Jean Dallongeville

Trends in plasma lipids, lipoproteins and dyslipidaemias in French adults, 1996–2007

BACKGROUNDnIn France, the reported decrease in cardiovascular death is due partly to improved cardiovascular prevention. The management of dyslipidaemias remains a priority of preventive cardiology.nnnAIMnTo assess trends in lipids, lipoproteins and dyslipidaemias between 1996 and 2007 in France.nnnMETHODSnRepresentative surveys of the general population were carried out in Lille, Strasbourg and Toulouse during two periods, 1996 to 1997 and 2006 to 2007. Men and women aged 35 to 64 years were included. Investigators recorded cardiovascular risk factors, and a blood sample was drawn to measure glycaemia and to provide a complete lipid profile. The data were corrected according to the respective original populations to study 10-year trends in the parameters measured.nnnRESULTSnFrom 1996 to 2007, a significant 5.7% decrease in low-density lipoprotein (LDL)-cholesterol levels was observed in adults aged 35 to 64 years (p<0.001). This decrease was greater in those aged 55 to 64 years (10.8% in men, 8.4% in women). A significant 7.8% increase in triglycerides was observed (p<0.001) over the same period. Variation in LDL-cholesterol was more striking in subjects treated with a lipid-lowering drug, with a 17.6% reduction (p<0.001). A decrease in most of dyslipidaemias was also observed over this 10-year interval.nnnCONCLUSIONnThis study shows a favourable downward trend in LDL-cholesterol concentration and dyslipidaemias in France. The significant decrease in LDL-cholesterol observed among all the subjects and more particularly among subjects treated with lipid-lowering drugs should provide an incentive for physicians to support the management of all French adults.

Guía Europea de Prevención Cardiovascular en la Práctica Clínica

Presentamos la adaptacion espanola realizada por el CEIPC de la Guia Europea de Prevencion de las Enfermedades Cardiovasculares (ECV) 2008. Esta guia recomienda el modelo SCORE de bajo riesgo para la valoracion del riesgo cardiovascular. El objetivo es prevenir la mortalidad y morbilidad debidas a las ECV mediante el manejo de sus factores de riesgo en la practica clinica. La guia hace enfasis en la prevencion primaria y en el papel del medico y la enfermeria de atencion primaria en la promocion de un estilo de vida saludable, basado en el incremento de los niveles de actividad fisica, la adopcion de una alimentacion saludable y, en los fumadores, el abandono del tabaco. La meta terapeutica para la presion arterial es en general <140/90 mmHg; pero en pacientes con diabetes, enfermedad renal cronica o ECV el objetivo es 130/80 mmHg. El colesterol debe mantenerse por debajo de 200 mg/dl (cLDL<130 mg/dl); en los pacientes con ECV o diabetes el objetivo es cLDL<100 mg/dl (80 mg/dl si factible en sujetos de muy alto riesgo). En diabetes tipo 2 y en pacientes con sindrome metabolico se debe reducir el peso y aumentar la actividad fisica y en su caso utilizar los farmacos indicados, para alcanzar los objetivos de indice de masa corporal (IMC) y de perimetro de cintura. El objetivo en diabeticos tipo 2 debe ser alcanzar un nivel de hemoglobina glucosilada (HbA1c) <7%. La amplia difusion de las guias y el desarrollo de los programas destinados a favorecer su implantacion, identificando barreras y buscando soluciones, son objetivos prioritarios del CEIPC, como uno de los medios fundamentales para trasladar las recomendaciones establecidas a la practica clinica diaria.

Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms and Coronary Heart Disease

Single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor γ (PPARG) gene have been associated with cardiovascular risk factors, particularly obesity and diabetes. We assessed the relationship between 4 PPARG SNPs (C-681G, C-689T, Pro12Ala, and C1431T) and coronary heart disease (CHD) in the PRIME (249 cases/494 controls, only men) and ADVANCE (1,076 cases/805 controls, men or women) studies. In PRIME, homozygote individuals for the minor allele of the PPARG C-689T, Pro12Ala, and C1431T SNPs tended to have a higher risk of CHD than homozygote individuals for the frequent allele (adjusted OR [95% CI] = 3.43 [0.96–12.27], P = .058, 3.41 [0.95–12.22], P = .060 and 5.10 [0.99–26.37], P = .050, resp.). No such association could be detected in ADVANCE. Haplotype distributions were similar in cases and control in both studies. A meta-analysis on the Pro12Ala SNP, based on our data and 11 other published association studies (6,898 CHD cases/11,287 controls), revealed that there was no evidence for a significant association under the dominant model (OR = 0.99 [0.92–1.07], P = .82). However, there was a borderline association under the recessive model (OR = 1.29 [0.99–1.67], P = .06) that became significant when considering men only (OR = 1.73 [1.20–2.48], P = .003). In conclusion, the PPARG Ala12Ala genotype might be associated with a higher CHD risk in men but further confirmation studies are needed.

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

BackgroundThe 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.MethodsThe 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.ResultsCompared 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.ConclusionThe APOA5 Trp19 allele increased susceptibility to metabolic syndrome via its impact on plasma triglyceride levels.

Risk stratification in cardiovascular disease primary prevention - scoring systems, novel markers, and imaging techniques.

The aim of this paper is to review and discuss current methods of risk stratification for cardiovascular disease (CVD) prevention, emerging biomarkers, and imaging techniques, and their relative merits and limitations. This report is based on discussions that took place among experts in the area during a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy in September 2009. Classical risk factors such as blood pressure and low‐density lipoprotein cholesterol levels remain the cornerstone of risk estimation in primary prevention but their use as a guide to management is limited by several factors: (i) thresholds for drug treatment vary with the available evidence for cost‐effectiveness and benefit‐to‐risk ratios; (ii) assessment may be imprecise; (iii) residual risk may remain, even with effective control of dyslipidemia and hypertension. Novel measures include C‐reactive protein, lipoprotein‐associated phospholipase A2, genetic markers, and markers of subclinical organ damage, for which there are varying levels of evidence. High‐resolution ultrasound and magnetic resonance imaging to assess carotid atherosclerotic lesions have potential but require further validation, standardization, and proof of clinical usefulness in the general population. In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk‐guided therapy in CVD prevention.

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; pu2009<u200910−4) among men and −9.0 (−11.6 to −6.4; pu2009<u200910−4) among women. In the 35–54 age group, the EAPC in mortality was −4.1 (−7.2 to −1.1; pu2009<u200910−2) among men and −2.5 (−8.7 to 3.7; pu2009=u20090.43) 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.

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. Eur J Cardiovasc Prev Rehabil 15:625–630

Multiple microRNA regulation of lipoprotein lipase gene abolished by 3'UTR polymorphisms in a triglyceride-lowering haplotype harboring p.Ser474Ter.

BACKGROUNDnLipoprotein lipase (LPL) is a key enzyme in triglyceride (TG) metabolism. LPL gene single nucleotide polymorphisms (SNPs) are associated with TG concentrations however the functionality of many of these SNPs remains poorly understood. MicroRNAs (miR) exert post-transcriptional down-regulation and their target sequence on the 3UTR may be altered by SNPs. We therefore investigated whether LPL 3UTR SNPs could modulate plasma TG concentration through the alteration of miR binding-sites.nnnMETHODS AND RESULTSnWe performed genetic association studies of LPL 3UTR SNPs with TG concentrations in 271 type 2 diabetic patients and in general population samples (2997 individuals). A specific LPL haplotype (Hap4) was associated with lower plasma TG concentration (TG-0.18, IC95% [-0.30, -0.07] mmol/L or logTG-0.13, IC95% [-0.18, -0.08], p = 4.77·10(-8)) in the meta-analysis. Hap4 comprises seven 3UTR SNP minor alleles and p.Ser474Ter (rs328) a well-documented nonsense mutation associated with low TG concentration although by an unknown mechanism so far. Bio-informatic studies identified several putative miRNA binding-sites on the wild-type Hap1 haplotype, lost on Hap4. Functional validation performed in HEK-293T cells using luciferase expression constructs with various LPL 3UTR allele combinations demonstrated a binding of miR-29, miR-1277 and miR-410 on Hap1, lost on Hap4. This loss of specific miR binding-site in presence of Hap4 was independent of the allelic variation of p.Ser474Ter (rs328).nnnCONCLUSIONSnWe report the regulation of LPL by the miR-29, miR-1277 and miR-410 that is lost in presence of Hap4, a specific LPL TG-lowering haplotype. Consequently p.Ser474Ter association with TG concentration could be at least partially explained by its strong linkage disequilibrium with these functional 3UTR SNPs.

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.

Changes over time in the prevalence and treatment of cardiovascular risk factors, and contributions to time trends in coronary mortality over 25 years in the Lille urban area (northern France)

BACKGROUNDnThe long-term collection of population-based data should improve our knowledge of the contribution of trend in cardiovascular risk factors to the steady fall in mortality associated with coronary heart disease in high-income countries.nnnAIMSnTo assess long-term time trends in the prevalence of cardiovascular risk factors, estimated coronary heart disease risk and mortality between 1986 and 2013 in the Lille urban area (northern France).nnnMETHODSnWe studied representative samples of inhabitants of the Lille urban area (aged 40-64 years) in 1986-1988 (n=860), 1995-1996 (n=1021), 2005-2007 (n=1021) and 2011-2013 (n=1636), together with data from the Lille MONICA registry.nnnRESULTSnIn men, the age-standardized prevalence fell between 1986 and 2013 from 70.5% to 42.5% for hypertension, from 71.1% to 58.3% for dyslipidaemia and from 44.1% to 24.7% for smoking (all P<0.001). The prevalence of being overweight increased from 59.6% to 65.1% (P<0.05). In women, the prevalences decreased from 56.6% to 34.3% for hypertension and from 60.9% to 42.2% for dyslipidaemia (both P<0.001). The prevalences of smoking (17%) and being overweight (50%) were stable. The mean 10-year (95% confidence interval) predicted risk of fatal coronary heart disease (estimated with the Systematic Coronary Risk Evaluation equation) decreased by 2.02% (1.78-2.25%) per year for men and by 1.55% (1.32-1.78%) for women. The observed coronary mortality rate fell by 2.6% (2.2-3.0%) in men and 2.8% (1.9-3.6%) in women.nnnCONCLUSIONSnPrevalences of main risk factors and estimated coronary mortality risk decreased concomitantly with the observed coronary mortality - indicating that primary prevention made a major contribution to the decrease in mortality.