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Biomedical subjects

F Cambien

Publications and source records attributed to F Cambien.

At least 109 records · Page 6Linked to original sources
PubMed1995

Insertion/deletion polymorphism in the angiotensin-I-converting enzyme gene is associated with coronary heart disease in IDDM patients with diabetic nephropathy.

Insulin-dependent diabetic (IDDM) patients with diabetic nephropathy have a highly increased morbidity and mortality from coronary heart disease. An insertion (I) /deletion (D) polymorphism in the angiotensin-I-converting enzyme (ACE) gene has been shown to be associated with coronary heart disease. Therefore, we have investigated the role of this ACE/ID polymorphism in 198 IDDM patients with diabetic nephropathy and 190 normoalbuminuric IDDM patients. The prevalence of myocardial infarction and other coronary heart disease was significantly elevated in patients with nephropathy, 19% (38/198) vs 8% (15/190), p < 0.001. In the nephropathic group 12 of 63 (19%), 23 of 95 (24%), and 3 of 40 (7.5%) patients with the DD, ID and II genotypes, respectively had a history of coronary heart disease, II vs DD and ID, p < 0.05 when compared to nephropathic patients without coronary heart disease. Multiple logistic regression analysis of the risk factors associated with coronary heart disease in univariate analysis revealed that the II genotype acts as an independent protective factor against coronary heart disease, odds ratio II/DD + ID 0.27 (95% confidence interval 0.07-0.97, p < 0.05). There was no difference in genotype or allele frequency (D/I) between patients with and without nephropathy, 0.56/0.44 in both groups, but plasma ACE concentration was elevated in patients with nephropathy 609 (151-1504) ng/ml as compared to patients with normoalbuminuria, 428 (55-1630) ng/ml, p < 0.001. We suggest that ACE/ID polymorphism may influence the frequency of life-threatening cardiac complications in IDDM patients suffering from diabetic nephropathy, a condition characterized by increased plasma ACE concentration.

Adult↗
PubMed1995

Cardiovascular risk factors and alcohol consumption in France and Northern Ireland.

The levels of different lipid, lipoprotein and haemostatic variables were assessed in 615 control subjects of the ECTIM Study, defined by five groups of alcohol consumption: non-drinkers, 0 < or = 15 g/day, 15 < . < or = 36 g/day, 36 < . < or = 66 g/day and > 66 g/day. After adjustment for age, body mass index, cigarette consumption and country, alcohol consumption was associated with an increase in HDL-cholesterol (0.47 +/- 0.02 to 0.59 +/- 0.01 g/l in non-drinkers and > 66 g/day consumers, mean +/- S.E.M., P < 0.0001), apolipoproteins A-I and A-II (1.37 +/- 0.03 to 1.60 +/- 0.03 g/l and 0.32 +/- 0.01 to 0.41 +/- 0.01 g/l, respectively, P < 0.0001), LpA-I, LpA-I:A-II (0.46 +/- 0.01 to 0.50 +/- 0.01 g/l and 0.75 +/- 0.02 to 0.91 +/- 0.02 g/l, respectively, P < 0.001) and PAi-1 activity (134 +/- 11 to 177 +/- 11 U/ml, P < 0.001). Conversely, no increases were found for total and LDL-cholesterol, triglycerides, apolipoproteins B and C-III, LpE:B, LpC-III:B, fibrinogen and factor VII. Hence, among the lipid and haemostatic variables studied, only HDL parameters and PAi-1 activity were increased by alcohol consumption.

Adult↗
PubMed1995

Angiotensin I converting enzyme gene polymorphism and coronary heart disease.

Genetic variations in the renin-angiotensin and kallikrein-kinin systems could prove to be significant pathophysiological mechanisms affecting coronary heart disease (CHD), particularly given the powerful vasoactivity of products such as angiotensin II and bradykinin. Indeed, studies show that angiotensin converting enzyme (ACE) gene polymorphism is associated with an increased risk of myocardial infarction and death, even in otherwise low-risk subjects. Genetic differences do not appear to be a risk factor for atherosclerosis or hypertension, however. Because ACE polymorphism modulates local production of angiotensin II, a powerful coronary vasoconstrictor, it may influence left ventricular mass in general as well as in coexisting disease states such as hypertension and cardiomyopathy. However, further study is needed to clarify the implications of ACE polymorphism in patients with left ventricular hypertrophy. Interactions between ACE and angiotensin II type-1 receptors may have clinical implications for preventing and managing CHD. Screening for genetic risk, as evidenced by certain variants in receptor coding sequence, may prove worthwhile if detrimental effects can be countered by drugs such as ACE inhibitors and angiotensin II receptor blockers. Given the important roles of angiotensin II and bradykinin as modulators of cellular growth and of vasoactivity, deleterious and beneficial effect at different stages of the atherosclerotic process and during acute events leading to myocardial infarction or sudden death can be suspected.

Aging↗
PubMed1995

Medical treatment of myocardial infarction in France and Northern Ireland. Results from the ECTIM study. Enquête cas-Témoins de l'Infarctus du Myocarde.

As part of the ECTIM Study, the medical treatment given to male patients (25-64 years) 3 to 9 months after myocardial infarction (MI) were analysed in France and Northern Ireland. On univariate analysis, hypolipidaemic drugs, angiotensin-converting enzyme inhibitors and antiarrhythmic drugs were found to be prescribed more frequently in France, while beta-blockers were more common in Northern Ireland. No differences were found for diuretics, calcium channel blockers, antithrombotic and anti-anginal drugs, although the Northern Irish patients were mainly on antiplatelet drugs and nitrates, while the French patients received nitrates and non-nitrates, as well as oral anticoagulants and antiplatelet drugs in similar amounts. These differences remained after adjustment for personal history of diabetes, hyperlipidaemia, hypertension, and previous myocardial infarction, but the beta-blocker prescription was no longer significant. When the French centres were analysed, patients from Strasbourg were more frequently on oral anticoagulants and diuretics and less frequently on antiplatelet drugs, while patients from Toulouse had fewer anti-anginal drugs. Hence, although the current guidelines for secondary prevention of myocardial infarction are generally well applied in France and Northern Ireland, significant differences exist regarding the choice of the active drug.

Adult↗
PubMed1995

Influence of angiotensin II type 1 receptor polymorphism on aortic stiffness in never-treated hypertensive patients.

Several clinical and experimental studies have suggested a significant role of angiotensin II in the development of alterations of small and large arteries. The present study was designed to assess the contribution of polymorphism (corresponding to an A1166-->C transversion) of the angiotensin II type 1 receptor (AT1) gene to aortic stiffness. One hundred thirty-four never-treated hypertensive patients were included in the study. Aortic distensibility was evaluated by measuring carotid-femoral pulse wave velocity. Age, systolic and diastolic pressure, and metabolic parameters were similar in the three genotypes. Pulse wave velocity was 11.4 +/- 2.5 m/s in AT1 AA homozygotes, 12.5 +/- 3.2 m/s in AC heterozygotes, and 14.7 +/- 4.0 m/s in CC homozygotes (P = .003, P < .001 after adjustment for age, blood pressure, and body mass index). Moreover, an interaction was found between AT1 genotype and the ratio of total to high-density lipoprotein cholesterol in terms of the development of aortic stiffness. Thus, a positive correlation was observed between the ratio of total to high-density lipoprotein cholesterol and pulse wave velocity in AC and CC (r = .42, P < .001) but not AA patients. These results suggest that the AT1 gene is involved in the development of aortic stiffness in hypertensive patients and could modulate the effects of lipids on large arteries.

Adult↗
PubMed1995

Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients.

Genotypic abnormalities of the renin-angiotensin system have been suggested as a risk factor for the development of diabetic nephropathy and proliferative retinopathy. We studied the relationship between an insertion(I)/deletion (D) polymorphism in the angiotensin-converting enzyme (ACE) gene in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy (121 men and 77 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years) and in IDDM patients with normoalbuminuria (118 men and 74 women, age 42.7 +/- 10 years, diabetes duration 26 +/- 8 years). A total of 155 patients (40%) had proliferative retinopathy, and 67 patients (17%) had no diabetic retinopathy. There was no difference in genotype distribution between IDDM patients with diabetic nephropathy and those with normalbuminuria: 63 (32%)/95 (48%)/40 (20%) vs. 67 (35%)/77 (41%)/46 (24%) had DD/ID/II genotypes, respectively. Patients with nephropathy had higher plasma ACE levels (609 [151-1,504] micrograms/l) compared with patients with normoalbuminuria (428 [55-1,630] micrograms/l) (P < 0.001). Multiple linear regression analysis revealed that the plasma ACE level in patients with nephropathy is partially determined by ACE/ID polymorphism, mean arterial blood pressure, and glomerular filtration rate (r2 = 0.30, P < 0.001). There was no difference in genotype distribution between IDDM patients with proliferative retinopathy and those without diabetic retinopathy: 52 (34%)/74 (48%)/29 (19%) vs. 26 (39%)/25 (37%)/16 (24%) had DD/ID/II genotypes, respectively. There was also no difference in plasma ACE concentration detected among patients with no, simplex, or proliferative retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Genetic variation at the angiotensinogen locus in relation to high blood pressure and myocardial infarction: the ECTIM Study.

OBJECTIVES: To study the association between polymorphisms of the angiotensinogen (AGT) gene and blood pressure in population-based samples, and to determine whether genetic variation at the AGT locus is involved in the susceptibility to myocardial infarction. METHODS: The study population comprised 630 cases who survived a myocardial infarction, recruited from the World Health Organization Monitoring Cardiovascular Diseases registers in Belfast, Lille, Strasbourg and Toulouse, and 741 controls drawn from the corresponding populations. The AGT polymorphisms investigated were T174M and M235T. High blood pressure was defined as diastolic blood pressure > 100 mmHg or the use of antihypertensive medication, or both. RESULTS: In the controls the mean +/- SEM frequency of the M174 allele was 0.116 +/- 0.008, and that of the T235 allele was 0.401 +/- 0.013. In the whole population blood pressure levels and prevalence of high blood pressure did not vary according to T174M and M235T genotypes. However, obesity appeared as a crucial factor influencing the relationship between high blood pressure and T174M. In subjects with body mass index < 26 kg/m2 there was a 2.4-fold increase of the prevalence of high blood pressure in carriers of the M174 allele compared with in homozygotes for the T174 allele, whereas no association was detected in subjects with body mass index > 26 kg/m2. The association between high blood pressure and M235T was not significant in either group. The T174M and M235T genotype distributions did not differ between survivors of myocardial infarction and controls. CONCLUSIONS: These data suggest that the AGT gene could be involved in the predisposition to high blood pressure in non-overweight, but not in overweight men, possibly reflecting genetically different types of hypertension. No significant impact of the AGT locus in the risk of non-fatal myocardial infarction was detected.

Adult↗
PubMed1995

The effect of diet on lipid, apoprotein and lipoparticle variation in the ECTIM study in Belfast.

The objective of the study was to evaluate the contribution of dietary factors to variation of plasma levels of lipids, apoproteins and lipoparticles in the Northern Ireland population. This study was part of a larger case-control study of the genetic and environmental determinants of myocardial infarction in France and Northern Ireland. A random sample of 175 middle aged men was drawn from the population covered by the Belfast MONICA project register. Habitual diet was assessed by a questionnaire. A blood sample was obtained after an over-night fast for determination of plasma levels of lipids, apoproteins and lipoparticles. All participants had a medical examination and completed a lifestyle questionnaire. In a stepwise regression, after adjusting for co-factors (i) vitamin C and (ii) alcohol consumption were the only nutrients which contributed significantly to the variation in, respectively, (i) Total Cholesterol, LDL Cholesterol and Apolipoprotein B (inverse correlation) and (ii) HDL Cholesterol and LpAI (positive correlation). The amount of variation explained by the final models was modest, ranging from 4% to 15%. In conclusion, in this Northern Ireland population, habitual diet contributes to little of the variation in plasma levels of lipids, apoproteins and lipoparticles.

Adult↗
PubMed1994

Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is considered a model of premature atherosclerosis with a strong genetic component. We have investigated the role of angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene in 316 unrelated NIDDM individuals, 132 who had myocardial infarction or significant coronary stenoses and 184 with no history of coronary heart disease (CHD). A deletion-polymorphism in the ACE gene was recently reported to be associated with myocardial infarction especially in people classified as low risk. Here we report that the D allele of the ACE gene is a strong and independent risk factor for CHD in NIDDM patients. The D allele is associated with early-onset CHD in NIDDM, independently of hypertension and lipid values. A progressively increasing relative risk in individuals heterozygous and homozygous for the D allele was observed (odds ratios of 1.41 and 2.35, respectively; P < 0.007), suggesting a codominant effect on the cardiovascular risk. The percentage of CHD attributable to the ACE deletion allele was 24% in this NIDDM population. Identification of NIDDM patients carrying this putative CHD-susceptibility genotype would help early detection and treatment of CHD.

Alleles↗
PubMed1994

Biomarkers of dietary fat composition in young adults with a parental history of premature coronary heart disease compared with controls. The EARS Study.

The European Atherosclerosis Research Study (EARS) is a study of the biological expression of a paternal history of premature coronary heart disease. The study was carried out in 14 centres in 11 European countries, where the offspring of fathers who suffered a documented myocardial infarction before the age of 55 years (cases) were compared with age- and sex-matched controls. In this paper we describe the measurement of plasma cholesteryl esters as biomarkers for the fatty acid composition of the diet in the cases and controls. No significant differences were found. Cholesteryl palmitate, oleate, linoleate and arachidonate were measured in plasma and correlated with plasma lipids and lipoproteins and with life-style variables including body-mass index, alcohol consumption, tobacco and physical activity. The strongest correlations were observed between cholesteryl esters and triglycerides, which are positively correlated with cholesteryl oleate and negatively with cholesteryl linoleate. Apo B was negatively correlated with cholesteryl linoleate and positively with palmitate. Among the other variables, alcohol was positively correlated with cholesteryl oleate and negatively with linoleate, both in males and in females. Furthermore, there are differences between regions, with the highest percentages of saturated cholesteryl palmitate measured in Finnish students, the highest percentage of cholesteryl linoleate in Belgium and of cholesteryl arachidonate in Southern Europe.

Adolescent↗
PubMed1994

The angiotensin I-converting enzyme gene polymorphism: implication in hypertension and myocardial infarction.

The angiotensin I-converting enzyme gene is one of the major genes of the renin-angiotensin and kallikrein-kinin systems and is a candidate gene for several cardiovascular diseases for which a genetic predisposition has been established. Based on analysis of the level of the enzyme in plasma, a genetic polymorphism of its expression has been well characterized. Use of a DNA marker on the angiotensin I-converting enzyme gene has shown that the gene polymorphism is located within the angiotensin I-converting enzyme gene itself. This review summarizes the results of various studies of this polymorphism in cardiovascular diseases and the hypotheses that can be proposed to explain this effect.

Animals↗
PubMed1994

The angiotensin-converting enzyme (ACE) genetic polymorphism: its relationship with plasma ACE level and myocardial infarction.

The angiotensin-converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin, two important peptides involved in vascular physiology. Plasma and cellular ACE levels in humans are influenced by an insertion (I)/deletion (D) polymorphism of the ACE gene, the ACE I/D polymorphism. The D allele has a frequency of approximately 0.53 in Caucasian populations and is codominantly associated with higher levels of ACE. We have studied this polymorphism in a large multicenter case-control study (the ECTIM study) and found that the D allele was associated with a parental history of fatal myocardial infarction (MI) in the controls and was more frequent in male patients with MI than in controls. This case-control difference was compatible with a codominant effect of allele D on the risk of MI with relative risks of 1.57 for DD vs II and 1.26 for ID vs II (test for trend p < 0.003). In subjects at low risk of MI (plasma ApoB < 1.25 g/l and body mass index < 26 kg/m2), the relative risk of DD vs ID + II was 2.7 (p < 0.0005). The results were very homogeneous in the four populations included in the study. In a family study, using linkage-segregation analysis, we have shown that the ACE I/D polymorphism is a marker for an unknown functional polymorphism (ACE S/s) which appears to be a new independent risk factor for MI.

Case-Control Studies↗
PubMed1994

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↗
PubMed1994

Plasma apolipoprotein concentrations in young adults with a parental history of premature coronary heart disease and in control subjects. The EARS Study. European Atherosclerosis Research Study.

The European Atherosclerosis Research Study (EARS) is a multicenter collaborative project within the European community. Its main objective is to study in young individuals the biological expression of a paternal history of premature coronary heart disease and to analyze the relative contribution of genetic and environmental factors to this expression. This study was carried out in 14 centers in 11 European countries, where the offspring of fathers who suffered a documented myocardial infarction before the age of 55 years (cases) were compared with age- and sex-matched control subjects. Plasma apolipoproteins A-I, B, A-II, A-IV, and E and lipoprotein (Lp) A-I lipoparticles were measured in this student population. Comparison of the values between cases and control subjects showed significantly higher apo B levels in cases compared with control subjects, and these differences were homogeneous throughout Europe. Regional differences were observed for apo E levels with an increasing north-south gradient, which was inversely related to that observed for triglycerides. A stepwise regression analysis including the lipid and apolipoprotein variables showed that apo B and triglycerides were the strongest discriminators between offspring of fathers with premature coronary heart disease and control subjects.

Adult↗
PubMed1994

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↗