A Role for Behavior in the Relationships Between Depression and Hostility and Cardiovascular Disease Incidence, Mortality, and All-Cause Mortality: the Prime Study.

BACKGROUND: Behavioral factors are important in disease incidence and mortality and may explain associations between mortality and various psychological traits. PURPOSE: These analyses investigated the impact of behavioral factors on the associations between depression, hostility and cardiovascular disease(CVD) incidence, CVD mortality, and all-cause mortality. METHODS: Data from the PRIME Study (N = 6953 men) were analyzed using Cox proportional hazards models, following adjustment for demographic and biological CVD risk factors, and other psychological traits, including social support. RESULTS: Following initial adjustment, both depression and hostility were significantly associated with both mortality outcomes (smallest SHR = 1.24, p < 0.001). Following adjustment for behavioral factors, all relationships were attenuated both when accounting for and not accounting for other psychological variables. Associations with all-cause mortality remained significant (smallest SHR = 1.14, p = 0.04). Of the behaviors included, the most significant contribution to outcomes was found for smoking, but a role was also found for fruit and vegetable intakes and high alcohol consumption. CONCLUSIONS: These findings demonstrate well-known associations between depression, hostility, and mortality and suggest the potential importance of behaviors in explaining these relationships.

Food groups associated with a reduced risk of 15-year all-cause death.

BACKGROUND/OBJECTIVES: Long-term observational cohorts provide the opportunity to investigate the potential impact of dietary patterns on death. We aimed to investigate all-cause death according to the consumption of selected food groups, and then to identify those independently associated with reduced mortality. SUBJECTS/METHODS: Population survey of middle-aged men randomly selected in the period 1995-1997 from the general population of three French areas and followed over a median of 14.8 years. Dietary data were collected through a 3-day food record. Cox modeling was used to assess the risk of death according to selected foods groups after extensive adjustment for confounders, including a diet quality index. RESULTS: The study population comprised 960 men (mean age 55.5 ±6.2 years). After a median follow-up of 14.8 (interquartile range 14.3-15.2) years, 150 (15.6%) subjects had died. Food groups that remained independently predictive of a lower risk of death after extensive adjustment were an above-median consumption of milk (adjusted relative risk: 0.61, 95% confidence interval (CI): 0.43-0.86, P-value=0.005), fruits and vegetables (0.68, 0.46-0.98, P-value=0.041) and a moderate consumption of yogurts and cottage cheese (0.50, 95% CI: 0.31-0.81, P-value=0.005), other cheeses (0.62, 0.39-0.97, P-value=0.036) and bread (0.57, 0.37-0.89, P-value=0.014). Besides, there was a nonsignificant trend for a higher risk of death associated with highest sodium intakes. CONCLUSIONS: Consumption of food groups that largely match recommendations is associated with a reduced risk of all-cause death in men. A diet providing moderate amounts of diverse food groups appears associated with the highest life expectancy.

Omega-3 index levels and associated factors in a middle-aged French population: the MONA LISA-NUT Study.

BACKGROUND/OBJECTIVES: The omega-3 index (the summed percentage content of eicosapentaenoic and docosahexaenoic acids in red blood cells) is associated with a lower risk of fatal coronary heart disease and sudden cardiac death. We aimed to determine which socio-demographic, behavioural or clinical factors are independently associated with the omega-3 index and the extent to which seafood consumption mediates the index's association with socio-economic status (SES). SUBJECTS/METHODS: As part of the cross-sectional MONA LISA-NUT survey (2005-2007), gas chromatography was used to analyse the red blood cell fatty acid composition in 503 French subjects aged 35-64 years. Dietary data were collected by trained dieticians via a validated food frequency questionnaire and a prospective 3-day food record. Risk factors were estimated with standardised measurements and questionnaires. SES was assessed through the self-reported educational and income tax levels. RESULTS: The mean ± s.d. omega-3 index was 6.02 ± 1.75%. In the best parsimonious predictive model (which explained 32% of the variability in the omega-3 index), age, educational level and seafood servings were significantly and positively associated with the index. In contrast, waist circumference and smoking were inversely associated with the index. In a mediation analysis that took account of all these factors, seafood servings explained about 40% of the association between educational level and the omega-3 index. Similar results were obtained for the income tax level. CONCLUSIONS: The inverse association between SES and omega-3 index is largely explained (40%) by an insufficient seafood intake. It remains to be seen which other factors mediate this association.

Depression and mortality: artifact of measurement and analysis?

BACKGROUND: Previous research demonstrates various associations between depression, cardiovascular disease (CVD) incidence and mortality, possibly as a result of the different methodologies used to measure depression and analyse relationships. This analysis investigated the association between depression, CVD incidence (CVDI) and mortality from CVD (MCVD), smoking related conditions (MSRC), and all causes (MALL), in a sample data set, where depression was measured using items from a validated questionnaire and using items derived from the factor analysis of a larger questionnaire, and analyses were conducted based on continuous data and grouped data. METHODS: Data from the PRIME Study (N=9798 men) on depression and 10-year CVD incidence and mortality were analysed using Cox proportional hazards models. RESULTS: Using continuous data, both measures of depression resulted in the emergence of positive associations between depression and mortality (MCVD, MSRC, MALL). Using grouped data, however, associations between a validated measure of depression and MCVD, and between a measure of depression derived from factor analysis and all measures of mortality were lost. LIMITATIONS: Low levels of depression, low numbers of individuals with high depression and low numbers of outcome events may limit these analyses, but levels are usual for the population studied. CONCLUSIONS: These data demonstrate a possible association between depression and mortality but detecting this association is dependent on the measurement used and method of analysis. Different findings based on methodology present clear problems for the elucidation and determination of relationships. The differences here argue for the use of validated scales where possible and suggest against over-reduction via factor analysis and grouping.

Attitudes toward healthy eating: a mediator of the educational level-diet relationship.

BACKGROUND/OBJECTIVES: A higher educational level is associated with a healthier diet. The goal of this study was to establish whether this association is mediated by attitudes toward healthy eating. SUBJECTS/METHODS: The cross-sectional MONA LISA-NUT study was performed in 2005-2007 on adults aged 35-64 years from northern and north-eastern France. Diet quality was assessed on the basis of a 3-day food record and a validated score based on French national dietary guidelines. Specific questions investigated attitudes toward healthy eating. Multivariate analyses were used to quantify the proportion of the educational level-diet relationship that was mediated by attitudes toward healthy eating. RESULTS: Among the 1631 subjects, favourable attitudes toward healthy eating were associated with both higher educational level and diet quality. In the mediation analysis, 'organic food consumption' explained 14% (95% confidence interval (8;24)) of the educational level-diet relationship and 'attention paid to health when buying food' explained 9% (3;16). In contrast, 'attention to food choice', 'searching for information about food' and 'perceived role of eating' were not mediators of the association between educational level and diet. In a multivariate model, the attitude items together accounted for 25% (10;45) of the relationship. The mediation was more pronounced in women than in men (37% (15;54) vs 16% (1;27), respectively) and was significant for consumption of fruits and vegetables (23% (13;37)), whole-grain food (32% (15;58)) and seafood (22% (9;55)). CONCLUSIONS: Our results suggest that poor attitudes toward healthy eating in groups with low socioeconomic status constitute an additional factor (along with cost constraints) in the choice of unhealthy foods.

Alcohol consumption patterns and body weight.

BACKGROUND/AIMS: The impact of alcohol on health depends on both the total amount ingested per week and the drinking pattern. Our goal was to assess the relationship between drinking occasions and anthropometric indicators of adiposity. METHODS: For this cross-sectional study, 7,855 men aged 50-59 years were recruited between 1991 and 1993 in France. Clinical and anthropometric data were obtained in a standardized clinical examination by trained staff. Alcohol intake was assessed by a questionnaire recording daily consumption of each type of alcohol during a typical week. RESULTS: 75% of the participants drank alcohol daily (264.7 ml per week). For a given total alcohol intake and after adjustment of confounders, the number of drinking episodes was inversely correlated with body mass index (p < 0.0001) and waist circumference (p < 0.0001). The odds ratio (95% confidence interval) for obesity was 1.8 (1.3-2.4) for occasional (1-2 days/week) and 1.6 (1.2-2.1) for frequent drinkers (3-5 days/week) compared with daily drinkers. This correlation was less pronounced in moderate (<140 ml/week) than intermediate consumers (140-280 ml/week). In heavy consumers (>280 ml/week), the intake was almost always daily. The results were similar for wine and beer consumption. CONCLUSION: Our findings suggest that drinking occasion is a risk indicator of obesity independent of total alcohol intake.

Sedentary behaviour, physical activity and dietary patterns are independently associated with the metabolic syndrome.

AIM: This study assessed the independent relationships of daily sitting time, levels of work and leisure-time physical activity (PA), and dietary patterns of patients with the metabolic syndrome (MetS). METHODS: This population-based, cross-sectional study included 3090 French subjects aged 35-64 years. Daily time spent sitting and PA levels were assessed by an interview-administered questionnaire, while dietary patterns were identified using the factorial method of principal component analysis. Independent associations of lifestyle behaviours with the MetS were assessed by multivariable logistic-regression models adjusted for age, centre, educational level, smoking status, total calorie intake, heart rate and menopausal status. RESULTS: The multivariable-adjusted ORs [95% CI] for MetS in the fourth quartile of sitting time and leisure-time PA were 1.65 [1.11-2.44] (P for trend < 0.01) and 0.58 [0.40-0.84] (P for trend < 0.001), respectively, for men, and 2.35 [1.41-3.92] (P for trend < 0.01) and 0.52 [0.33-0.82] (P for trend < 0.01), respectively, for women. Work PA was not favourably related to the MetS, particularly in women. An 'energy-dense' dietary pattern was independently associated with higher ORs for the MetS in both genders. However, accounting for body mass index (BMI) weakened the associations, which otherwise remained significant for leisure-time PA and the energy-dense dietary pattern in men, suggesting that BMI may be a potential mediator of these relationships. CONCLUSION: This study demonstrated a dose-response association between sitting time, an energy-dense dietary pattern and the MetS, together with a graded inverse association between leisure-time PA and the MetS. In addition to the usual advice for PA and healthy eating, limiting the amount of time spent sitting should also be promoted through public-health initiatives.

[Assessment and characteristics of chronic renal insufficiency in France]. / Estimation et caractérisation de l'insuffisance rénale chronique en France.

Chronic kidney disease (CKD) is a major public health issue. In France, few studies have evaluated CKD prevalence. The objective of the MONA LISA study was to estimate and to characterize CKD in three representative cross-sectional surveys in subjects aged 35-74.9 years. CKD was defined as subjects having MDRD glomerular filtration rate lower than 60 mL/min/1.73 m(2). Prevalence of CKD in MONA LISA was standardized according to the French population. A multiple logistic regression analysis was performed in order to find independent factors associated to CKD. The French estimate of CKD prevalence was 8.2% (95% confidence interval: 7.4-8.9%), that is 2,454,548 (95% confidence interval: 2,215,080-2,664,082) subjects aged 35-74.9 years. Factors significantly and independently associated to CKD were older age, hypertension and dyslipidemias. In conclusion, the MONA LISA study evaluated for the first time in France CKD prevalence in subjects aged 35-74.9 years. This prevalence probably underestimates the real CKD size due to selection bias present in every representative cross-sectional survey.

Do lifestyle behaviours explain socioeconomic differences in all-cause mortality, and fatal and non-fatal cardiovascular events? Evidence from middle aged men in France and Northern Ireland in the PRIME Study.

OBJECTIVE: To examine the contribution of lifestyle behaviours to the socioeconomic gradient in all-cause mortality, and fatal and non-fatal cardiovascular events. METHOD: 10,600 men aged 50-59 years examined in 1991-1994 in Northern Ireland (NI) and France and followed annually for deaths and cardiovascular events for 10 years. Baseline smoking habit, physical activity, and fruit, vegetable, and alcohol consumption were assessed. RESULTS: All lifestyle behaviours showed marked socioeconomic gradients for most indicators in NI and France, with the exception of percentage of alcohol consumers in NI and frequency of alcohol consumption in NI and France. At 10 years, there were 544 deaths from any cause and 440 fatal and non-fatal cardiovascular events. After adjustment for country and age, socioeconomic gradients were further adjusted for lifestyle behaviours. For total mortality, the median residual contribution of lifestyle behaviours was 28% and for cardiovascular incidence, 41%. When cardiovascular risk factors were considered in conjunction with lifestyle behaviours these percentages increased to 38% and 67% respectively. CONCLUSION: Lifestyle behaviours contribute to the gradient in mortality and cardiovascular incidence between socioeconomic groups, particularly for cardiovascular incidence, but a substantial proportion of these differentials was not explained by lifestyle behaviours and cardiovascular risk factors.

Contribution of lifetime smoking habit in France and Northern Ireland to country and socioeconomic differentials in mortality and cardiovascular incidence: the PRIME Study.

BACKGROUND: This study examines the contribution of lifetime smoking habit to the socioeconomic gradient in all-cause and smoking-related mortality and in cardiovascular incidence in two countries. METHODS: 10,600 men aged 50-59 years were examined in 1991-4 in centres in Northern Ireland and France and followed annually for 10 years. Deaths and cardiovascular events were documented. Current smoking habit, lifetime smoking (pack-years) and other health behaviours were evaluated at baseline. As socio-occupational coding schemes differ between the countries seven proxy socioeconomic indicators were used. RESULTS: Lifetime smoking habit showed marked associations with most socioeconomic indicators in both countries, but lifetime smoking was more than 10 pack-years greater overall in Northern Ireland and smoking patterns differed. Total mortality was 49% higher in Northern Ireland than in France, and smoking-related mortality and cardiovascular incidence were 93% and 92% higher, respectively. Both lifetime smoking and fibrinogen contributed independently to these differentials, but together explained only 42% of the difference in total mortality between countries, adjusted for both biological and lifestyle confounders. Socioeconomic gradients were steeper for total and smoking-related mortality than for cardiovascular incidence. Residual contributions of lifetime smoking habit ranged from 6% to 34% for the seven proxy indicators of socioeconomic position for total and smoking-related mortality. Socioeconomic gradients in cardiovascular incidence were minimal following adjustment for confounders. CONCLUSION: In Northern Ireland and France lifetime smoking appeared to explain a significant part of the gradients in total and smoking-related mortality between socioeconomic groups, but the contribution of smoking was generally small for cardiovascular incidence.

Cancer mortality according to lipid-lowering drugs and lipoproteins in a general population.

OBJECTIVE: The beneficial effect of lipid-lowering drugs (LLD) on cardiovascular risk is established, but long term safety data remain scarce. Our aim was to assess 10-year risk of cancer mortality according to blood lipoprotein levels and LLD exposure, in a general population. METHODS: Our analysis was based on the Third French MONICA survey on cardiovascular risk factors (1994-1997). Participants were randomly recruited from the general population of three French areas and were aged 35-64 years. Subjects with a history of cancer at baseline were excluded from the analysis. Vital status and cause of mortality were obtained 10 years after inclusion. RESULTS: There were 3262 participants and 177 deaths were recorded over the 10-year period (78 due to a cancer). The sample comprised 64% of normolipidaemic, 25% of untreated dyslipidaemic and 11% of dyslipidaemic subjects treated with LLD (4% statins, 6% fibrates and 1% other hypolipidaemic drugs). After adjustment for centre, age, gender, smoking, gamma-glutamyl transpeptidase and mean corpuscular volume, the hazard ratios (HR) for cancer mortality in subjects with non-HDL cholesterol <3.5 mmol/L (135 mg/dL) and in those with HDL cholesterol <0.90 mmol/L (35 mg/dL) were 2.74 (95% confidence interval: 1.66-4.52, p < 0.001) and 2.83 (1.62-4.96, p < 0.001), respectively. The adjusted HR for cancer mortality was 0.31 (0.11-0.86, p = 0.025) in people on LLD compared to untreated subjects. CONCLUSIONS: In the present study, we confirm the significant association between low cholesterol and cancer mortality without finding any harmful signal regarding cancer risk associated with the use of LLD. The main limitations are remaining baseline differences between treated and untreated subjects (due to the observational design but minimized by the use of extensive adjustments and propensity score methods), and the lack of re-assessment of LLD exposure and cholesterol levels during follow-up, possibly leading to a misclassification bias.

Systemic chemokine levels, coronary heart disease, and ischemic stroke events: the PRIME study.

OBJECTIVES: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. METHODS: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. RESULTS: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05-2.74), IP-10 (HR = 1.53; 95% CI 1.06-2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02-2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68-1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). CONCLUSIONS: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors.

Effects of insulin-like growth factor 1 in preventing acute coronary syndromes: the PRIME study.

OBJECTIVE: Insulin-like growth factor-1 (IGF-1) has been associated with cardiovascular risk factors and atherosclerosis. The aim of the present study was to evaluate the prognostic value of IGF-1 concentrations with respect to occurrence of well-defined coronary syndromes. METHODS: The PRIME study is a prospective cohort having included 10,600 subjects from Northern Ireland and France. Detailed information on cardiovascular risk factors, socioeconomic and behavioural variables were collected and a cardiologic examination was performed. At 5-year follow-up, 317 incident cases of coronary events were recorded according to strict protocols. They were matched to 634 age- and centre-paired controls from the same cohort, free of coronary disease. Baseline IGF-1 concentrations were measured, together with variables of lipid and glucose metabolism and markers of vascular and systemic inflammation. RESULTS: Baseline IGF-1 concentration was lower in subjects developing an acute coronary syndrome than in unaffected controls. IGF-1 levels correlated negatively with age, waist circumference, tobacco consumption and markers of inflammation. Subjects in the highest quartile of IGF-1 distribution had a 55% reduction in the relative risk of developing myocardial infarction and a 45% decrease for all-combined acute coronary syndromes. A similar trend, although non-significant, was noted for angina pectoris. Multiple adjustments on classical risk factors and inflammation markers did not affect IGF-1 results. Elevated levels of both IGF-1 and apo A-I conferred a significantly greater risk reduction than either one alone. However, interaction between the two markers was not significant. CONCLUSION: Like HDL markers, high levels of IGF-1 confer protection against coronary artery disease.

Regional factors interact with educational and income tax levels to influence food intake in France.

BACKGROUND/OBJECTIVES: The goal of the present study was to assess whether geographic factors affect the relationship between socioeconomic indicators and adherence to the French National Nutritional Health Programme (Programme National Nutrition Santé (PNNS)) guidelines. SUBJECTS/METHODS: The MONA LISA-NUT study (2005-2007) is a cross-sectional survey of a representative sample from northern, northeastern and southwestern France. Educational level and household income tax were recorded by trained interviewers. Food intake was assessed with a 3-day food diary in 3188 subjects aged from 35-64 years. Adherence to the PNNS guidelines was assessed with a validated score (the French score of indicators of the PNNS objective (FSIPO)). Multivariate analyses were adjusted for gender, age, marital status, body mass index, energy intake and medically prescribed diets. RESULTS: The FSIPO score was higher in southwestern France than in the two other regions (P<0.0001). The FSIPO score was correlated with the educational level in northern and northeastern France (P<0.0001) but not in southwestern France (region-education interaction: P<0.001). This interaction was accounted for by fruit and vegetable (P<0.0001), calcium (P=0.03), saturated fatty acid (P<0.0001), and fibre (P=0.0001) components of the FSIPO score. In contrast, the income tax level and the FSIPO score were positively correlated (P<0.0001) to a similar extent in all three regions (region × income tax interaction: P=0.09). CONCLUSIONS: The relationship between educational level and adherence to the national nutritional health guidelines differs from one region of France to another, suggesting that nutrition education programmes should perhaps be adapted on a regional basis. In contrast, guideline adherence is correlated with income tax level independently of geographical factors, suggesting that financial constraints on food choices are uniform across France.

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

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

Adipocytokines and the risk of coronary heart disease in healthy middle aged men: the PRIME Study.

BACKGROUND: Adipokines play an important role in glucose, lipid and lipoprotein metabolisms, as well as in coagulation and inflammatory processes. So far, studies have evaluated the association of individual adipokines with future coronary heart disease (CHD) event and provided mixed results. OBJECTIVES: We sought to investigate the association of a set of adipocytokines, including total adiponectin, adipsin, resistin, leptin and plasminogen activator inihibitor-1 (PAI-1), with future CHD events in apparently healthy men. METHODS: We built a nested case-control study within the PRIME Study, a multicenter prospective cohort of 9779 healthy European middle-aged men. Total adiponectin, adipsin, resistin, leptin and PAI-1 were measured in the baseline plasma sample of 617 men who developed a first CHD event (coronary death, myocardial infarction, stable or unstable angina) during 10 years of follow-up and in 1215 study-matched controls, by multiplex assays using commercial kits. HRs for CHD were estimated by conditional logistic regression analysis. RESULTS: Median concentrations of total adiponectin, adipsin and resistin were similar in cases and in controls, whereas those of leptin and PAI-1 were higher in cases than in controls, 6.30 vs 5.40 ng ml(-1), and 10.09 vs 8.48 IU ml(-1), respectively. The risk of future CHD event increased with increasing quintiles of baseline leptin and PAI-1 concentrations only in unadjusted analysis (P-value for trend <0.003 and <0.0001, respectively). However, these associations were no longer significant after adjustment for usual CHD risk factors including hypertension, diabetes, smoking, total cholesterol, triglycerides and HDL cholesterol. Conversely, baseline CRP and IL-6 levels remained associated with CHD risk in multivariate analysis. CONCLUSIONS: In apparently healthy men, circulating total adiponectin, adipsin, resistin, leptin and PAI-1 were not independent predictors of future CHD event.

Menopause and modifiable coronary heart disease risk factors: a population based study.

OBJECTIVES: The aim of our study was to determine the effect of the menopause on various coronary heart disease (CHD) risk factors and on the global risk of CHD in a population based sample of women, making the difference between menopause and age related effects. STUDY DESIGN: The Third French MONICA cross-sectional survey on cardiovascular risk included 1730 randomly selected women, aged 35-64 years, representative from the general population. MAIN OUTCOME MEASURES: Women were defined as post-menopausal (postM; n=696), peri-menopausal (periM; n=183) or pre-menopausal (preM; n=659) based on the date of last menses. Socio-demographic, clinical and biological data were collected. Analyses of variance were used to compare means. RESULTS: PostM women had significantly higher age-adjusted levels of total cholesterol (6.0mmol/L in postM vs. 5.7mmol/L in preM, p<0.05) and LDL cholesterol (3.9mmol/L vs. 3.6mmol/L, p<0.05). There was no difference in HDL cholesterol or triglyceride levels, glycemia or blood pressure. Further adjustment on body mass index and hormonal treatments did not modify the results. No risk factor was significantly different between periM and postM. However, the Framingham 10-year risk of CHD was higher in postM, as compared with periM (5.1% vs. 5.0%, p<0.05). In postM women, lipids and the Framingham risk were not associated with elapsed time since menopause. CONCLUSIONS: The CHD risk increases during the sixth decade could be explained not only by estrogen deprivation but also by an effect on lipid profile, which is likely to occur in the peri-menopause period.

Residual cardiovascular risk in treated hypertension and hyperlipidaemia: the PRIME Study.

Although pharmacological treatments of hypertension and dyslipidaemia are both associated with a reduction in cardiovascular risk, little is known about the degree of cardiovascular risk remaining in treated individuals, by assessing the levels of their risk factors achieved, that is their 'residual cardiovascular risk'. We then used the data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME), which involved 9649 men aged 50-59 years, from France and Northern Ireland with a 10-year follow-up, to test the presence of specific residual cardiovascular risks of coronary heart disease, stroke, total of fatal and non-fatal cardiovascular events and cardiovascular mortality, in patients treated with antihypertensive agents or lipid-lowering agents. In the whole cohort, a total of 796 patients developed a fatal or non-fatal cardiovascular event. Antihypertensive drug use at baseline was significantly associated (RR=1.50, 95% CI: 1.25-1.80) with total cardiovascular event risk, but not lipid-lowering drug use, after adjusting for classic risk factors (age, smoking, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure and diabetes). Similar results were obtained for coronary heart disease (RR=1.46, 95% CI: 1.18-1.80), stroke (RR=1.75, 95% CI: 1.14-2.70) and cardiovascular death (RR=1.62, 95% CI: 1.02-2.58), but neither for total death (RR=1.15, 95% CI: 0.89-1.48) nor for non-cardiovascular death (RR=1.00, 95% CI: 0.74-1.36). For any cardiovascular end point, residual risks did not globally differ according to the antihypertensive drug class prescribed at baseline. In conclusion, treatment with antihypertensive agents, but not with lipid-lowering agents, was associated with a sizeable residual cardiovascular risk, suggesting that more efficient risk reduction strategies in hypertension should be developed as a priority.

Association between angiopoietin-like 6 (ANGPTL6) gene polymorphisms and metabolic syndrome-related phenotypes in the French MONICA Study.

AIM: Although the ANGPTL6 (angiopoietin-like 6) gene product is now known to be involved in the regulation of fat mass and insulin sensitivity in mice, its physiological functions in humans have yet to be determined. METHODS: Subjects from the population-based French MONICA Study (n=3402) were genotyped for single nucleotide polymorphisms (SNPs) in ANGPTL6, and associations with anthropometric or biochemical phenotypes were looked for. RESULTS: On evaluating the frequency of 17 ANGPTL6 SNPs in 100 randomly selected subjects on the basis of linkage disequilibrium mapping, four SNPs (rs6511435, rs8112063, rs11671983 and rs15723) were found to cover more than 95% of the known ANGPTL6 genetic variability. Subjects from the entire MONICA Study were then genotyped for these four SNPs. No significant association was detected for rs11671983 and rs15723. In contrast, the G allele of rs8112063 was associated with lower plasma glucose levels (P=0.009). Also, obese subjects carrying the G allele of rs6511435 had higher plasma insulin levels than AA subjects (P=0.0055). Moreover, the G allele of rs6511435 tended to be associated with a 20% higher risk of the metabolic syndrome (P=0.034). However, when false discovery rate testing (40 tests) was applied, these associations were no longer statistically significant. CONCLUSION: These findings constitute the first study in humans of ANGPTL6 genetic variability. Although there was no evidence that polymorphisms in ANGPTL6 might be significantly associated with the metabolic syndrome-related phenotypes, a weak association of these polymorphisms with these parameters cannot be excluded. Further association studies are needed to arrive at any definite conclusions.

Association of macronutrient intake patterns with being overweight in a population-based random sample of men in France.

AIM: Diet is considered an important modifiable factor in the overweight. The role of macronutrients in obesity has been examined in general in selected populations, but the results of these studies are mixed, depending on the potential confounders and adjustments for other macronutrients. For this reason, we examined the association between macronutrient intake patterns and being overweight in a population-based representative sample of middle-aged (55.1+/-6.1 years) men (n=966), using various adjustment modalities. METHODS: The study subjects kept 3-day food-intake records, and the standard cardiovascular risk factors were assessed. Weight, height and waist circumference (WC) were also measured. RESULTS: Carbohydrate intake was negatively associated and fat intake was positively associated with body mass index (BMI) and WC in regression models adjusted for energy intake and other factors, including age, smoking and physical activity. However, with mutual adjustments for other energy-yielding nutrients, the negative association of carbohydrate intake with WC remained significant, whereas the associations between fat intake and measures of obesity did not. Adjusted odds ratios (95% confidence interval) comparing the highest and lowest quartiles of carbohydrate intake were 0.50 (0.25-0.97) for obesity (BMI>29.9) and 0.41 (0.23-0.73) for abdominal obesity (WC>101.9 cm). CONCLUSION: Consistent negative associations between carbohydrate intake and BMI and WC were seen in this random representative sample of the general male population. The associations between fat intake and these measures of being overweight were attenuated on adjusting for carbohydrate intake. Thus, the balance of carbohydrate-to-fat intake is an important element in obesity in a general male population, and should be highlighted in dietary guidelines.