Marcel Kornitzer

Ankle brachial index combined with Framingham risk score to predict cardiovascular events and mortality - A meta-analysis

CONTEXT Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Design and Methods of the Raloxifene Use for The Heart (RUTH) Study

Raloxifene is a selective estrogen receptor modulator that lowers total and low-density lipoprotein (LDL) cholesterol, reduces the risk of vertebral fracture, and is associated with a reduced incidence of invasive breast cancer in postmenopausal women with osteoporosis. The Raloxifene Use for The Heart (RUTH) trial is designed to determine whether raloxifene 60 mg/day compared with placebo: (1) lowers the risk of the coronary events (coronary death, nonfatal myocardial infarction [MI], or hospitalized acute coronary syndromes other than MI); and (2) reduces the risk of invasive breast cancer in women at risk for a major coronary event. RUTH is a double-blind, placebo-controlled, randomized clinical trial of 10,101 postmenopausal women aged > or =55 years from 26 countries. Women are eligible for randomization if they are postmenopausal and have documented coronary heart disease (CHD), peripheral arterial disease, or multiple risk factors for CHD. Use of estrogen within the previous 6 months is an exclusion factor. The study will be terminated after a minimum of 1,670 participants experience a primary coronary end point. Secondary end points include cardiovascular death, myocardial revascularization, noncoronary arterial revascularization, stroke, all-cause hospitalization, all-cause mortality, all breast cancers, clinical fractures, and venous thromboembolic events, in addition to the individual components of the composite primary coronary end point. RUTH will provide important information about the risk-benefit ratio of raloxifene in preventing acute coronary events and invasive breast cancer, as well as information about the natural history of CHD in women at risk of major coronary events.

Ankle/arm pressure index in asymptomatic middle-aged males: an independent predictor of ten-year coronary heart disease mortality.

Purpose of the study: to evaluate the predictive power of a reduced ankle/brachial pressure index (ABPI) (≤ .90) in an asymptomatic middle-aged male working population free of coronary heart disease. Materials and Methods: 2023 subjects forty to fifty-five years old were screened at their work place. Standard techniques were used. Blood was drawn in the fasting state. Ankle and brachial blood pressures were measured by Doppler signals and all measures were done by one observer, duly trained in epidemiologic methodology Results: in univariate analysis, an ABPI ≤ .90 was significantly associated with age, total serum cholesterol, body mass index, smoking, and awareness of diabetes. In multi- variate analysis, it was associated with awareness of diabetes, age, Ln triglycerides (P=.073), and smoking (P=.088). Relative risks for reduced versus normal ABPI are 2.77 (P=.010), 4.16 (P=.011) and 4.97 (P=.006) for ten-year all causes, cardiovascular, and coronary mortality, respec tively. In a multiple logistic regression analysis, the following variables were significant independent predictors of coronary mortality: smoking (odds ratio [OR] =4.84), reduced ABPI (OR=3.63), and low density lipoprotein cholesterol (OR for 1 SD=1.69). Reduced ABPI is also an independent predictor of cardiovascular mortality Conclusion: a reduced ABPI is an independent risk factor for coronary and cardio vascular mortality in asymptomatic middle-aged Belgian males.

Effects of the Selective Estrogen Receptor Modulator Raloxifene on Coronary Outcomes in The Raloxifene Use for the Heart Trial: Results of Subgroup Analyses by Age and Other Factors

Background— The Raloxifene Use for The Heart (RUTH) trial showed that raloxifene, a selective estrogen receptor modulator, had no overall effect on the incidence of coronary events in women with established coronary heart disease or coronary heart disease risk factors. We provide detailed results of the effect of raloxifene on coronary outcomes over time and for 24 subgroups (17 predefined, 7 post hoc). Methods and Results— Postmenopausal women (n=10 101; mean age, 67 years) were randomized to raloxifene 60 mg/d or placebo for a median of 5.6 years. Coronary outcomes were assessed by treatment group in women with coronary heart disease risk factors and those with established coronary heart disease. Raloxifene had no effect on the incidence of coronary events in any subgroup except in the case of a post hoc age subgroup analysis using age categories defined in the Womens Health Initiative randomized trials. The effect of raloxifene on the incidence of coronary events differed significantly by age (interaction P=0.0118). The incidence of coronary events in women <60 years of age was significantly lower in those assigned raloxifene (50 events) compared with placebo (84 events; hazard ratio, 0.59; 95% confidence interval, 0.41 to 0.83; P=0.003; absolute risk reduction, 36 per 1000 women treated for 1 year). No difference was found between treatment groups in the incidence of coronary events in women ≥60 and <70 or ≥70 years of age. Conclusions— In postmenopausal women at increased risk of coronary events, the overall lack of benefit of raloxifene was similar across the prespecified subgroups.

The impact of psychosocial factors on low back pain : Longitudinal results from the belstress study

Study Design. An epidemiological cohort study. Objective. To describe the impact of psychosocial factors, both work and nonwork-related, on the prevalence of low back pain (LBP) after 6.6 years on average. Summary of Background Data. There is growing consensus that psychosocial factors play a role in the development of LBP, although results are not consistent across studies. Methods. Within a sample of 2556 middle-aged men and women from the Belstress study, baseline psychosocial factors were measured through self-administered questionnaires and related to prevalent cases of LBP after a mean time interval of 6.6 years through Cox regression analysis. Results. After adjustment for individual and physical risks, including occasional back pain at baseline, the prevalence rate of LBP in men is significantly related to baseline low decision latitude and low social support at work, and nonsignificantly to high job strain, low wage and job satisfaction, feeling stressed at work, and feeling depressed. High job insecurity, feeling stressed at work, and feeling depressed nonsignificantly increase the relative risks for LBP in women. Conclusions. Based on the results of this study, psychosocial factors (both work and nonwork-related) constitute nonnegligible risks for the development of LBP.

Occupational stress and incidence of sick leave in the Belgian workforce: the Belstress study

Context: Sick leave is a major problem in public health. The Karasek demands/control/social support/strain (JDCS) model has been largely used to predict a wide range of health outcomes and to a lesser extent sickness absence. Study objective: The aim of the study was to test the predictive power of the JDCS model in relation with one year incidence of sick leave in a large cohort of workers. Design and setting: Cohort study conducted between 1994 and 1998 in 25 companies across Belgium. Participants: A total of 20 463 workers aged 35 to 59 years were followed up for sick leave during one year after the baseline survey. Outcomes: The outcomes were a high sick leave incidence, short spells (⩾7 days), long spells (⩾28 days), and repetitive spells of sickness absence (⩾3 spells/year). Main results: Independently from baseline confounding variables, a significant association between high strained jobs with low social support and repetitive spells of sickness absence was observed in both sexes with odds ratios of 1.32 (99% CI, 1.04 to 1.68) in men and 1.61 (99% CI, 1.13 to 2.33) in women. In men, high strained jobs with low social support was also significantly associated with high sick leave incidence, and short spells of sick leave with odds ratios of 1.38 (99% CI, 1.16 to 1.64) and 1.22 (99% CI, 1.05 to 1.44) respectively. Conclusions: Perceived high strain at work especially combined with low social support is predictive of sick leave in both sexes of a large cohort of the Belgian workforce.

Baseline characteristics of participants in the Raloxifene Use for The Heart (RUTH) trial

The Raloxifene Use for The Heart (RUTH) trial is a randomized, placebo-controlled, double-blind trial designed to determine whether raloxifene 60 mg/day compared with placebo lowers the risk of coronary events (coronary death, nonfatal myocardial infarction [MI], or hospitalized acute coronary syndromes other than MI) and reduces the risk of invasive breast cancer in women at risk for a major coronary event. Raloxifene is a selective estrogen receptor modulator that improves cardiovascular risk factors, reduces the risk of vertebral fracture, and is associated with a reduced incidence of invasive breast cancer in postmenopausal women with osteoporosis. Between June 1998 and August 2000, 10,101 women were enrolled at 187 sites in 26 countries. Approximately half of the women had documented coronary heart disease (CHD) (n = 5,031); the remainder had multiple CHD risk factors that increased their risk for a CHD event (n = 5,070). The mean age of participants was 68 years (39% were >70 years old), and did not differ between those with documented CHD and those at increased CHD risk. Most women were Caucasian (84%); 60% had a body mass index >/=27 kg/m(2), 46% had diabetes mellitus, 78% had systemic hypertension, and 14% had low-density lipoprotein cholesterol >160 mg/dl. Compared with women at increased CHD risk, women with documented CHD had higher cardiovascular risk scores, a higher prevalence of abnormal electrocardiograms, greater use of cardiovascular medications, were more likely to have had cardiac rehabilitation, and were more likely to have previously used estrogen or oral contraceptives, but had a slightly lower prevalence of CHD risk factors such as smoking, obesity, diabetes mellitus, and systemic hypertension, and had lower serum levels of total and low-density lipoprotein cholesterol. The RUTH cohort is the largest group of postmenopausal women at increased risk of CHD events ever assembled in a clinical trial, and is the first trial designed to determine the effect of a selective estrogen receptor modulator on the risk of CHD events.

Epidemiology of risk factors for hypertension: Implications for prevention and therapy

We review the present knowledge of risk factors for arterial hypertension. Both genetic and environmental factors as well as their interaction and biological plausibility are reviewed. Recent data confirm that the interaction of genetics with multiple environmental risk factors explains the high prevalence of hypertension in the industrialised countries. The most important modifiable environmental risk factors are high salt intake, alcohol intake, obesity and low physical activity.The role of stress in the aetiology of high blood pressure is still under investigation, but recent clinical experimental and epidemiological data have shed light on how stress could be related to hypertension.The implications for prevention and treatment are discussed both at the population and individual levels. The population approach involves a public health policy aiming at modification of the major risk factors. The individual approach involves nonpharmacological measures to prevent the development of hypertension and to treat high normal blood pressure and mild hypertension with no additional cardiovascular risk factors. Pharmacological treatment of hypertension in most individuals should use agents that have been proven to be effective in randomised controlled trials with ‘hard’ endpoints such as cardiovascular and cerebrovascular morbidity and mortality.

Psycho-socio-biological correlates of moderate overweight in an industrial population

Abstract This paper deals with the study of the relation between psycho-socio-biological factors and moderate overweight of subjects participating to the Belgian Heart Disease Prevention Project. The 8284 male subjects of the trial, working in 30 Belgian Flemish or French-speaking factories, aged 40–59 yr, were medically screened and asked to answer medical, social and psychological questionnaires. Base-line data are here analysed in regard to relative weight (mean relative weight and tertiles of relative weight). Stepwise discriminant analyses between tertile III and tertile I introducing psychological, social and bioclinical variables, showed that the ‘obese’ subjects (tertile III) are less frequently cigarette smokers, are less neurotic, are of a lower occupational class, are more frequently living in Wallonia (south of Belgium) and are more extravert compared to the ‘lean’ subjects (tertile I). Moreover, prospective studies are further needed to determine the causal or sequential effects on moderate overweight of the two psychological factors: neuroticism and extraversion.

Effect of Raloxifene on Stroke and Venous Thromboembolism According to Subgroups in Postmenopausal Women at Increased Risk of Coronary Heart Disease

Background and Purpose— Raloxifene, a selective estrogen receptor modulator, reduces risk of invasive breast cancer and osteoporosis, but the effect on risk for stroke and venous thromboembolism in different patient subgroups is not established. The purpose of this analysis was to evaluate the effect of raloxifene on the incidence of all strokes, stroke deaths, and venous thromboembolic events according to participant subgroups. Methods— This was a secondary end point analysis of an international, randomized, placebo-controlled clinical trial of 10 101 postmenopausal women with or at increased risk of coronary heart disease followed a median of 5.6 years. Strokes, venous thromboembolic events, and deaths were adjudicated by expert centralized committees. Strokes were categorized as ischemic, hemorrhagic, or undetermined and venous thromboembolic events were subclassified. Results— The incidences of all strokes did not differ between raloxifene (incidence rate per 100 woman-years=0.95) and placebo (incidence rate=0.86) treatment groups (P=0.30). In women assigned raloxifene versus placebo, there was a higher incidence of fatal strokes (incidence rates=0.22 and 0.15, respectively, P=0.0499) and venous thromboembolic events (incidence rates=0.39 and 0.27, respectively, P=0.02). No significant subgroup interactions were found except that there was a higher incidence of stroke associated with raloxifene use among current smokers. Conclusions— In postmenopausal women at increased risk for coronary events, the incidences of venous thromboembolism and fatal stroke but not all strokes were higher in those assigned raloxifene versus placebo. Raloxifene’s effect did not differ across subgroups, except that the risk of stroke differed by smoking status. Treatment decisions about raloxifene should be based on a balance of projected absolute risks and benefits.