Adipocytokines and the risk of ischemic stroke: the PRIME Study.

OBJECTIVE: Adipocytokines are hormones secreted from adipose tissue that possibly link adiposity and the risk of cardiovascular disease, but limited prospective data exist on plasma adipocytokines and ischemic stroke risk. We investigated associations and predictive properties of 4 plasma adipocytokines, namely resistin, adipsin, leptin, and total adiponectin, with regard to incident ischemic stroke in the PRIME Study. METHODS: A cohort of 9,771 healthy men 50 to 59 years of age at baseline was followed up over a period of 10 years. In a nested case-control study, 95 ischemic stroke cases were matched with 190 controls on age, study center, and date of examination. Hazard ratios (HRs) per standard deviation increase in plasma adipocytokine levels were estimated using conditional logistic regression analysis. The additive value of adipocytokines in stroke risk prediction was evaluated by discrimination and reclassification metrics. RESULTS: Resistin (HR, 1.88; 95% confidence interval [CI], 1.16-3.03), adipsin (HR, 2.01; 95% CI, 1.33-3.04), and total adiponectin (HR, 1.53; 95% CI, 1.01-2.34), but not leptin, were independent predictors of ischemic stroke. The performance of a traditional risk factor model predicting ischemic stroke was significantly improved by the simultaneous inclusion of resistin, adipsin, and total adiponectin (c-statistic: 0.673 [95% CI, 0.631-0.766] vs 0.826 [95% CI, 0.792-0.892], p < 0.001; net reclassification improvement: 38.1%, p < 0.001). INTERPRETATION: Higher plasma levels of resistin, adipsin, and total adiponectin were associated with an increased 10-year risk of ischemic stroke among healthy middle-aged men. Resistin, adipsin, and total adiponectin provided incremental value over traditional risk factors for the prediction of ischemic stroke risk.

Depressive symptoms, a time-dependent risk factor for coronary heart disease and stroke in middle-aged men: the PRIME Study.

BACKGROUND AND PURPOSE: To date, the association between depressive symptoms and the risk of cardiovascular diseases remains controversial. We investigated prospectively, within the same population, the time course of the association between baseline depressive symptoms and first stroke or coronary heart disease event. METHODS: In the Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study, a multicenter, observational, prospective cohort, 9601 men from France and Northern Ireland were surveyed for the occurrence of first coronary heart disease (n=647) and stroke events (n=136) over 10 years. At baseline, the fourth quartile of a 13-item modified Center for Epidemiological Studies questionnaire was used to define the presence of depressive symptoms. We sought the best time-dependent function to assess the association between depressive symptoms and outcomes. Thus, the hazard ratios were estimated by a Cox proportional hazard model after splitting the follow-up before and after 5 years of follow-up time periods. RESULTS: Depressive symptoms at baseline were associated with coronary heart disease in the first 5 years of follow-up (hazard ratio, 1.43; 1.10-1.87) and with stroke in the second 5 years of follow up (hazard ratio, 1.96; 1.21-3.19) after adjustment for age, study centers, baseline socioeconomic factors, traditional vascular risk factors, and antidepressant treatment. The association was even stronger for ischemic stroke (n=108; hazard ratio, 2.48; 1.45-4.25). CONCLUSIONS: The current study suggests that in healthy, European, middle-aged men, baseline depressive symptoms are associated with an increased risk of coronary heart disease in the short-term, and for stroke in the long-term.

Effects of occupational and educational changes on obesity trends in France: the results of the MONICA-France survey 1986-2006.

OBJECTIVE: In the past decade, the obesity prevalence in France steadily increased. In the meantime the occupational and educational status of the population improved. This study examined the impact of these changes on obesity trends in France. METHODS: In the MONICA-France surveys in 1986, 1996 and 2006, 5423 men and 5271 women (35-64 yr old) were randomly recruited from electoral rolls in three areas of France (northern, eastern and south-western). We used a logistic regression to assess the association between obesity and time and occupational/educational categories and their interactions and a counterfactual analysis to assess the contributions of occupational and educational changes to obesity trends. RESULTS: Between 1986 and 2006, the prevalence of obesity rose from 15.0% to 18.4% (p < 0.004) in men and remained stable between 15.9% and 17.2% (p = 0.72) in women. Obesity increased in all occupational categories only in men (men: p = 0.0005; women: p < 0.22) and all educational categories in both genders (p < 0.0001). The estimated contributions of occupational (educational) changes to obesity trends were -0.3% (-2.8%) in men and -1.9% (-4.6%) in women. CONCLUSION: The improvement in the French population's occupational status and educational level between 1986 and 2006 tended to reduce the impact of secular trends on the obesity prevalence.

Paris Prospective Study III: a study of novel heart rate parameters, baroreflex sensitivity and risk of sudden death.

Resting heart rate has been related to the risk of cardiovascular disease and sudden death in several large prospective studies. To investigate prospectively the association of novel heart rate parameters and of carotid artery stiffness with sudden death and other cardiovascular disease. The Paris Prospective Study III (PPS3) is a new, ongoing French prospective study. From June 2008 to December 2011, 10,000 men and women aged 50-75 years who will have a preventive medical check-up at the Centre d'Investigations Préventives et Cliniques in Paris (France), will be enrolled in the study, after signing an informed consent. In addition to the general health examination, each subject's heart rhythm will be recorded during the course of the health check-up (approximately 2(1/2) h) and an echo-tracking of the right carotid bulb will be performed by trained technicians. A bio bank and DNA bank will be established for further biomarker and genetic analyses. The occurrence of cardiovascular disease including acute coronary syndrome, stroke, peripheral artery disease and sudden death, and of mortality, of the participants will be followed up during 20 years. With an estimated mean annual rate of sudden death of 0.1% and its increasing incidence rate with age, between 250 and 300 sudden deaths are expected. This unique study should provide new insights into the regulation of heart rate and blood pressure and should enable to identify novel heart rate parameters that are associated with sudden death.

Characteristics of current smokers, former smokers, and second-hand exposure and evolution between 1985 and 2007.

AIMS: The aim of this study was to assess trends in the prevalence of adult smoking habits between 1985-1987 and 2005-2007 in three distinct areas of France and their contribution to coronary heart disease (CHD) death rates. METHODS: Participants were recruited as part of the French Monitoring trends and determinants in Cardiovascular disease survey in 1985-1987 (n=3760), 1995-1997 (n=3347), and 2005-2007 (n=3573). They were randomly selected from electoral rolls after stratification for sex, 10-year age group (35-64 years), and town size. Smoking habits were analyzed by questioning the participants about earlier or current consumption, the number of cigarettes smoked per day, age at first cigarette, pipe tobacco and cigarillo consumption, quit attempts, age at quitting, and second-hand exposure. Predicted CHD death rates as a function of smoking were predicted with the SCORE risk equation. RESULTS: In men, a significant decrease in tobacco exposure (from 40 to 24.3%) between 1985-1987 and 2005-2007 was observed. In women, the prevalence of current smokers increased from 18.9 to 20% and that of former smokers rose from 8.7 to 25.5%. In both men and women, average daily cigarette consumption and second-hand exposure to smoke fell between 1995-1997 and 2005-2007. Predicted CHD death rates as a function of smoking trends decreased in men (range 10-15%) but increased in women (range 0.1-3.6%). CONCLUSION: This study found divergent trends in the prevalence of smoking in men and women aged between 35 and 64 years over the period of 1985 to 2007. These changes may have contributed to the decline in CHD death in men but not in women.

Study of the genetic variability of ZAC1 (PLAGL1) in French population-based samples.

OBJECTIVES: ZAC1 (zinc finger protein regulating apoptosis and cell cycle arrest) is a member of the new subfamily of zinc-finger transcription factors, designated as PLAG (pleomorphic adenoma gene) family. The ZAC1 gene is maternally imprinted and is linked to developmental disorders such as growth retardation and transient neonatal diabetes mellitus. We wanted to assess whether the genetic variability of the ZAC1 gene was associated with anthropometric (weight, BMI, waist-to-hip ratio) or biochemical (plasma lipid, insulin, glucose levels, blood pressure level) phenotypes. METHODS: We selected 37 independent SNPs (single nucleotide polymorphisms) or tagSNPs in the ZAC1 locus from the literature and several databases and, based on the linkage disequilibrium map, identified 27 independent SNPs. Those 27 SNPs were genotyped in a French population-based sample (n = 1155). Associations with a P value lower than 0.0019 (Bonferroni correction) were considered significant. RESULTS: We found that women carrying the T allele of rs9403542 had lower waist-to-hip ratio (P = 0.0006) than women with the CC genotype. Also, men bearing the T allele of rs13218225 had lower systolic (P = 3.6 x 10(-5)) and diastolic (P = 4.1 x 10(-4)) blood pressure than GG men. As a consequence, the adjusted (for age, smoking habit, alcohol consumption, physical activity level and BMI) odds ratio (95% confidence interval) of hypertension for T allele carrier men was 0.55 [0.35-0.86], P = 0.009. We genotyped two other independent samples (MONICA Toulouse, n = 1130 and MONICA Strasbourg, n = 1048) for rs9403542 and rs13218225 but we could not confirm these associations. CONCLUSION: We found no evidence that polymorphisms in ZAC1 might influence anthropometric, biochemical or clinical parameters in French individuals.

Respective contribution of conventional risk factors and antihypertensive treatment to stable angina pectoris and acute coronary syndrome as the first presentation of coronary heart disease: the PRIME Study.

OBJECTIVE: To test whether conventional risk factors and antihypertensive treatment were more predictive of stable angina (SA) than acute coronary syndrome (ACS) as the first presentation of coronary heart disease (CHD). DESIGN: We used data from the PRIME Study (Prospective Epidemiological Study of Myocardial Infarction), a prospective cohort of 9758 asymptomatic middle-aged men recruited from WHO MONICA centers in Northern Ireland and France between 1991 and 1993. SA and ACS events were registered during 5 years of follow-up. METHODS: Hazard ratios (HRs) of each risk factor measured at baseline for SA and ACS events were assessed using separate Cox proportional hazard models. Difference between HRs was estimated by the bootstrap method. RESULTS: After 5 years of follow-up, there were 114 SA and 178 ACS as the first presentation of CHD. Diastolic blood pressure [adjusted HRs for 1 standard deviation increase = 1.34; 95% confidence interval (CI): 1.17-1.54 vs. 1.04; 95% CI: 0.87-1.25; P for comparison between HRs = 0.012], and possibly cigarette smoking over or equal to 20 pack-years (adjusted HR = 2.07; 95% CI: 1.43-2.99 vs. 1.29; 95% CI: 0.83-2.01; P for comparison between HRs = 0.062) were more predictive of ACS than SA, whereas this was the opposite for antihypertensive treatment (adjusted HR = 2.18; 95% CI: 1.39-3.41 for SA vs. 1.28; 95% CI: 0.85-1.93 for ACS, P for comparison between HRs = 0.049). CONCLUSION: The present data support that SA and ACS, as the first presentation of CHD, may not share exactly the same determinants.

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.

The APOA5 Trp19 allele is associated with metabolic syndrome via its association with plasma triglycerides.

BACKGROUND: The goal of the present study was to assess the effect of genetic variability at the APOA5/A4/C3/A1 cluster locus on the risk of metabolic syndrome. METHODS: The APOA5 Ser19Trp, APOA5 -12,238T>C, APOA4 Thr347Ser, APOC3 -482C>T and APOC3 3238C>G (SstI) polymorphisms were analyzed in a representative population sample of 3138 men and women from France, including 932 individuals with metabolic syndrome and 2206 without metabolic syndrome, as defined by the NCEP criteria. RESULTS: Compared with homozygotes for the common allele, the odds ratio (OR) [95% CI] for metabolic syndrome was 1.30 [1.03-1.66] (p = 0.03) for APOA5 Trp19 carriers, 0.81 [0.69-0.95] (p = 0.01) for APOA5 -12,238C carriers and 0.84 [0.70-0.99] (p = 0.04) for APOA4 Ser347 carriers. Adjustment for plasma triglycerides, (but not for waist girth, HDL, blood pressure or glycemia - the other components of metabolic syndrome) abolished these associations and suggests that triglyceride levels explain the association with metabolic syndrome. There was no association between the APOC3 -482C>T or APOC3 3238C>G polymorphisms and metabolic syndrome. The decreased risk of metabolic syndrome observed in APOA5 -12,238C and APOA4 Ser347 carriers merely reflected the fact that the APOA5 Trp19 allele was in negative linkage disequilibrium with the common alleles of APOA5 -12,238T>C and APOA4 Thr347Ser polymorphisms. CONCLUSION: The APOA5 Trp19 allele increased susceptibility to metabolic syndrome via its impact on plasma triglyceride levels.

Smoking habits, waist circumference and coronary artery disease risk relationship: the PRIME study.

INTRODUCTION: Abdominal obesity is an important risk factor for coronary artery disease (CAD). The extent to which tobacco exposure influences the effect of abdominal adiposity on CAD incidence remains uncertain. Therefore, the goal of this study was to assess the effects of tobacco exposure on CAD risk associated with abdominal obesity. METHODS: A cohort of 9763 men, aged 50-59 years, without known CAD was followed 10 years for CAD events. Risk factors were recorded using a questionnaire, a clinical examination, including waist circumference (WC) and waist-to-hip ratio (WHR) and biological measurements. Cox regression was used for statistical analyses. RESULTS: During follow-up, there were 659 incident CAD events. BMI, WC, WHR, blood pressure, cholesterol, high-density lipid cholesterol and triglycerides, physical activity and alcohol intake varied across smoking exposure categories. The incidence of CAD increased across tertiles of waist circumference in never (5.1, 6.1 and 7.2 CAD events/1000 in first, second and third tertiles of WC distribution, respectively), former (6.6, 7.8 and 9.3 events/1000, across tertiles) and current smokers (9.4, 11 and 13.1 events/1000, across tertiles). After adjusting for age, centre, educational level, alcohol intake and physical activity, the relative risk of CAD was 1.28 (1.08-1.51) for 1 standard deviation increase of WC in never smokers, 1.23 (1.08-1.38) in former smokers and 1.14 (1.00-1.29) in current smokers. Similar results were observed for WHR. No evidence for heterogeneity among tobacco exposure strata for both WC and WHR was observed. CONCLUSION: In conclusion, the relative risk of CAD associated with abdominal obesity is homogeneous in never, former and current smokers. Therefore, smokers with abdominal obesity are at high absolute risk of CAD.

Independent contribution of dairy products and calcium intake to blood pressure variations at a population level.

PURPOSE: Previous studies have shown a potential inverse relationship between blood pressure and daily calcium intake. The aim of the study was to assess the independent contribution of dairy product and calcium intake to blood pressure variations at a population level. METHODS: A sample of 912 men aged 45-64 years was randomly selected from the general population, as part of the French MONICA cross-sectional survey on cardiovascular risk factors (1995-1996). Extensive questionnaires on risk factors were filled out and each participant completed a three-consecutive-day food record. Two blood pressure measurements were performed at rest. In statistical analyses subjects were grouped according to quintiles of dairy product or calcium intakes. RESULTS: Systolic and diastolic blood pressures significantly decreased from the lowest [145.4 (standard error (SE) 1.55) and 89.0 (SE 0.94) mmHg respectively] to the highest quintile [135.6 (SE 1.26) and 85.3 (SE 0.84) mmHg respectively] of dairy product intakes in bivariate analysis. After multivariate linear regression analysis adjusted for confounders [centre, age, daily sodium, magnesium, calcium and alcohol intake, daily energy intake without alcohol, dieting, physical activity, body mass index (BMI), smoking, and use of antihypertensive or lipid-lowering drugs], the difference in systolic blood pressure remained significant. Results were similar when calcium intake was considered. After adjustment for confounders, the association between calcium-dairy product combination and blood pressure was the most significant when intakes of dairy products and calcium were both higher than the median. CONCLUSION: Dairy products and dietary calcium are both significantly and independently associated with low levels of systolic blood pressure.

Fasting insulin concentrations and coronary heart disease incidence in France and Northern Ireland: the PRIME Study.

BACKGROUND: Reports about the relationships between insulin concentrations and CHD risk are controversial. The objective of this survey was to study the association between insulin levels and CHD risk in middle-aged male participants of the PRIME Study after 5 years of follow-up. METHODS: Our study adopted a nested case-control design including 294 cases of CHD and 536 controls randomly selected among healthy participants from the PRIME cohort. Data were obtained by questionnaires (medical history, lifestyle), standardised clinical measurements (blood pressure, anthropometric measurements), and a blood sample was obtained for biological measurements. Odds-Ratios for associations of four ordered classes of insulin concentration with CHD risk after adjustment for confounding factors were estimated using conditional logistic regression. RESULTS: In Belfast, a significant trend (p<0.03) was observed between insulin classes and CHD risk in bivariate analyses, but this association lost its significance after multiple adjustments. In the French centres, a high risk of CHD (OR=3.24 [1.80-5.85], p<0.0001) was observed only for the second class of insulin concentration (6.5 to 9.9 mIU/l), compared with the reference class (<6.5 mIU/l). After multiple adjustments, this association remained highly significant (OR=2.92 [1.44-5.92], p<0.005). CONCLUSIONS: In Belfast (high-risk population), a significant trend was observed between insulin concentration classes and CHD risk but hyperinsulinaemia lost its association with CHD risk in multivariate analyses. In the French centres (lower risk population), slightly increased insulin concentrations were associated with a high risk of CHD, independently of cardiovascular risk factors and other features of the metabolic syndrome, but very high insulin concentrations were not.

Household income is associated with the risk of metabolic syndrome in a sex-specific manner.

OBJECTIVE: To assess the relationship between household income and metabolic syndrome in men and women. RESEARCH DESIGN AND METHODS: A total of 1,695 men and 1,664 women, aged 35-64 years, from three distinct geographical areas of France were investigated. Waist girth, plasma triglycerides, HDL cholesterol, glucose, and systolic blood pressure were used to define metabolic syndrome according to the National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATPIII) guidelines. Household income, educational level, occupational category, working status, consumption of psychotropic drugs, accommodation status, household composition, physical activity at work and during leisure time, alcohol consumption, and smoking habits were recorded with a standardized questionnaire. RESULTS: There were 390 (23.0%) men and 381 (16.9%) women who satisfied NCEP/ATPIII criteria for metabolic syndrome. Household income (P < 0.0001) and consumption of psychotropic drugs (P = 0.0005) were associated with metabolic syndrome in women but not in men. In contrast, educational level, occupational category, working status, and accommodation status were associated with metabolic syndrome in both men and women. After adjustment on lifestyle variables, household income (interaction P < 0.004) remained inversely associated with metabolic syndrome in women but not in men. CONCLUSIONS: These data suggest that limited household income, which reflects a complex unfavorable social and economic environment, may increase the risk of metabolic syndrome in a sex-specific manner.

Fish consumption is associated with lower heart rates.

BACKGROUND: Fish consumption decreases risk of sudden death. The goal of the present study was to assess the relationship between fish consumption and heart rate. METHODS AND RESULTS: A cross-sectional analysis was conducted of 9758 men, age 50 to 59 years, without coronary heart disease (CHD) who were recruited in France and Belfast, Ireland, from 1991 to 1993. Heart rate and CHD risk factors were compared among 4 categories of fish consumption, as follows: (1) less than once per week (n=2662), (2) once per week (n=4576), (3) twice per week (n=1964), and (4) more than twice per week (n=556). Fatty acid profiles of erythrocyte phospholipids were determined in a random subsample of 407 subjects. In erythrocyte phospholipids, eicosapentaenoic acid (P<0.0005), docosahexaenoic acid (P<0.0001), and total n-3 fatty acid (P<0.0008) increased across the categories of fish intake. Triglycerides (P<0.0001), systolic blood pressure (P<0.006), and diastolic blood pressure (P<0.0001) were lower and HDL cholesterol levels (P<0.004) were higher in fish consumers than in nonconsumers. Similarly, heart rate decreased across the categories of fish intake (P<0.0001). After adjustment for age, center, education level, physical activity, smoking habit, alcohol consumption, body mass index, and antiarrhythmic medications, heart rate remained statistically lower among fish consumers than among nonconsumers (P for trend <0.0001). Docosahexaenoic acid content of erythrocyte phospholipids was inversely correlated with heart rate (P<0.03). CONCLUSIONS: Fish consumption is associated with decreased heart rate in men. Because heart rate is positively associated with risk of sudden death, this association may explain, at least in part, the lower risk of sudden death among fish consumers.

Lack of association between serological evidence of past Coxiella burnetii infection and incident ischaemic heart disease: nested case-control study.

BACKGROUND: Coxiella burnetii causes the common worldwide zoonotic infection, Q fever. It has been previously suggested that patients who had recovered from acute Q fever (whether symptomatic or otherwise) may be at increased risk of ischaemic heart disease. We undertook this study to determine if past infection with Coxiella burnetii, the aetiological agent of Q fever, is a risk factor for the subsequent development of ischaemic heart disease. METHODS: A nested case-control study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME). The PRIME study is a cohort study of 10,593 middle-aged men undertaken in France and Northern Ireland in the 1990s. A total of 335 incident cases of ischaemic heart disease (IHD) were identified and each case was matched to 2 IHD free controls. Q fever seropositivity was determined using a commercial IgG ELISA method. RESULTS: Seroprevalence of Q fever in the controls from Northern Ireland and France were 7.8% and 9.0% respectively. No association was seen between seropositivity and age, smoking, lipid levels, or inflammatory markers. The unadjusted odds ratio (95% CI) for Q fever seropositivity in cases compared to controls was 0.95 (0.59, 1.57). The relationship was substantially unaltered following adjustment for cardiovascular risk factors and potential confounders. CONCLUSION: Serological evidence of past infection with C. burnetii was not found to be associated with an increased risk of IHD.

Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population.

The distribution of risk factors for cardiovascular disease in patients aged 35-44 years who were treated for human immunodeficiency virus type 1 (HIV-1) infection was compared with that for a population-based cohort. HIV-1-infected men treated with a protease inhibitor-containing regimen (n=223), compared with HIV-1-uninfected men (n=527), were characterized by a lower prevalence of hypertension, a lower mean high-density lipoprotein cholesterol level, a higher prevalence of smoking, a higher mean waist-to-hip ratio, and a higher mean triglyceride level. No difference was found for total plasma or low-density cholesterol levels, nor for the prevalence of diabetes. Similar trends were observed among female subjects. The predicted risk of coronary heart disease was greater among HIV-1-infected men (relative risk [RR], 1.20) and women (RR, 1.59; P<10(-6) for both), compared with the HIV-1-uninfected cohort. The estimated attributable risks due to smoking were 65% and 29% for HIV-1-infected men and women, respectively. Because most HIV-1-infected people will ultimately need antiretroviral therapy, risk factors for cardiovascular disease should be determined at the initiation of treatment, and interventions should be considered for all patients who have them.

Residual coronary risk in men aged 50-59 years treated for hypertension and hyperlipidaemia in the population: the PRIME study.

OBJECTIVE: Since the proportion of subjects taking antihypertensive and lipid-lowering drugs is currently increasing in industrialized countries, it is important to evaluate, at the population level, coronary risk of treated individuals, while taking into account the achieved level of their risk factors (i.e. their 'residual coronary risk'). DESIGN AND METHODS: We used the data from the Prospective Study of Myocardial Infarction (PRIME), which involved populations from France (three centres) and Northern Ireland (one centre) (in each centre, 2500 men, aged 50-59 years, free of coronary heart disease, with a 5-year follow-up), to analyse the relationships between cardiovascular drug use and subsequent coronary risk. RESULTS: Antihypertensive drug use was significantly positively associated (relative risk = 1.60; 95% confidence interval, 1.18-2.16) with total coronary risk, but not lipid-lowering drug use (relative risk = 1.15; 95% confidence interval, 0.77-1.73), while adjusting on classical risk factor levels (age, smoking, total cholesterol, high-density lipoprotein-cholesterol and systolic blood pressure). Subgroup analysis showed that these results applied to beta-blockers and calcium channel antagonists, but not to diuretics and angiotensin-converting enzyme inhibitors, to both angina pectoris and hard coronary event risk, but in the French population only and not in Belfast. Although the PRIME study was not designed to test the ability of different drugs to prevent coronary heart disease, this analysis raises the hypothesis that antihypertensive drugs could be associated with a sizeable residual coronary risk in middle-aged men. CONCLUSION: Treatment with antihypertensive agents, beta-blockers and calcium channel antagonists in particular, was associated with a sizeable residual coronary risk. It seems, therefore, important to consider antihypertensive treatment in the cardiovascular risk assessment of individuals.

Body mass index, hypertension and 5-year coronary heart disease incidence in middle aged men: the PRIME study.

OBJECTIVE: The aim of the present study was to assess the joint contribution of hypertension and body mass index to coronary heart disease risk. DESIGN Prospective study on men aged 50-59 years free of coronary heart disease at entry recruited in three regions of France (n = 7359) and in Northern Ireland (n = 2399). PARTICIPANTS: The recruitment frame was based on industry and various employment groups, on health screening centers and general practice. MAIN OUTCOME: Incident cases of effort angina, unstable angina, myocardial infarction and coronary death were recorded over a 5-year follow-up. RESULTS: Compared with the reference group [body mass index (BMI) 25 kg/m2], the relative risk of coronary event was higher in the second (25 < or =BMI 27.6) and third BMI tertiles: 1.27 (95% confidence interval 0.94-1.70) and 1.14 (0.84-1.56) after adjustment for confounders and covariates, including diabetes, hypertension and lipoprotein levels. Further analyses revealed a significant interaction between hypertension and BMI on coronary disease risk (P <0.05), suggesting that hypertension modifies coronary heart disease (CHD) risk attributable to BMI. Among hypertensive men, the relative risk of coronary heart disease was 1.34 (0.85-2.11) and 1.61 (1.04-2.50) in the second and third BMI tertiles, respectively. In normotensive men, BMI was not associated with CHD risk; relative risk 1.25 (0.85-1.85) and 0.66 (0.40-1.09) in the second and third BMI, respectively. CONCLUSION: These results indicate that hypertension and overweight jointly increase coronary heart disease risk.

Gender- and age-specific trends in coronary heart disease mortality in France from 2000 to 2007: results from the MONICA registers.

BACKGROUND: Several recent studies in the USA, the UK and Australia have raised concern about a possible plateau or even reverse trend in coronary heart disease (CHD) mortality in younger populations. We aimed to assess the recent gender- and age-specific trends in CHD mortality among inhabitants aged 35-74 years from the three geographical areas covered by the French MONICA population registers. METHODS: Registered events were fatal myocardial infarctions and coronary deaths selected after a thorough investigation by the physician who signed the death certificate, general practitioners and cardiologists, and by public and private hospitals for in-hospital deaths. RESULTS: From 2000 to 2007 age-standardized CHD mortality rates decreased significantly by 24% in men and 38% in women. In the age group 55-74, the estimated annual percentage change (EAPC) in mortality was -5.2 (95% confidence interval: -6.6 to -3.7; p < 10(-4)) among men and -9.0 (-11.6 to -6.4; p < 10(-4)) among women. In the 35-54 age group, the EAPC in mortality was -4.1 (-7.2 to -1.1; p < 10(-2)) among men and -2.5 (-8.7 to 3.7; p = 0.43) among women. These trends remained similar when possible coronary deaths were also accounted for, except in young men where the decline was no longer significant. CONCLUSIONS: A clear decline in recent CHD mortality rates was observed among subjects above 54 years, but not among younger subjects, particularly in women. These results may be due to unfavourable trends in some risk factors in the latter age group and call for a strengthening of primary prevention.