C-reactive protein, depressed mood, and the prediction of coronary heart disease in initially healthy men: results from the MONICA-KORA Augsburg Cohort Study 1984-1998.

AIMS: C-reactive protein and depressive mood (DM) are novel risk factors for coronary heart disease (CHD). The goal of the present study was to assess possible combined effects of these factors on the prediction of a future fatal and non-fatal coronary event. METHODS AND RESULTS: Baseline highly sensitive (hs) C-reactive protein and DM were analysed in 3021 apparently healthy male subjects aged 45-74 from three subsequent population based surveys (1984-95) of the MONICA-KORA Augsburg Cohort Study. During a median follow-up period of 7.7 years (IQR=6.9 years), 165 CHD events occurred. Risks of CHD were estimated from Cox proportional hazard models adjusted for age and survey and multiple risk factors. The age and survey adjusted interaction term of continuous hs-C-reactive protein by DM disclosed a significant effect (HR 1.03; 95% CI 1.00-1.06; P=0.037). A stratified analysis of subpopulations with (n=986) and without (n=2035) DM revealed that high hs-C-reactive protein (>3 mg/L) was predictive in the group with DM (HR 2.69; 95% CI 1.32-5.47) but was not significant in the low-level depression group (HR 1.55; 95% CI 0.89-2.69). Relative to the low C-reactive protein/no depression subgroup (n=712), high C-reactive protein/no depression (n=565) did not significantly predict a future CHD event. However, combined high C-reactive protein and DM (n=282) significantly predicted future CHD events (HR 2.91; 95% CI 1.25-2.18; P>0.0001). CONCLUSION: In apparently healthy men, a DM substantially increases the power of elevated C-reactive protein to predict a subsequent myocardial infarction. Both conditions may share a common underlying mechanism.     

Depression as an antecedent to heart disease among women and men in the NHANES I study. National Health and Nutrition Examination Survey

BACKGROUND: Depression predicts morbidity and mortality among individuals who have coronary heart disease (CHD), and there is increasing evidence that depression may also act as an antecedent to CHD. The studies that have reported a relationship between depression and CHD incidence or mortality either were restricted to men only or analyzed women and men together. The present investigation was conducted to evaluate the differential effect depression may have on CHD incidence and mortality in women and men. RESEARCH METHODS: We analyzed data from 5007 women and 2886 men enrolled in the first National Health and Nutrition Examination Survey (NHANES I) who were free of CHD at the 1982-1984 interview and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D). Participants were evaluated from the 1982 interview date either until the end of the study (1992 interview date) or until the occurrence of a CHD event. Using CHD incidence and CHD mortality (International Classification of Disease, Ninth Revision, codes 410-414) as the outcome variables, Cox proportional hazards regression models were developed to evaluate the relative risk (RR) of CHD incidence and mortality in the depressed women and men separately, controlling for standard CHD risk factors. RESULTS: The women experienced 187 nonfatal and 137 fatal events, compared with 187 nonfatal and 129 fatal events among the men. The adjusted RR of CHD incidence among depressed women was 1.73 (95% confidence internal [CI], 1.11-2.68) compared with nondepressed women. Depression had no effect on CHD mortality in the women (RR, 0.74; 95% CI, 0.40-1.48). The adjusted RR of CHD incidence among depressed men was 1.71 (95% CI, 1.14-2.56) compared with nondepressed men. Depressed men also had an increased risk of CHD mortality compared with their nondepressed counterparts, with an adjusted RR of 2.34 (95% CI, 1.54-3.56). CONCLUSIONS: In this sample, while controlling for possible confounding factors, depression was associated with an increased risk of CHD incidence in both men and women, as well as CHD mortality in men. Depression had no effect on CHD mortality in women.     

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.     

Obesity and depression: results from the longitudinal Northern Finland 1966 Birth Cohort Study

OBJECTIVE: To examine the association between body size and depression in a longitudinal setting and to explore the connection between obesity and depression in young adults at the age of 31 years. DESIGN: This study forms part of the longitudinal Northern Finland 1966 Birth Cohort Study (N = 12,058). The follow-up studies were performed at 14 and 31 years. Data were collected by postal inquiry at 14 years and by postal inquiry and clinical examination at 31 years. SUBJECTS: A total of 8,451 subjects (4,029 men and 4,422 women) who gave a written informed consent and information on depression by three depression indicators at 31 years. MEASUREMENTS: Body size at 14 (body mass index (BMI) and 31 (BMI and waist-to-hip ratio (WHR)) years and depression at 31 years by three different ways: depressive symptoms by the HSCL-25-depression questionnaire (HSCL-25), the use of antidepressants and self-reported physician-diagnosed depression. RESULTS: Obesity at 14 years associated with depressive symptoms at 31 years; among male subjects using the cutoff point 2.01 in the HSCL-25 (adjusted odds ratio (OR) 1.97, 95% CI 1.06-3.68), among female subjects using the cutoff point 1.75 (adjusted OR 1.64, 95% CI 1.16-2.32). Female subjects who were obese both at baseline and follow-up had depressive symptoms relatively commonly (adjusted OR 1.40, 95% CI 1.06-1.85 at cutoff point 1.75); a similar association was not found among male subjects. The proportion of those who used antidepressants was 2.17-fold higher among female subjects who had gained weight compared to female subjects who had stayed normal-weighted (adjusted OR 2.17, 95% CI 1.28-3.68). In the cross-sectional analyses male subjects with abdominal obesity (WHR >or=85th percentile) had a 1.76-fold risk of depressive symptoms using the cutoff 2.01 in the HSCL-25 (adjusted OR 1.76, 95% CI 1.08-2.88). Abdominally obese male subjects had a 2.07-fold risk for physician-diagnosed depression (adjusted OR 2.07, 95% CI 1.23-3.47) and the proportion of those who used antidepressants was 2.63-fold higher among obese male subjects than among male subjects without abdominal obesity (adjusted OR 2.63, 95% CI 1.33-5.21). Abdominal obesity did not associate with depression in female subjects. CONCLUSION: Obesity in adolescence may be associated with later depression in young adulthood, abdominal obesity among male subjects may be closely related to concomitant depression, and being overweight/obese both in adolescence and adulthood may be a risk for depression among female subjects.     

Outcomes of obese and nonobese patients undergoing revision total hip arthroplasty

OBJECTIVE: To evaluate the effect of obesity on the incidence of adverse events (surgical site infection, dislocation, re-revision, or > or =1 adverse event), functional outcome, residual pain, and patient satisfaction after revision total hip arthroplasty (THA). METHODS: We conducted a university hospital-based prospective cohort study including 52 obese and 152 nonobese patients with revision THA performed between 1996 and 2006. We used incidence rates, rate ratios, and hazard ratios (HRs) to compare the incidence of events in obese and nonobese patients and in 4 body mass index (BMI) categories (<25, 25-29.9, 30-34.9, > or =35). Functional outcome and pain were measured 5 years postoperative using the Harris Hip Score. RESULTS: The incidence rate for > or =1 complication increased with rising BMI (1.8, 3.4, 10.3, and 17.9 cases/100 person-years). The increase was small between normal and overweight patients (adjusted HR 1.5, 95% confidence interval [95% CI] 0.5, 4.7), significantly greater with BMI 30-34.9 (adjusted HR 4.5, 95% CI 1.4, 14.0), and most evident with BMI > or =35 (adjusted HR 10.9, 95% CI 2.9, 41.1). The adjusted HR for surgical site infection (obese versus nonobese) was 4.1 (95% CI 1.1, 15.0) and for dislocation 3.5 (95% CI 1.3, 9.3). Eighty patients had a followup visit at 5 years. Obese patients had moderately lower functional results and higher levels of residual pain, but patient satisfaction was almost similar. CONCLUSION: Revision THA is technically challenging, particularly in obese patients, probably due to more difficult anatomic conditions. We found an increased risk of adverse events, notably surgical site infection and dislocation in these patients.     

Anthropometric characteristics as predictors of coronary heart disease in women

Objectives. Obesity and other anthropometric measures are clearly related to risk of coronary heart disease (CHD), although debate remains as to which measures are most important and how the impact of obesity varies over the life course. Aim. We aimed to investigate these issues in a large cohort of Swedish women. The Women’s Lifestyle and Health Cohort Study includes 49 259 women, aged 30–50 years at baseline (1991–1992) when an extensive questionnaire was completed. Methods. Women were given standard instructions for self‐measurement of anthropometric characteristics. Women were followed through linkages to national registries until December 2003, during which time 256 cases of incident fatal CHD or nonfatal myocardial infarction occurred. Results. Waist circumference was associated with increased CHD risk after multivariate adjustment for confounders (HR = 1.9; 95% CI:1.1–3.3; highest versus lowest quartile), whereas height, weight and hip circumference were not. Measures of obesity were strongly related to CHD, and after mutual adjustment, waist‐hip ratio (HR = 1.9, 95% CI: 1.2–3.2) was more closely related to CHD risk than BMI (HR = 1.5, 95% CI: 1.0–2.4). Risk of CHD was increased in women who remained heavy, those who were heavy at age 18, and those with low birth weight. Conclusions. In conclusion, there is strong evidence for supporting control of obesity, in particular avoidance of abdominal obesity, as a strategy to prevent CHD.     

Primary risk factors influence risk of recurrent myocardial infarction/death from coronary heart disease: results from the Stockholm Heart Epidemiology Program (SHEEP).

BACKGROUND: Prognosis after a first myocardial infarction (MI) is influenced by primary risk factors as well as secondary risk factors. There is still a lack of follow-up studies of well-characterized patient cohorts assessing the relative importance of these factors. DESIGN: A cohort of 1635 patients (aged 45-70 years) surviving at least 28 days after a first MI were followed for 6-9 years with regard to recurrent MI/fatal coronary heart disease (CHD). Data were collected through questionnaires, physical examinations, and medical records. METHODS: Hazard ratios (HR) with 95% confidence intervals (CI) for different risk factors were calculated using the Cox proportional hazard model. RESULTS: Of the primary risk factors, diabetes in both sexes was the most important predictor of recurrent MI/fatal CHD, multivariate-adjusted HR in men 1.6 (95% CI; 1.0-2.4) and in women 2.5 (95% CI; 0.9-6.9). Other primary risk factors with prognostic influence were job strain, HR 1.5 (95% CI; 1.0-2.1), and central obesity, HR 1.4 (95% CI; 1.0-2.0), in men and a low level of apolipoprotein A1, HR 2.3 (95% CI; 1.1-5.0), and high-density lipoprotein cholesterol, HR 1.9 (95% CI; 0.9-4.1), in women. The secondary risk factors most detrimental for prognosis were heart failure in men, HR 2.2 (95% CI; 1.2-4.0), and a high peak acute cardiac enzyme level in women, HR 4.4 (95% CI; 2.0-9.7). CONCLUSIONS: Long-term follow-up of patients who survived at least 28 days after a first MI shows that several primary cardiovascular risk factors, particularly diabetes, contribute to the increased risk of recurrent MI/fatal CHD.     

Mild renal insufficiency as a cardiovascular risk factor in non-proteinuric type II diabetes

OBJECTIVES: To evaluate cardiovascular risk according to baseline renal function in a group of non-proteinuric type II diabetic patients. MATERIAL AND METHODS: Prospective study with a follow-up of 423 non-proteinuric type II diabetic patients with creatinine <150 micromol/l for an average of 4.7 years (S.D. 1.55). Creatinine clearance (CC) was estimated using the Cockcroft-Gault formula and expressed in millilitre per minute. The hazard ratio (HR) associated with each millilitre per minute decrease in baseline CC on fatal or non-fatal cardiovascular events and total mortality was evaluated using the Cox regression model. RESULTS: Baseline creatinine was 89 micromol/l (S.D. 15.9) and CC was 69.5 ml/min (S.D. 20). There were 63 cardiovascular events (15 unstable angina, 10 non-fatal myocardial infarctions, 25 non-fatal strokes, two amputations, nine fatal myocardial infarctions and two fatal strokes) and 39 total deaths (11 for cardiovascular causes). The cardiovascular event rate was 31.7/1000 patient-years and the total mortality rate was 19.6/1000 patient-years. The independent predictors of cardiovascular events were: CC (HR=1.035; confidence interval (CI) 95% 1.02-1.05; P<0.0001), total cholesterol/HDL cholesterol ratio (HR=1.25; CI 95% 1.1-1.4; P=0.0008), baseline coronary heart disease (HR=2.05; CI 95% 1.07-3.9; P=0.04) and baseline microalbuminuria (HR=2.3; CI 95% 1.3-3.8; P=0.003). The independent total mortality predictors were: CC (HR=1.04; CI 95% 1.02-1.08; P<0.0001), male (HR=2.1; CI 95% 1.1-4; P=0.027) and baseline microalbuminuria (HR=2.1; CI 95% 1.1-4;P=0.03). CONCLUSIONS: Mild renal insufficiency increases cardiovascular risk in non-proteinuric patients with type II diabetes.     

Thrombosis prevention trial: compliance with warfarin treatment and investigation of a retained effect

BACKGROUND: The Thrombosis Prevention Trial was a primary prevention factorial trial that reported a reduction in the risk of coronary heart disease (CHD) with warfarin and/or aspirin. This article examines compliance (duration of treatment) with warfarin treatment and whether warfarin has a retained effect. METHODS: Risk of CHD while complying with warfarin treatment was compared with risk of CHD in all participants randomized to placebo. Simultaneously, risk of CHD in ex-warfarin users was compared with controls receiving placebo to determine the possibility of a retained effect. A second analysis, preserving the advantage of randomization, estimated the potential increase in the time to a CHD event in patients randomized to active treatment compared with patients randomized to placebo, if all patients in both active and placebo groups had fully complied with the trial treatment. RESULTS: Risk of all CHD while complying with warfarin treatment was associated with a hazard ratio (HR) of 0.75 (95% confidence interval [CI], 0.60-0.94), which was lower than the HR obtained by intention-to-treat analysis (0.79; 95% CI, 0.65-0.96). Regarding fatal cases of CHD, the HR was 0.49 (95% CI, 0.32-0.75) while compliant with warfarin treatment, which is also lower than the HR obtained by intention-to-treat analysis (0.61, 95% CI, 0.43-0.85). Ex-warfarin users had a retained risk reduction of 23% for all CHD (0.77; 95% CI, 0.58-1.02) and of 34% for fatal events (0.66; 95% CI, 0.41-1.04). Expected survival time to a CHD event if patients randomized to warfarin had fully complied with treatment was 1.39 times greater (95% CI, 1.12-1.69) than if patients randomized to placebo had fully complied with placebo, whereas for fatal CHD the relative increase in survival time was 2.04 times greater for the former (95% CI, 1.43-2.86). CONCLUSIONS: Full compliance with warfarin treatment may lower by 50% the risk of fatal CHD. There is also evidence of a retained effect. These results strengthen previous evidence of the potential benefits of low-intensity oral anticoagulation with warfarin.     

Heart rate adjustment of exercise-induced ST segment depression. Improved risk stratification in the Framingham Offspring Study

BACKGROUND. Simple heart rate adjustment of ST segment depression during exercise (delta ST/HR index) and the pattern of ST depression as a function of heart rate during exercise and recovery (the rate-recovery loop) have been shown to improve the ability of the exercise electrocardiogram to detect the presence of coronary heart disease (CHD), but the performance of these methods for the prediction of future coronary events remains to be examined. METHODS AND RESULTS. We compared the delta ST/HR index and the rate-recovery loop with standard electrocardiographic criteria for prediction of CHD events in 3,168 asymptomatic men and women in the Framingham Offspring Study who underwent treadmill exercise electrocardiography and who, at entry, were free of clinical and electrocardiographic evidence of CHD. After a mean follow-up of 4.3 years, there were 65 new CHD events: four sudden deaths, 24 new myocardial infarctions, and 37 incident cases of angina pectoris. When a Cox proportional hazards model with adjustment for age and sex was used, a positive exercise electrocardiogram by standard criteria (greater than or equal to 0.1 mV horizontal or downsloping ST segment depression) was not predictive of new CHD events (chi 2 = 0.40, p = 0.52). In contrast, stratification according to the presence or absence of a positive delta ST/HR index (greater than or equal to 1.6 microV/beat/min) and a positive (counterclockwise) rate-recovery loop was associated with CHD event risk (chi 2 = 9.45, p less than 0.01) and separated subjects into three groups with varying risks of coronary events: high risk, when both tests were positive (relative risk 3.6; 95% confidence interval, 2.4-5.4); intermediate risk, when either the delta ST/HR index or the rate-recovery loop was positive (relative risk, 1.9; 95% confidence interval, 1.3-2.8); and low risk, when both tests were negative. After multivariate adjustment for age, sex, smoking, total cholesterol level, fasting glucose level, diastolic blood pressure, and electrocardiographic evidence of left ventricular hypertrophy, the combined delta ST/HR index and rate-recovery loop criteria remained predictive of coronary events (chi 2 = 5.45, p = 0.02). CONCLUSIONS. Heart rate adjustment of ST segment depression by the delta ST/HR index and the rate-recovery loop during exercise electrocardiography can improve prediction of future coronary events in asymptomatic men and women.     

Relative importance of atherosclerotic risk factors for coronary heart disease in Taiwan.

BACKGROUND: The relative importance of atherosclerotic risk factors, such as hypertension, dyslipidemia, diabetes and smoking, was associated with cardiovascular events and varied among different ethnic groups. For a population with relatively low coronary heart disease (CHD) such as Asian-Pacific countries, it is crucial to differentiate the roles of these risk factors. METHODS: We examined the relative importance of various risk factors for CHD in a community-based cohort in Taiwan, consisting of 3602 adults aged 35 and older with a median follow-up time of 9.0 years since 1990. Regular death certificate verification and medical record reviews were performed in the follow-up activities. RESULTS: There were 85 cases defined as CHD. In the Cox proportional hazard analysis, men were at higher risk than women [hazard risk (HR)=2.22, 95% confidence interval (CI)=1.39-3.56]. Hypertension was the most common risk factor for CHD. Dyslipidemia, especially lowered high-density lipoprotein cholesterol, also played an important role (HR=2.09, 95% CI=1.33-3.29) in CHD events. Hypertension had a greater influence in males (HR=6.08, P<0.001) than in females (HR=2.80, P<0.001). No independent association was found for smoking or body mass index in cardiovascular events. CONCLUSION: This study found that in a community-based cohort, hypertension, and dyslipidemia attribute an important role to cardiovascular events.     

Hormone replacement therapy and mortality in 52- to 70-year-old women: the Kuopio Osteoporosis Risk Factor and Prevention Study

OBJECTIVES: To analyze prospectively the association between hormone replacement therapy (HRT) and mortality in women before old age. DESIGN AND METHODS: A group of 11,667 women (91% of the age cohort of the area) aged 52-62 years from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study were followed for 7 years in 1994-2001. Information about HRT use and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about deaths and causes of death from the follow-up period was obtained from the Statistics Finland. Cox's proportional-hazards models were used to calculate risk of death related to the use of HRT. RESULTS: At the start of follow-up, 2203 women had used HRT > 5 years, 3945 women < or = 5 years and 5519 women had never used it. During the follow-up, 361 deaths occurred. Compared with non-users of HRT, the adjusted hazard ratio (HR) of death from any cause was 1.05 (95% confidence interval (CI) 0.80-1.36) in women who used HRT < or = 5 years and 1.06 (95% CI 0.78-1.46) in women who used HRT > 5 years. The adjusted HR for coronary heart disease (CHD) mortality in women who used HRT < or = 5 years was 0.79 (95% CI 0.36-1.73), and in women who used HRT > 5 years, 2.16 (95% CI 0.93-4.98). For breast cancer mortality the adjusted HR for < or = 5 years of HRT use was 0.96 (95% CI 0.32-2.82) and 2.62 (95% CI 0.98-7.00) for > 5 years of HRT use. CONCLUSIONS: History of HRT use does not affect overall or CHD mortality in women. More than 5 years of HRT use may increase the risk of breast cancer mortality.     

Obesity and colorectal cancer risk： A meta-analysis of cohort studies

TO evaluate the association between obesity and colorectal cancer risk. METHODS： We searched PubMed, EMBASE, and the Cochrane Library up to January 1, 2007. Cohort studies permitting the assessment of causal association between obesity and colorectal cancer, with clear definition of obesity and well-defined outcome of colorectal cancer were eligible. Study design, sample size at baseline, mean follow-up time, co-activators and study results were extracted. Pooled standardized effect sizes were calculated.     

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.     

Body Mass Index and Survival in Men and Women Aged 70 to 75

OBJECTIVES: To examine in an older population all‐cause and cause‐specific mortality associated with underweight (body mass index (BMI)<18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), and obesity (BMI≥30.0). DESIGN: Cohort study. SETTING: The Health in Men Study and the Australian Longitudinal Study of Women's Health. PARTICIPANTS: Adults aged 70 to 75, 4,677 men and 4,563 women recruited in 1996 and followed for up to 10 years. MEASUReMENTS: Relative risk of all‐cause mortality and cause‐specific (cardiovascular disease, cancer, and chronic respiratory disease) mortality. RESULTS: Mortality risk was lowest for overweight participants. The risk of death for overweight participants was 13% less than for normal‐weight participants (hazard ratio (HR)=0.87, 95% CI=0.78–0.94). The risk of death was similar for obese and normal‐weight participants (HR=0.98, 95% CI=0.85–1.11). Being sedentary doubled the mortality risk for women across all levels of BMI (HR=2.08, 95% CI=1.79–2.41) but resulted in only a 28% greater risk for men (HR=1.28 (95% CI=1.14–1.44). CONCLUSION: These results lend further credence to claims that the BMI thresholds for overweight and obese are overly restrictive for older people. Overweight older people are not at greater mortality risk than those who are normal weight. Being sedentary was associated with a greater risk of mortality in women than in men.     

Potential synergy between lipid-lowering and blood-pressure-lowering in the Anglo-Scandinavian Cardiac Outcomes Trial.

AIMS: A prespecified objective of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was to assess whether any synergistic effects were apparent between the lipid-lowering and blood-pressure-lowering regimens in preventing cardiovascular events. METHODS AND RESULTS: A total of 19 257 hypertensive subjects were randomized to an amlodipine-based regimen or an atenolol-based regimen. Of these, 10 305 subjects with total cholesterol < or =6.5 mmol/L were further randomized to atorvastatin 10 mg daily or placebo. In this analysis, the effects of atorvastatin were compared with placebo on coronary heart disease (CHD), cardiovascular and stroke events in those assigned amlodipine-based and atenolol-based regimens. In the ASCOT lipid-lowering arm (LLA), overall, atorvastatin reduced the relative risk of the primary endpoint of non-fatal myocardial infarction and fatal CHD events by 36% (HR 0.64, CI 0.50-0.83, P=0.0005), total cardiovascular events by 21% (HR 0.79, CI 0.69-0.90, P=0.0005), and stroke by 27% (HR 0.73, CI 0.56-0.96, P=0.024). However, atorvastatin reduced the relative risk of CHD events by 53% (HR 0.47, CI 0.32-0.69, P<0.0001) among those allocated the amlodipine-based regimen, and by 16% (HR 0.84, CI 0.60-1.17, p: n.s.) among those allocated the atenolol-based regimen (P=0.025 for heterogeneity). There were no significant differences between the effects of atorvastatin on total cardiovascular events or strokes among those assigned amlodipine (HR 0.73, CI 0.60-0.88, P<0.005 and HR 0.69, CI 0.45-1.06, P: n.s., respectively) or atenolol (HR 0.85, CI 0.71-1.02, P: n.s and HR 0.76, CI 0.53-1.08, P: n.s, respectively). Differences in blood pressure and lipid parameters (placebo corrected) between the two antihypertensive treatment limbs could not account for the differences observed in CHD outcome. CONCLUSION: These findings of an apparent interaction between atorvastatin and an amlodipine-based regimen in the prevention of CHD events are of borderline significance, and hence generate an hypothesis that merits independent evaluation in other trials.     

Long QT syndrome and pregnancy.

OBJECTIVES: This study was designed to investigate the clinical course of women with long QT syndrome (LQTS) throughout their potential childbearing years. BACKGROUND: Only limited data exist regarding the risks associated with pregnancy in women with LQTS. METHODS: The risk of experiencing an adverse cardiac event, including syncope, aborted cardiac arrest, and sudden death, during and after pregnancy was analyzed for women who had their first birth from 1980 to 2003 (n = 391). Time-dependent Kaplan-Meier and Cox proportional hazard methods were used to evaluate the risk of cardiac events during different peripartum periods. RESULTS: Compared with a time period before a woman's first conception, the pregnancy time was associated with a reduced risk of cardiac events (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.10 to 0.76, p = 0.01), whereas the 9-month postpartum time had an increased risk (HR 2.7, 95% CI 1.8 to 4.3, p < 0.001). After the 9-month postpartum period, the risk was similar to the period before the first conception (HR 0.91, 95% CI 0.55 to 1.5, p = 0.70). Genotype analysis (n = 153) showed that women with the LQT2 genotype were more likely to experience a cardiac event than women with the LQT1 or LQT3 genotype. The cardiac event risk during the high-risk postpartum period was reduced among women using beta-blocker therapy (HR 0.34, 95% CI 0.14 to 0.84, p = 0.02). CONCLUSIONS: Women with LQTS have a reduced risk for cardiac events during pregnancy, but an increased risk during the 9-month postpartum period, especially among women with the LQT2 genotype. Beta-blockers were associated with a reduction in cardiac events during the high-risk postpartum time period.     

Obesity and cardiovascular events in patients with established coronary disease.

AIMS: To explore the association between obesity and major adverse coronary events (MACE) in patients with established coronary artery disease (CAD). METHODS AND RESULTS: The Prevention of Events with Angiotensin Converting Enzyme-Inhibition (PEACE) Trial randomized 8290 patients with stable CAD and left ventricular (LV) ejection fraction (EF) (LVEF) > or =0.40 to trandolapril or placebo and followed them for a median of 4.8 years. In PEACE patients who were non-diabetic at baseline (5693 men and 1171 women), we used proportional hazards models to conduct a post hoc analysis to examine whether obesity, defined as a body mass index (BMI) > or =30 kg/m(2), is an independent risk factor for the composite endpoint of MACE, defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, or stroke. The analysis was conducted separately for men and women. The baseline prevalence of obesity was 28.5% in men and 28.9% in women. After adjusting for significant confounders, obesity was associated with MACE in men [hazard ratio (HR) = 1.28, 95% CI 1.13-1.46, P < 0.01], but not in women (HR = 0.96, 95% CI 0.70-1.31, P = 0.77). Further categorization of BMI showed a J-shaped association between BMI and MACE in the men, and no association in the women. CONCLUSION: In the presence of established CAD, obesity is associated with risk for MACE in men, but there is no support of an association in women. This finding requires further evaluation.     

Is exercise testing useful to improve the prediction of coronary events in asymptomatic subjects?

OBJECTIVE: The value of exercise testing (ET) in asymptomatic subjects remains controversial and is unknown in countries with a low coronary heart disease (CHD) incidence. The aim of this study was to investigate the ability of ET to improve the prediction of a first coronary event in such a population. METHODS: Using a prospective cohort study, 1051 consecutive healthy asymptomatic adults were enrolled in a cardiovascular screening program including ET. The pre-test risk of CHD was evaluated by the 10-year Framingham risk function. Positive ET was defined as a horizontal or downsloping ST-segment depression >/=1.0 mm. The primary outcome was total coronary events (CE) occurrence, including cardiac deaths, acute myocardial infarction and stable or unstable angina. The mean follow-up period was 6 years. RESULTS: Subjects were aged 18-79 years and 36% were women. A total of 89 subjects (8.5%) had a positive ET. Positive exercise testing was associated with CE occurrence in a univariate analysis only in subjects with higher pre-test risk, defined by a 10-year Framingham risk >10.4% [hazards ratio (HR)=2.61; 95% confidence interval (CI) (1.07-6.40)]. In this risk category, ET was able to provide incremental information over the major risk factors in both men and women [risk factor-adjusted HR for positive ET=2.86; 95% CI (1.14-7.20)]. This risk excess in subjects with positive ET persisted even when a coronary revascularization was performed. Subjects with intermediate pre-test probability (10-15%) and positive ET had a post-test probability of CE largely equivalent to the probability in subjects with known CHD. CONCLUSION: Additional information provided by ET in subjects with a pre-test risk at 10-years >10% should lead to a more efficient use of risk-reducing therapies than it would be the case in this risk category with the analysis of traditional risk factors only.     

Depression, falls, and risk of fracture in older women. Study of Osteoporotic Fractures Research Group

BACKGROUND: Previous studies have suggested that depression is associated with falls and with low bone density, but it is not known whether depression leads to an increased risk of fracture. SUBJECTS AND METHODS: We conducted a prospective cohort study in elderly white women who were recruited from population-based listings in the United States. At a second visit (1988-1990), 7414 participants completed the 15-item Geriatric Depression Scale and were considered depressed if they reported 6 or more symptoms of depression. We measured bone mineral density (BMD) in the spine and hip using dual energy x-ray absorptiometry at the second visit, and asked participants about incident falls (yes/no) at 4 follow-up visits. Nonvertebral fractures were ascertained for an average of 6 years following the depression measure, and verified radiologically. We determined incident vertebral fractures by comparing lateral spine films obtained at the first visit (1986-1988) with repeat films obtained an average of 3.7 years later (1991-1992). RESULTS: The prevalence of depression (Geriatric Depression Scale score > or = 6) was 6.3% (467/7414). We found no difference in mean BMD of the hip and lumbar spine in women with depression compared with those without depression. Women with depression were more likely to experience subsequent falls than women without depression (70% vs 59%; age-adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9; P<.001), an association that persisted after adjusting for potential confounding variables (OR, 1.4; 95% CI, 1.1-1.8; P=.004). Women with depression had a 40% (age-adjusted hazard ratio [HR], 1.4; 95% CI, 1.2-1.7; P<.001) increased rate of nonvertebral fracture (124 fractures in 3805 woman-years of follow-up) compared with women without depression (1367 fractures in 59 503 woman-years of follow-up). This association remained strong after adjusting for potential confounding variables, including medication use and neuromuscular function (HR, 1.3; 95% CI, 1.1-1.6; P=.008). Further adjustment for subsequent falls appeared to explain part of this association (HR, 1.2; 95% CI, 1.0-1.5; P = .06). Women with depression were also more likely to suffer vertebral fractures than women without depression, adjusting for history of vertebral fracture, history of falling, arthritis, diabetes, steroid use, estrogen use, supplemental calcium use, cognitive function, and hip BMD (OR, 2.1; 95% CI, 1.4-3.2; P<.001). CONCLUSIONS: Depression is a significant risk factor for fracture in older women. The greater frequency of falls among individuals with depression partially explains this finding. Other mechanisms responsible for the association between depression and fracture remain to be determined.