All-Cause Mortality up to and After Coronary Heart Disease and Stroke Events in European Middle-Aged Men: The PRIME Study.

BACKGROUND AND PURPOSE: The aim was to investigate prospectively the all-cause mortality risk up to and after coronary heart disease (CHD) and stroke events in European middle-aged men. METHODS: The study population comprised 10 424 men 50 to 59 years of age recruited between 1991 and 1994 in France (N=7855) and Northern Ireland (N=2747) within the Prospective Epidemiological Study of Myocardial Infarction. Incident CHD and stroke events and deaths from all causes were prospectively registered during the 10-year follow-up. In Cox's proportional hazards regression analysis, CHD and stroke events during follow-up were used as time-dependent covariates. RESULTS: A total of 769 CHD and 132 stroke events were adjudicated, and 569 deaths up to and 66 after CHD or stroke occurred during follow-up. After adjustment for study country and cardiovascular risk factors, the hazard ratios of all-cause mortality were 1.58 (95% confidence interval 1.18-2.12) after CHD and 3.13 (95% confidence interval 1.98-4.92) after stroke. CONCLUSIONS: These findings support continuous efforts to promote both primary and secondary prevention of cardiovascular disease.

Expired-air carbon monoxide as a predictor of 16-year risk of all-cause, cardiovascular and cancer mortality.

BACKGROUND: Measurement of expired-air carbon monoxide (EACO) is commonly used to ascertain non-smoking status, although it can also reflect exposures not related to smoking. Our aim was to assess 16-year mortality according to EACO measured at baseline, in a general population. METHODS: Our analysis was based on the Third French MONICA population survey (1994-1997). Causes of death were obtained 16 years after inclusion, and assessment of determinants of mortality was based on Cox modeling. RESULTS: EACO was measured in 2232 apparently healthy participants aged 35-64. During follow-up, 195 deaths occurred (19% were due to cardio-vascular (CV) causes and 49% to cancer). At baseline, the mean EACO was 11.8 (±7.4)ppm, 4.6 (±2.5)ppm, 4.3 (±2.2)ppm for current, former and never smokers, respectively (P<0.001). After adjustment for main mortality risk factors and smoking, the hazard ratio (HR) for total mortality was 1.03[95% confidence interval: 1.01-1.06] per 1-unit increase in EACO, and it was 1.04[1.01-1.07] for cancer mortality. Adjusted HR for CV mortality was 1.05[1.01-1.10] but did not remain significant after additional adjustment for smoking (0.98[0.91-1.04]). Interactions between EACO and smoking were not significant. CONCLUSIONS: In a general population, baseline EACO is an independent predictor of 16-year all-cause and cancer mortality, after adjustment for confounders including smoking. Given that the effect of EACO is similar among smokers and non-smokers, EACO is probably not solely related to smoking but could also be a marker of inhaled ambient carbon monoxide and/or endogenous production. Besides, smoking better predicts CV mortality than EACO.

Brain alterations in individuals with exercise dependence: A multimodal neuroimaging investigation.

Background: Exercise dependence (ED) is characterised by behavioural and psychological symptoms that resemble those of substance use disorders. However, it remains inconclusive whether ED is accompanied by similar brain alterations as seen in substance use disorders. Therefore, we investigated brain alterations in individuals with ED and inactive control participants. Methods: In this cross-sectional neuroimaging investigation, 29 individuals with ED as assessed with the Exercise Dependence Scale (EDS) and 28 inactive control participants (max one hour exercising per week) underwent structural and functional resting-state magnetic resonance imaging (MRI). Group differences were explored using voxel-based morphometry and functional connectivity analyses. Analyses were restricted to the striatum, amygdala, and inferior frontal gyrus (IFG). Exploratory analyses tested whether relationships between brain structure and function were differently related to EDS subscales among groups. Results: No structural differences were found between the two groups. However, right IFG and bilateral putamen volumes were differently related to the EDS subscales "time" and "tolerance", respectively, between the two groups. Resting-state functional connectivity was increased from right IFG to right superior parietal lobule in individuals with ED compared to inactive control participants. Furthermore, functional connectivity of the angular gyrus to the left IFG and bilateral caudate showed divergent relationships to the EDS subscale "tolerance" among groups. Discussion: The findings suggest that ED may be accompanied by alterations in cognition-related brain structures, but also functional changes that may drive compulsive habitual behaviour. Further prospective studies are needed to disentangle beneficial and detrimental brain effects of ED.

Measures of abdominal adiposity and the risk of stroke: the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) study.

BACKGROUND AND PURPOSE: Excess fat accumulates in the subcutaneous and visceral adipose tissue compartments. We tested the hypothesis that indicators of visceral adiposity, namely, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), are better predictors of stroke risk than body mass index (BMI). METHODS: The association of BMI, WC, WHR, and WHtR with stroke was assessed in 31,201 men and 23,516 women, free of vascular disease at baseline, from the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) study. During a mean follow-up of 11 years, 1130 strokes were recorded. Relative risks (95% CI) were calculated by Cox regression after stratification for center and adjustment for age, smoking, educational level, alcohol consumption, hypertension, diabetes, total cholesterol, high-density lipoprotein cholesterol, and BMI and model fit was assessed using log-likelihoods. RESULTS: BMI, WC, WHR, and WHtR were associated with the risk of stroke in men. After full adjustment including BMI, the relative risks for stroke remained significant for WC (1.19 [1.02 to 1.34] per 1 SD increase in WC), WHR (1.14 [1.03 to 1.26]), and WHtR (1.50 [1.28 to 1.77]). Among women, the extent of the associations with stroke risk was similar for WHtR (1.31 [1.04 to 1.65]), WC (1.19 [0.96 to 1.47]), and WHR (1.08 [0.97 to 1.22]). Further analyses by World Health Organization obesity categories showed that WC, WHR, and WHtR were associated with the risk of stroke also in lean men and women (BMI<25 kg/m2), independently of confounders, cardiovascular risk factors, and BMI. CONCLUSIONS: Indicators of abdominal adiposity, especially WHtR, are more strongly associated with stroke risk than BMI. These results emphasize the importance of measuring abdominal adiposity, especially in lean subjects.

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.

Ten-year risk of all-cause mortality: assessment of a risk prediction algorithm in a French general population.

While assessment of global cardiovascular risk is uniformly recommended for risk factor management, prediction of all-cause death has seldom been considered in available charts. We established an updated algorithm to predict absolute 10-year risk of all-cause mortality in apparently healthy subjects living in France, a country with high life expectancy. Analyses were based on the Third French MONICA Survey on cardiovascular risk factors (1995-1996) carried out in 3,208 participants from the general population aged 35-64. Vital status was obtained 10 years after inclusion and assessment of determinants of mortality was based on multivariable Cox modelling. One-hundred-fifty-six deaths were recorded. Independent determinants of mortality were living area (Northern France), older age, male gender, no high-school completion, smoking, systolic blood pressure ≥ 160 mmHg, LDL-cholesterol ≥ 5.2 mmol/l, and diabetes. Score sheets were developed to easily estimate 10-year risk of death. For example, a non diabetic, heavy smoker, 46-year old man, living in South-Western France, who did not complete high-school, with LDL-cholesterol ≥ 5.2 mmol/l and systolic blood pressure < 160 mmHg, has a 17% probability of death in the ten coming years. The C-statistic of the prediction model was 0.76 [95% CI: 0.72-0.80] with a degree of overoptimism estimated at 0.0058 in a bootstrap sample. Calibration was satisfying: P value for Hosmer-Lemeshow χ(2) test was 0.483. This prediction algorithm is a simple tool for guiding practitioners towards a more or less aggressive management of risk factors in apparently healthy subjects.

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.

Trends in the risk of myocardial infarction among HIV-1-infected individuals relative to the general population in France: Impact of gender and immune status.

We examined trends in the MI incidence and age at MI diagnosis among adults living with HIV-1 between 2000 and 2009, by comparison with the French MI registries, by gender. Age standardized incidence rates and standardized incidence-ratios (SIRs) were estimated for individuals included in the French hospital database on HIV (n = 71 204, MI = 663) during three periods: 2000-2002, 2003-2005 and 2006-2009. Median ages at MI diagnosis were compared using the Brown-Mood test. Over the study periods, the absolute rate difference and relative risks were higher in women than in men in 2000-2002 and 2006-2009, with respective SIRs 1.99 (1.39-2.75) and 1.12 (0.99-1.27) in 2006-2009. The trends were different for men and women with a decreasing trend in SIRs in men and no change in women. In both sexes, among individuals with CD4 ≥500/µL and controlled viral-load on cART, the risk was no longer elevated. Age at MI diagnosis was significantly younger than in the general population, especially among women (-6.2 years, p<0.001; men: -2.1 years, p = 0.02). In HIV-1-positive adults, absolute rate difference and relative risks and trends of MI were different between men and women and there was no additional risk among individuals on effective cART.

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.

Dietary linoleic acid interacts with FADS1 genetic variability to modulate HDL-cholesterol and obesity-related traits.

BACKGROUND & AIMS: Blood levels of polyunsaturated fatty acids (PUFAs) are under control of endogenous synthesis via Δ5- and Δ6-desaturases, encoded by the FADS1 and FADS2 genes, respectively and of diet. Genome-wide associations studies (GWAS) reported associations between polymorphisms in FADS1-FADS2 and variations in plasma concentrations of PUFAs, HDL- and LDL-cholesterol and triglycerides. However, it is not established whether dietary PUFAs intake modulates these associations. We assessed whether dietary linoleic acid (LA) or α-linolenic acid (ALA) modulate the association between the FADS1 rs174547 polymorphism (a GWAS hit) and lipid and anthropometric phenotypes. METHODS: Dietary intakes of LA and ALA, FADS1 rs174547 genotypes, lipid and anthropometric variables were determined in three French population-based samples (n = 3069). These samples were stratified according to the median dietary LA (<9.5 and ≥9.5 g/d) and ALA (<0.80 and ≥0.80 g/d) intakes. The meta-analysis was performed using a random-effect. RESULTS: Our meta-analysis confirmed the association between rs174547 and plasma lipid levels and revealed an association with waist circumference and body mass index. These associations were not modified by dietary ALA intake (all p-interaction > 0.05). In contrast, the associations with HDL-cholesterol levels, waist circumference and BMI were modulated by the dietary intake of LA (p interaction < 0.05). In high LA consumers only, the rs174547 minor allele was significantly associated with lower HDL-cholesterol levels (ß = -0.05 mmol/L, p = 0.0002). Furthermore, each copy of the rs174547 minor allele was associated with a 1.58 cm lower waist circumference (p = 0.0005) and a 0.46 kg m-2 lower BMI (p = 0.01) in the low LA intake group, but not in the high LA intake group. CONCLUSIONS: The present study suggests that dietary LA intake may modulate the association between the FADS gene variants and HDL-cholesterol concentration, waist circumference and BMI. These gene-nutrient interactions, if confirmed, suggest that subjects carrying the rs174547 minor allele might benefit from low dietary LA intakes.

Identification of a functional FADS1 3'UTR variant associated with erythrocyte n-6 polyunsaturated fatty acids levels.

BACKGROUND: Blood polyunsaturated fatty acid (PUFA) levels are determined by diet and by endogenous synthesis via Δ5- and Δ6-desaturases (encoded by the FADS1 and FADS2 genes, respectively). Genome-wide association studies have reported associations between FADS1-FADS2 polymorphisms and the plasma concentrations of PUFAs, HDL- and LDL-cholesterol, and triglycerides. However, much remains unknown regarding the molecular mechanisms explaining how variants affect the function of FADS1-FADS2 genes. OBJECTIVE: Here, we sought to identify the functional variant(s) within the FADS gene cluster. METHODS: To address this question, we (1) genotyped individuals (n = 540) for the rs174547 polymorphism to confirm associations with PUFA levels used as surrogate estimates of desaturase activities and (2) examined the functionality of variants in linkage disequilibrium with rs174547 using bioinformatics and luciferase reporter assays. RESULTS: The rs174547 minor allele was associated with higher erythrocyte levels of dihomo-γ-linolenic acid and lower levels of arachidonic acid, suggesting a lower Δ5-desaturase activity. In silico analyses suggested that rs174545 and rs174546, in perfect linkage disequilibrium with rs174547, might alter miRNA binding sites in the FADS1 3'UTR. In HuH7 and HepG2 cells transfected with FADS1 3'UTR luciferase vectors, the haplotype constructs bearing the rs174546T minor allele showed 30% less luciferase activity. This relative decrease reached 60% in the presence of miR-149-5p and was partly abolished by cotransfection with an miR-149-5p inhibitor. CONCLUSION: This study identifies FADS1 rs174546 as a functional variant that may explain the associations between FADS1-FADS2 polymorphisms and lipid-related phenotypes.

Ideal Cardiovascular Health and Incident Cardiovascular Disease: Heterogeneity Across Event Subtypes and Mediating Effect of Blood Biomarkers: The PRIME Study.

BACKGROUND: The aim of this study was to investigate whether the association between baseline cardiovascular health (CVH) and incident cardiovascular disease differs according to coronary heart disease (CHD) and stroke subtypes, and to assess the mediating effect of inflammatory and hemostatic blood biomarkers. METHODS AND RESULTS: The association of ideal CVH with outcomes was derived in 9312 middle-aged men from Northern Ireland and France (whole cohort) in multivariable Cox proportional hazards regression analysis. The mediating effect of baseline inflammatory and hemostatic blood biomarkers was evaluated in a case-control study nested within the cohort after 10 years of follow-up. After a median follow-up of 10 years, 614 first CHD events and 117 first stroke events were adjudicated. Compared with those with poor CVH, those with an ideal CVH profile at baseline had a 72% lower risk of CHD (hazard ratio=0.28; 95% confidence interval, 0.17; 0.46) and a 76% lower risk of stroke (hazard ratio =0.24; 95% confidence interval, 0.06; 0.98). The magnitude of the risk reductions was similar for incident angina and myocardial infarction, but was lower for ischemic stroke. In the controls, the mean concentrations of high-sensitivity C-reactive protein, IL-6, and fibrinogen decreased with higher CVH status. Furthermore, the association of behavioral CVH with incident CHD was partly mediated by high-sensitivity C-reactive protein (16.69%), IL-6 (8.52%), and fibrinogen (7.30%) CONCLUSIONS: Our study shows no clear heterogeneity in the association of baseline CVH with the main subtypes of cardiovascular disease. This supports a universal promotion of ideal CVH for all cardiovascular disease subtypes. Furthermore, our mediation analysis suggests that the lower risk of CHD associated with ideal CVH is partly mediated by lower inflammatory and hemostatic blood biomarkers.

Predictive Accuracy of the European Society of Cardiology SCORE Among French People.

PURPOSE: Assessment of cardiovascular (CV) risk with a predictive algorithm is recommended for managing CV disease prevention. The aim of this study was to assess the predictive accuracy of the European Society of Cardiology SCORE among French people. METHODS: Our analysis was based on the Third French MONICA population-based survey (1995-1996) and on a sample of subjects referred (from 1995 to 2000) for a CV checkup in a preventive cardiology unit. Vital status was obtained 10 years after inclusion. The 10-year predicted risk of CV death was calculated using the SCORE equation for low-risk countries and was compared with the 10-year incidence of CV death observed in the cohort. RESULTS: The sample was composed of 6915 participants aged 35 to 64 years, among whom 56 CV deaths occurred during the followup. The median risk SCORE (0.97%) did not differ from the 10-year incidence of CV death observed in the cohort (1.05%; 95% CI, 0.81-1.37). The median risk SCORE calculated for different categories of sex, age, educational level, family history of premature CV disease, physical activity, impaired fasting glucose, smoking, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol did not differ from the 10-year incidence of CV death observed in these categories. The C-statistic of the SCORE equation was 79% (73-85). Using a 5% threshold to discriminate people at high risk, 93% of participants were correctly classified (subjects with SCORE ≥5% who died from a CV causes during followup and those with SCORE <5% who did not). CONCLUSIONS: Among middle-aged French people, the SCORE equation adequately predicts CV death.

Impact of cardiovascular risk factor control on long-term cardiovascular and all-cause mortality in the general population.

PURPOSE: In clinical trials, lowering cardiovascular risk factors (CVRFs) reduces cardiovascular (CV) morbidity and mortality. We assessed the impact of controlling CVRFs at baseline on long-term all-cause and CV mortality in the general population. METHODS: Analysis was based on the Third French MONICA population-based survey (1994-1997). Vital status was obtained 18 years after inclusion. Statistical analysis was based on Cox-modelling. RESULTS: About 3402 participants aged 35-64 were included and 569 (17%) presented with 2 or more uncontrolled CVRFs, 1194 (35%) had one uncontrolled CVRF, 770 (23%) had all CVRFs controlled under treatment (or were former smokers) and 869 (25%) exhibited no CVRF. During the follow-up, 389 deaths occurred (76 were due to CV causes). Considering all-cause mortality, the adjusted hazard ratios (aHR) for subjects with one uncontrolled CVRF and for those with two or more were 1.38 [1.03-1.83] (p = 0.029) and 1.80 [1.33-2.43](p < 0.001), respectively, as compared with subjects presenting with all their CVRFs controlled. For subjects exhibiting no CVRF, the aHR was 0.66 [0.44-0.98] (p = 0.042). Considering CV mortality, aHRs for subjects presenting with one and two or more uncontrolled CVRF were 1.70 [0.84-3.42] (p = 0.138) and 3.67 [1.85-7.29] (p < 0.001), respectively, as compared with subjects who had either all their CVRFs controlled or exhibited no CVRF. CONCLUSIONS: Failing to control CVRFs significantly increases long-term all-cause and CV mortality in the French general population. Key messages Only 30% of patients with cardiovascular risk factors were controlled. Failing to control cardiovascular risk factors significantly increased long-term cardiovascular and all-cause mortality. A residual risk for all-cause mortality remained even when patients were controlled.

Physical activity and coronary event incidence in Northern Ireland and France: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).

BACKGROUND: The influence of physical activity on the incidence of angina pectoris and hard coronary events (myocardial infarction and coronary deaths) was examined in Northern Ireland and France at contrasting risk for coronary heart disease (CHD) and with different physical activity patterns. METHODS AND RESULTS: Participants of the Prospective Epidemiological Study of Myocardial Infarction (PRIME) (n=9758; age, 50 to 59 years), free of CHD at baseline, were followed up for 5 years: 167 hard CHD and 154 angina events were recorded. Net energy expenditure (EE) as the result of physical activity was assessed by means of the MONICA Optional Study of Physical Activity Questionnaire (MOSPA-Q). Leisure-time physical activity EE was calculated; subjects were also categorized as to whether they performed high-intensity leisure-time activities or walked or cycled to work. After multivariate adjustment, leisure-time physical activity EE was associated with a lower risk of hard CHD events (P<0.04), whereas walking or cycling to work was not independently related to hard CHD events. No interaction by country was found. The beneficial effect of leisure-time physical activity was also present among subjects who did not report high-intensity activities (P<0.04), with similar results in France and Northern Ireland. In contrast, an increasing level of leisure-time physical activity was associated with a higher risk of angina in both countries. CONCLUSIONS: These data indicate a beneficial effect of leisure-time physical activity EE on hard CHD incidence in middle-aged men, which could partly explain the unfavorable rate of CHD in Northern Ireland. The higher level of leisure-time activities in France could, in part, explain its lower rate of CHD.

Low-fat and high-fat dairy products are differently related to blood lipids and cardiovascular risk score.

BACKGROUND: Fat content of dairy foods is diverse, potentially leading to varying effects on cardiovascular risk. We studied relationships of low- and high-fat dairy products with lipids and level of cardiovascular risk (assessed by the SCORE equation), in a cross-sectional population survey conducted in three French areas. SUBJECTS AND METHODS: A sample of 3078 participants aged 35-64 years underwent a standardized cardiovascular risk assessment. Subjects were asked to record the types and amounts of foods and beverages they consumed over a three-consecutive-day period. Dairy products were separated into two groups: the low-fat group comprised milk (including milk in desserts and beverages), yogurts and cottage cheese, whereas other cheeses formed the high-fat group. RESULTS: After adjustment (including physical activity and a diet quality score), the probability of an increased cardiovascular mortality score (≥1%) decreased from the lowest to the highest quartile (Q) of low-fat dairy intake: odds ratio (OR) ORQ1 = 1; ORQ2 = 0.89 (95% confidence interval: 0.73-1.10), ORQ3 = 0.78 (0.63-0.97) and ORQ4 = 0.68 (0.55-0.85) for the first, second, third and fourth quartile, respectively. Results were notably different for high-fat dairy intake: ORQ2 = 1.02 (0.82-1.25); ORQ3 = 0.90 (0.73-1.11); ORQ4 = 1.07 (0.86-1.32). Intake of low-fat dairy products was inversely associated with low-density lipoprotein cholesterol (LDL-C), but no significant independent relationship was found with high-density lipoprotein cholesterol (HDL-C) or triglycerides. None of the lipid parameters was significantly associated with the consumption of high-fat dairy products. CONCLUSION: Participants with the highest intake of low-fat dairy products had the lowest mortality risk score and exhibited the best LDL-C profile. Such favourable associations were not observed with cheese consumption.

Validation of a short, qualitative food frequency questionnaire in French adults participating in the MONA LISA-NUT study 2005-2007.

BACKGROUND: Food frequency questionnaires (FFQs) are often used to evaluate individuals' food intakes in epidemiologic studies because of their simplicity and low cost. OBJECTIVE: To assess the validity of a short (24 items), qualitative FFQ used in the MONA LISA-NUT study. DESIGN: Cross-sectional study of a representative sample in three French counties. PARTICIPANTS/SETTING: The sample included 2,630 participants aged 35 to 65 years from the MONA LISA-NUT study. MAIN OUTCOME MEASURES: Food consumption was measured with the FFQ and via food records for 3 consecutive days. Plasma fatty acids were measured from a subset of participants. STATISTICAL ANALYSES PERFORMED: The FFQ items' validity was assessed by calculating crude and deattenuated Pearson correlation coefficients between frequencies reported by the FFQ and average weights reported by the food records. Furthermore, the validity of some items of the FFQ measuring the consumption of fatty foods was assessed by calculating Pearson correlation coefficients between frequencies of consumption of these foods and dosages of the corresponding plasma fatty acids: fish and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), olive oil and oleic acid, margarine and elaidic acid, and dairy products and pentadecanoic and heptadecanoic acids. RESULTS: The mean of the deattenuated Pearson correlation coefficients for all items was 0.46, with values ranging from 0.22 (fried food) to 0.77 (breakfast cereal). The correlation coefficient was ≤ 0.4 for one third of the 24 items. Moderate correlations were found between fish and EPA/DHA (EPA: r=0.43, 95% CI 0.33 to 0.51; DHA: r=0.39, 95% CI 0.30 to 0.47), but not for other food items. CONCLUSIONS: One third of the 24 items in the short, qualitative FFQ evaluated here were not sufficiently valid. However, for the food groups most commonly studied in the literature, this FFQ had the same degree of validity as other questionnaires designed to classify subjects according to their level of intake.

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.