Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

Behavioural and psychosocial correlates of nondipping blood pressure pattern among middle-aged men and women at work.

The underlying pathogenetic mechanisms of nondipping blood pressure (BP) pattern are not completely understood. Especially the role of psychosocial correlates remains unclear. The aim was to assess the association between nondipping BP pattern, behavioural and psychosocial factors in a sample of working men and women. The study sample included 167 working men and women aged 40-64 years from the BELSTRESS cohort. Socio-demographic, behavioural and psychosocial factors were assessed by self-administered questionnaires. Participants were medically examined and underwent an ambulatory BP monitoring during 24 h. Nondipping was defined when the average nocturnal decline in BP was <10%. The prevalence of nondipping for both systolic and diastolic BP was 7.8%. Nondipping was not significantly related to smoking, alcohol consumption and leisure time physical activity. A crude significant association was observed between nondipping and sleep problems. After adjusting for gender, education and body mass index, the risk for nondipping was associated with job strain, living alone, being unsatisfied about the contact with one's children, depressive symptoms and vital exhaustion. Nondipping BP pattern was consistently related to psychosocial factors in this study: positive associations were observed with measures of job strain, poor private life support (living alone and being unsatisfied about the contact with one's children) and mental health problems (depressive symptoms and vital exhaustion).

Working conditions predict incidence of long-term spells of sick leave due to depression: results from the Belstress I prospective study.

BACKGROUND: During the last few years, a high incidence of sick leave due to depression has been reported, resulting in important economic and social impacts. Only a limited number of studies investigating the influence of psychosocial working conditions on sick leave have been prospective and have utilised a valid methodology, while none have studied sick leave due to depression. In this study, the impact of adverse psychosocial working conditions is analysed on the risk for long-term sick leave due to depression. METHODS: This study resulted from the large-scale Belstress I study on the relationship between perceived job stress and health problems. Subjects were Belgian employees selected from 11 large companies (n = 9396). Using a longitudinal design, the association between the three Karasek stress dimensions (job control, psychological demand, and social support) was explored, separately and combined according to the demand-control and demand-control-support models and the incidence of long-term sick leave for depression as diagnosed by the family physician. RESULTS: After adjusting for age, occupational categories, living situation, and baseline depression score, 'passive jobs' (OR 2.67; 95% CI 1.15 to 6.19) and 'high strain' jobs (OR 3.23; 95% CI 1.40 to 7.43) predicted sick leave due to depression at follow-up in men. Job control predicted sick leave due to depression in both men (OR 2.43; 95% CI 1.27 to 4.66) and women (OR 2.21; 95% CI 1.05 to 4.68). CONCLUSIONS: This study provides evidence that the psychosocial working environment influences long-term sick leave due to depression. Efforts to improve skill discretion and decision authority at work could help prevent depression.

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.

Predictors of misreporting in an elderly population: the 'Quality of life after 65' study.

OBJECTIVES: To evaluate the prevalence and identify some predictors of misreporting in an elderly Belgian population and to assess the effect of underreporting on estimated intakes of macronutrients and foods. DESIGN: A 1-day food record was completed by 2083 adult men and women aged 65 years or more. Individuals whose energy intake was lower than 0.90 x BMR (basal metabolic rate) were defined as underreporters. Overreporting was defined as energy intake greater than 2 x BMR. RESULTS: Underreporting and overreporting occurred in 13.6% and 7.9% of food records, respectively. Results from logistic regression models indicated that gender and body mass index (BMI) were predictors of misreporting. Whereas women were more likely to underreport energy intake, the prevalence of overreporting was higher in men. Underreporting was more prevalent among obese people and overreporting more prevalent in normal-weight subjects. Smoking status and education level did not predict underreporting; however, overreporting was more likely to occur in more highly educated subjects. A cultural difference in reporting of nutrient intakes was also found, with the percentage of underreporters being higher among Walloons compared with Flemish. CONCLUSION: BMI seemed to be one of the most important factors in misreporting. This calls for special attention when dietary surveys are performed on obese or lean people.

Gender and regional differences in perceived job stress across Europe.

BACKGROUND: Over the last 20 years stress at work has been found to be predictive of several conditions such as coronary heart disease, high blood pressure and non-specific sick leave. The Karasek demand/control/strain concept has been the most widely used in prospective epidemiological studies. OBJECTIVES: To describe distribution in Karasek's demand/control (DC) dimensions as well as prevalence of strain in samples from different parts of Europe grouped into three regions (South, Middle, Sweden), adjusting for occupation. To describe gender differences in Karasek's DC dimensions along with strain prevalence and assess the regional stability of those differences in different occupational groups. DESIGN: The Job stress, Absenteeism and Coronary heart disease in Europe (JACE) study, a Concerted Action (Biomed I) of the European Union, is a multicentre prospective cohort epidemiological study: 38,019 subjects at work aged 35-59 years were surveyed at baseline. Standardised techniques were used for occupation coding (International Standardised Classification of Occupations) and for the DC model (Karasek scale): five items for the psychological demand and nine items for the control or decision latitude dimensions, respectively. RESULTS: A total of 34,972 subjects had a complete data set. There were important regional differences in the Karasek scales and in prevalence of strain even after adjustment for occupational class. Mean demand and control were higher in the Swedish centres when compared to two centres in Milano and Barcelona (Southern region) and values observed in four centres (Ghent, Brussels, Lille and Hoofddorp) in Middle Europe were closer to those observed in the Southern cities than to those obtained in the Swedish cities. Clerks (ISCO 4) and, more specifically, office clerks (ISCO 41) exhibited the smallest regional variation. In a multivariate model, the factor 'region' explained a small fraction of total variance. In the two Southern centres as well as in the four Middle European centres, men perceived marginally less job-demand as compared to women whereas the reverse was observed in the two Swedish centres. Differences were larger for control: men appeared to perceive more control at work than did women. In a multivariate model, gender explained a small fraction whereas occupational level explained a large fraction of the variance. CONCLUSIONS: In this standardised multicentre European study Karasek's DC model showed large gender and occupational differences whereas geographic region explained a small fraction of the total DC variance, notwithstanding large differences in labour market and working conditions as pointed out by the European Commission as recently as 2000.

[Application of a dietary pattern approach in the Belgium context]. / Application de l'approche globale de l'alimentation dans la population belge.

BACKGROUND: Dietary pattern analysis has recently emerged as a new direction and a complementary approach to study the relationship between diet and morbidity or mortality. At present, two methods have been developed to construct dietary patterns: "a priori" method and "a posteriori" method. OBJECTIVE: This paper presents the two methods and their application based on dietary data from the "Belgium Interuniversity on Nutrition and Health Study". METHODS: A prospective study was conducted (1979-1984) in a sample of 5,225 males and 4,476 females from the Belgian population aged 25 to 74 years at the initial survey and followed for 10 years for all causes and specific mortality. Dietary data was collected by a 24-hour recall and for a sub-sample also by a 7 day-diet record. The "a priori" method was used by calculating an index based on the national dietary guidelines. We used the principal component analysis to identify dietary patterns a posteriori. We conducted a first principal component analysis using the data from the 24-hour recall and a second on the data collected by the 7 day-record. RESULTS: Both of the currently used approaches for extracting dietary patterns have advantages and limitations. We applied first the "a priori" approach by calculating an Index (IAR) which measures the adherence of the sample to the Belgian dietary guidelines. We obtained an index that ranged from 0 to 8, a higher score represented a "healthier diet". The index mean (sd) was 3.7 (+/- 1.2) for the entire sample with a significantly higher IAR for women. Using factor analysis, we identified 8 dietary patterns for men and for women. These were difficult to translate in terms of dietary intake profile. Inversely, with the factors identified with the 7 day record, we could find a "western" dietary profile and a "prudent" profile. CONCLUSION: Dietary pattern analysis offers the opportunity to evaluate the overall quality of the diet. The dietary profiles constructed by the two approaches should be related to morbidity or mortality in order to evaluate their predictive capacity.

Perceived job stress and incidence of coronary events: 3-year follow-up of the Belgian Job Stress Project cohort.

Psychosocial characteristics have been linked to coronary heart disease. In the Belgian Job Stress Project (1994-1999), the authors examined the independent role of perceived job stress on the short-term incidence of clinical manifest coronary events in a large occupational cohort. A total of 14,337 middle-aged men completed the Job Content Questionnaire to determine the dimensions of the extended job strain model, job demands, decision latitude, and social support. Jobs were categorized into high strain, low strain, active jobs, and passive jobs. During the 3-year follow-up, 87 coronary events were registered. At baseline, 17% of workers experienced high strain. Job demands and decision latitude were not significantly related to the development of coronary heart disease after adjustment for covariates. The 38% risk excess among subjects classified in the high-strain category did not reach statistical significance. However, coronary heart disease incidence was substantially associated with the social support scale independently of other risk factors, with an adjusted hazard ratio of 2.4 (95% confidence interval: 1.4, 4.0) between extreme tertiles. No convincing evidence for an association of job demands, decision latitude, or job strain with the short-term incidence of coronary heart disease was found. However, our study underscores the importance of a supportive social work environment in the prevention of coronary heart disease.

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.

Obesity, body fat distribution and incidence of sick leave in the Belgian workforce: the Belstress study.

OBJECTIVES: In many studies, obesity has been associated with morbidity or mortality, but only a few have studied the relation between obesity and sick leave. Our aim is to analyse the independent effects of both adiposity and body fat distribution in relation to the 1-y incidence of sick leave in a large cohort of male and female workers covering a variety of occupations, taking into account a wide range of socio-demographic, behavioural and bioclinical variables. DESIGN AND SETTING: The baseline survey of the Belstress study was conducted in 25 companies across Belgium between 1994 and 1998. A cohort of 20 463 workers (15 557 males and 4906 females) aged 35-59 y was followed for absenteeism during 1 y. The 75th percentile of the distribution of the total annual sickness days was used as a cutoff to classify the workers with a high 1-y incidence rate of sick leave. The relation between sick leave and both obesity and body fat distribution assessed by the body mass index (BMI) and the waist circumference, respectively, was analysed by multivariate logistic regression models. RESULTS: Using a backward procedure based on the likelihood ratio, we found central abdominal fatness to be an independent predictor of sick leave in both genders (high sick-leave incidence and long spells), but not BMI. In men, the odds ratios was 1.31 (99% CI 1.12-1.52, P<0.0001) and in women it ranged from 1.32 (99% CI 1.03-1.70, P=0.005) to 1.47 (99% CI 1.14-1.90, P<0.0001). Two baseline covariables, respiratory problems and perceived health, are confounders or mediators. CONCLUSIONS: In this study, body fat distribution was associated with a high annual sick-leave incidence and long spells of sickness absence. If this link is reversible, employers may benefit from programs aiming at the prevention and treatment of central obesity.

Serum selenium and cancer mortality: a nested case-control study within an age- and sex-stratified sample of the Belgian adult population.

OBJECTIVE: To study the predictive power of serum selenium with regard to cancer mortality in a large sample of the Belgian population given the lack of coherence in the results of observational epidemiological studies in this domain. DESIGN: A prospective case-control study within a stratified sample of the Belgian male and female population. SUBJECTS: A total of 201 cases randomly selected from all cancer deaths (N=343) during a 10-y mortality follow-up of a large age- and sex-stratified sample of the total Belgian population aged 25-74 y were matched for age and gender with 603 controls. STATISTICS: Conditional logistic regression for both univariate and multivariate analyses using tertile distribution of serum selenium in controls. Odds ratios (ORs) are adjusted for 10 baseline characteristics. RESULTS: Unadjusted ORs of cancer deaths taking the highest tertile of serum selenium as a reference: in male subjects T1/T3 is 2.2 (CI 1.3-3.7) (P for trend 0.011), whereas in female subjects a nonsignificant OR of 0.8 is observed. In multivariate analyses, no significant modifications of the ORs are observed for the predictive relation of serum selenium with cancer mortality. Besides serum selenium, beta-carotene intake and smoking are independent predictors in male subjects. CONCLUSIONS: In this nested case-control study of a stratified sample from the Belgian population, serum selenium is an independent predictor of cancer mortality in male subjects only, in a country with rather high serum selenium levels with respect to most other European countries.

Job conditions and fibrinogen in 14226 Belgian workers: the Belstress study.

AIMS: To investigate the relationship between fibrinogen and stressful work conditions, where perceived strain is defined by the simultaneous presence of high psychological demands and low control, according to Karasek's Demand/Control/(Social Support) model. METHODS AND RESULTS: A cross-sectional study was realized between 1994 and 1998 in 24 Belgian enterprises, on 16335 male and 5084 female middle-aged workers of different Belgian companies participating in the Belstress study. This study confirmed the well-documented bivariate relationship between plasma fibrinogen levels and gender, age, educational level, smoking, obesity, physical activity, alcohol consumption, total cholesterol, HDL-cholesterol, arterial hypertension and diabetes. No independent multivariate relationship was observed between job control, psychological job demands or social support at work and plasma fibrinogen, but after stratification a positive association (P< or =0.05) was observed between psychological job demands and plasma fibrinogen for males in the lowest educational level. Moreover a positive statistically significant association between job strain and plasma fibrinogen was observed in males but not in females. After stratification for educational level this association remained significant for males especially in the lowest educational level (P< or =0.001) and became significant for females in the middle educational level. CONCLUSIONS; As suggested in our study and others, plasma fibrinogen could be one of the potential mediators explaining the relationship between job stress and coronary heart disease.

Parameters of inflammation and infection in a community based case-control study of coronary heart disease.

BACKGROUND: increased levels of systemic inflammatory markers appear to be related to coronary heart disease (CHD) both in asymptomatic individuals and in subjects with established CHD. Whether these associations are related to confounding coronary risk factors or are explicable through chronic infectious conditions is not clear. OBJECTIVES: (1) to determine whether subjects with stable CHD differ from normal controls in inflammatory markers (CRP, SAA and fibrinogen) and/or in serostatus of four infectious agents (Helicobacter pylori, Chlamydia pneumoniae, CMV and EBV), independent of classical coronary risk factors. (2) To determine whether these inflammatory markers are related to the serostatus against these four infectious agents either in patients with CHD or in normal subjects. METHODS: in a large epidemiologic survey, 446 out of 16307 men at work, aged 35-59 years, had antecedents of myocardial infarction, CABG or PTCA or had prominent Q/QS waves on their resting ECG. They were compared with double the number (n=892) of men, matched for age, educational level and industry. Inflammatory biomarkers (CRP, fibrinogen and SAA) and antibodies against H. pylori, C. pneumoniae, CMV and EBV were measured, besides classical coronary risk factors. RESULTS: in univariate analyses, cases had higher CRP, fibrinogen and SAA levels than controls, but no differences were observed in serumantibody levels to any of the infectious agents. Markers of previous infections were not related to inflammatory biomarkers. In multivariate analyses CRP was significantly different between cases and controls independent of differences in other coronary risk factors and in the use of lipid lowering drugs and antiplatelet aggregants. CONCLUSIONS: in men at work with CHD, CRP levels are significantly different from controls, independent of known risk factors. No association was found between inflammatory biomarkers and positive serostatus against four infectious agents, neither in the patients nor in the healthy controls.

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.

Haptoglobin polymorphism as a risk factor for coronary heart disease mortality.

OBJECTIVES: the aim of our study was to evaluate the independent role of the haptoglobin (Hp) polymorphism as a risk factor for coronary heart disease (CHD) mortality. METHODS: within the framework of the longitudinal part of the Belgian Interuniversity Research on Nutrition and Health (BIRNH) survey, a nested case-control study design was performed through matching the 107 deaths from CHD, occurring within a 10-year follow-up period, with three controls for age and gender. RESULTS: the distribution of the Hp types was found to be in Hardy-Weinberg equilibrium. Conditional logistic regression analysis for matched sets revealed that the Hp polymorphism was significantly associated with CHD death. Rather surprisingly, the finding was that Hp 1-1 individuals were at doubled risk for CHD mortality compared with the others, the odds ratio being 2.09 (95% CI: 1.22-3.60). The association was independent from other classical cardiovascular risk factors and the Hp concentration, and of comparable magnitude between men and women. Moreover, evaluating the interaction term in a multiplicative model showed that the Hp type did not play a synergistic role in the prognostic value of established cardiovascular risk factors. CONCLUSION: in contrast to the findings from cross-sectionally based studies, the results from this longitudinal study show that Hp 1-1 individuals are at elevated risk for CHD mortality.

[Relation between uricemia and total, cardiovascular and coronary mortality in both genders of non-selected sample of the Belgium population]. / Relation entre l'uricémie et la mortalité totale, cardio-vasculaire et coronarienne dans un échantillon non sélectionné de la population belge.

BACKGROUND: Despite more than 40 years of research on the prognostic value of hyperuricemia in relation to all-causes cardiovascular and coronary mortality, no clear consensus appears in the medical literature. Moreover, the observed relationship between hyperuricemia and the incidence of coronary heart disease mortality is related to gender. However, prospective studies including both genders are rare. METHODS: A prospective study was conducted in a random sample of 5225 males and 4476 females from the Belgian population aged 25 to 74 years at the initial survey and followed for 10 years for all-causes and specific mortality. RESULTS: The number of observed total, cardiovascular, and coronary heart disease deaths were 648 and 239, 150 and 225, and 96 and 51 in males and females respectively. At multivariate analysis, uricemia was significantly correlated with all-causes mortality in males whereas a tendency was observed in females. The same diverging association was observed for cardiovascular mortality. However, for coronary heart disease mortality, there was a very significant correlation only in females. CONCLUSIONS: Our findings confirm the observed gender-related differences in the relation of hyperuricemia with all-causes and coronary heart disease mortality. We propose possible pathogenic mechanisms concerning the relationship with coronary heart disease mortality observed only in females.