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D Arveiler

Publications and source records attributed to D Arveiler.

At least 127 records · Page 7Linked to original sources

Synergistic effects of angiotensin-converting enzyme and angiotensin-II type 1 receptor gene polymorphisms on risk of myocardial infarction.

We reported from our previous multicentre case-control study that the deletion (D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE) was associated with increased risk of myocardial infarction. The main function of ACE is to convert angiotensin I into angiotensin II, which exerts its known cellular actions through the angiotensin II AT1 receptor subtype (AGT1R). We have now investigated the role of a common polymorphism of the AT1 receptor gene (an A-->C transversion at position 1166 of AGT1R) and looked for an interaction between ACE and AGT1R gene polymorphisms on the risk of myocardial infarction. We analysed DNA from 613 patients with myocardial infarction and 723 age-matched population controls. We found a significant interaction between ACE and AGT1R gene polymorphisms; the odds ratio for myocardial infarction associated with the ACE DD genotype was 1.05 (95% CI 0.75-1.49) for subjects without the AGT1R C allele, 1.52 (1.06-2.18) in AC heterozygotes, and 3.95 (1.26-12.4) in CC homozygotes (test for trend, p < 0.02). Among patients defined as low risk by traditional risk factors (serum apolipoprotein B < 1.25 g/L, body-mass index < 26 kg/m2) the interaction was even stronger (odds ratios 1.64 [0.68-3.92], 7.03 [2.61-19.0], and 13.3 [p = 0.05], respectively). These findings, if confirmed, could have clinical implications for the prevention and treatment of coronary heart disease.

Adult↗

Myocardial infarction case-fatality gradient in three French regions: the influence of acute coronary care.

The objective of this study was to evaluate the influence of acute coronary care on the myocardial infarction (MI) case-fatality gradient observed in three French regions. In 1989, a total of 813 hospitalized events of premature MI, occurring in men and women aged 25-64, were registered in three WHO-MONICA sites established in Lille (North of France), Strasbourg (East of France) and Toulouse (South of France). The case-fatality rates observed 28 days after the onset of the MI, were 30.6% in Lille, 17.5% in Strasbourg and 9.9% in Toulouse (P < 0.0001). We compared the management of events and the use of cardiovascular therapies in these centres before admission to hospital, during the stay and on discharge from hospital. Differences were observed between the three centres in the use of medical treatments: in Strasbourg, aspirin and antiplatelet agents were prescribed 15% less frequently, (P < 0.0001) while diuretics were prescribed twice as often as in Toulouse (P < 0.0001). Thrombolytic agents (P < 0.01) and invasive techniques (coronary angiography, coronary angioplasty and coronary bypass surgery) (P < 0.0001) were more widely used in Toulouse compared with the two other centres. Lille might have a higher rate of coronary case fatality than Strasbourg and Toulouse because of a series of cumulative characteristics. The disease presented in a more serious form: more frequent electrocardiographic changes in anterior leads (P < 0.02), higher percentage of use of inotropic drugs in association with diuretic agents (P < 0.04), and longer duration of stay in intensive care units (P < 0.0001). However, when case-fatality rates were adjusted for all these variables in a multivariate model, the rate remained significantly higher in Lille than in the two other centres (P < 0.0001), as suggested by the odds ratio (3.27, 95% confidence interval: 1.69-6.32). In conclusion, the influence of acute coronary care on the MI case-fatality gradient observed between the North and South of France is very weak.

Acute Disease↗

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)

Adult↗

Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents.

BACKGROUND: The WHO MONICA Project is a 10-year study that monitors deaths due to coronary heart disease (CHD), acute myocardial infarction, coronary care, and risk factors in men and women aged 35 to 64 years in defined communities. This analysis of methods and results of coronary event registration in 1985 through 1987 provides data on the relation between CHD morbidity and mortality. METHODS AND RESULTS: Fatal and nonfatal coronary events were monitored through population-based registers. Hospital cases were found by pursuing admissions ("hot pursuit") or by retrospective analysis of discharges ("cold pursuit"). Availability of diagnostic data on identified nonfatal myocardial infarction was good. Information on fatal events (deaths occurring within 28 days) was limited and constrained in some populations by problems with access to sources such as death certificates. Age-standardized annual event rates for the main diagnostic group in men aged 35 to 64 covered a 12-fold range from 915 per 100,000 for North Karelia, Finland, to 76 per 100,000 for Beijing, China. For women, rates covered an 8.5-fold range from 256 per 100,000 for Glasgow, UK, to 30 per 100,000 for Catalonia, Spain. Twenty-eight-day case-fatality rates ranged from 37% to 81% for men (average, 48% to 49%), and from 31% to 91% for women (average, 54%). There was no significant correlation across populations for men between coronary event and case-fatality rates (r = -.04), the percentages of coronary deaths known to have occurred within 1 hour of onset (r = .08), or the percentages of known first events (r = -.23). Event and case-fatality rates for women correlated strongly with those for men in the same populations (r = .85, r = .80). Case-fatality rates for women were not consistently higher than those for men. For women, there was a significant inverse correlation between event and case-fatality rates (r = -.33, P < .05), suggesting that nonfatal events were being missed where event rates were low. Rankings based on MONICA categories of fatal events placed some middle- and low-mortality populations, such as the French, systematically higher than they would be based on official CHD mortality rates. However, rates for nonfatal myocardial infarction correlated quite well with the official mortality rates for CHD for the same populations. For men (age 35 to 64 years), approximately 1.5 (at low event rates) to 1 (at high event rates) episode of hospitalized, nonfatal, definite myocardial infarction was registered for every death due to CHD. The problem in categorizing deaths due to CHD was the large proportion of deaths with no relevant clinical or autopsy information. Unclassifiable deaths averaged 22% across the 38 populations but represented half of all registered deaths in 2 populations and a third or more of all deaths in 15 populations. CONCLUSIONS: The WHO MONICA Project, although designed to study longitudinal trends within populations, provides the opportunity for relating rates of validated CHD deaths to nonfatal myocardial infarction across populations. There are major differences between populations in nonfatal as well as fatal coronary event rates. They refute suggestions that high CHD mortality rates are associated with high case-fatality rates or a relative excess of sudden deaths. The high proportion of CHD deaths for which no diagnostic information is available is a cause for concern.

Adult↗

Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction.

BACKGROUND: The angiotensin-converting enzyme (ACE) plays an important role in the production of angiotensin II and the degradation of bradykinin, two peptides involved in cardiovascular homeostasy. Presence of a polymorphism in the ACE gene (ACE Ss) has been postulated from segregation analysis of plasma ACE in families. This putative polymorphism, which strongly affects the plasma and cellular levels of ACE, probably by modulating ACE gene transcription, has not yet been identified at the molecular level; however, an insertion/deletion polymorphism is present in the 16th intron of the ACE gene (ACE I/D) and appears to be a very good marker for ACE Ss. The biological role of ACE suggests that the ACE gene polymorphism could affect the predisposition to myocardial infarction (MI). METHODS AND RESULTS: We have recently shown, in a large case-control study (ECTIM), that the marker allele D of the ACE gene, which is associated with higher levels of ACE in plasma and cells, was more frequent in male patients with MI than in control subjects, especially in patients considered at low risk. ACE activity has now been measured from frozen aliquots of plasma in a large subsample of the ECTIM study (n = 1086). Plasma ACE level did not differ between patients and control subjects in the older age group (> or = 55 years) but was higher in patients than in control subjects in the younger age group (< 55 years); P < .005 after adjustment on ACE I/D and other risk factors. In patients, plasma ACE levels decreased with age (R = -.225, P < 10(-4)), but in control subjects no such trend was observed. In the low-risk group (ApoB < 1.25 mg/dL, body mass index < 26 kg/m2, and not treated with hypolipidemic drugs), plasma ACE level was increased in patients when compared with control subjects among homozygotes and heterozygotes for the ACE I allele (P < .015). Analysis of the distribution of plasma ACE by using commingling analysis conditional on the marker genotype ACE I/D enabled us to infer the frequencies and effects of the postulated ACE Ss genotypes. The results suggest that the higher plasma ACE levels in patients than in control subjects in the younger age group were due to a difference in frequency of the postulated S allele (.47 versus .36). CONCLUSIONS: These results extend our previous findings and indicate that plasma ACE level may be a risk factor for MI, independent of the ACE I/D polymorphism.

Alleles↗

[Towards a decrease of myocardial infarction in the Bas-Rhin region? Results of the 6 first years of the Strasbourg MONIC Register].

The Bas-Rhin MONICA Register shows trends in myocardial infarction and other acute ischemic events between 1984 and 1989. Coronary heart disease mortality decreased by 27% in men and 30% in women. Morbidity trends were less favourable. The annual event rate for total acute ischemic events remained stable. However, a decrease of 14% for myocardial infarction was seen in men, particularly in patients with a past history of coronary disease. Another positive point is that the 28-day mortality rate in recent infarctions decreased in men by 33% during the 5 year period.

Acute Disease↗

Deletion polymorphism in angiotensin-converting enzyme gene associated with parental history of myocardial infarction.

In a European study an insertion (I)/deletion (D) polymorphism in the angiotensin converting enzyme (ACE) gene has been shown to be associated with the risk of myocardial infarction (MI). In the same study, we investigated the association of the polymorphism with a parental history of fatal MI. There was an excess of both DD (odds ratio 2.6, p = 0.02) and ID (odds ratio = 1.9, p = 0.08) genotypes among those having a parental history of MI, confirming that genetic variation in the ACE locus could be involved in the risk of MI.

Adult↗

Apolipoprotein B signal peptide polymorphism in patients with myocardial infarction and controls. "The ECTIM study".

We report the allele frequencies of the apolipoprotein B (Apo B) signal peptide polymorphism in patients with myocardial infarction and compare them with controls. The first sample consists of 197 myocardial infarction patients and 168 controls from Belfast (UK). The second sample consists of 167 myocardial infarction patients and 205 controls from Strasbourg (France), and the third consists of 71 patients and 146 controls from Haute-Garonne (Toulouse, France). No significant differences were observed in the frequency distribution of genotypes among cases and controls or between populations. However, there were more rare homozygotes in the Belfast cases. Significant associations were observed between the Apo B signal peptide polymorphism and mean levels of total cholesterol, low density lipoprotein cholesterol, Apo B and lipoprotein particles containing Apo (a) [Lp(a)] in the Strasbourg control population. Individuals homozygous for the rare allele had higher levels of these lipid parameters. In Belfast, although not statistically significant, the Apo B signal peptide polymorphism had a similar effect on Apo-B-related parameters as seen in Strasbourg. No significant associations were observed in the Haute-Garonne population where the risk of myocardial infarction is three times lower than in Belfast. In all three populations, the average Lp(a) levels were consistently different among Apo B signal peptide genotypes. These data implicate the Apo B signal peptide in determining some of the risks of myocardial infarction in these populations. Regardless of the exact mechanism, the Apo B signal peptide is an important candidate locus for the study of potentially atherogenic lipid variants.

Adult↗

Genetic variation at the beta-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study.

Increased plasma fibrinogen concentration is a major cardiovascular risk factor. Conflicting results on genetic variations in plasma fibrinogen levels have been reported. Furthermore, whether fibrinogen genotype is associated with the risk of ischemic heart disease has not been studied so far. An HaeIII restriction fragment length polymorphism of the beta-fibrinogen gene was used in a case-control study to investigate the genetic variation at this locus in relation to plasma fibrinogen concentrations and the risk of myocardial infarction (MI). Five hundred thirty-three male patients aged 27-66 years and 648 control subjects were recruited from four World Health Organization MONICA centers in Northern Ireland and in France. The absence of the HaeIII cutting site (H2 allele) was associated with a significant rise in fibrinogen concentrations in both patients and control subjects. The effect of the HaeIII polymorphism on plasma fibrinogen levels did not significantly differ between centers. Fibrinogen levels were higher in smokers than in nonsmokers. The difference between the two groups was larger in subjects with the genotype H2H2 than in those with either genotype H1H1 or H1H2, regardless of the case-control status. However, there was no significant interaction between smoking status and genotype in their effects on variance in fibrinogen levels, whereas fibrinogen levels. HaeIII genotype accounted for approximately 1% of the total variance in fibrinogen levels, whereas smoking and age together explained 7% and 5% in control subjects and patients, respectively. The frequency of the H2 allele was 0.21 in control subjects and 0.19 in patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction.

Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction contribute to the development of coronary heart disease. In a study comparing patients after myocardial infarction with controls, we have explored a possible association between coronary heart disease and a variation found in the gene encoding angiotensin-converting enzyme (ACE). The polymorphism ACE/ID is strongly associated with the level of circulating enzyme. This enzyme plays a key role in the production of angiotensin II and in the catabolism of bradykinin, two peptides involved in the modulation of vascular tone and in the proliferation of smooth muscle cells. Here we report that the DD genotype, which is associated with higher levels of circulating ACE than the ID and II genotypes, is significantly more frequent in patients with myocardial infarction (n = 610) than in controls (n = 733) (P = 0.007), especially among subjects with low body-mass index and low plasma levels of ApoB (P < 0.0001). The ACE/ID polymorphism seems to be a potent risk factor of coronary heart disease in subjects formerly considered to be at low risk according to common criteria.

Adult↗

Comparison of dietary intakes in four selected European populations.

The composition of diet and food intakes in four selected European populations were compared. Dietary data (from the World Health Organization Project on Monitoring Trends and Determinants in Cardiovascular Disease) were measured by record methods and were available for middle-aged men in Finland (n = 653), France (n = 1128), Northern Ireland (n = 356), and southern Germany (Augsburg region; n = 899). Nutritional variables--which are independent of the absolute energy intake, such as the percentage supply of energy from macronutrients and the ratio of polyunsaturated to saturated fatty acids--were on the whole similar. However, striking differences were found in food intake and in the percentage supply of fat from different foods. The results indicate that detailed knowledge of consumption figures is necessary to develop prudent and acceptable nutrition intervention programs.

Adult↗

The polymorphism ApoB/4311 in patients with myocardial infarction and controls: the ECTIM Study.

The polymorphism affecting codon 4311 of the apolipoprotein B gene (ApoB/4311) was investigated in a large case-control study in two French and one Northern Irish geographically defined populations. Cases were recruited 3 to 9 months after a myocardial infarction (MI) and controls were randomly selected from the population. The polymorphism was assessed using allele-specific oligonucleotides (ASO). The genotype frequencies of the ApoB/4311 polymorphism did not differ in Northern Ireland and France and were in Hardy-Weinberg equilibrium in all groups; strong associations with three other polymorphisms of the ApoB gene (XbaI, EcoRI, VNTR(34 repeats)) were observed and it was possible to identify highly sensitive and specific markers of the ApoB/4311 rare variant. Homozygotes for the ApoB 4311 rare variant were slightly less frequent in cases than in controls: 22 (4.4%) and 35 (6.7%) respectively (population adjusted chi 2 = 3.3 P less than 0.07), especially in Belfast: 6 (3.1%) and 12 (7.6%), respectively (P less than 0.06). Several lipid and lipoprotein parameters were measured. Consistently among control groups, rare homozygotes had lower mean levels of ApoB (P less than 0.02), triglycerides (P less than 0.02), and lipoprotein particles containing ApoE and ApoB (LpE:B; P less than 0.001) and a higher mean level of lipoprotein particles containing ApoAI and not ApoAII (LpAI; P less than 0.02) than heterozygotes and frequent homozygotes combined. The strong association between the ApoB/4311 polymorphism and LpE:B was also observed in patients with MI. When present in the homozygous form, the ApoB/4311 Asn----Ser variant is associated with a lipoprotein profile that is apparently favourable.

Apolipoproteins B↗

Relationship between smoking and diet: the MONICA-France project.

The association between smoking habits and diet was examined in a sample of 1126 men, aged 45-64 years, from the general population living in the three French MONICA monitoring areas: Bas-Rhin (BR) (n = 346), Haute-Garonne (HG) (n = 400) and Urban Community of Lille (UCL) (n = 380). Diet was assessed by the 3-day record method. The energy and nutrient intakes were calculated for each of the 3 centres, using the same food composition tables. Alcohol consumption was higher among smokers (P less than 0.001). Taking into account alcohol consumption, age, body mass index, centre, educational level and family size, the analyses showed no difference in non-alcoholic energy intake, proteins, carbohydrates, and total fat. However, smokers had a lower intake of polyunsaturated fatty acids (P less than 0.05) and dietary fibre (P less than 0.01) than non-smokers. With regard to food items, smokers had a higher intake of sucrose (P less than 0.05) and a lower intake of vegetables (P less than 0.001), dairy products (P less than 0.05) and cheese (P less than 0.05). These results suggest that analyses in future epidemiological research regarding the role of diet in the aetiology of tobacco-related diseases should consider this association of potential risk factors.

Alcohol Drinking↗

A case-control study of lipoprotein particles in two populations at contrasting risk for coronary heart disease. The ECTIM Study.

The incidence of coronary heart disease (CHD) in middle-aged men is more than three times higher in Northern Ireland than in France. The ECTIM study, which is based on WHO MONICA centers in Belfast (Northern Ireland), Strasbourg (eastern France), Toulouse (southwestern France), and Lille (northern France), has been established to investigate this striking difference. Male patients aged 25-64 years with myocardial infarction (MI) and control subjects sampled from the general population were recruited in the four centers. Hypolipidemic drug treatment was much more frequent in France than in Belfast. "Hypercholesterolemia" defined by the presence of hypolipidemic drug treatment or a low density liproprotein cholesterol level greater than 200 mg/dl was more frequent in cases than in controls in both countries but was similar in both control groups. An in-depth study of lipid variables, including measurements of cholesterol fractions, triglycerides, apolipoproteins (apo), and lipoprotein particles (Lp), was performed in nonhypercholesterolemic subjects. In Northern Ireland and France, patients in comparison with controls had lower levels of high density lipoprotein cholesterol, apo A-I, apo A-II, Lp A-I, and Lp A-II:A-I and higher levels of Lp E:B and Lp(a):B. The levels of triglycerides, very low density lipoprotein cholesterol, apo B, and Lp C-III:B were higher in cases than in controls only in Belfast. In control subjects, the mean levels of cholesterol fractions and apolipoproteins were similar in Northern Ireland and France; however, the level of Lp A-I was lower and the levels of Lp E:B and Lp(a):B were higher in Northern Ireland than in France.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Lipid profile in adult population representative of a French district (Bas-Rhin)].

Serum total cholesterol (TC), HDL-cholesterol (HDL-C) and A1, A2 and B apoprotein levels were determined in a population of 967 adults aged 25 to 64 years representative of the general population of the Bas-Rhin region localized in North-Eastern France. Age and sex were found to have a significant influence on most parameters studied; however, HDL-cholesterol, Apo A1, and Apo A2 were independent from age in males. HDL-cholesterol levels were consistently found to be higher in females than in males. Cholesterol, HDL-cholesterol, Apo A1, Apo A2 and Apo B levels, but not the HDL-cholesterol/cholesterol ratio, were higher in females above 45 years of age. A cholesterol level indicating increased cardiovascular risk, i.e., above 5.1 mmol/l, was found in 55% of males and 53% of females; HDL-cholesterol was under 0.9 mmol/l in 46% of males and 29% of females. The close linear correlations seen between cholesterol and Apo B (r = 0.820) and between HDL-cholesterol and Apo A1 (r = 0.580) were used to estimate theoretical threshold levels of apoproteins indicating increased risk: the Apo B level was greater than 0.77 g/l in 60% of males and 45% of females and the Apo A1 level was smaller than 1.58 g/l in 42% of males and 28% of females. Apo A2 level seems less useful as marker of increased risk. In conclusion, increased vascular risk due to unfavorable lipid profiles was common in the studied population especially among males and among females above 45 years of age. Apoproteins A1 and B reliably reflect cholesterol and HDL-cholesterol levels and can help evaluate cardiovascular risk.

Adult↗

[Primary results of the MONICA project].

The MONICA project is an international study coordinated by the WHO, designed to explain the important variations of coronary mortality observed in the industrialised countries over the last 20 years. Thirty-nine centres in 27 countries are participating in the project which, over a 10 year period will, in geographically determined zones; a) record the numbers of acute myocardial infarcts and coronary deaths, b) analyse the treatment of acute cardiac events, and c) evaluate the cardiovascular risk factors and preventive measures in the general population. The MONICA-France project comprises three registers (Bas-Rhin, Haute-Garonne and the urban community of Lille), and a coordinating centre. The preliminary results confirm the wide geographic variability of coronary mortality with a prevalence slightly higher in Alsace and the North than in the South-West of France. The approximative frequency of coronary events in France is estimated at 112,000 infarcts and over 175,000 acute coronary episodes and deaths. Information is provided about the severity of the principal coronary risk factors and the conditions of their treatment in the register zones. A study of the accessibility of emergency treatment of acute infarction in the Bas-Rhin area, has demonstrated the key role of the general practitioner as the first contact but confirmed the long delay to hospital admission which nullified the potential benefits of thrombolysis in a high proportion of cases. However, the significant decrease in hospital mortality of acute infarction observed over a 3 year period in the three register zones, is probably related to the number of patients thrombolysed in that time.

Adult↗

Between-register and within-register variability in event-finding and rates in the MONICA-France Project.

The 1985 and 1986 coronary event data from the three French MONICA Registers in Haute-Garonne (Toulouse), Bas-Rhin (Strasbourg) and the Urban Community of Lille (UCL) are used to compare the sources of information, the distribution of events in different diagnostic categories, and their possible effects on event rates. All three registers follow the MONICA protocol, and use the "cold pursuit" method, with data abstracted retrospectively from medical files or from the doctors establishing the causes of death. The health system and medical background are similar in the three centers. The distribution of the sources of information (in-hospital and out-of-hospital) and the distribution of events by diagnostic categories are different among centres. The possible effects of these differences on rates of definite myocardial infarction or possible coronary death are estimated between registers and within registers during a 2-year period. Cross-sectional comparisons are questionable, and possible false trends in event rates require special attention.

Adult↗