PubMed Health⌕ Search

Biomedical subjects

Alun Evans

Publications and source records attributed to Alun Evans.

At least 19 recordsLinked to original sources
PubMed2006

Haplotypes of the caspase-1 gene, plasma caspase-1 levels, and cardiovascular risk.

Caspase-1 processes the interleukin (IL)-1beta and IL-18 inactive precursors to the biologically active cytokines that are known to have proatherogenic effects. The present study investigated the genetic variability of the CASP1 gene and plasma levels of caspase-1 in relation to cardiovascular risk. In Europeans, 3 tag SNPs captured 4 common haplotypes of the CASP1 gene. Among these, the A(in6) allele of the G+7/in6A polymorphism was less frequent in 246 cases with myocardial infarction and a parental history of disease than in 253 controls free of familial history of disease (0.13+/-0.02 versus 0.20+/-0.02; P=0.005). However, in a larger case/control study (n=1774), these effects are borderline restricted to the UK population. In a prospective cohort of 1168 patients with coronary artery disease followed up during a median period of 6.0 years, the A(in6) allele exhibited a borderline association with future cardiovascular death (hazard ratio [HR]: 0.64, 0.41 to 1.01; P=0.053) and was associated with lower serum IL-18 levels (P=0.014). Baseline caspase-1 levels in the top quartile of the distribution were predictive of cardiovascular deaths (HR=3.62, 1.81 to 7.27; P=0.0003 compared with the bottom quartile). Finally, in vitro assays of allelic imbalance showed that the CASP1 haplotype carrying the A(in6) allele was associated with a lower mRNA expression. These results indicate that caspase-1 levels are predictive of future cardiovascular death in patients with coronary artery disease. The role of CASP1 genetic variations in the susceptibility to myocardial infarction requires further investigation.

Adult↗
PubMed2006

Angiographically confirmed coronary heart disease and periodontal disease in middle-aged males.

BACKGROUND: The aim of this study was to investigate whether an association could be demonstrated between coronary heart disease (CHD) and chronic periodontitis in a population of middle-aged males in Northern Ireland. METHODS: A case-control design was used. Cases were men aged over 40 years with angiographically proven CHD. Controls were age-matched males, with no evidence of CHD, randomly drawn from the same locality as the cases. Each subject had a clinical periodontal examination and completed a detailed sociodemographic questionnaire. High sensitivity C-reactive protein (CRP) was measured in serum by immunoturbidimetry. RESULTS: There were 92 cases (mean age 56.7 years; SD = 6.3) and 79 controls (mean age 58.2 years; SD = 6.7). The CHD cases had an average of three teeth less than the controls (P <0.0001). A higher proportion of sites examined in cases than controls had plaque (P = 0.004), bleeding on probing (P = 0.013), and probing depths of > or = 4 mm (P = 0.006) or > or = 6 mm (P = 0.03). Subjects with > or = 4 mm pocketing in more than 20% of their interproximal sites and those with deep pocketing (> or = 6 mm) were classified as having poor periodontal status. A total of 35 cases (38%), compared to only 13 controls (16%), had a poor periodontal status (P = 0.0017). Men with a poor periodontal condition had higher levels of CRP (median 2.19 mg/l) than those with good periodontal health (median 1.42 mg/l), P = 0.007. After adjusting for smoking, academic achievement, alcohol consumption, unemployment, ability to maintain body weight, regular exercise, ability to relax daily, having a hobby or pastime, plaque, and CRP, logistic regression analysis showed that poor periodontal status was significantly associated with CHD, with an adjusted odds ratio of 3.06 and 95% confidence intervals of 1.02 to 9.17, P = 0.046. CONCLUSIONS: There was an association between coronary heart disease and poor periodontal status in the middle-aged males investigated. This association was independent of diabetes and all other cardiovascular risk factors investigated.

Adult↗
PubMed2005

Plasma cystatin-C and development of coronary heart disease: The PRIME Study.

The pathogenesis of ischemic coronary events involves degradation of the extracellular matrix in atherosclerotic lesions. The cysteine protease inhibitor cystatin-C may be involved in this phenomenon. The association of plasma cystatin-C with the incidence of myocardial infarction-coronary death and angina, was examined in a nested case-control (two controls per case) design within the prospective cohort study (Prospective Epidemiological Study of Myocardial Infarction (PRIME Study)) which included 9,758 men aged 50-59 years who were free of coronary heart disease (CHD) on entry and followed for a 5-year period. Three hundred and thirteen participants suffered myocardial infarction or coronary death (n = 159) or angina pectoris (n = 154) during follow-up. Cystatin-C was positively correlated with body mass index (BMI), low-density lipoprotein (LDL)-cholesterol, triglycerides and several inflammatory markers such as fibrinogen (r = 0.18), C-reactive protein (CRP) (r = 0.24), interleukin-6 (= 0.20), tumor necrosis factor-alpha (TNFalpha) (r = 0.27) and two TNFalpha receptors: TNFR1A (r = 0.43) and TNFR1B (r = 0.41); and negatively with high-density lipoprotein (HDL)-cholesterol (r = -0.25). After adjustment for traditional risk factors (age, diabetes, smoking, hypertension, BMI, triglycerides, LDL- and HDL-cholesterol), cystatin-C was significantly associated with the occurrence of the first ischemic coronary event. However, this association was no longer significant when CRP was included in the analysis. A decrease in glomerular filtration rate did not explain higher cystatin-C in cases than in controls. Cystatin-C appears to participate in the inflammatory phenomenon observed in the atherosclerotic process. Cystatin-C is not a more predictive risk marker of CHD than CRP or interleukin-6, but could be useful in detecting moderate chronic renal disease.

Biomarkers↗
PubMed2005

Family-based association studies of lipid gene polymorphisms in coronary artery disease.

Dysfunction of lipid-metabolizing proteins is implicated in the pathogenesis of coronary artery disease. Single nucleotide polymorphisms in genes that encode sterol regulatory binding protein-1a, adenosine triphosphate binding cassette-A1, hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein were assessed as potential markers of disease susceptibility in a family-based study of 1,012 patients from 386 families. Association between single nucleotide polymorphisms and coronary artery disease was tested by the combined transmission disequilibrium test/sib transmission disequilibrium test and pedigree disequilibrium test. After Bonferroni's correction, the pedigree disequilibrium test demonstrated significant excess transmission (p <0.0083) to affected patients of the hepatic lipase -514 T allele, which suggests that this may constitute a novel disease-susceptibility locus.

Adult↗
PubMed2005

Genetic stratification of pathogen-response-related and other variants within a homogeneous Caucasian Irish population.

Selection pressures from pathogens impact on the worldwide geographic distribution of polymorphisms in certain pathogen-response-associated genes. Such gene-specific effects could lead to confounding by geographic disease associations. We wished to determine if such constraints impinge on the genetic structure of a population of Irish patients and whether variants associated with responses to pathogens showed greater stratification. The counties of origin of each subject's grandparents were used as the geographic variable. F(st), proportional to the extent of population structure, was low (mean F(st)=0.004 across 25 SNPs, range 0.001-0.008) and it was not significantly higher for pathogen response SNPs (F(st)=0.004) than for other SNPs (F(st)=0.003, P=0.21). Correspondence analysis revealed weak trends primarily in approximately northeast to southwest and secondarily in northwest to southeast directions. One-dimensional spatial autocorrelation analysis revealed a weak (Moran's I autocorrelation of -0.10) tendency for SNP frequencies to diverge with greater distance. Two-dimensional autocorrelation indicated a northeast to southwest gradient that was similar for both the pathogen response and other SNPs. The southeastern county, Wexford, showed a distinctive pattern, perhaps consistent with Anglo-Norman settlements. In conclusion, these results indicate that pathogen response SNPs do not exhibit significantly more population structure than other SNPs within this Caucasian population. This suggests that the specific population structure of particular genes may not typically be a cause of strong confounding in genetic studies where population structure is controlled.

Arylsulfotransferase↗
PubMed2005

Prevalence, awareness and treatment of hypercholesterolaemia in 32 populations: results from the WHO MONICA Project.

BACKGROUND: Several studies have been conducted to estimate the population prevalence of hypertension, or its diagnosis and treatment. There is no multinationally comparable information on the prevalence of hypercholesterolaemia, or its diagnosis and treatment, since individual studies are often not directly comparable. METHODS: Data from the WHO MONICA Project's final risk factor surveys were used. Data were collected using standardized methods between 1989 and 1997 for the 35-64 year age range in 32 populations, in 19 countries on 3 continents. RESULTS: The prevalence of hypercholesterolaemia (total cholesterol > or = 6.5 mmol/l or taking lipid-lowering drugs) varied across populations from 3% to 53% in men, and from 4% to 40% in women. Awareness of hypercholesterolaemia varied from 1% to 33% in men, and from 0% to 31% in women. In most populations, over 50% of men and women on lipid-lowering drugs had a cholesterol level < 6.5 mmol/l. CONCLUSIONS: There is wide variation in the prevalence, awareness, and treatment of hypercholesterolaemia between populations. For the planning and implementation of primary prevention programmes and for the development of health care systems, monitoring of changes, both within and between populations, is essential. To obtain reliable information on these changes, well-standardized methods must be applied.

Adult↗
PubMed2004

Sex hormone-binding globulin is a major determinant of the lipid profile: the PRIME study.

The prevalence of coronary heart disease is much higher in men than in women and sex hormones might play a role in these differences through their influence on the lipid profile. The aim of this cross-sectional study was to study the relationship between hormonal markers (total testosterone (TT), estradiol (E2), sex-hormone-binding globulin (SHBG)) and plasma lipids in a population-based sample. Subjects were 352 men, 50-59 years old, selected in France (Lille, Strasbourg and Toulouse) and Northern-Ireland (Belfast) who had questionnaires and a medical examination at baseline of the PRIME prospective study (1991-1993). Pearson correlation coefficients and Student's t tests were used to identify factors associated with plasma lipids. Multiple linear regression models were used for multivariate analyses, using triglycerides (TG) (log-transformed) and high density-lipoprotein cholesterol (HDL-C) as dependent variables. SHBG and TT were negatively correlated with TG (p<0.0001 and p<0.05, respectively) and positively correlated with HDL-C (p<0.0001 and p<0.01). E2 was positively correlated with TG (p<0.05). No significant association was found between sex-hormones and LDL-C. In multiple linear regression analyses, SHBG remained independently associated negatively with TG (p<0.01) and positively with HDL-C (p<0.0001) after adjustment for centre of recruitment, age, body mass index, systolic blood pressure, smoking, alcohol intake and physical activity. After further adjustment for insulin, the association between SHBG and HDL-C remained highly significant (p<0.0001). The association between SHBG and TG was weakened but remained also significant. Our results suggest that SHBG might to be a central protein in the hormonal regulation of the lipid profile.

Biomarkers↗
PubMed2004

Association of European population levels of thrombotic and inflammatory factors with risk of coronary heart disease: the MONICA Optional Haemostasis Study.

AIMS: Classical risk factors do not fully explain international differences in risk of coronary heart disease (CHD). We therefore measured thrombotic and inflammatory markers in a substudy of the WHO MONICA project and correlated these with CHD event rates. METHODS AND RESULTS: We measured levels of fibrinogen (clottable and nephelometric), von Willebrand factor (vWf), tissue plasminogen activator antigen, plasminogen activator inhibitor activity, fibrin D-dimer, plasma viscosity, C-reactive protein, and total cholesterol in 12 MONICA populations (listed at the end of this paper), all but one European. Men and women aged 45-64 years were studied from 10 countries. All samples were collected using a carefully standardized protocol, and analysed centrally. Results were available for 3996 subjects (nephelometric fibrinogen and viscosity), 2378 subjects (other thrombotic assays), and 1757 subjects (C-reactive protein and total cholesterol). Significant differences in levels of thrombotic and inflammatory factors exist in MONICA populations mainly from European countries. These differences persist after adjustment for age, smoking habit, and body mass index. Cross-sectional correlations between coronary event rates and these thrombotic/inflammatory markers were significant for vWF antigen in both sexes, nephelometric fibrinogen in men, and D-dimer in women. CONCLUSION: In particular, vWF, nephelometric fibrinogen, and D-dimer should be examined in further research as potential risk factors which may help explain differences in coronary risk between European populations.

Biomarkers↗
PubMed2004

In-depth haplotype analysis of ABCA1 gene polymorphisms in relation to plasma ApoA1 levels and myocardial infarction.

OBJECTIVE: By regulating the cellular cholesterol efflux from peripheral cells to high-density lipoprotein, the ABCA1 protein is suspected to play a key role in lipid homeostasis and atherosclerosis. Twenty-six polymorphisms of the ABCA1 gene were genotyped and tested for association with plasma levels of ApoA1 and myocardial infarction (MI) in the ECTIM study. METHODS AND RESULTS: In addition to single-locus analysis, a systematic exploration of all possible haplotype effects was performed, with this exploration being performed on a minimal set of "tag" polymorphisms that define the haplotype structure of the gene. Two polymorphisms were associated with plasma levels of ApoA1, 1 in the promoter (C-564T) and 1 in the coding (R1587K) regions, whereas only 1 polymorphism (R219K) was associated with the risk of MI. However, no haplotype effect was detected on ApoA1 variability or on the risk of MI. CONCLUSIONS: ABCA1 gene polymorphisms but not haplotypes are involved in the variability of plasma ApoA1 and the susceptibility to coronary artery disease.

ATP Binding Cassette Transporter 1↗
PubMed2004

Polymorphism R92Q of the tumour necrosis factor receptor 1 gene is associated with myocardial infarction and carotid intima-media thickness--the ECTIM, AXA, EVA and GENIC Studies.

The TNFRSF1A gene was screened for polymorphisms in 95 subjects with premature myocardial infarction (MI), who also had one parent who had an MI. A total of 10 polymorphisms were found: three in the promoter region, two in exons and five in introns. All polymorphisms were genotyped in ECTIM, a case-control study of MI (1815 subjects). The nonsynonymous 92Q allele was found in 1.8, 1.0 and 1.7% of controls from Strasbourg, Belfast and Glasgow - respectively; in cases: 4.2, 2.2 and 3.2%. The population-adjusted odds ratio (OR) for MI associated with allele Q carrying was 2.15 (95% CI: 1.09-4.23). To check its possible implication in atherosclerosis, this polymorphism was then genotyped in the AXA Study (ultrasound examinations of carotid and femoral arteries in the context of an employment medical examination, 733 subjects), the EVA Study (ultrasound examinations of carotid arteries in a study of cognitive and vascular ageing, 1092 subjects) and the GENIC Study (on brain infarction (BI), 912 subjects). In the AXA Study, among smokers, carrying the 92Q allele was positively associated with the presence of a carotid plaque (OR 5.07; 95% CI: 1.64-15.63) and with a thickening of the carotid intima-media thickness (IMT) (0.59 (0.11) vs 0.54 (0.11), P=0.045). In the EVA Study, carriers of allele 92Q had an increased mean carotid IMT (0.70 (0.09) vs 0.67 (0.13), P=0.02). No significant association of the 92Q allele was found with BI in the GENIC Study. Overall, these results may suggest that carriers of the 92Q allele may be at increased risk of atherosclerosis.

Adult↗
PubMed2004

Frequency of fruit and vegetable consumption and coronary heart disease in France and Northern Ireland: the PRIME study.

Fruit and vegetable consumption is associated with low CHD risk in the USA and Northern Europe. There is, in contrast, little information about these associations in other regions of Europe. The goal of the present study was to assess the relationship between frequency of fruit and vegetable intake and CHD risk in two European populations with contrasting cardiovascular incidence rates; France and Northern Ireland. The present prospective study was in men aged 50-59 years, free of CHD, who were recruited in France (n 5982) and Northern Ireland (n 2105). Fruit and vegetable intake was assessed by a food-frequency questionnaire. Incident cases of acute coronary events and angina were recorded over a 5-year follow-up. During follow-up there was a total of 249 ischaemic events. After adjustment on education level, smoking, physical activity, alcohol consumption, employment status, BMI, blood pressure, serum total and HDL-cholesterol, the relative risks (RR) of acute coronary events were 0.67 (95% CI 0.44, 1.03) and 0.64 (95% CI 0.41, 0.99) in the 2nd and 3rd tertiles of citrus fruit consumption, respectively (P for trend <0.03). Similar results were observed in France and Northern Ireland. In contrast, the RR of acute coronary events for 'other fruit' consumption were 0.70 (95% CI 0.31, 1.56) and 0.52 (95% CI 0.24, 1.14) respectively in Northern Ireland (trend P<0.05) and 1.29 (95% CI 0.69, 2.4) and 1.15 (95% CI 0.68, 1.94) in France (trend P=0.5; interaction P<0.04). There was no evidence for any association between vegetable intake and total CHD events. In conclusion, frequency of citrus fruit, but not other fruits, intake is associated with lower rates of acute coronary events in both France and Northern Ireland, suggesting that geographical or related factors might affect the relationship between fruit consumption and CHD risk.

Acute Disease↗
PubMed2004

Residual coronary risk in men aged 50-59 years treated for hypertension and hyperlipidaemia in the population: the PRIME study.

OBJECTIVE: Since the proportion of subjects taking antihypertensive and lipid-lowering drugs is currently increasing in industrialized countries, it is important to evaluate, at the population level, coronary risk of treated individuals, while taking into account the achieved level of their risk factors (i.e. their 'residual coronary risk'). DESIGN AND METHODS: We used the data from the Prospective Study of Myocardial Infarction (PRIME), which involved populations from France (three centres) and Northern Ireland (one centre) (in each centre, 2500 men, aged 50-59 years, free of coronary heart disease, with a 5-year follow-up), to analyse the relationships between cardiovascular drug use and subsequent coronary risk. RESULTS: Antihypertensive drug use was significantly positively associated (relative risk = 1.60; 95% confidence interval, 1.18-2.16) with total coronary risk, but not lipid-lowering drug use (relative risk = 1.15; 95% confidence interval, 0.77-1.73), while adjusting on classical risk factor levels (age, smoking, total cholesterol, high-density lipoprotein-cholesterol and systolic blood pressure). Subgroup analysis showed that these results applied to beta-blockers and calcium channel antagonists, but not to diuretics and angiotensin-converting enzyme inhibitors, to both angina pectoris and hard coronary event risk, but in the French population only and not in Belfast. Although the PRIME study was not designed to test the ability of different drugs to prevent coronary heart disease, this analysis raises the hypothesis that antihypertensive drugs could be associated with a sizeable residual coronary risk in middle-aged men. CONCLUSION: Treatment with antihypertensive agents, beta-blockers and calcium channel antagonists in particular, was associated with a sizeable residual coronary risk. It seems, therefore, important to consider antihypertensive treatment in the cardiovascular risk assessment of individuals.

Adrenergic beta-Antagonists↗
PubMed2004

Alcohol consumption and cardiovascular disease: differential effects in France and Northern Ireland. The PRIME study.

BACKGROUND: The effects of wine and other alcoholic beverages on coronary heart disease (CHD) have seldom been studied in several countries using a common methodology. DESIGN: Five-year prospective study conducted among 9750 men (7352 in France and 2398 in Northern Ireland) free of CHD at entry. Outcomes were angina pectoris, myocardial infarction or CHD death. RESULTS: In all, 90% of subjects in France reported drinking at least once per week, versus 61% in Northern Ireland. In France, after adjusting for other CHD risk factors, subjects in the highest quartile of alcohol consumption had a significantly lower risk of developing angina pectoris relative to non-drinkers. For myocardial infarction and all CHD events, the risk also decreased from the first to the fourth quartile (P for trend=0.02). Conversely, in Northern Ireland, no significant relationship was found between alcohol consumption and the incidence of angina pectoris or all CHD events, although alcohol consumption appeared to decrease the risk for myocardial infarction. Similar findings were obtained when the 5% higher alcohol consumers were excluded from the analysis. Finally, splitting the alcohol consumption into wine, beer and spirits did not improve the relationships, the three types of beverage exerting comparable effects on CHD events. CONCLUSIONS: Alcohol consumption patterns exert differential effects on CHD risk in middle-aged men from France and Northern Ireland. Further, the amount of alcohol consumption, rather than the type of alcoholic beverage, is related to both angina pectoris and myocardial infarction in France, whereas no relationship was found in Northern Ireland.

Alcohol Drinking↗
PubMed2004

The matrix metalloproteinase-3 (MMP-3) 5A/6A promoter polymorphism is not associated with ischaemic heart disease: analysis employing a family based approach.

Matrix metalloproteinase-3 (MMP-3) has been proposed as an important mediator of the atherosclerotic process. The possible role of the functional -1612 5A/6A polymorphism of the MMP-3 gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the MMP-3 -1612 5A/6A polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the MMP-3 -1612 5A/6A polymorphism is not associated with IHD.

Adult↗
PubMed2004

The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland.

Low plasma folate and its derivatives have been linked with depressive disorders in studies dating back over 30 years. A thermolabile variant (677C>T) of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with low serum folate. The present study aimed to explore whether the thermolabile variant of MTHFR is associated with a vulnerability to depressive episodes. MTHFR C677T genotype frequencies in a cohort of patients (mean age 48 years) with depressive disorder (n = 100) were compared with those in age- and sex-matched controls. Serum levels of folate, homocysteine and vitamin B(12) were also compared between groups. The thermolabile variant of MTHFR was significantly more common in the group with a history of depressive disorder (P= 0.03). Serum levels of folate, homocysteine and vitamin B(12) did not differ significantly between groups. A MTHFR C677T genotype is associated with increased risk of depressive episodes in this homogenous patient population.

Adolescent↗