Philippe Amouyel

Predictors of Restenosis After Coronary Stent Implantation

OBJECTIVESnWe sought to determine predictors of restenosis after coronary stenting (CS) in a consecutive series of patients.nnnBACKGROUNDnAlthough stenting in highly selected patient groups reduces restenosis, the results of stenting in a heterogeneous patient group and the effects of clinical and procedural factors on stent restenosis are currently unclear.nnnMETHODSnWe analyzed the 6-month angiographic outcome of 500 lesions in 463 consecutive patients undergoing successful CS. Clinical, qualitative and quantitative angiographic variables were correlated with restenosis assessed as both a binary and a continuous variable.nnnRESULTSnRestenosis, defined as the presence of >50% diameter stenosis in the dilated segment, was present in 105 (26%) of the 405 lesions with angiographic follow-up. The mean late lumen loss during the follow-up period was 0.79+/-0.64 mm. Implantation of multiple stents (p < 0.0001) and a high acute gain (p < 0.0002) were independently associated with a higher late lumen loss. In contrast, the use of high inflation pressure (p < 0.02) and Palmaz-Schatz stents (p < 0.005) was independently associated with a lower late lumen loss. When restenosis was defined as a qualitative variable, implantation of multiple stents (p < 0.001), stenosis length (p < 0.01), small reference diameter (p < 0.02) and stent type other than Palmaz-Schatz (p < 0.01) were independent predictors of restenosis. None of the clinical variables tested was associated with restenosis.nnnCONCLUSIONSnCoronary stenting in an unselected patient group is associated with an acceptable restenosis rate. Although some risk factors were identified, the risk of restenosis was not related to most of the variables tested. This suggests that the superiority of CS over balloon angioplasty, in terms of restenosis, might also apply to subgroups of patients that were not included in the recent randomized studies.

Impact of apolipoprotein E polymorphism on lipoproteins and risk of myocardial infarction. The ECTIM Study.

Human apolipoprotein (apo) E, a polymorphic protein with three common alleles, epsilon 2, epsilon 3, and epsilon 4, plays an important role in lipoprotein metabolism. This article describes the association of this polymorphism with lipids, apolipoproteins, and lipoproteins with a particular regard to lipoprotein particles, as defined by their apolipoprotein content, as well as the risk of myocardial infarction in a multicenter population-based case-control study (ECTIM study). In the ECTIM study, 574 male patients aged 25 to 64 were examined 3 to 9 months after myocardial infarction in four regions participating in the World Health Organization MONICA project: Belfast (Northern Ireland) and Lille, Strasbourg, and Toulouse (France). Control subjects (n = 722) were randomly selected from the regional populations. The distribution of apoE phenotypes was significantly different across the four control samples (P = .04), with a higher frequency of the epsilon 4 allele in Belfast (14.3%) than in Toulouse (8.2%). The association of apoE polymorphism with biological measurements was studied in the control groups (n = 640) after men with coronary heart disease or those taking hypolipidemic drugs were omitted, with the apoE3/3 phenotype as a reference after adjustment for concomitant factors. Individuals carrying the epsilon 2 allele had lower levels of plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), and apoB and higher levels of triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), apoC-III, apoE, lipoprotein (Lp) C-III:B, and Lp E:B. However, the effect of the epsilon 2 allele on triglyceride, VLDL-C, apoE, and Lp E:B parameters was heterogeneous across the populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: The PRIME Study

The Epidemiological Study of Myocardial Infarction Study which enrolled 9758 apparently healthy men aged 50-59 years, is a prospective cohort study designed to evaluate markers of coronary risk. Soluble forms of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels were measured in plasma obtained at baseline from 317 subjects who suffered a coronary event during the 5-year follow-up and in twice the number of control subjects who were matched for center, age and day of inclusion in a nested case-control design. The relative risk associated with the highest compared with the lowest thirds of ICAM-1 (>625 versus <502 ng/ml) was 2.45 (95% CI: 1.64-3.65, P<0.001) without adjustment; it decreased moderately (RR: 2.09; 95% CI: 1.34-3.24, P<0.001) after control for lipid and non-lipid factors and remained significantly elevated after adjustment for C-reactive protein (CRP) (RR: 1.90; 95% CI: 1.21-2.96, P=0.005). Plasma ICAM-1 was essentially associated with the risk of myocardial infarction or coronary death and also with angina pectoris. Subjects with CRP presented elevated coronary risk only if ICAM-1 was high. An elevated level of VCAM-1 was not associated with any risk of future acute coronary event, or with angina pectoris. This data indicates that plasma levels of ICAM-1 may serve as risk markers for future coronary events whatever their clinical presentation and that risk is better defined using simultaneous measurements of ICAM-1 and CRP than any of these levels separately.

Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).

Objective To investigate the effect of alcohol intake patterns on ischaemic heart disease in two countries with contrasting lifestyles, Northern Ireland and France. Design Cohort data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) were analysed. Weekly alcohol consumption, incidence of binge drinking (alcohol >50 g on at least one day a week), incidence of regular drinking (at least one day a week, and alcohol <50 g if on only one occasion), volume of alcohol intake, frequency of consumption, and types of beverage consumed were assessed once at inclusion. All coronary events that occurred during the 10 year follow-up were prospectively registered. The relation between baseline characteristics and incidence of hard coronary events and angina events was assessed by Cox’s proportional hazards regression analysis. Setting One centre in Northern Ireland (Belfast) and three centres in France (Lille, Strasbourg, and Toulouse). Participants 9778 men aged 50-59 free of ischaemic heart disease at baseline, who were recruited between 1991 and 1994. Main outcome measures Incident myocardial infarction and coronary death (“hard” coronary events), and incident angina pectoris. Results A total of 2405 men from Belfast and 7373 men from the French centres were included in the analyses, 1456 (60.5%) and 6679 (90.6%) of whom reported drinking alcohol at least once a week, respectively. Among drinkers, 12% (173/1456) of men in Belfast drank alcohol every day compared with 75% (5008/6679) of men in France. Mean alcohol consumption was 22.1 g/day in Belfast and 32.8 g/day in France. Binge drinkers comprised 9.4% (227/2405) and 0.5% (33/7373) of the Belfast and France samples, respectively. A total of 683 (7.0%) of the 9778 participants experienced ischaemic heart disease events during the 10 year follow-up: 322 (3.3%) hard coronary events and 361 (3.7%) angina events. Annual incidence of hard coronary events per 1000 person years was 5.63 (95% confidence interval 4.69 to 6.69) in Belfast and 2.78 (95% CI 2.41 to 3.20) in France. After multivariate adjustment for classic cardiovascular risk factors and centre, the hazard ratio for hard coronary events compared with regular drinkers was 1.97 (95% CI 1.21 to 3.22) for binge drinkers, 2.03 (95% CI 1.41 to 2.94) for never drinkers, and 1.57 (95% CI 1.11 to 2.21) for former drinkers for the entire cohort. The hazard ratio for hard coronary events in Belfast compared with in France was 1.76 (95% CI 1.37 to 2.67) before adjustment, and 1.09 (95% CI 0.79 to 1.50) after adjustment for alcohol patterns and wine drinking. Only wine drinking was associated with a lower risk of hard coronary events, irrespective of the country. Conclusions Regular and moderate alcohol intake throughout the week, the typical pattern in middle aged men in France, is associated with a low risk of ischaemic heart disease, whereas the binge drinking pattern more prevalent in Belfast confers a higher risk.

Influence of alcohol consumption and various beverages on waist girth and waist-to-hip ratio in a sample of French men and women

OBJECTIVE: The goal of the present study was to assess the association between alcohol consumption and abdominal fat deposition in France, a country where wine is the most commonly consumed alcoholic beverage.METHODS: We analyzed the association between alcohol consumption and various markers of body weight, in a population sample recruited in three distinct geographical areas of France (MONICA centers). This sample included men (n=1778) and women (n=1730) aged 35– 64u2005y, randomly selected from electoral rolls. Alcohol consumption was assessed with a quantitative frequency questionnaire.RESULTS: Alcohol intake ranged from 0–1655u2005ml of alcohol per week. Wine was the main source of alcohol, representing 67% of total alcohol intake in both genders. In men, there was no association between alcohol intake and body mass index (BMI) or body weight, whereas in women, alcohol consumption was inversely correlated with BMI (P<0.0001) and body weight (P<0.0002). In men, total alcohol consumption was positively associated with waist-to-hip ratio (WHR, P<0.0002) and waist girth (P<0.004), independently of BMI. Similarly, in women, positive associations were found between alcohol intake and WHR (P<0.0001) as well as waist girth (P<0.0001), independently of BMI. In a linear regression model including types of beverages and usual confounders, reporting consumption of either wine, beer or spirit was poorly associated with WHR in men, whereas wine (P<0.0008) and beer (P<0.0001) consumptions were both positively associated with WHR in women. However, there was no evidence of a statistically significant heterogeneous effect of wine, beer and spirits on WHR in both genders.CONCLUSION: In a sample of representative French people, in whom wine is the most common alcoholic beverage, alcohol consumption is associated with greater WHR independently of BMI in both men and women.

Bilirubin and coronary heart disease risk in the Prospective Epidemiological Study of Myocardial Infarction (PRIME)

Background Classic coronary heart disease risk factors fail to explain the large coronary heart disease incidence gradient between Northern Ireland and France. The Prospective Epidemiological Study of Myocardial Infarction (PRIME), a multicentre prospective study of 10 593 men, aims to investigate novel risk factors in these populations. We tested the hypothesis that higher bilirubin, a bile pigment possessing antioxidant properties, is associated with decreased coronary heart disease risk. Methods Bilirubin was measured in 216 participants who had developed coronary heart disease at 5-year follow-up and in 434 matched controls. Results Bilirubin was significantly lower in cases (geometric mean 7.95 μmol/l; interquartile range 5.32–12.33 μmol/l) compared with controls (9.07; 6.16–12.76; P = 0.005). Conditional logistic regression, adjusted for classical and putative risk factors, showed a U-shaped pattern, with coronary heart disease risk significantly lower for bilirubin in the third and fourth fifths, compared with the first. Additionally, there was a significant quadratic relationship between coronary heart disease risk and fifths of bilirubin concentration (χ2 = 6.80, df = 2; P = 0.035). Conclusions These findings suggest that bilirubin is a novel coronary heart disease risk marker in middle-aged men, with a U-shaped relationship observed between bilirubin concentration and coronary heart disease risk. Eur J Cardiovasc Prev Rehabil 14: 79-84

Change in cardiovascular risk factors in France, 1985–1997

The change in the main cardiovascular risk factors in France was assessed using the MONICA population surveys conducted in the Urban Community of Lille, Bas-Rhin and Haute-Garonne. Trends in obesity, tobacco smoking, hypertension, hypercholesterolaemia and self-reported diabetes were established for the first (1985–1988) and the last (1995–1997) survey. The results indicate that the prevalence of overweight and obesity remained stable in both genders; tobacco smoking decreased in men but increased in women. Prevalence of hypertension decreased, and preventive measures improved in both genders. Prevalence of hypercholesterolaemia remained stable, and preventive measures improved only in men. Prevalence of self-reported diabetes increased solely in women, and preventive measures improved in both genders. However, in 1995–1997 still 40% of the treated hypertensive and 30% of the treated hypercholesterolaemic subjects were not adequately controlled. We conclude that prevalence and prevention of the main cardiovascular risk factors have evolved favourably in France, but the management of hypercholesterolaemia and hypertension can still be improved.

Polymorphism of the prion protein is associated with cognitive impairment in the elderly: The EVA study

Background: Little is known about the role of the prion protein (PrPsen/gene PRNP). PRNP knockout mice studies suggest that PrPsen may be involved in CNS degeneration. This observation prompted us to examine the influence of PRNP genetic variability on cognitive abilities in the elderly. Methods: In a community-based sample of 1,163 subjects aged 59 to 71 years, we characterized the valine (Val) and methionine (Met) allele of the PRNP polymorphism at codon 129. The effect of this polymorphism was estimated on the Mini-Mental State Examination (MMSE) and on a global composite score built from a battery of nine different neuropsychological tests. The results were adjusted for age, gender, education, and apolipoprotein E (apoE) polymorphism. Results: Cognitive impairment (MMSE score < 24) was present in 2.5% of the Met-Met individuals, 2.9% of the Met-Val individuals, and 7.0% of Val-Val subjects (p = 0.02). Subjects homozygous for the PRNP Val allele had a lower MMSE and global score than the two other genotypes (p< 0.003). This effect was of the same magnitude as that of the apoEϵ4 allele on cognitive performances. Both apoE ϵ4 and PRNP Val allelic effects were additive. Conclusion: This observation suggests that variability of the PRNP locus may be associated with cognitive performance in the elderly. This result, if confirmed, offers potential clues for the role of PRNP in the human brain.

Ischemic Stroke Is Associated with the ABO Locus: The EuroCLOT Study

Objective: End‐stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end‐stage coagulation in healthy REFVIDunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype.

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.