Bernadette Haas

Contributions of Depressive Mood and Circulating Inflammatory Markers to Coronary Heart Disease in Healthy European Men The Prospective Epidemiological Study of Myocardial Infarction (PRIME)

Background—Data on the possible association between depressive disorders and inflammatory markers are scarce and inconsistent. We investigated whether subjects with depressive mood had higher levels of a wide range of inflammatory markers involved in coronary heart disease (CHD) incidence and examined the contribution of these inflammatory markers and depressive mood to CHD outcome. Methods and Results—We built a nested case-referent study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study of healthy middle-aged men from Belfast and France. We considered the baseline plasma sample from 335 future cases (angina pectoris, nonfatal myocardial infarction, coronary death) and 670 matched controls (2 controls per case). Depressive mood characterized men whose baseline depression score (13-item modification of the Welsh depression subscale) was in the fourth quartile (mean score, 5.75; range, 4 to 12). On average, men with depressive mood had 46%, 16%, and 10% higher C-reactive protein, interleukin-6, and intercellular adhesion molecule-1 levels, respectively, independently of case-control status, social characteristics, and classic cardiovascular risk factors; no statistical difference was found for fibrinogen. The odds ratios of depressive mood for CHD were 1.35 (95% CI, 1.05 to 1.73) in univariate analysis and 1.50 (95% CI, 1.04 to 2.15) after adjustment for social characteristics and classic cardiovascular risk factors. The latter odds ratio remained unchanged when each inflammatory marker was added separately, and in this analysis, each inflammatory marker contributed significantly to CHD event risk. Conclusions—These data support an association of depressive mood with inflammatory markers and suggest that depressive mood is related to CHD even after adjustment for these inflammatory markers.

Relative Risks for Stroke by Age, Sex, and Population Based on Follow-Up of 18 European Populations in the MORGAM Project

Background and Purpose— Within the framework of the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, the variations in impact of classical risk factors of stroke by population, sex, and age were analyzed. Methods— Follow-up data were collected in 43 cohorts in 18 populations in 8 European countries surveyed for cardiovascular risk factors. In 93 695 persons aged 19 to 77 years and free of major cardiovascular disease at baseline, total observation years were 1 234 252 and the number of stroke events analyzed was 3142. Hazard ratios were calculated by Cox regression analyses. Results— Each year of age increased the risk of stroke (fatal and nonfatal together) by 9% (95% CI, 9% to 10%) in men and by 10% (9% to 10%) in women. A 10-mm Hg increase in systolic blood pressure involved a similar increase in risk in men (28%; 24% to 32%) and women (25%; 20% to 29%). Smoking conferred a similar excess risk in women (104%; 78% to 133%) and in men (82%; 66% to 100%). The effect of increasing body mass index was very modest. Higher high-density lipoprotein cholesterol levels decreased the risk of stroke more in women (hazard ratio per mmol/L 0.58; 0.49 to 0.68) than in men (0.80; 0.69 to 0.92). The impact of the individual risk factors differed somewhat between countries/regions with high blood pressure being particularly important in central Europe (Poland and Lithuania). Conclusions— Age, sex, and region-specific estimates of relative risks for stroke conferred by classical risk factors in various regions of Europe are provided. From a public health perspective, an important lesson is that smoking confers a high risk for stroke across Europe.

Anthropometric assessment of abdominal obesity and coronary heart disease risk in men: the PRIME study

Objective: Waist-to-height ratio is an anthropometric indicator of abdominal obesity that accounts for stature. Earlier studies have reported marked associations between the waist-to-height ratio and cardiovascular risk factors. The goal of this study was to compare the associations of waist-to-height ratio, waist girth, waist-to-hip ratio or body mass index (BMI) with incidence of coronary events. Design: Prospective study with 10 602 men, aged 50–59 years, recruited between 1991 and 1993 in three centres in France and one centre in Northern Ireland. Clinical and biological data were obtained at interview by trained staff. During the 10 years of follow-up 659 incident coronary events (CHD) were recorded. The relations between anthropometric markers and coronary events were estimated by Cox proportional hazards models. Results: Waist circumference, waist-to-hip ratio, waist-to-height ratios and BMI were positively associated with blood pressure (p<0.0001), diabetes (p<0.0001), low-density lipoprotein (LDL)-cholesterol (p<0.0001), triglycerides (p<0.0001) and inversely correlated to high-density lipoprotein (HDL)-cholesterol (p<0.0001). There was a linear association between waist circumference, waist-to-hip ratio, waist-to-height ratio, BMI and CHD events. The age-adjusted and centre-adjusted relative risks (95% CI) for CHD were 1.57 (1.22 to 2.01), 1.75 (1.34 to 2.87), 2.3 (1.79 to 2.99) and 1.99 (1.54 to 2.56) in the 5th quintile vs the first quintile of waist circumference, waist-to-hip ratio, waist-to-height ratio and BMI distribution, respectively. After further adjustment for school duration, physical activity, tobacco and alcohol consumption, hypertension, diabetes, HDL-cholesterol and triglycerides, the relative risks for CHD were 0.99 (0.76 to 1.30) for waist circumference (p = 0.5), 1.22 (0.93 to 1.60) for waist-to-hip ratio (p = 0.1), 1.53 (1.16 to 2.01) for waist-to-height ratio (p = 0.03) and 1.30 (0.99 to 1.71) for BMI (p = 0.06). Conclusion: In middle-aged European men, waist-to-height ratio identifies coronary risk more strongly than waist circumference, waist-to-hip ratio or BMI, though the difference is marginal.

Trends in plasma lipids, lipoproteins and dyslipidaemias in French adults, 1996–2007

BACKGROUND In France, the reported decrease in cardiovascular death is due partly to improved cardiovascular prevention. The management of dyslipidaemias remains a priority of preventive cardiology. AIM To assess trends in lipids, lipoproteins and dyslipidaemias between 1996 and 2007 in France. METHODS Representative surveys of the general population were carried out in Lille, Strasbourg and Toulouse during two periods, 1996 to 1997 and 2006 to 2007. Men and women aged 35 to 64 years were included. Investigators recorded cardiovascular risk factors, and a blood sample was drawn to measure glycaemia and to provide a complete lipid profile. The data were corrected according to the respective original populations to study 10-year trends in the parameters measured. RESULTS From 1996 to 2007, a significant 5.7% decrease in low-density lipoprotein (LDL)-cholesterol levels was observed in adults aged 35 to 64 years (p<0.001). This decrease was greater in those aged 55 to 64 years (10.8% in men, 8.4% in women). A significant 7.8% increase in triglycerides was observed (p<0.001) over the same period. Variation in LDL-cholesterol was more striking in subjects treated with a lipid-lowering drug, with a 17.6% reduction (p<0.001). A decrease in most of dyslipidaemias was also observed over this 10-year interval. CONCLUSION This study shows a favourable downward trend in LDL-cholesterol concentration and dyslipidaemias in France. The significant decrease in LDL-cholesterol observed among all the subjects and more particularly among subjects treated with lipid-lowering drugs should provide an incentive for physicians to support the management of all French adults.

Contribution of novel biomarkers to incident stable angina and acute coronary syndrome: the prime study

AIMS To compare whether novel inflammatory and haemostatic biomarkers are more predictive of well-characterized incident acute coronary syndrome (ACS) than stable angina (SA). METHODS AND RESULTS We used data from the PRIME Study, a prospective cohort of 9758 asymptomatic middle-aged men recruited in Northern Ireland and France between 1991 and 1993. A nested case-control study was established with the baseline plasma sample of 269 incident cases and 538 matched controls. Odds ratios (ORs) for SA and ACS were estimated by conditional logistic regression analysis. After 5 years of follow-up, 107 incident SA and 162 ACS cases were validated. After adjustment for traditional risk factors, higher circulating levels of hs-CRP, ICAM1, interleukin 6 and interleukin 18 were equally predictive of SA and ACS (all P-values of OR comparison >0.05). In contrast, elevated levels of fibrinogen, von Willebrand factor, and possibly higher level of D-dimers and lower level of tissue factor pathway inhibitor were associated with ACS only. The comparison of the ORs showed a statistically significant difference for von Willebrand factor only [OR(4th vs. 1st quartile) = 2.99 (1.49-6.02) for ACS vs. 0.80 (0.33-1.94) for SA; P(z test) = 0.02]. CONCLUSION This is the first population-based study suggesting that higher levels of circulating haemostatic markers and of von Willebrand factor, in particular, are significantly more predictive of incident ACS than SA.

Residential environment and blood pressure in the PRIME Study: is the association mediated by body mass index and waist circumference?

Objectives Few studies have examined whether social characteristics of the residential environment are associated with blood pressure after controlling for individual sociodemographic characteristics. Even less is known about the processes by which these associations operate. Therefore, we examined whether distinct dimensions of the residential environment (socioeconomic position and urbanicity) were associated with systolic blood pressure. To better understand the processes involved in the associations between contextual factors and blood pressure, we assessed the extent to which these associations were mediated by body mass index and waist circumference. Methods We analysed data from the PRIME Study (7850, 50–60-year-old men surveyed in 1991–1993 in three French regions and recently geocoded on a local scale). We used multilevel regression models to estimate associations between contextual factors and blood pressure, and path analysis to investigate possible mediators of these associations. Results After adjustment for individual socioeconomic variables, systolic blood pressure increased independently with decreasing municipality population density and decreasing neighbourhood educational level. Path analysis indicated that approximately 37% of the association between neighbourhood education and blood pressure was statistically explained by the heavier weight and stronger central adiposity of people from deprived neighbourhoods. Approximately 19% of the association with population density was mediated by anthropometric factors. Conclusions These data suggest that the neighbourhood environment may influence blood pressure; only part of the associations between contextual factors and blood pressure may operate through body weight and body shape modification.

Relationships between alcoholic beverages and cardiovascular risk factor levels in middle-aged men the PRIME study

The relationships between alcoholic beverages and cardiovascular risk factors were assessed in 6730 men living in France or Northern Ireland. In France, all alcoholic beverages were significantly correlated with body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), high density lipoprotein (HDL) parameters, PAI-1 and Factor VII, whereas only wine was negatively related with fibrinogen levels. After adjusting for center, age, BMI, educational level, smoking and marital status, wine had a lesser effect on blood pressure, triglyceride, apo B and LpE:B levels than beer. Wine was associated with lower fibrinogen levels and beer with higher PAI-1 activity levels independent of the amount of alcohol consumed. In Northern Ireland, wine was negatively correlated with BMI, triglycerides, LpE:B and fibrinogen, whereas beer was positively correlated with SBP and DBP, triglycerides, HDL, apoprotein A-I and fibrinogen. Multivariate analysis showed wine to be positively associated with HDL parameters, and negatively with fibrinogen levels. Wine was also associated with higher LpA-I levels and lower fibrinogen levels independent of the amount of alcohol consumed. We conclude that alcohol consumption is related to lipid, lipoprotein and haemostatic variables, but the magnitude of the relationships depends on the type of alcoholic beverage. Also, some effects might be related to non-alcoholic components.

Association between the frequency of fruit and vegetable consumption and cardiovascular disease in male smokers and non-smokers

Background/Objectives:Consumption of fruit and vegetables (F&V) is associated with a lower cardiovascular disease (CVD) risk. Smoking may affect the strength of this association. The objective of this study was to compare the relationship between the frequency of F&V intake and CVD risk in male current, former and never smokers.Subjects/Methods:A prospective study in men (n=8060) aged 50–59 years who were recruited in France and Northern Ireland. The frequency of F&V intake was assessed by using a food frequency questionnaire. The outcome criteria were incident cases of acute coronary syndrome (ACS) and total CVD (coronary heart disease and stroke) over 10-year period.Results:A total of 367 ACS and 612 CVD events occurred during the follow-up period. A multivariate analysis revealed a statistically significant interaction between smoking status and F&V intake for ACS and for CVD (both Ps<0.05). In current smokers, the relative risks for ACS were 0.78 (0.54–1.13) and 0.49 (0.30–0.81) in the second and third tertiles of F&V intake, respectively (P for trend<0.001); for CVD, the values were 0.80 (0.59–1.08) and 0.64 (0.44–0.93) respectively (P for trend<0.001). In contrast, no statistically significant associations were observed for never and former smokers. Similar statistical interactions for ACS were observed for fruit intake (P=0.07) and vegetable intake (P<0.05) taken separately.Conclusions:These results suggest that high fruit and vegetable intake is associated with a lower risk of CVD in male smokers.

Patterns of alcohol consumption in middle-aged men from France and Northern Ireland. The PRIME Study

Objective: To assess the patterns of alcohol consumption in France and Northern Ireland.Design: Four cross-sectional studies.Setting: Sample of 50–59 y old men living in France and Northern Ireland, consuming at least one unit of alcoholic beverage per week.Subjects: 5363 subjects from France and 1367 from Northern Ireland.Interventions: None.Results: Consumption of wine was higher in France whereas consumption of beer and spirits was higher in Northern Ireland. Alcohol drinking was rather homogeneous throughout the week in France, whereas Fridays and Saturdays accounted for 60% of total alcohol consumption in Northern Ireland. In both countries, current smokers had a higher consumption of all types of alcoholic beverages than non-smokers. Similarly, obese and hypertensive subjects had a higher total alcohol consumption than non-obese or normotensive subjects, but the type of alcoholic beverages differed between countries. In Northern Ireland, subjects which reported some physical activity consumed significantly less alcoholic beverages than sedentary subjects, whereas no differences were found in France. Conversely, subjects with dyslipidemia consumed more alcoholic beverages than normolipidemic subjects in France, whereas no differences were found in Northern Ireland. In France, total alcohol, wine and beer consumption was negatively related to socioeconomic status and educational level. In Northern Ireland, total alcohol, beer and spirits consumption was negatively related whereas wine consumption was positively related to socioeconomic status and educational level.Conclusions: Alcohol drinking patterns differ between France and Northern Ireland, and also according to cardiovascular risk factors, socioeconomic and educational levels.Sponsorship: Merck, Sharp & Dohme-Chibret (France), the NICHSA and the Department of Health and Social Service (Northern Ireland).European Journal of Clinical Nutrition (2000) 54, 321–328

Multiple Biomarkers for the Prediction of Ischemic Stroke The PRIME Study

Objective—To simultaneously evaluate 14 biomarkers from distinct biological pathways for risk prediction of ischemic stroke, including biomarkers of hemostasis, inflammation, and endothelial activation as well as chemokines and adipocytokines. Methods and Results—The Prospective Epidemiological Study on Myocardial Infarction (PRIME) is a cohort of 9771 healthy men 50 to 59 years of age who were followed up over 10 years. In a nested case–control study, 95 ischemic stroke cases were matched with 190 controls. After multivariable adjustment for traditional risk factors, fibrinogen (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03–2.28), E-selectin (OR, 1.76; 95% CI, 1.06–2.93), interferon-&ggr;-inducible-protein-10 (OR, 1.72; 95% CI, 1.06–2.78), resistin (OR, 2.86; 95% CI, 1.30–6.27), and total adiponectin (OR, 1.82; 95% CI, 1.04–3.19) were significantly associated with ischemic stroke. Adding E-selectin and resistin to a traditional risk factor model significantly increased the area under the receiver-operating characteristic curve from 0.679 (95% CI, 0.612–0.745) to 0.785 and 0.788, respectively, and yielded a categorical net reclassification improvement of 29.9% (P=0.001) and 28.4% (P=0.002), respectively. Their simultaneous inclusion in the traditional risk factor model increased the area under the receiver-operating characteristic curve to 0.824 (95% CI, 0.770–0.877) and resulted in an net reclassification improvement of 41.4% (P<0.001). Results were confirmed when using continuous net reclassification improvement. Conclusion—Among multiple biomarkers from distinct biological pathways, E-selectin and resistin provided incremental and additive value to traditional risk factors in predicting ischemic stroke.