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.

Interregional differences in the clinical, biological and electrical characteristics of first acute coronary events in France: results from the MONICA registries.

BACKGROUND: In France, there is a large north-to-south, decreasing gradient in case fatality rates of hospitalized patients for an acute coronary event. This gradient may be explained by differences in the presenting patients' clinical, biological and electrocardiographic characteristics. GOAL: To compare the characteristics of patients hospitalized for an acute episode of coronary insufficiency in three regions of France with contrasting fatality rates. METHODS: We assessed all men and women (aged 35-74 years) covered by the MONICA registries in three geographical areas (north, east and south-west France) and hospitalized in 2006 for a first acute coronary event. The symptoms, electrocardiogram features, left ventricular ejection fraction (LVEF) and troponin levels were systematically transcribed from medical files. Vital status was followed up for one year. RESULTS: Fatality rates at 28 days and 1 year were higher in the north (7% and 12%, respectively) than in the east (5% and 7%) and in the south-west (2% and 5%). Major symptoms (such as cardiac arrest, acute pulmonary oedema and cardiac shock), altered LVEF and ST+ myocardial infarction (STEMI) were more frequent in the north than in the south-west (all p < 0.0001) - pointing to marked inter-regional differences in the presentation of acute coronary syndromes (ACSs). In multivariate analyses, age, major symptoms, altered LVEF and STEMI remained strongly associated with 28-day lethality, whereas the relationship with geographical area was attenuated. Similar results were observed for 1-year outcomes. CONCLUSIONS: The clinical, biological and electrocardiographic presentations of hospitalized incident ACSs differ from one region of France to another. These differences explain (at least in part) the 28-day and 1-year decreasing case fatality gradient in hospitalized patients from northern France to south-western France.

Lipoprotein(a) plasma levels and the risk of cancer: the PRIME study.

Although experimental studies have shown lipoprotein(a) antiangiogenic and antitumoral effects, the association of lipoprotein(a) levels with cancer in population studies remains elusive and poorly documented. The aim of this study was to analyse the relationship between lipoprotein(a) plasma levels and the incidence of cancer over 10 years of follow-up. Data from two French centres of the PRIME cohort were used, representing 5237 men aged 50-59 years and free from a history of cancer at baseline. Data on medical history, socioeconomic and lifestyle factors were obtained by questionnaire. Lipoprotein(a) plasma levels were analysed from fasting blood samples collected at baseline. The relationship between lipoprotein(a) levels and first incident cancer was studied using the multivariate Cox proportional hazards models for all-site and the main-site-specific cancers, adjusted for various potential confounders including age, centre, smoking status and alcohol consumption. During follow-up, 456 new cancers were identified. No significant association was found between lipoprotein(a) and the all-site or main-site-specific cancers (hazard ratios for quartiles 2-4 vs. 1, respectively: 1.24, 1.11, 1.29, P=0.23). However, a higher risk seemed to be observed for highest lipoprotein(a) levels in all sites, lung, colorectal or tobacco/alcohol-related cancers. For prostate cancer, the lowest risk was observed for the highest levels of lipoprotein(a) (P=0.12). In conclusion, no evident association was found between the lipoprotein(a) levels and the incidence of cancer. Nevertheless, a higher cancer risk seemed to be observed for the highest lipoprotein(a) levels. Further research focusing on the lipoprotein(a) qualitative structure, that is, apolipoprotein(a) polymorphism could help clarify this highly complex relation.

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.

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.

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.

Heart rate and risk of cancer death in healthy men.

BACKGROUND: Data from several previous studies examining heart-rate and cardiovascular risk have hinted at a possible relationship between heart-rate and non-cardiac mortality. We thus systematically examined the predictive value of heart-rate variables on the subsequent risk of death from cancer. METHODS: In the Paris Prospective Study I, 6101 asymptomatic French working men aged 42 to 53 years, free of clinically detectable cardiovascular disease and cancer, underwent a standardized graded exercise test between 1967 and 1972. Resting heart-rate, heart-rate increase during exercise, and decrease during recovery were measured. Change in resting heart-rate over 5 years was also available in 5139 men. Mortality including 758 cancer deaths was assessed over the 25 years of follow-up. FINDINGS: There were strong, graded and significant relationships between all heart-rate parameters and subsequent cancer deaths. After adjustment for age and tobacco consumption and, compared with the lowest quartile, those with the highest quartile for resting heart-rate had a relative risk of 2.4 for cancer deaths (95% confidence interval: 1.9-2.9, p<0.0001) This was similar after adjustment for traditional cardiovascular risk factors and was observed for the commonest malignancies (respiratory and gastrointestinal). Similarly, significant relationships with cancer death were observed between poor heart rate increase during exercise, poor decrease during recovery and greater heart-rate increase over time (p<0.0001 for all). INTERPRETATION: Resting and exercise heart rate had consistent, graded and highly significant associations with subsequent cancer mortality in men.

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.

Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).

OBJECTIVE: To investigate the effect of alcohol intake patterns on ischaemic heart disease in two countries with contrasting lifestyles, Northern Ireland and France. DESIGN: Cohort data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) were analysed. Weekly alcohol consumption, incidence of binge drinking (alcohol >50 g on at least one day a week), incidence of regular drinking (at least one day a week, and alcohol <50 g if on only one occasion), volume of alcohol intake, frequency of consumption, and types of beverage consumed were assessed once at inclusion. All coronary events that occurred during the 10 year follow-up were prospectively registered. The relation between baseline characteristics and incidence of hard coronary events and angina events was assessed by Cox's proportional hazards regression analysis. SETTING: One centre in Northern Ireland (Belfast) and three centres in France (Lille, Strasbourg, and Toulouse). PARTICIPANTS: 9778 men aged 50-59 free of ischaemic heart disease at baseline, who were recruited between 1991 and 1994. MAIN OUTCOME MEASURES: Incident myocardial infarction and coronary death ("hard" coronary events), and incident angina pectoris. RESULTS: A total of 2405 men from Belfast and 7373 men from the French centres were included in the analyses, 1456 (60.5%) and 6679 (90.6%) of whom reported drinking alcohol at least once a week, respectively. Among drinkers, 12% (173/1456) of men in Belfast drank alcohol every day compared with 75% (5008/6679) of men in France. Mean alcohol consumption was 22.1 g/day in Belfast and 32.8 g/day in France. Binge drinkers comprised 9.4% (227/2405) and 0.5% (33/7373) of the Belfast and France samples, respectively. A total of 683 (7.0%) of the 9778 participants experienced ischaemic heart disease events during the 10 year follow-up: 322 (3.3%) hard coronary events and 361 (3.7%) angina events. Annual incidence of hard coronary events per 1000 person years was 5.63 (95% confidence interval 4.69 to 6.69) in Belfast and 2.78 (95% CI 2.41 to 3.20) in France. After multivariate adjustment for classic cardiovascular risk factors and centre, the hazard ratio for hard coronary events compared with regular drinkers was 1.97 (95% CI 1.21 to 3.22) for binge drinkers, 2.03 (95% CI 1.41 to 2.94) for never drinkers, and 1.57 (95% CI 1.11 to 2.21) for former drinkers for the entire cohort. The hazard ratio for hard coronary events in Belfast compared with in France was 1.76 (95% CI 1.37 to 2.67) before adjustment, and 1.09 (95% CI 0.79 to 1.50) after adjustment for alcohol patterns and wine drinking. Only wine drinking was associated with a lower risk of hard coronary events, irrespective of the country. CONCLUSIONS: Regular and moderate alcohol intake throughout the week, the typical pattern in middle aged men in France, is associated with a low risk of ischaemic heart disease, whereas the binge drinking pattern more prevalent in Belfast confers a higher risk.

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.

Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population.

The incidence of myocardial infarction (MI) is lower in France than in English-speaking and northern European countries. We estimated the incidence of MI in the HIV-infected population in France, on the basis of the data from the FHDH-ANRS CO4 cohort, by comparison with the general population. The sex- and age-standardized morbidity ratio was estimated as 1.5 [95% confidence interval (CI) 1.3-1.7] overall, 1.4 (95% CI 1.3-1.6) in men and 2.7 (95% CI 1.8-3.9) in women.

Low plasma retinol predicts coronary events in healthy middle-aged men: the PRIME Study.

The role of plasma retinol and carotenoids in coronary heart disease (CHD) remains unclear. The PRIME Study prospectively evaluated these in France and Northern Ireland in 9758 men aged 50-59 years who were free of CHD at baseline. After five years' follow-up 150 incident cases of CHD (non-fatal myocardial infarction and fatal CHD) were compared with 285 controls matched for age, date of blood collection and study centre. Geometric means of major carotenoids did not differ significantly between cases and controls (P>0.05), whereas the absolute and lipid-standardized plasma retinol levels were 9% lower in cases than controls in both countries (P<0.002), without correlation with carotenoids. After adjusting for risk factors, the relative risks (RRs) of CHD in the first four quintiles of retinol distribution in controls (< or =601, -683, -760, and -846 microg/l) were 2.65 (P=0.0009), 1.70, 1.03, and 1.12 (all P>0.05) respectively, relative to the top quintile (retinol > or =846 microg/l; linear trend P=0.0001). The 10th percentile of lipid-standardized retinol (< or =544 microg/l) predicted an RR of 4.7 (P<0.001). The risk associated with low retinol was comparable to strong risk factors (e.g. HDL-cholesterol, Interleukin-6) and behaved additively. In conclusion, plasma retinol levels of < 601 microg/l in a fifth of middle-aged European men place them at an approximately threefold RR of developing CHD. Thus the intake of vitamin A might be too low in middle-aged men. These findings must be confirmed.

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 cardiovascular risk factors to coronary risk in patients with intermittent claudication in the PRIME Cohort Study of European men.

BACKGROUND: Intermittent claudication (IC) is associated with an increased cardiovascular morbidity. The goal of the present study was to assess the contribution of conventional cardiovascular risk factors (CVRFs) to this increased risk. METHOD: The PRIME Study is a multicenter Prospective Cohort Study of 10 602 men recruited in 1991-1993, aged 50-59 at baseline and followed over 10 years. At baseline, a questionnaire on socio demographic data was self-administered and CVRFs were measured. Composite outcome consisted of incident MI, effort angina, unstable angina and coronary death. The standardized questionnaire of the London School of hygiene was used to identify claudicants. Data were analyzed using multivariate Cox models. RESULTS: Probable and possible cases of IC were reported by 1.4% (135) and 4.6% (442) of subjects, respectively. Compared to subjects with no claudication, the probable cases demonstrated higher rates of CVRFs. The incidence of CAD events was 7.23/1000 person-year. Compared to non claudicants, probable claudicants had an increased age and country adjusted risk of coronary events (HR (95% CI), 2.4 (1.5-3.7), p<0.0001). After further adjustments for school duration, family history of early myocardial infarction, tobacco consumption, alcohol consumption, BMI, systolic blood pressure, antihypertensive treatment, diabetes, total cholesterol, HDL-cholesterol, triglycerides and lipid-lowering treatment, participants with probable claudication had an increased risk of coronary events but this was no longer significant (HR (95% CI), 1.3 (0.8-2.1), p=0.23). CONCLUSION: IC is associated with an increased risk of developing coronary events. This association is largely explained by the coexistence of CVRFs.

Effect of an FTO polymorphism on fat mass, obesity, and type 2 diabetes mellitus in the French MONICA Study.

We investigated the association between the rs9939609 (T>A) polymorphism in the FTO (fat mass- and obesity-associated) gene and obesity- and type 2 diabetes mellitus-related phenotypes in the French Multinational MONItoring of Trends and Determinants in CArdiovascular Disease (MONICA) Study (n = 3367). In the study, TA or AA subjects had higher body mass index (BMI) (P = .017), waist circumference (P = .017), and hip (P = .01) circumference in an A allele dose-dependent manner. The A allele was also significantly associated with higher plasma insulin levels (P = .05), higher insulin resistance index (homeostasis model assessment) (P = .02), and higher systolic blood pressure (P = .003); but these associations disappeared after adjustment for BMI. In the study, 598 subjects were obese (BMI >or=30 kg/m(2)); and 2769 subjects were not obese (BMI <30 kg/m(2)). Subjects bearing the A allele of rs9939609 had a higher risk of obesity (adjusted odds ratio [95% confidence interval] = 1.29 [1.06-1.58], P = .01) compared with TT subjects. Moreover, the homozygous AA genotype of rs9939609 was associated with a higher risk of type 2 diabetes mellitus (odds ratio = 1.45 [1.05-1.99], P = .02, 283 subjects with and 2601 subjects without type 2 diabetes mellitus), independently of BMI. In conclusion, the role of the A allele of the FTO rs9939609 polymorphism on the risk of obesity and type 2 diabetes mellitus was confirmed in the French MONICA Study.

Ten-year all-cause mortality in presumably healthy subjects on lipid-lowering drugs (from the Prospective Epidemiological Study of Myocardial Infarction [PRIME] prospective cohort).

Lipid-lowering drugs are one of the most prescribed drugs worldwide. The aim was to compare 10-year all-cause mortality according to initial dyslipidemia status and lipid-lowering drug exposure. The PRIME study was a multicenter population-based prospective cohort study of men recruited in 1991 to 1993, aged 50 to 59 years at baseline, and followed up for 10 years. The 4 groups compared were normolipidemic, untreated dyslipidemic, and dyslipidemic subjects on fibrate or statin therapy. Data were analyzed using multivariate Cox models. The cohort included 7,722 French men (statin group 4.0%, fibrate group 7.9%, untreated dyslipidemic subjects 19.0%, and normolipidemic subjects 69.1%). After 10 years, 4.8% of the sample was lost to follow-up and 416 deaths occurred (cancers 53.1%, cardiovascular diseases 17.1%, and other 29.8%). After adjustment for center, age, educational level, cardiovascular risk factors, lipids, alcohol intake, and history of cardiovascular and severe chronic diseases, hazard ratios (HRs) for all-cause mortality were 0.49 (95% confidence interval [CI] 0.26 to 0.94, p = 0.031) for subjects treated with a statin, 0.65 (95% CI 0.42 to 0.99, p = 0.046) for those on fibrate therapy, and 0.76 (95% CI 0.56 to 1.03, p = 0.080) for normolipidemic men compared with untreated dyslipidemic subjects. In the statin group, HRs for death from cardiovascular disease, cancer, and other causes were 0.55 (p = 0.348), 0.41 (p = 0.067), and 0.68 (p = 0.546) compared with dyslipidemic subjects, respectively. In the fibrate group, HRs were 0.76 (p = 0.499), 0.52 (p = 0.041), and 0.87 (p = 0.746). In conclusion, in this cohort study carried out in a real-life setting, all-cause mortality was significantly lower in dyslipidemic subjects on fibrate or statin therapy than in untreated dyslipidemic patients. No excess risk of noncardiovascular death was observed.

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.

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.