Biomedical subjects

Alun Evans

Publications and source records attributed to Alun Evans.

At least 37 records · Page 2Linked to original sources

PubMed2003

Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).

BACKGROUND: Interleukin (IL)-18 promotes atherosclerotic plaque growth and vulnerability. It is unknown, however, whether elevations of circulating IL-18 precede the onset of coronary events in apparently healthy individuals. METHODS AND RESULTS: We evaluated the relationship between baseline plasma levels of IL-18 and the subsequent incidence of coronary events over a 5-year follow-up in the Prospective Epidemiological Study of Myocardial Infarction (PRIME),which included 10 600 healthy European men aged 50 to 59 years at baseline. Analysis was performed in a nested case-control manner comparing 335 cases with a coronary event to 670 age-matched controls. Baseline levels of IL-18 were significantly higher in men who developed a coronary event than in controls (225.1 versus 203.9 pg/mL, P=0.005). After adjustment for most potential confounders, including C-reactive protein, IL-6, and fibrinogen, the relative risk of future coronary events associated with increasing tertiles of IL-18 was 1.65 (95% CI 1.14 to 2.40, P=0.008) in Northern Ireland, 1.29 (95% CI 0.96 to 1.73, P=0.09) in France, and 1.42 (95% CI 1.13 to 1.79, P=0.003) in both populations combined (P=0.31 for the test of homogeneity between populations). In all models, IL-18 made an independent contribution to the prediction of risk over lipids or other inflammatory markers such as C-reactive protein, IL-6, or fibrinogen. CONCLUSIONS: Plasma IL-18 level was identified as an independent predictor of coronary events in healthy, middle-aged European men. Determination of circulating IL-18 might improve the prediction of coronary events.

Biomarkers↗

PubMed2003

C-reactive protein, interleukin-6, and fibrinogen as predictors of coronary heart disease: the PRIME Study.

OBJECTIVE: This study was undertaken to examine the association of plasma inflammatory markers such as C-reactive protein (CRP), interleukin-6, and fibrinogen with the incidence of coronary heart disease within the prospective cohort study on myocardial infarction (PRIME study). METHODS AND RESULTS: Multiple risk factors were recorded at baseline in 9758 men aged 50 to 59 years who were free of coronary heart disease (CHD) on entry. Nested case-control comparisons were carried out on 317 participants who suffered myocardial infarction (MI)-coronary death (n=163) or angina (n=158) as an initial CHD event during a follow-up for 5 years. After adjustment for traditional risk factors, incident MI-coronary death, but not angina, was significantly associated with CRP, interleukin-6, and fibrinogen, but only interleukin-6 remained significantly associated with MI-coronary death when the 3 inflammatory markers were included in the model. The different interleukin-6 levels in Northern Ireland and France partly explained the difference in risk between these countries. Interleukin-6 appeared as a risk marker of MI-coronary death, and it improved the definition of CHD risk beyond LDL cholesterol. CONCLUSIONS: This association may reflect the underlying inflammatory reaction located in the atherosclerotic plaque or a genetic susceptibility on the part of CHD subjects to answer a proinflammatory stimulus and subsequent increase in hepatic CRP gene expression.

Angina Pectoris↗

PubMed2003

Plasma fibrinogen explains much of the difference in risk of coronary heart disease between France and Northern Ireland. The PRIME study.

The incidence of coronary heart disease is higher in Northern Ireland than in France. These differences have not been adequately explained. We have investigated the associations of plasma fibrinogen concentration and factor VII activity with the incidence of coronary heart disease in a prospective cohort study involving 10600 men aged 50-59 living in four regions (Lille, Strasbourg, and Toulouse in France, Belfast in Northern Ireland). Baseline fibrinogen and factor VII were measured in 9489 men free of coronary heart disease at entry (7167 in France and 2322 in Northern Ireland). Over 5 years of follow-up, 161 participants developed myocardial infarction (MI) or coronary death (100 in France and 61 in Belfast) and 151 developed angina pectoris (94 in France and 57 in Belfast). The risk of future coronary events was 1.9 times higher in Belfast than in France (95% confidence interval: 1.5-2.4). Baseline mean levels of fibrinogen were significantly higher in Belfast than in France and they were higher in participants who experienced coronary events compared with those who did not in both countries. The age-adjusted relative risk of coronary heart disease associated with a rise of one standard deviation in fibrinogen level was 1.56 (95% confidence interval: 1.29-1.95, P<0.0001) in the whole cohort. This association remained significant after adjustment for other cardiovascular risk factors (relative risk:1.36; 95% confidence interval: 1.14-1.68; P<0.0001). There was no clear geographical variation in factor VII and no significant association between factor VII levels and the risk of coronary events was observed. Classic risk factors explained 25% of the excess risk of coronary heart disease in Belfast compared with France, while fibrinogen alone accounted for 30%. These findings add to the epidemiological evidence that elevated fibrinogen is a major risk factor for coronary heart disease.

Coronary Disease↗

PubMed2003

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.

Biomarkers↗

PubMed2003

Family history, longevity, and risk of coronary heart disease: the PRIME Study.

BACKGROUND: To assess the contribution of family history of coronary heart disease (CHD) and longevity in parents to 5-year incidence of coronary events in middle-aged men. METHODS: A prospective study in men from Northern Ireland and the French cities and environs of Lille, Strasbourg, and Toulouse. A total of 10 600 men aged 50-59 years were examined between 1991 and 1994 and followed annually by questionnaire for incident cases of coronary disease. A detailed family history was taken and a quantitative family risk score for CHD was calculated for each subject. Five-year follow-up is complete; all coronary events (coronary deaths, myocardial infarction, and angina) documented by clinical records were reviewed by an independent medical committee. RESULTS: At screening, 9758 subjects were free of clinical and historical evidence of CHD; in this group there were 317 coronary events by 5 years of follow-up. Subjects whose parents had both survived until >/=80 years showed a relative odds of 0.49 (95% CI: 0.31-0.77) for risk of a coronary event compared with subjects whose parents had not survived until >/=80 years old with adjustment for age and nine other risk factors including family history. The pattern of results was similar in France and Northern Ireland, although parental survival was longer in France. Likewise, subjects with a strong family history showed a relative odds of 1.93 (95% CI: 1.25-3.00) compared with subjects without such a history, after adjustment for age and the nine risk factors including parental longevity. The pattern of results was similar in France and Northern Ireland. CONCLUSIONS: These results indicate that a family history of coronary disease and parental longevity, although related, act independently of one another and of other major cardiovascular risk factors in predicting 5-year risk of subsequent coronary events.

Aged↗

PubMed2003

Body mass index, hypertension and 5-year coronary heart disease incidence in middle aged men: the PRIME study.

OBJECTIVE: The aim of the present study was to assess the joint contribution of hypertension and body mass index to coronary heart disease risk. DESIGN Prospective study on men aged 50-59 years free of coronary heart disease at entry recruited in three regions of France (n = 7359) and in Northern Ireland (n = 2399). PARTICIPANTS: The recruitment frame was based on industry and various employment groups, on health screening centers and general practice. MAIN OUTCOME: Incident cases of effort angina, unstable angina, myocardial infarction and coronary death were recorded over a 5-year follow-up. RESULTS: Compared with the reference group [body mass index (BMI) 25 kg/m2], the relative risk of coronary event was higher in the second (25 < or =BMI 27.6) and third BMI tertiles: 1.27 (95% confidence interval 0.94-1.70) and 1.14 (0.84-1.56) after adjustment for confounders and covariates, including diabetes, hypertension and lipoprotein levels. Further analyses revealed a significant interaction between hypertension and BMI on coronary disease risk (P <0.05), suggesting that hypertension modifies coronary heart disease (CHD) risk attributable to BMI. Among hypertensive men, the relative risk of coronary heart disease was 1.34 (0.85-2.11) and 1.61 (1.04-2.50) in the second and third BMI tertiles, respectively. In normotensive men, BMI was not associated with CHD risk; relative risk 1.25 (0.85-1.85) and 0.66 (0.40-1.09) in the second and third BMI, respectively. CONCLUSION: These results indicate that hypertension and overweight jointly increase coronary heart disease risk.

Body Mass Index↗

PubMed2003

The genetics of coronary heart disease: the contribution of twin studies.

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

Australia↗

PubMed2003

Ethical issues and GenomEUtwin.

The post-genomic era is witnessing a proliferation of large-scale and population based genetic and genomic research projects. Many countries have or are establishing research biobanks and, as with GenomEUtwin, there is great interest in building multinational projects that link genotypic and phenotypic information from different centers. Clearly, the conduct of these projects raises multiple ethical issues, and the knowledge generated will continually recast the ethical, legal and social implications (ELSI) of such research. Maximising the scientific profit from this work while minimizing the risks to the participants requires full integration of ethics components into the structure and functioning of these projects. GenomEUtwin is organized around five intellectual cores, including an Ethics Core which operates across the entire project. This paper describes the role of the Ethics Core and presents an overview of the guidelines on which the principles followed in GenomEUtwin are based. We outline the major ethical concerns of our project and highlight complexities arising from diverse national legislations. Finally, the role of empirically based ethics research is discussed for understanding the ethical, legal, social and economic implications of human genetics and genomics research.

Confidentiality↗

PubMed2003

Association between TAFI antigen and Ala147Thr polymorphism of the TAFI gene and the angina pectoris incidence. The PRIME Study (Prospective Epidemiological Study of MI).

Thrombin activatable fibrinolysis inhibitor (TAFI), a recently described inhibitor of fibrinolysis, has been hypothesized as playing a role in atherothrombosis. However, the evidence from retrospective studies, which have evaluated the role of TAFI in vascular risk, is conflicting. In a prospective cohort (the PRIME Study) of nearly 10 000 apparently healthy men recruited in France (Lille, Strasbourg, Toulouse) and Northern Ireland (Belfast), we measured baseline plasma concentration of TAFI antigen among 143 participants (81 from France and 62 from Ireland) who subsequently developed angina pectoris and among 286 age-matched participants who remained free of disease during the 5 years of follow-up. Genotyping of the Ala147Thr polymorphism located in the TAFI gene was performed using an allele specific PCR. In France, mean levels of TAFI were significantly higher at baseline among men who subsequently developed angina pectoris compared with their control subjects (119 versus 107 %; p = 0.02). The risk of future angina pectoris increased with increasing tertiles of TAFI (p = 0.02), such that men in the highest tertile at study entry had a 5-fold higher relative risk than those in the lowest tertile (95% confidence interval, 1.38 to 18.58) after controlling for the conventional cardiovascular risk factors. No such difference was observed in Northern Ireland. In France, Thr/Thr carriers of the Ala147Thr polymorphism were significantly more frequent in cases than in controls (p = 0.01) leading to a relative risk of angina pectoris of 2.7 (95%CI 1.2-5.8). Increase in plasma TAFI antigen levels is a risk factor for angina pectoris in France. Genotyping for the Ala147Thr polymorphism seems to be a reliable tool to assess the risk mediated by TAFI.

Amino Acid Substitution↗

PubMed2002

Value of HDL cholesterol, apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I/A-II in prediction of coronary heart disease: the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction.

OBJECTIVE: We have examined the association between the incidence of coronary heart disease (CHD) and plasma high density lipoprotein (HDL) cholesterol, apolipoprotein A-I (apoA-I), and 2 HDL fractions, lipoprotein A-I and lipoprotein A-I:A-II. METHODS AND RESULTS: These parameters were measured in subjects recruited in France and in Northern Ireland in the Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study, a prospective cohort study. Among the subjects free of CHD on entry, 176 in France and 113 in Northern Ireland suffered an ischemic attack (CHD patients) during the 5-year follow-up, whereas 6612 French and 2172 Northern Irish men showed no CHD symptoms (CHD-free subjects). All 4 HDL parameter levels were lower in CHD patients than in CHD-free subjects. After the cohort was divided into quintiles based on the distribution of HDL parameter levels, a significant (P<0.0001) linear increase in relative risk was observed for each HDL parameter level. However, regression logistic analyses showed that apoA-I was the strongest predictor (more powerful than HDL cholesterol) and that lipoprotein A-I and lipoprotein A-I:A-II did not supplement apoA-I in predicting CHD. CONCLUSIONS: Among the parameters related to HDL, apoA-I appears to be the strongest independent risk factor.

Angina Pectoris↗

PubMed2002

Serotonin transporter gene polymorphism and myocardial infarction: Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM).

BACKGROUND: Depression is a risk factor for myocardial infarction (MI). Selective serotonin reuptake inhibitors reduce this risk. The site of action is the serotonin transporter (SLC6A4), which is expressed in brain and blood cells. A functional polymorphism in the promoter region of the SLC6A4 gene has been described. This polymorphism may be associated with the risk of MI. METHODS AND RESULTS: The SLC6A4 polymorphism has been investigated by polymerase chain reaction in 671 male patients with MI and in 688 controls from the Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM) multicentric study. Percentages for LL, LS, and SS genotypes were 35.5%, 45.4%, and 19.1%, respectively, for cases versus 28.1%, 49.1%, and 22.8%, respectively, for controls. S allele frequency was 41.8% and 47.4% for cases and controls, respectively. After adjustment for age and center by using multivariable logistic regression, the odds ratio for MI associated with the LL genotype was 1.40 (95% CI 1.11 to 1.76, P=0.0047). CONCLUSIONS: The LL genotype of the SLC6A4 polymorphism is associated with a higher risk of MI. This could be attributable to the effect of the polymorphism on serotonin-mediated platelet activation or smooth muscle cell proliferation or on other risk factors, such as depression or response to stress.

Carrier Proteins↗

PubMed2002

Significant impact of the highly informative (CA)n repeat polymorphism of the APOA-II gene on the plasma APOA-II concentrations and HDL subfractions: The ECTIM study.

High density lipoproteins (HDL) are heterogeneous in their apolipoprotein composition and the role of apolipoprotein A-II (APOA-II) in HDL structure and metabolism is poorly understood. Yet, studies of naturally occurring variations of APOA-II in mice and experiments in transgenic mice overexpressing the APOA-II gene (APOA-II) have shown that APOA-II expression influences APOA-II plasma levels and HDL size and composition. In humans, two RFLPs (BstNI and MspI) have been described in the APOA-II gene. These RFLPs, however, have been inconstantly associated with variations in APOA-II plasma levels. In particular, the large multicentric ECTIM Study did not show any significant effect of the two RFLPs. Other polymorphisms consisting of repetitive sequences have been proposed as more informative markers than RFLPs. Thus, data from the ECTIM Study were reconsidered by integrating the additional information obtained from a highly informative multiallelic (CA)(n)-repeat polymorphism located in the second intron of the gene. The population study was composed of 763 non-treated male controls and 594 cases of myocardial infarction. In controls, the (CA)(19) allele was associated with significantly decreased APOA-II (P < 0.0009) and LpA-II:A-I (P < 0.02) plasma levels. Although the APOA-I plasma levels were not affected by the polymorphism, the (CA)(19) allele was associated with an increased LpA-I/LpA-II:A-I ratio (P < 0.004). No effect, however, could be detected on myocardial infarction. Study of the linkage disequilibrium and the estimation of haplotype frequencies indicated that the impact of the APOA-II locus could hardly be detected by using the BstNI and MspI RFLPs. These data revive interest in evaluating the role of the APOA-II locus in the control of APOA-II plasma levels and HDL composition.

Adult↗

PubMed2002

Physical activity and coronary event incidence in Northern Ireland and France: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).

BACKGROUND: The influence of physical activity on the incidence of angina pectoris and hard coronary events (myocardial infarction and coronary deaths) was examined in Northern Ireland and France at contrasting risk for coronary heart disease (CHD) and with different physical activity patterns. METHODS AND RESULTS: Participants of the Prospective Epidemiological Study of Myocardial Infarction (PRIME) (n=9758; age, 50 to 59 years), free of CHD at baseline, were followed up for 5 years: 167 hard CHD and 154 angina events were recorded. Net energy expenditure (EE) as the result of physical activity was assessed by means of the MONICA Optional Study of Physical Activity Questionnaire (MOSPA-Q). Leisure-time physical activity EE was calculated; subjects were also categorized as to whether they performed high-intensity leisure-time activities or walked or cycled to work. After multivariate adjustment, leisure-time physical activity EE was associated with a lower risk of hard CHD events (P<0.04), whereas walking or cycling to work was not independently related to hard CHD events. No interaction by country was found. The beneficial effect of leisure-time physical activity was also present among subjects who did not report high-intensity activities (P<0.04), with similar results in France and Northern Ireland. In contrast, an increasing level of leisure-time physical activity was associated with a higher risk of angina in both countries. CONCLUSIONS: These data indicate a beneficial effect of leisure-time physical activity EE on hard CHD incidence in middle-aged men, which could partly explain the unfavorable rate of CHD in Northern Ireland. The higher level of leisure-time activities in France could, in part, explain its lower rate of CHD.

Angina Pectoris↗

PubMed2002

A novel cholesteryl ester transfer protein promoter polymorphism (-971G/A) associated with plasma high-density lipoprotein cholesterol levels. Interaction with the TaqIB and -629C/A polymorphisms.

The plasma cholesteryl ester transfer protein (CETP) plays a key role in reverse cholesterol transport (RCT) by mediating the transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to atherogenic ApoB-containing lipoproteins, including VLDL, IDL and LDL. We describe a new polymorphism located at position -971 in the human CETP gene promoter, which corresponds to a G/A substitution at a potential AvaI restriction site. The relationship between the -971G/A polymorphism, plasma lipid parameters and plasma CETP concentration was evaluated in the Etude Cas-Témoins de l'Infarctus du Myocarde (control-myocardial infarction cases) cohort, and revealed that the -971G/A polymorphism (A allele frequency: 0.491) was significantly associated with both plasma high-density lipoprotein cholesterol (HDL-C) levels and CETP concentration (P=0.006 and 0.009, respectively). Subjects with genotype -971GG displayed both low HDL-C levels and high plasma CETP concentration, while genotype -971AA subjects displayed the inverse relationship. Evaluation of potential interactions between the -971G/A and the -629C/A or TaqIB polymorphisms demonstrated that the -971G/A polymorphism interacts significantly with the functional -629C/A site and the TaqIB polymorphism with respect to plasma HDL-C levels (P=0.0014 and 0.012, respectively), but does not affect plasma CETP concentration. These results clearly suggest that the interaction between the 971G/A polymorphism and either the -629C/A or the TaqIB polymorphism on plasma CETP concentration is different than that implicated in HDL-C levels. Transient transfection of HepG2 cells revealed that the -971G/A polymorphism did not modulate transcriptional activity of the human CETP gene promoter. The -971G/A promoter polymorphism therefore constitutes a non-functional marker. Furthermore, the observed effects of the -971G/A polymorphism on both plasma CETP concentration and HDL-C levels are due to functional variants in linkage disequilibrium with it. Our findings strongly suggest the existence of as yet unidentified functional polymorphisms in the CETP gene promoter that could explain the association between specific polymorphisms of the CETP gene and both plasma HDL-C and CETP concentrations.

Adult↗

PubMed2002

High expressor paraoxonase PON1 gene promoter polymorphisms are associated with reduced risk of vascular disease in younger coronary patients.

Human paraoxonase-1 is hypothesised to protect serum lipoproteins from oxidative stress. Decreased serum activity of paraoxonase-1 in animal models is associated with an increased risk of vascular disease and has been linked to the anti-oxidant capacity of the enzyme. Promoter polymorphisms of the human paraoxonase-1 gene strongly influence serum concentrations of the enzyme. The present study examined the hypothesis that promoter polymorphisms may be genetic risk factors for vascular disease in man. Genotypes arising from the promoter C(-907)G polymorphism were analysed in the ECTIM2 population. The global odds ratio for myocardial infarction, comparing the high expressor GG genotype to other genotypes, was 0.77 (0.61-0.97) (P=0.024). The association with the promoter genotype was more pronounced in the youngest age group (odds ratio 0.52 (0.31-0.87), P=0.012) and was progressively lost with age (respectively 50 years to <60 years, P=0.26; >60 years, P=0.45). There was no association between the promoter genotypes and serum lipids. The data are consistent with the high expressor promoter genotype being linked to reduced risk of myocardial infarction. The influence of the genotype may be compromised in older patients.

Adult↗

PubMed2002

Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study.

The association of an elevated level of lipoprotein (a) (Lp(a)) with the development of coronary heart disease (CHD) remains controversial. Lp(a) was investigated as a CHD risk factor in the PRIME Study, a prospective cohort study which included 9133 French and Northern Irish men aged 50-59 at entry, without a history of CHD and not on hypolipidaemic drugs. During a follow-up of 5 years, 288 subjects experienced at least one CHD event (myocardial infarction (MI), coronary death, angina pectoris). Lp(a) was measured by immunoassay in all subjects on fresh plasma obtained at entry. Traditional cardiovascular risk factors such as low-density lipoproteins (LDL)-cholesterol, HDL-cholesterol, triglycerides, the presence of diabetes, hypertension or smoking were determined. Logistic regression analysis was used to evaluate Lp(a) level as a CHD risk factor after controlling for the other risk factors. In addition, its possible interaction with LDL- and HDL-cholesterol levels was investigated. Lp(a) appeared a significant risk factor (P<0.0006) in the whole cohort without between-population interaction, even if the association was not statistically significant in the Belfast sample. The relative risk (RR) of CHD events in subjects with Lp(a) levels in the highest quartile was 1.5 times that of subjects in the lowest quartile (RR: 1.56; 95% confidence intervals (CIs): 1.10-2.21). A high Lp(a) level was a risk for MI, coronary death and angina pectoris. A significant interaction term between Lp(a) and LDL-cholesterol levels, however, was found. The relative CHD risk associated with a Lp(a) level > or =33 mg/dl in comparison with Lp(a) <33 mg/dl increasing gradually from 0.82 (95% CI: 0.28-2.44) in men with LDL-cholesterol in the lowest quartile (<121 mg/dl) to 1.58 (95% CI: 1.06-2.40) in the highest quartile (>163 mg/dl). In conclusion, Lp(a) increased the risk for MI and angina pectoris, especially in men with a high LDL-cholesterol level. This study which analyzed Lp(a) level using a measurement independent of apolipoprotein (a) size on fresh plasma, has confirmed utility of Lp(a) as a predictor of CHD.

Biomarkers↗

PubMed2002

The importance of plasma apolipoprotein E concentration in addition to its common polymorphism on inter-individual variation in lipid levels: results from Apo Europe.

Interindividual variation in the concentration of plasma lipids which are associated with coronary artery disease (CAD) risk is determined by a combination of genetic and environmental factors. This study investigates the effects of apoE genotype and plasma concentration on cholesterol and triglycerides (TG) levels in subjects from five countries: Finland, France, Northern Ireland, Portugal, and Spain. Age and sex significantly influenced serum cholesterol, TG and apoE concentrations. The age effect differs in males and females. The allele frequencies of the apoE gene, one of the most widely studied CAD susceptibility genes, were determined: the epsilon2 allele frequency and the apoE concentration showed a north-south increasing gradient while the epsilon4 allele frequency showed the reverse. ApoE plays an important role in lipid metabolism. Total cholesterol and TG concentrations were significantly dependent on apoE genotype in both sexes. These differences in lipids between genotypes were more pronounced when plasma apoE concentrations were taken into account.

Adult↗

PubMed2002

Polymorphisms of the beta2 -adrenoceptor (ADRB2) gene and essential hypertension: the ECTIM and PEGASE studies.

OBJECTIVES: The beta2-adrenoceptor (ADRB2) plays a pivotal role in signalling in relation to hypertension and obesity. Polymorphisms of the ADRB2 gene have been shown to be potentially related to essential hypertension and other non-cardiovascular disease phenotypes. We investigated whether genetic variation of the ADRB2 gene might be related to essential hypertension or myocardial infarction (MI). METHODS: Four ADRB2 gene polymorphisms C19R (T-47C), T-20C, G16R (G+46A), Q27E (C+79G) were investigated in two studies: PEGASE, a study of moderate to severe hypertension (707 cases) conducted in France, and ECTIM, a case-control study of MI (1178 cases, 1187 controls) conducted in France, Northern Ireland and Scotland. Genotyping was performed using allele-specific oligonucleotides. RESULTS: The ADRB2 polymorphisms T-20C and Q27E were found to be completely concordant, generating the haplotypes [T-20-Q27] and [C-20-E27]. Three main haplotypes accounted for 94% of all haplotypes: [R19-G16-E27] (39%), [C19-R16-Q27] (35%) and [C19-G16-Q27] (20%). Haplotype frequencies were not significantly different between countries. Allele and genotype frequencies did not differ significantly between cases with essential hypertension or MI and control subjects. There was no association of the polymorphisms with early onset hypertension, blood pressure level, coronary artery stenosis or any other phenotype measured in these study populations. In the ECTIM Study, our calculation revealed that we could have detected an odds ratio (OR) for MI of 1.3 with 80% power at a 5% type I error probability, the corresponding value for the PEGASE Study being an OR of 1.6 for hypertension. CONCLUSIONS: From our present analysis we conclude that the ADRB2 gene polymorphisms studied do not contribute in any important way to the risk of essential hypertension or MI in subjects of European ancestry.

Adult↗