217 research outputs found
HDL: facteur causal de l’athérosclérose ? Arguments épidémiologiques
RésuméLes lipoprotéines HDL doivent répondre aux critères épidémiologiques classiques. Les études épidémiologiques qui ont été menées semblent exemptes de biais et des facteurs de confusion. Ces études montrent de manière convergente que les taux de HDLcholestérol bas sont associés à un risque coronaire élevé. La prévalence du HDL-cholestérol bas en population générale étant élevée, il est logique de pousser la démonstration jusqu’à la réversibilité du risque lorsque les taux de HDL-cholestérol sont modifiés. La randomisation mendélienne offre une opportunité intéressante afi n de discuter du rôle du HDL-cholestérol dans le risque cardiovasculaire. Malheureusement, la randomisation mendélienne ne permet pas de se faire une idée définitive de cette réversibilité dans des études de nature épidémiologique. Il existe des arguments partiels permettant d’envisager que des taux élevés de HDL-cholestérol occasionnés par des thérapeutiques variées sont associés à une baisse du risque coronaire à long terme. En conclusion, les arguments épidémiologiques sont nombreux pour penser que le HDL-cholestérol est un facteur causal dans l’athérosclérose coronaire. Nous sommes dans l’attente d’essais thérapeutiques spécifiques permettant d’affirmer définitivement que le HDL-cholestérol doit être augmenté par des thérapeutiques dans la pratique de tous les jours.SummaryClassic epidemiological rules must be applied to the relationship between HDL lipoproteins and coronary artery disease risk. After having eliminated bias and confounding factors, these epidemiological studies have consistently shown that low HDL-cholesterol is associated with coronary artery disease risk. Since prevalence of low HDL-cholesterol levels is high at a population level, it is crucial to demonstrate that HDL-cholesterol levels can be improved. Mendelian randomization offers a good opportunity to study the role of HDL-cholesterol in coronary artery disease risk. Unfortunately, Mendelian randomization does not allow to conclude definitely about the reversibility of coronary artery disease risk when HDL-cholesterol is spontaneously low and then increased. There are a few arguments showing that increased HDL-cholesterol levels by various therapeutic avenues are associated with a lower long-term coronary artery disease risk. In conclusion, epidemiological studies are numerous to show that HDL-cholesterol might be a causal factor in atherosclerosis. Trials are underway to definitely conclude that HDL-cholesterol levels must be increased by lipid-modifying agents in current practice
Effects of insulin-like growth factor 1 in preventing acute coronary syndromes: the PRIME Study
Supraventricular cardiac conduction system exposure in breast cancer patients treated with radiotherapy and association with heart and cardiac chambers doses
Purpose: To assess sinoatrial node (SAN) and atrioventricular node (AVN) doses for breast cancer (BC) patients treated with 3D-CRT and evaluate whether “large” cardiac structures (whole heart and four cardiac chambers) would be relevant surrogates. Material and methods: This single center study was based on 116 BCE patients (56 left-sided, 60 right-sided) treated with 3D-CRT without respiratory gating strategies and few IMN irradiations from 2009 to 2013. The heart, the left and right ventricles (LV, RV), the left and right atria (LA, RA) were contoured using multi-atlases for auto-segmentation. The SAN and the AVN were manually delineated using a specific atlas. Based on regression analysis, the coefficients of determination (R2) were estimated to evaluate whether “large” cardiac structures were relevant surrogates (R2 > 0.70) of SAN and AVN doses. Results: For left-sided BC, mean doses were: 3.60 ± 2.28 Gy for heart, 0.47 ± 0.24 Gy for SAN and 0.74 ± 0.29 Gy for AVN. For right-sided BC, mean heart dose was 0.60 ± 0.25 Gy, mean SAN dose was 1.57 ± 0.63 Gy (>85 % of patients with SAN doses > 1 Gy) and mean AVN dose was 0.51 ± 0.14 Gy. Among all “large” cardiac structures, RA appeared as the best surrogate for SAN doses (R2 > 0.80). Regarding AVN doses, the RA may also be an interesting surrogate for left-sided BC (R2 = 0.78), but none of “large” cardiac structures appeared as relevant surrogates among right-sided BC (all R2 < 0.70), except the LA for patients with IMN (R2 = 0.83). Conclusions: In BC patients treated 10 years ago with 3D-CRT, SAN and AVN exposure was moderate but could exceed 1 Gy to the SAN in many right-sided patients with no IMN-inclusion. The RA appeared as an interesting surrogate for SAN exposure. Specific conduction nodes delineation remains necessary by using modern radiotherapy techniques
Clinical research Are the Framingham and PROCAM coronary heart disease risk functions applicable to different European populations? The PRIME StudyM
Aims To assess whether the Framingham and PROCAM risk functions were applicable to men in Belfast and France. Methods and results We performed an external validation study within the PRIME (Prospective Epidemiological Study of Myocardial Infarction) cohort study. It comprised men recruited in Belfast (2399) and France (7359) who were aged 50 to 59 years, free of CHD at baseline (1991 to 1993) and followed over 5 years for CHD events (coronary death, myocardial infarction, angina pectoris). We compared the relative risks of CHD associated with the classic risk factors in PRIME with those in Framingham and PROCAM cohorts. We then compared the number of predicted and observed 5-year CHD events (calibration). Finally, we estimated the ability of the risk functions to separate high risk from low risk subjects (discrimination). The relative risk of CHD calculated for the various factors in the PRIME population were not statistically different from those published in the Framingham and PROCAM risk functions. The number of CHD events predicted by these risk functions however clearly overestimated those observed in Belfast and France. The two risk functions had a similar ability to separate high risk from low risk subjects in Belfast and France (c-statistic range: 0.61-0.68). Conclusion The Framingham and PROCAM risk functions should not be used to estimate the absolute CHD risk of middle-aged men in Belfast and France without any CHD history because of a clear overestimation. Specific population risk functions are needed
The object of regulation: tending the tensions of food safety
“I’m struggling to see what it actually is,” says Alison, peering into a colander of defrosting meat. What “it” is, we propose in this paper, is helpfully thought of as “the object of regulation” in at least three senses, which together signal both our inheritance of a Foucauldian problematic and our departure from it. Our suggestion is that much of even the best work on biopolitics, biopower, and biosecurity that has been inspired and informed by these writings has replicated Foucault’s own struggle to get to grips with the complexity of matters that he variously refers to “natural” or “artificial” “givens”. By following science and technology studies (STS) scholars in using broadly ethnographic techniques to explore objects as and at the intersection of practices, we redress this balance somewhat by thinking through an empirical study of the securing of food safety, specifically Alison’s inspection of a restaurant kitchen. What we find is that the securing of meat as a material object of regulation is primarily done by involving multiple versions of the future, something which requires a great deal of usually under-recognised, under-valued, and under-theorised articulation work. With risk based regulation, cost sharing, and public sector cuts in the UK set to redefine the ways in which Alison and her colleagues engage with food business operators, we conclude by arguing for a greater appreciation of the skilful work of tending the tensions of food safety, as well as recognition of its limitation
Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.
BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research
Ten-year risk of all-cause mortality: assessment of a risk prediction algorithm in a French general population
Study of the impact of perilipin polymorphisms in a French population
BACKGROUND: Perilipins are proteins localized at the surface of the lipid droplet in adipocytes, steroid-producing cells and ruptured atherosclerotic plaques playing a role in the regulation of triglyceride deposition and mobilization. We investigated whether perilipin gene polymorphisms were associated with obesity, type 2 diabetes, and their related variables (anthropometric variables, plasma leptin, lipids, glucose and insulin concentrations) in a cross-sectional random sample of 1120 French men and women aged 35 to 65 years old, including 227 obese (BMI ≥ 30 kg/m(2)) and 275 type 2 diabetes subjects. RESULTS: Among 7 perilipin polymorphisms tested, only 2 (rs4578621 and rs894160) of them were frequent enough to be fully investigated and we genotyped the sample using the PCR-RFLP method. No significant associations could be found between any of these polymorphisms and the studied phenotypes. CONCLUSION: The rs4578621 and rs894160 polymorphisms of the perilipin gene are not major genetic determinants of obesity and type 2 diabetes-related phenotypes in a random sample of French men and women
Impact of early statin therapy on development of atrial fibrillation at the acute stage of myocardial infarction: data from the FAST-MI register
Background Atrial fibrillation developing at the acute stage of myocardial infarction is associated with untoward clinical outcomes. The aim of this study was to determine correlations between early statin therapy and atrial fibrillation in acute myocardial infarction.Methods Patients (3396) with sinus rhythm developing acute myocardial infarction were enrolled in the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI). Results Atrial fibrillation developed in 7.0% of patients without and 3.9% of patients with early (≤48 h of admission) statin therapy (p<0.001). Multivariable analysis, including the propensity score for early statin treatment, showed that statin therapy was associated with reduced risk of atrial fibrillation (OR 0.64; 95% CI 0.45 to 0.92, p=0.017). Compared to patients without early statin therapy, the OR for atrial fibrillation were 0.72 (0.49 to 1.04, p=0.080), 0.52 (0.28 to 0.95, p=0.034) and 0.40 (0.18 to 0.92, p=0.030) in patients on conventional, intermediate and high doses respectively. Conclusions This study is the first to document a correlation between early statin therapy and atrial fibrillation at the early stage of acute myocardial infarction
Metabolic syndrome and coronary heart disease risk in a population-based study of middle-aged men from France and Northern Ireland
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