0015: High LDL cholesterol decreases life expectancy in primary prevention

BackgroundThe 2012 ESC guidelines recommend a LDL-cholesterol (LDL-C) lower than 3mmol/L for subjects at low or moderate risk with a class I/A and a strong grade. According to ESC, statins should be used as the drugs of first choice. The aim of this study was to assess the association between elevated LDL-C with total and cardiovascular (CV) mortality in primary prevention.MethodsOur study population consisted in patients who had been admitted from 1995 to 2011 in a preventive cardiology unit of a large French university hospital. We excluded patients whose age was less than 30 and all patients with previous ischemic heart disease. Vital status in 2011 was checked through the death national database.Results4885 patients were included (59% men; 53±10 yrs). After a mean follow-up of 8.6 years, 129 deaths, including 31 CV deaths, were recorded. The mean LDL-C was 3.98±1.18mmol/L (3.90 in men and 4.11 in women). Among these 4885 patients, 2648 (54.2%) had LDL-C lower than 4mmol/L, 1890 (38.7%) had LDL-C between 4 and 6mmol/L, 347 (7.1%) had LDL-C higher than 6mmol/L, and 1833 (37.5%) were on current lipid-lowering treatment. After adjustment for age, gender, smoking, hypertension and diabetes, an increased LDL-C > 4mmol/L was significantly associated with all cause mortality (hazard ratio (HR) 2.06; 95% confidence interval (CI) [1.42-3.00], p=0.001) and with CV mortality (HR 2.18; 95% CI [1.04-4.57], p=0.04). After adjustment for these classical risk factors and for lipid-lowering treatment, LDL-C remained significantly associated with an increasing risk of all cause mortality; with LDL-C < 4mmol/L as a reference class, LDL-C levels between 4 and 6mmol/L were associated with an increased all cause mortality (HR 1.72; 95% CI [1.17-2.54], p=0.006) as well as LDL-C > 6mmol/L (HR 2.60; 95% CI [1.49-4.85], p=0.001).ConclusionsLDL-C levels higher than 4mmol/L were significantly associated with all-cause and cardiovascular mortality in primary prevention

0098: Erythrocyte membrane phospholipid fatty acids, dairy intakes and cardiovascular risk

IntroductionThe impact of dairy fats on cardiovascular risk has been debated. Circulating Pentadecanoic (15:0) and heptadecanoic (17:0) saturated fatty acids are good biomarkers of dairy product consumption as they are mainly provided by dairy fats. We described the prevalence of cardiovascular risk factors according to erythrocyte membrane phospholipid content in 15:0 and 17:0 fatty acids.Methods402 women and men aged 45-64 were randomly selected in 2005-2007, from the general population of three French areas. Nutritional data were collected through a 3-day food record. Fatty acid content was measured in erythrocyte membrane phospholipids.ResultsErythrocyte membrane contents in 15:0 and 17:0 fatty acids significantly increased with the consumption of dairy products collected during the 3-day food record. Prevalence of hypertension significantly decreased from the lowest to the highest quartile of 15:0 erythrocyte content (48.1%; 33.3%; 29.9%; 25.5%; p=0.005). A similar trend was observed for metabolic syndrome prevalence (39.4%; 28.1%; 25.2%; 21.3%; p=0.029). Prevalence of hypertension, hypertriglyceridaemia, overweight and metabolic syndrome significantly decreased from the lowest to the highest quartile of 17:0 erythrocyte content (44.1%; 36.5%; 28.1%; 25.6%; p=0.020 for hypertension; 30.3%; 15.4%; 16.9%; 16.7%; p=0.017 for hypertriglyceridaemia; 68.1%; 58.7%; 46.6%; 44.4%; p=0.002 for overweight; and 43.2%; 26.9%; 22.5%; 17.8%; p<0.001 for metabolic syndrome). All these relationships remained significant after adjustment for age and gender. The link did not reach significance level for diabetes.ConclusionElevated erythrocyte membrane phospholipid contents in 15:0 and 17:0 saturated fatty acids are associated with a lower prevalence of the metabolic syndrome and several of its components. These results suggest that saturated fat intake should not be systematically associated with high cardiovascular risk and can be considered as part of a balanced diet

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

SummaryBackgroundWhile the death rate from acute coronary syndromes (ACS) has been in decline for more than 50years, out-of-hospital mortality remains high despite improvements in care.AimTo evaluate the importance of out-of-hospital mortality and identify the main predictors of in-hospital and 1-year mortality in France.MethodsAnalyses were based on data from the French MONICA population-based registry, which included all cases of ACS occurring in people aged 35–74years 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.ResultsAfter 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 28days 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.ConclusionA 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

Frequency of fruit and vegetable consumption and coronary heart disease in France and Northern Ireland: the PRIME study

Fruit and vegetable consumption is associated with low CHD risk in the USA and Northern Europe. There is, in contrast, little information about these associations in other regions of Europe. The goal of the present study was to assess the relationship between frequency of fruit and vegetable intake and CHD risk in two European populations with contrasting cardiovascular incidence rates; France and Northern Ireland. The present prospective study was in men aged 50-59 years, free of CHD, who were recruited in France (n 5982) and Northern Ireland (n 2105). Fruit and vegetable intake was assessed by a food-frequency questionnaire. Incident cases of acute coronary events and angina were recorded over a 5-year follow-up. During follow-up there was a total of 249 ischaemic events. After adjustment on education level, smoking, physical activity, alcohol consumption, employment status, BMI, blood pressure, serum total and HDL-cholesterol, the relative risks (RR) of acute coronary events were 0·67 (95% CI 0·44, 1·03) and 0·64 (95% CI 0·41, 0·99) in the 2nd and 3rd tertiles of citrus fruit consumption, respectively (P for trend <0·03). Similar results were observed in France and Northern Ireland. In contrast, the RR of acute coronary events for ‘other fruit' consumption were 0·70 (95% CI 0·31, 1·56) and 0·52 (95% CI 0·24, 1·14) respectively in Northern Ireland (trend P<0·05) and 1·29 (95% CI 0·69, 2·4) and 1·15 (95% CI 0·68, 1·94) in France (trend P=0·5; interaction P<0·04). There was no evidence for any association between vegetable intake and total CHD events. In conclusion, frequency of citrus fruit, but not other fruits, intake is associated with lower rates of acute coronary events in both France and Northern Ireland, suggesting that geographical or related factors might affect the relationship between fruit consumption and CHD ris

RNY-derived small RNAs as a signature of coronary artery disease

International audienceBackgroundData from next generation sequencing technologies uncovered the existence of many classes of small RNAs. Recent studies reported that small RNAs are released by cells and can be detected in the blood. In this report, we aimed to discover the occurrence of novel circulating small RNAs in coronary artery disease (CAD).MethodsWe used high-throughput sequencing of small RNAs from human and mouse apoptotic primary macrophages, and analyzed the data by empirical Bayes moderated t-statistics to assess differential expression and the Benjamini and Hochberg method to control the false discovery rate. Results were then confirmed by Northern blot and RT-qPCR in foam cells and in two animal models for atherosclerosis, namely ApoE −/− and Ldlr −/− mouse lines. Quantitative RT-PCR to detect identified small RNAs, the RNY-derived small RNAs, was performed using sera of 263 patients with CAD compared to 514 matched healthy controls; the Student t-test was applied to statistically assess differences. Associations of small RNAs with clinical characteristics and biological markers were tested using Spearman’s rank correlations, while multivariate logistic regressions were performed to test the statistical association of small RNA levels with CAD.ResultsHere, we report that, in macrophages stimulated with pro-apoptotic or pro-atherogenic stimuli, the Ro-associated non-coding RNAs, called RNYs or Y-RNAs, are processed into small RNAs (~24–34 nt) referred to as small-RNYs (s-RNYs), including s-RNY1-5p processed from RNY1. A significant upregulation of s-RNY expression was found in aortic arches and blood plasma from ApoE −/− and Ldlr −/− mice and in serum from CAD patients (P <0.001). Biostatistical analysis revealed a positive association of s-RNY1-5p with hs-CRP and ApoB levels; however, no statistical interaction was found between either of these two markers and s-RNY1-5p in relation to the CAD status. Levels of s-RNY1-5p were also independent from statin and fibrate therapies.ConclusionOur results position the s-RNY1-5p as a relevant novel independent diagnostic biomarker for atherosclerosis-related diseases. Measurement of circulating s-RNY expression would be a valuable companion diagnostic to monitor foam cell apoptosis during atherosclerosis pathogenesis and to evaluate patient’s responsiveness to future therapeutic strategies aiming to attenuate apoptosis in foam cells in advanced atherosclerotic lesions

Lack of association between serological evidence of past Coxiella burnetii infection and incident ischaemic heart disease: nested case-control study

BACKGROUND: Coxiella burnetii causes the common worldwide zoonotic infection, Q fever. It has been previously suggested that patients who had recovered from acute Q fever (whether symptomatic or otherwise) may be at increased risk of ischaemic heart disease. We undertook this study to determine if past infection with Coxiella burnetii, the aetiological agent of Q fever, is a risk factor for the subsequent development of ischaemic heart disease. METHODS: A nested case-control study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME). The PRIME study is a cohort study of 10,593 middle-aged men undertaken in France and Northern Ireland in the 1990s. A total of 335 incident cases of ischaemic heart disease (IHD) were identified and each case was matched to 2 IHD free controls. Q fever seropositivity was determined using a commercial IgG ELISA method. RESULTS: Seroprevalence of Q fever in the controls from Northern Ireland and France were 7.8% and 9.0% respectively. No association was seen between seropositivity and age, smoking, lipid levels, or inflammatory markers. The unadjusted odds ratio (95% CI) for Q fever seropositivity in cases compared to controls was 0.95 (0.59, 1.57). The relationship was substantially unaltered following adjustment for cardiovascular risk factors and potential confounders. CONCLUSION: Serological evidence of past infection with C. burnetii was not found to be associated with an increased risk of IHD

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>The <it>APOA5 </it>Ser19Trp, <it>APOA5 </it>-12,238T>C, <it>APOA4 </it>Thr347Ser, <it>APOC3 </it>-482C>T and <it>APOC3 </it>3238C>G (<it>Sst</it>I) 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.</p> <p>Results</p> <p>Compared with homozygotes for the common allele, the odds ratio (OR) [95% CI] for metabolic syndrome was 1.30 [1.03–1.66] (<it>p </it>= 0.03) for <it>APOA5 </it>Trp19 carriers, 0.81 [0.69–0.95] (<it>p </it>= 0.01) for <it>APOA5 </it>-12,238C carriers and 0.84 [0.70–0.99] (<it>p </it>= 0.04) for <it>APOA4 </it>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 <it>APOC3 </it>-482C>T or <it>APOC3 </it>3238C>G polymorphisms and metabolic syndrome. The decreased risk of metabolic syndrome observed in <it>APOA5 </it>-12,238C and <it>APOA4 </it>Ser347 carriers merely reflected the fact that the <it>APOA5 </it>Trp19 allele was in negative linkage disequilibrium with the common alleles of <it>APOA5 </it>-12,238T>C and <it>APOA4 </it>Thr347Ser polymorphisms.</p> <p>Conclusion</p> <p>The <it>APOA5 </it>Trp19 allele increased susceptibility to metabolic syndrome via its impact on plasma triglyceride levels.</p