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.

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.

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.

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.

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.

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.

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.

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.

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.

Impact of age and gender on the prevalence and prognostic importance of the metabolic syndrome and its components in Europeans. The MORGAM Prospective Cohort Project.

OBJECTIVE: To investigate the influence of age and gender on the prevalence and cardiovascular disease (CVD) risk in Europeans presenting with the Metabolic Syndrome (MetS). METHODS: Using 36 cohorts from the MORGAM-Project with baseline between 1982-1997, 69094 men and women aged 19-78 years, without known CVD, were included. During 12.2 years of follow-up, 3.7%/2.1% of men/women died due to CVD. The corresponding percentages for fatal and nonfatal coronary heart disease (CHD) and stroke were 8.3/3.8 and 3.1/2.5. RESULTS: The prevalence of MetS, according to modified definitions of the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII), increased across age groups for both genders (P<0.0001); with a 5-fold increase in women from ages 19-39 years to 60-78 years (7.4%/7.6% to 35.4%/37.6% for IDF/NCEP-ATPIII) and a 2-fold increase in men (5.3%/10.5% to 11.5%/21.8%). Using multivariate-adjusted Cox regressions, the associations between MetS and all three CVD events were significant (P<0.0001). For IDF/NCEP-ATPIII in men and women, hazard ratio (HR) for CHD was 1.60/1.62 and 1.93/2.03, for CVD mortality 1.73/1.65 and 1.77/2.06, and for stroke 1.51/1.53 and 1.58/1.77. Whereas in men the HRs for CVD events were independent of age (MetS*age, P>0.05), in women the HRs for CHD declined with age (HRs 3.23/3.98 to 1.55/1.56; MetS*age, P=0.01/P=0.001 for IDF/NCEP-ATPIII) while the HRs for stroke tended to increase (HRs 1.31/1.25 to 1.55/1.83; MetS*age, P>0.05). CONCLUSION: In Europeans, both age and gender influenced the prevalence of MetS and its prognostic significance. The present results emphasise the importance of being critical of MetS in its current form as a marker of CVD especially in women, and advocate for a redefinition of MetS taking into account age especially in women.

14-Year risk of all-cause mortality according to hypoglycaemic drug exposure in a general population.

PURPOSE: Guidelines for management of patients with type 2 diabetes mellitus recommend the use of hypoglycaemic drugs when lifestyle interventions remain insufficient for glycaemic control. Recent trials have provided worrying safety data on certain hypoglycaemic drugs. The aim of this study was to assess 14-year risk of all-cause mortality according to hypoglycaemic drug exposure at baseline, in a general population. METHODS: Our analysis was based on the observational Third French MONICA survey on cardiovascular risk factors (1995-1997). Vital status was obtained 14 years after inclusion, and assessment of determinants of mortality was based on multivariable Cox modelling. RESULTS: There were 3336 participants and 248 deaths over the 14-year period. At baseline, there were 3162 (95%) non-diabetic, 46 (1%) untreated type 2 diabetic and 128 (4%) type 2 diabetic subjects with hypoglycaemic drug treatment (metformin alone (31%), sulfonylureas alone or in combination (49%), insulin alone or in combination (10%), or other treatments (9%)). After adjustment for duration of diabetes, history of diabetes complications, area of residence (centre), age, gender, educational level, alcohol consumption, smoking, blood pressure, LDL and HDL cholesterol, which all were significant and independent determinants of mortality, the hazard ratio for all-cause mortality was 3.22 [95% confidence interval: 0.87-11.9] for untreated diabetic subjects, 2.28 [0.98-5.26] for diabetics treated with metformin alone, 1.70 [0.92-3.16] for diabetics with sulfonylureas and 4.92 [1.70-14.3] for diabetic with insulin versus non-diabetic subjects. CONCLUSIONS: Our results support the conclusion that until more evidence is provided from randomized trials, a prudent approach should be to restrain use of insulin to situations in which combinations of non-insulin agents have failed to appropriately achieve glycemic control, as it is recommended in the current guidelines for the management of type 2 diabetes.

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.

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.

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.

Attainment of low-density lipoprotein cholesterol target in the French general population according to levels of cardiovascular risk: Insights from the MONA LISA study.

BACKGROUND: Controlling low-density lipoprotein (LDL)-cholesterol concentration is of tremendous importance to reduce cardiovascular risk. AIMS: To investigate the attainment of LDL-cholesterol targets recommended in French and European guidelines on cardiovascular prevention, according to levels of cardiovascular risk. METHODS: Participants aged 35 to 74 years (n=4609) were randomly selected from the general population of three French regions. A standardized data collection was performed to assess cardiovascular risk as described in the French and European guidelines. RESULTS: Overall, 17.5% of participants were considered to be at high risk and 25.4% at high or very high risk, according to the French and European guidelines, respectively. Only 1.2% of participants with no cardiovascular risk factors according to the French guidelines had an LDL-cholesterol concentration above the recommended target, whereas 82.5% of high-risk subjects did not attain their goal (70.8% among high-risk subjects receiving lipid-lowering therapy). Among untreated people, the median reduction in LDL-cholesterol needed to reach target ranged from 6.6% (lowest-risk groups) to 36.0% (highest-risk subjects). When risk was classified according to the European guidelines, the majority of participants did not reach the recommended LDL-cholesterol targets, irrespective of their level of risk or lipid-lowering therapy. CONCLUSION: In a majority of primary prevention candidates with multiple risk factors and in most high-risk subjects, LDL-cholesterol targets recommended by French guidelines are not being achieved, either because of insufficient treatment or because subjects are not recognized as being at risk. More stringent targets proposed by the European guidelines are not being achieved in most cases.

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.

The major element of 1-year prognosis in acute coronary syndromes is severity of initial clinical presentation: Results from the French MONICA registries.

BACKGROUND: While the death rate from acute coronary syndromes (ACS) has been in decline for more than 50 years, out-of-hospital mortality remains high despite improvements in care. AIM: To evaluate the importance of out-of-hospital mortality and identify the main predictors of in-hospital and 1-year mortality in France. METHODS: Analyses were based on data from the French MONICA population-based registry, which included all cases of ACS occurring in people aged 35-74 years during 2006 in three geographic areas in France. We first evaluated out-of-hospital mortality; then, using data from patients with incident ACS who reached hospital alive, Cox models were performed to determine the main predictors of 1-year mortality. The number of attributable deaths was assessed for variables of interest. RESULTS: After 1-year follow-up, case-fatality was 29.3% for incident events (n=2547); the proportion of out-of-hospital deaths was 70.3%, and 91.5% of deaths occurred in the 28 days following the ACS. On multivariable analysis, the number of attributable deaths associated with three scenarios (out-of-hospital life-and-death emergency, hospitalization before ACS occurrence, and lack of coronary angiography) was 130 (accounting for 59% of deaths occurring after reaching the hospital) during 1-year follow-up. These scenarios corresponded to patients with an initial severe clinical presentation in whom rates of use of specific treatments and invasive procedures were very low. CONCLUSION: A large proportion of fatalities after an ACS occurs in the out-of-hospital phase. Moreover, the major component of 1-year mortality is associated with a poor prognosis at initial presentation. This finding highlights the importance of cardiovascular prevention, population education and better out-of-hospital emergency management in improving prognosis after an ACS.