women. Compared with never smokers, the relative risks (RRs) for CHD were 1.21 (95% confidence interval [CI], 0.97-1.51) for past smokers, 1.66 (95% CI, 1.10-2.52) for current smokers of 1 to 14 cigarettes per day, and 2.68 (95% CI, 2.07-3.48) for current smokers of 15 or more cigarettes per day in multivariate analyses (P<.001 for trend). The multivariate RR of CHD among diabetic women who had stopped smoking for more than 10 years was similar to that among diabetic women who were never smokers (RR, 1.01; 95% CI, 0.73-1.38). In secondary analyses involving diabetic and nondiabetic women, the multivariate-adjusted RR of CHD for those with diabetes who currently smoked (> or = 15 cigarettes per day) compared with those who never smoked was 7.67 (95% CI, 5.88-10.01). CONCLUSIONS: Cigarette smoking is strongly associated with an increased risk of CHD among women with type 2 diabetes mellitus. Furthermore, quitting smoking seems to decrease this excess risk substantially; women with diabetes should be strongly advised against smoking.CK     

Fluvastatin Reduces Cardiac Mortality in Patients with Coronary Heart Disease

PURPOSE: To test the effectiveness of fluvastatin, 40-80 mg, in reducing the occurrence of cardiac and all-cause mortality in patients with coronary heart disease (CHD). METHODS: Meta-analysis of all clinical trials that assessed the effects of fluvastatin in CHD patients on major adverse cardiac events (MACE) as a prespecified endpoint was performed. A pooled analysis of four studies (n = 3525) was performed on an intent-to-treat basis. Clinical endpoints were the incidence, and time to first occurrence, of MACE (cardiac death, nonfatal MI, revascularization), noncardiac death, or all-cause death. Lipid parameters were also analyzed. RESULTS: Fluvastatin treatment significantly prolonged the time to cardiac death (p = 0.0174) and the time to cardiac death or nonfatal MI (p = 0.0055) compared with placebo. Fluvastatin significantly reduced the risk of any MACE (Cox risk ratio [RR], 0.85; 95% confidence interval [CI], 0.73-0.98), cardiac death (RR, 0.53; 95% CI, 0.31-0.90), cardiac death or MI (RR, 0.66; 95% CI, 0.49-0.89), all-cause death (RR, 0.65; 95% CI, 0.45-0.94) and all-cause death or MI (RR, 0.69; 95% CI, 0.53-0.90). Fluvastatin significantly lowered total cholesterol and low-density lipoprotein cholesterol levels and was well tolerated, with no cases of rhabdomyolysis in any of the studies assessed in the meta-analysis. CONCLUSIONS: This meta-analysis demonstrates clear beneficial effects of fluvastatin on cardiac and all-cause mortality in CHD patients, and supports the use of fluvastatin to reduce the incidence of MACE in a wide range of at-risk patients.     

Waist circumference,body mass index,and risk for stroke in older people: a 15 year longitudinal population study of 70- year-olds

OBJECTIVES: To investigate waist circumference (WC) and body mass index (BMI) at age 70 as risk factors for stroke. DESIGN: Cohort study of 70-year-olds with 15-year follow-up. SETTING: Geriatric Medicine Department, G?teborg University, Sweden. PARTICIPANTS: Two thousand two hundred eighty-seven (1,045 men; 1,242 women) 70-year-olds examined between 1971 and 1981 in G?teborg, Sweden. MEASUREMENTS: Cox regression model was used to calculate relative risk (RR) and 95% confidence interval (CI) for first-ever stroke (fatal and nonfatal) in reference to the lowest quartiles of WC and BMI. Tests for trend were performed fitting WC and BMI in their original continuous form. RESULTS: In men and women, RRs for stroke, in the highest WC quartile were 1.65 (95% CI = 1.08-2.51) and 1.31 (95% CI = 0.88-1.92), respectively, after adjustment for cohorts, smoking habit, coronary heart disease (CHD), diabetes mellitus, total cholesterol (TC), systolic blood pressure (SBP), and height at age 70. In men, RR for stroke in the highest BMI quartile (> or=28 kg/m2) was 1.68 (95% CI = 1.12-2.53) after adjustment for cohorts, smoking habits, CHD, diabetes mellitus, TC, and SBP at age 70. In women, adjusted RRs for stroke across the BMI quartiles were not significantly different. In men, population attributable fractions of stroke were 24.8% and 25.2% for the highest quartiles of WC and BMI, respectively. CONCLUSIONS: High WC (> or =99 cm) and BMI (> or =28 kg/m2) are risks for stroke in older men but not in older women.     

A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study

PURPOSE: To describe the effect of atrial fibrillation on long-term morbidity and mortality. SUBJECTS AND METHODS: The Renfrew/Paisley Study surveyed 7052 men and 8354 women aged 45-64 years between 1972 and 1976. All hospitalizations and deaths occurring during the subsequent 20 years were analyzed by the presence or absence of atrial fibrillation at baseline. Lone atrial fibrillation was defined in the absence of other cardiovascular signs or symptoms. Cox proportional hazards models were used to adjust for age and cardiovascular conditions. RESULTS: After 20 years, 42 (89%) of the 47 women with atrial fibrillation had a cardiovascular event (death or hospitalization), compared with 2276 (27%) of the 8307 women without this arrhythmia. Among men, 35 (66%) of 53 with atrial fibrillation had an event, compared with 3151 (45%) of 6999 without atrial fibrillation. In women, atrial fibrillation was an independent predictor of cardiovascular events (rate ratio [RR] = 3.0; 95% confidence interval [CI]: 2.1-4.2), fatal or nonfatal strokes (RR = 3.2; 95% CI: 1.0-5.0), and heart failure (RR = 3.4; 95% CI: 1.9-6.2). The rate ratios among men were 1.8 (95% CI: 1.3-2.5) for cardiovascular events, 2.5 (95% CI: 1.3-4.8) for strokes, and 3.4 (95% CI: 1.7-6.8) for heart failure. Atrial fibrillation was an independent predictor of all-cause mortality in women (RR = 2.2; 95% CI: 1.5-3.2) and men (RR = 1.5; 95% CI: 1.2-2.2). However, lone atrial fibrillation (which occurred in 15 subjects) was not associated with a statistically significant increase in either cardiovascular events (RR = 1.5; 95% CI: 0.6-3.6) or mortality (RR = 1.8; 95% CI: 0.9-3.8). CONCLUSIONS: Atrial fibrillation is associated with an increased long-term risk of stroke, heart failure, and all-cause mortality, especially in women.     

Effectiveness of statin therapy in adults with coronary heart disease

BACKGROUND: We conducted a meta-analysis of patients with coronary heart disease (CHD) to determine the effectiveness of statin therapy; whether effectiveness varied according to patient characteristics, outcomes, or pretreatment low-density lipoprotein cholesterol (LDL-C) levels; and the optimal LDL-C goal and the level at which to initiate statin therapy. METHODS: Randomized trials or systematic reviews for secondary prevention of CHD with statin therapy published between January 1966 and December 2002 were identified through MEDLINE and the Cochrane Library. Studies were included if they randomly assigned adults with CHD to statin therapy or control, enrolled at least 100 individuals per arm, reported clinical outcomes and LDL-C levels, and were published as full studies in English. Two reviewers abstracted data using a prospectively designed protocol. RESULTS: Twenty-five studies enrolling 69 511 individuals were included. Participants in 19 placebo-controlled trials had a mean age of 63 years and a mean pretreatment LDL-C level of 149 mg/dL (3.85 mmol/L); 23% were women. Statin therapy reduced CHD mortality or nonfatal myocardial infarction 25% (relative risk [RR], 0.75; 95% confidence interval [CI], 0.71-0.79), all-cause mortality 16% (RR, 0.84; 95% CI, 0.79-0.89), and CHD mortality 23% (RR, 0.77; 95% CI, 0.71-0.83). Beneficial effects were seen in women and the elderly. There were no data to determine whether lowering the LDL-C level to less than 100 mg/dL (<2.59 mmol/L) was superior to lowering it to 100 to 130 mg/dL (2.59-3.36 mmol/L). Meta-regression analyses revealed risk reductions for CHD mortality or nonfatal myocardial infarction and major vascular events across available pretreatment LDL-C levels. CONCLUSION: Statin therapy reduces mortality and morbidity in adults with CHD, even at pretreatment LDL-C levels as low as 100 mg/dL (2.59 mmol/L).     

Prevalence, incidence, predictors and outcome of type 2 diabetes in Turkey.

OBJECTIVES: To investigate prospectively the incidence, certain predictors and outcomes of type 2 diabetes (DM), as well as to determine its prevalence cross-sectionally, in a representative sample of Turkish men and women. METHODS: Prospective evaluation of 3401 male and female participants (aged 48.2 +/-12 years). Follow-up constituted 19,050 person-years. Individuals with DM were diagnosed with criteria of the American Diabetes Association. Fatal and nonfatal coronary heart disease (CHD) was identified by clinical findings and Minnesota coding of resting electrocardiograms. Cut-points of > or = 95 cm in males and > or = 91 cm in females were selected for abdominal obesity. For prospective evaluations, cases with DM or CHD were excluded. RESULTS: Prevalence of DM in Turkish adults was estimated as 2.89 million (11.0% of the population aged > or = 35 years). Over a mean follow-up of 5.9 years, incident DM developed in 223 subjects, yielding an incidence per 1000 person-years of 11.0 in women and 12.4 in men. This corresponded to a 300,000 annual incidence. Following risk parameter levels but not HDL-cholesterol were significantly elevated at baseline in subjects developing DM compared to those without: age (5 years), waist girth (7 cm), blood pressure (12/6 mmHg), apolipoprotein B (7 mg/dl), total cholesterol (14 mg/dl), and fasting triglycerides (only in women, 52 mg/dl). Abdominal obesity (RR 2.61 [95%CI 1.87; 3.63]) and age in both genders, hypertension (RR 1.81 [95%CI 1.10; 2.98]) and low HDL-cholesterol in men alone were significant independent predictors of DM. Diabetes mellitus was a significant and independent predictor of fatal and nonfatal CHD, with a RR of 1.81 (95%CI 1.19; 2.75), after adjustment for sex, age, hypertension, waist circumference, serum total cholesterol and smoking status. CONCLUSIONS: The annual incidence of DM in Turkey rises very rapidly, currently stands at 300,000, and, hence, its prevalence also rises correspondingly. Insulin resistance appears to be a weak determinant of DM in Turkish women while abdominal obesity is the main determinant. Multivariately adjusted DM is a significant independent predictor of fatal and nonfatal CHD. These observations emphasize that measures to reverse or stop the "epidemic" of abdominal obesity are severely required.     

Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies

OBJECTIVE: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. BACKGROUND: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. DESIGN: Systematic review and meta-analysis of longitudinal studies. METHODS: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. RESULTS: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. CONCLUSIONS: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.