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J W Yarnell

Publications and source records attributed to J W Yarnell.

At least 19 recordsLinked to original sources

The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations.

Epidemiological evidence has revealed that an elevated plasma homocysteine level (hyperhomocysteinemia) confers an increased risk of cardiovascular disease and neural tube defects. Hyperhomocysteinemia is caused by both nutritional (e.g. folate, vitamins B(6) and B(12)) and genetic factors, including functional polymorphisms of key enzymes involved in homocysteine metabolism. One such enzyme, methionine synthase reductase (MTRR), maintains adequate levels of methylcob(III)alamin, the activated cofactor for methionine synthase, which catalyzes the remethylation of homocysteine to methionine. A common MTRR polymorphism, i.e. a 66 A-->G substitution specifying an isoleucine to methionine substitution (I22M), was recently identified. To assess the influence of this polymorphism on total plasma homocysteine (tHcy), we undertook a genotype/phenotype analysis in a study population of 601 Northern-Irish men, aged 30--49, for which biochemical and genetic data relevant to folate/homocysteine metabolism had already been acquired. The 66AA genotype has a frequency of 29% in this population. We established that there was a significant influence of MTRR genotype on tHcy ranking (P=0.004) and that the 66AA genotype contributes to a moderate increase in tHcy levels across the distribution [OR 1.59 (95% CI: 1.10--2.25) for the 66AA genotype to be in the upper half of the tHcy distribution, P=0.03]. The homocysteine-elevating effect of the 66AA genotype is independent of serum folate, vitamin B(12) and vitamin B(6) levels. Based on published estimates of the enhanced cardiovascular disease risk conferred by defined increments of plasma tHcy, we estimate that 66AA homozygotes have, on average, an approximately 4% increase in cardiovascular disease risk compared to 66GG homozygotes. This study provides the first evidence that the MTRR A66G polymorphism significantly influences the circulating tHcy concentration.

Adult↗

Central obesity: predictive value of skinfold measurements for subsequent ischaemic heart disease at 14 years follow-up in the Caerphilly Study.

OBJECTIVE: To assess the predictive value of central obesity for risk of ischaemic heart disease (IHD) in a long-term follow-up, measured by skinfold thickness in comparison to general measures of overweight and obesity such as Quetelet's index. SUBJECTS AND DESIGN: A total of 2512 men aged 45-59 y from the general population first examined in 1979-1982. Men were re-examined at approximately 5 y intervals. All fatal and non-fatal cases of IHD during a 14 y follow-up were recorded. MEASUREMENTS: Skinfold thickness was measured at four sites. Height (m) and weight (kg) were also measured and Quetelet's index (weight/height(2)) was used as the reference body mass index (BMI). RESULTS: Data were available for 2512 men among whom 411 new cases of IHD (fatal and non-fatal) occurred during 14 y of follow-up. Increasing values of BMI showed a statistically significant trend with increasing risk of new IHD that contributed independently to risk of IHD when adjusted for age, smoking habit and social class. Skinfold thickness measures were entered singly and in combination into this model with and without the additional inclusion of BMI. All individual skinfolds were significantly associated with risk of new IHD when BMI was excluded from the regression model, as was the sum of four skinfolds and the sum of subscapular and abdominal skinfolds. Only the subscapular skinfold measure contributed independently to risk of subsequent IHD when BMI was included in the model although biceps, biceps plus triceps and total sum of skinfolds were close to achieving statistical significance. The relative odds of IHD in the upper quintile of subscapular skinfold compared to the lowest was 1.9 (95% CI 1.3-2.8) when adjusted for age, smoking habit and social class. CONCLUSIONS: In general skinfold measurements contribute only marginally to improved prediction of risk of IHD as measured by BMI, but central obesity, as measured by the subscapular skinfold, is predictive of IHD independently of BMI.

Abdomen↗

Lifestyle factors and coagulation activation markers: the Caerphilly Study.

Coagulation activation markers are being investigated as risk factors for cardiovascular disease; we examined the contribution of several lifestyle factors to variation in plasma levels of several activation markers measured in a population-based study of 1947 men. Smoking, alcohol, body mass index (BMI), leisure and work activity, social class, and use of prescribed medicines were each examined in turn. Specific assays of fibrin D-dimer and von Willebrand factor (vWF) activity showed similar relationships to lifestyle variables as we observed previously for less specific assays of D-dimer and vWF antigen. D-dimer levels increased with age, in smokers and in men taking prescribed medication, and were negatively associated with leisure time activity. vWF activity increased with age and showed a U-shaped distribution with BMI. Factors VIIc and VIIIc and thrombin-antithrombin complexes were associated with BMI, factor VIIIc and prothrombin fragments 1 + 2 (F1 + 2) were associated with age, activated partial thromboplastin time (aPTT) and F1 + 2 were associated with smoking, and aPTT showed a small negative association with alcohol consumption. We conclude that lifestyle modification has the possibility of favourably influencing several of these risk markers. In particular, cigarette smoking has a possibly reversible effect on coagulation activation (measured by F1 + 2 and D-dimer).

Aged↗

C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell study: are inflammation and fibrin turnover linked in pathogenesis?

Plasma levels of C-reactive protein (CRP, a marker of the reactant plasma protein component of the inflammatory response) and of fibrin D-dimer (a marker of cross-linked fibrin turnover) have each been associated in recent studies with the risk of future ischemic heart disease (IHD). Previous experimental studies have shown that fibrin degradation products, including D-dimer, have effects on inflammatory processes and acute-phase protein responses. In the Speedwell Prospective Study, we therefore measured CRP and D-dimer levels in stored plasma samples from 1690 men aged 49 to 67 years who were followed-up for incident IHD for an average of 75+/-4 months (mean+/-SD) and studied their associations with each other, with baseline and incident IHD, and with IHD risk factors. CRP and D-dimer levels were each associated with age, plasma fibrinogen, smoking habit, and baseline evidence of IHD. CRP was associated with D-dimer (r=0.21, P<0.00001). On univariate analyses, both CRP and D-dimer were associated with incident IHD. The incidence of IHD increased with CRP independently of the level of D-dimer (P=0.0002) and also increased with D-dimer independently of the level of CRP (P=0.048). In multivariate analyses, inclusion of D-dimer and conventional risk factors reduced the strength of the association between CRP and incident IHD; likewise, inclusion of CRP and conventional risk factors reduced the strength of the association between D-dimer and incident IHD. We conclude that although these respective markers of inflammation and fibrin turnover show modest association with each other in middle-aged men, they may have additive associations with risk of incident IHD. Further larger studies are required to test this hypothesis.

Acute-Phase Proteins↗

Do total and high density lipoprotein cholesterol and triglycerides act independently in the prediction of ischemic heart disease? Ten-year follow-up of Caerphilly and Speedwell Cohorts.

Several studies have suggested that men with raised plasma triglycerides (TGs) in combination with adverse levels of other lipids may be at special risk of subsequent ischemic heart disease (IHD). We examined the independent and combined effects of plasma lipids at 10 years of follow-up. We measured fasting TGs, total cholesterol (TC), and high density lipoprotein cholesterol (HDLC) in 4362 men (aged 45 to 63 years) from 2 study populations and reexamined them at intervals during a 10-year follow-up. Major IHD events (death from IHD, clinical myocardial infarction, or ECG-defined myocardial infarction) were recorded. Five hundred thirty-three major IHD events occurred. All 3 lipids were strongly and independently predictive of IHD after 10 years of follow-up. Subjects were then divided into 27 groups (ie, 3(3)) by the tertiles of TGs, TC, and HDLC. The number of events observed in each group was compared with that predicted by a logistic regression model, which included terms for the 3 lipids (without interactions) and potential confounding variables. The incidence of IHD was 22.6% in the group with the lipid risk factor combination with the highest expected risk (high TGs, high TC, and low HDLC) and 4.7% in the group with the lowest expected risk (P<0.01). A comparison of the predicted number of events in the 27 groups with the number of events observed showed that a logistic regression provided an adequate fit without the need to incorporate interactions between lipids in the model. Conclusions are as follows: (1) Serum TGs, TC, and HDLC are independently predictive of IHD at 10 years of follow-up. (2) Combinations of adverse levels of the 3 major lipid risk factors have no greater impact on IHD than that expected from their individual contributions in a logistic regression model. There was no evidence that men with low HDL/raised TGs were at significantly greater risk than that predicted from the independent effects of the 2 lipids considered individually.

Cholesterol, HDL↗

Fibrin D-dimer, markers of coagulation activation and the risk of major ischaemic heart disease in the caerphilly study.

We have previously reported that plasma fibrin D-dimer (a marker of turnover of cross-linked fibrin) showed a strong and independent association with incident ischaemic heart disease (IHD) in the Caerphilly Study cohort of 1,998 men aged 49-65. To establish the specificity of this finding, we assayed plasma samples from this cohort with a more specific assay for fibrin D-dimer: this showed an association with incident IHD which was at least as strong and independent as that for the original assay (odds ratio, OR for top fifth compared to bottom fifth 3.79; 95% CI 1.77-8.10; p < 0.0001). To establish potential causes of the increased fibrin turnover, we also assayed several potential markers of coagulation activation or thrombotic tendency (prothrombin fragment F1+2, thrombin-antithrombin complexes, factor VIIc, activated partial thromboplastin time [APTT] and activated protein C resistance): none of these variables were associated with incident IHD in this cohort. We suggest that further studies are required to establish the causes of increased cross-linked fibrin turnover, which is associated with incident IHD in the general population when measured by a specific assay.

Activated Protein C Resistance↗

Prevalence and awareness of excess weight in 13 and 14 year olds in Northern Ireland using recent international guidelines.

UNLABELLED: Concern has been expressed in recent years over the rising trends in overweight and obesity, particularly in children in developed countries. No recent data were available for Northern Ireland, therefore measurements of height and weight were included in a study in Northern Ireland originally designed as part of an international study to estimate the prevalence of symptoms of asthma and atopy in childhood. Twenty-six schools across the province were sampled. 2484 children aged mainly 13 and 14 y completed questionnaires, and 2307 were weighed and measured. Using recently proposed international guidelines on defining overweight and obesity in children the prevalence of overweight in boys was 16%, with 4% being obese. In girls 16% were also overweight and 2% were obese. This concurs with figures for English and Scottish schoolchildren up to 12 y of age from 1994. Less than one-sixth of obese boys but more than one-third of obese girls were on weight-reducing diets (the majority self-prescribed), reflecting differing attitudes towards excess weight. CONCLUSION: In line with figures in younger children from England and Scotland this study shows that 16% of boys and girls from Northern Ireland are classed as overweight using recent international guidelines. Only 15% of obese boys compared with 38% of obese girls stated that they were on weight-reducing diets.

Adolescent↗

Apolipoproteins A-I, A-II and B, lipoprotein(a) and the risk of ischaemic heart disease: the Caerphilly study.

Apolipoproteins B, A-I and Lp(a) have been proposed as independent predictors of subsequent ischaemic heart disease (IHD) improving on the prediction obtained by routine lipid measurements. In this report we have investigated the relative predictive ability of apolipoproteins and plasma lipids in a prospective study of middle aged men. 2398 men aged 49-65 years from the general population of Caerphilly, South Wales, UK were screened for evidence of IHD. After an overnight fast 2225 men each provided a venous blood sample on which plasma lipids, apolipoproteins B, A-I, A-II, and lipoprotein (a) (Lp(a)) were measured. Over a follow-up period of nearly 9 years, 282 (12%) men developed major IHD. Multiple logistic regression analysis showed that after adjusting for standard cardiovascular risk factors other than lipids there was a strong trend (standardised relative odds (SRO) = 1.20; P = 0.009) for incidence of IHD to increase with apolipoprotein B. However, on further adjusting for total cholesterol this trend largely disappeared (SRO = 1.05; P = 0.57). Similarly, a trend for incidence of IHD to increase with decreasing apolipoprotein A-I (SRO = 1.18; P = 0.02) disappeared when HDL cholesterol was added to the model. Levels of apolipoprotein A-II were not related to risk of subsequent IHD. Incidence of IHD was effectively constant over nearly 90% of the range of Lp(a). Only among the 5% of men with Lp(a) greater than 70 mg dL-1 was the risk of IHD significantly (P = 0.04) greater than among men with Lp(a) less than 10 mg dL-1. Apolipoproteins B and A-I do not improve on the prediction of risk of IHD provided by total and HDL cholesterol, respectively. Apolipoprotein A-II was not related to risk of IHD. Lp(a) may be independently associated with incident IHD among the 5-10% of men with the highest levels.

Apolipoprotein A-I↗

Comparison of weight in middle age, weight at 18 years, and weight change between, in predicting subsequent 14 year mortality and coronary events: Caerphilly Prospective Study.

OBJECTIVE: The prevalence of obesity is increasing in many European countries and in the United States. This report examines the mortality and morbidity associated with being overweight and obese in the Caerphilly Prospective Study and the relative effects of weight in middle age and self reported weight at 18 years. DESIGN: All men aged 45 to 59 years from the town of Caerphilly, South Wales and outlying villages were identified and 2512 men were examined for the first time between 1979 and 1983. Men were asked to recall their weight at 18 years of age (when the majority had been examined for National Service) so that weight then, weight at screening, and the difference could be related to their 14 year follow up from screening. A total of 2335 men could recall their weight at 18 years. By 14 years of follow up from screening 465 men had died and 382 had had coronary events. RESULTS: Mean body mass index in men who reported their weight at 18 years was 22.3 (SD 2.8) kg/m(2) and only 41 of these men (1.8%) were classified as obese (index >/= 30 kg/m(2)). The index did not predict all cause mortality when examined by quintile. For major ischaemic heart disease (non-fatal or fatal ischaemic heart disease) the relative odds was 1.73 (95% CI 1.21, 2.48) in the top fifth of the distribution (body mass index >/= 24.2 kg/m(2)) compared with the bottom fifth (body mass index <20.1 kg/m(2)). In men with an index >/= 30 kg/m(2) however, the relative odds were 2.03 (95% CI, 1.03, 4.01) for all cause mortality and 2.17 (95% CI, 1.08, 4.34) for major ischaemic heart disease, adjusted for age, smoking habit and social class. When men were recruited to the study, from 1979 to 1983; the mean body mass index had increased to 26.2 (SD 3.6), a mean increase of 3.9 kg/m(2) or 11. 2 kg; 299 men (12.1%) were classified as obese and showed significantly increased relative odds of both all cause mortality (1. 53 (95% CI 1.14, 2.06) and major ischaemic heart disease (1.55 (95% CI 1.13, 2.11)), adjusted for age, smoking habit and social class relative to the non-obese men. The effect of gain in weight from 18 years to recruitment was also examined; all cause mortality showed highest mortality in the fifth of the distribution who experienced weight loss or minimal weight gain. For major ischaemic heart disease an inconsistent, weak trend was shown, the relative odds rising to a maximum of 1.26 (0.89, 1.80) in the top fifth of weight gain compared with the bottom fifth. Weight gain showed strong associations with potential cardiovascular risk factors measured at recruitment; insulin, triglyceride, glucose, diastolic and systolic blood pressure and high density lipoprotein-cholesterol. CONCLUSIONS: Body mass at 18 years of age of 30 kg/m(2) or more conferred increased risk for all cause mortality and major ischaemic heart disease during 14 years of follow up of men aged 45 to 59 years. By the baseline examination the prevalence of obesity (body mass index >/=30) had increased from 1.8% to 12.1%; obese men also showed an excess risk of major ischaemic heart disease and overall mortality, but these risks were lower than those predicted from 18 years of age. Weight gain was strongly associated with smoking habit, the greatest weight gain being among ex-smokers and the least among light smokers. Weight gain from 18 years of age to baseline examination showed little relation with subsequent mortality and risk of major ischaemic heart disease when adjusted for age, smoking habit and social class. The lowest mortality rate occurred in the "fifth" of men who gained a mean weight of 16.1 kg. Weight gain is closely associated with some adverse cardiovascular risk factors; in particular with insulin, triglyceride, glucose and diastolic blood pressure.

Adolescent↗

Lifestyle and hemostatic risk factors for ischemic heart disease : the Caerphilly Study.

We have recently shown that fibrin D-dimer, tissue plasminogen activator (tPA) antigen, von Willebrand factor antigen, fibrinogen, plasma viscosity, and white cell count are associated with subsequent ischemic heart disease (IHD) in men aged 49 to 65 years in the Caerphilly Study from South Wales. We now report the contribution of major lifestyle factors to plasma levels of these new risk predictors for IHD. Results were available for up to 2188 men. The contribution of factors associated with lifestyle (smoking, alcohol, body mass index, leisure and work activity, social class, and use of prescribed medicines) to variation in plasma levels of 8 hemostatic variables was examined. All results were adjusted for other lifestyle variables, age, and time of day. Most hemostatic variables increased with age and smoking habit. Increasing levels of alcohol consumption were associated with increases in tPA and plasminogen activator inhibitor (PAI-1) activity and with decreases in fibrinogen and white cell count. tPA, PAI-1, fibrinogen (nephelometric), and viscosity were positively associated with body mass index. Increasing levels of leisure activity were inversely associated with D-dimer, von Willebrand factor, nephelometric fibrinogen, and viscosity. Use of prescribed medicines (a marker for chronic illness) was associated with adverse levels of D-dimer, fibrinogen, plasma viscosity, and white cell count. tPA, PAI-1, and plasma viscosity were associated with blood pressure, cholesterol, and triglycerides but not with lipoprotein(a) or homocysteine. We conclude that several lifestyle factors are associated with hemostatic risk predictors for IHD. Lifestyle modifications may reduce IHD risk partly by altering hemostatic function; large intervention studies are required to test this hypothesis.

Aged↗

Chlamydia pneumoniae serology, lung function decline, and treatment for respiratory disease.

Associations have been reported between Chlamydia pneumoniae seropositivity and both acute and chronic obstructive airway diseases. Plasma specimens collected between 1979 and 1983 from 1, 773 men 45 to 59 yr of age in Caerphilly, South Wales, were tested for IgG and IgA antibodies to C. pneumoniae (TW183) by microimmunofluorescence. Subsequent mortality and medication for obstructive airway disease were ascertained at 5-yr follow-up examinations. Spirometry was performed at the first and second examinations and analyzed both cross-sectionally and longitudinally; 642 men (36%) had IgG antibodies at a titer of 1:16 or above, of whom 362 also had detectable IgA antibodies. No statistically significant associations were found between either IgG titer or IgA titer and any of the outcome measures: inhaler therapy at entry; commencement of inhalers during follow-up; death from respiratory causes; baseline FEV(1), FVC, and FEV(1)/FVC ratio; and decline in FEV(1) (p > 0.1 throughout). Men with high IgG titers (>/= 1:64) had a slower rate of decline of FEV(1) than did seronegative subjects (adjusted mean difference in 5-yr change in FEV(1): +22 ml, 95% confidence interval: -31 ml to +76 ml). Men with high IgA titers (>/= 1:16) had a slightly faster rate of decline (-12 ml, - 96 ml to +71 ml). This first prospective assessment suggests that chronic C. pneumoniae infection is not a major risk factor for progressive airflow obstruction.

Antibodies, Bacterial↗

Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations.

Elevation in plasma homocysteine concentration has been associated with vascular disease and neural tube defects. Methionine synthase is a vitamin B(12)-dependent enzyme that catalyses the remethylation of homocysteine to methionine. Therefore, defects in this enzyme may result in elevated homocysteine levels. One relatively common polymorphism in the methionine synthase gene (D919G) is an A to G transition at bp 2,756, which converts an aspartic acid residue believed to be part of a helix involved in co-factor binding to a glycine. We have investigated the effect of this polymorphism on plasma homocysteine levels in a working male population (n = 607) in which we previously described the relationship of the C677T "thermolabile" methylenetetrahydrofolate reductase (MTHFR) polymorphism with homocysteine levels. We found that the methionine synthase D919G polymorphism is significantly (P = 0.03) associated with homocysteine concentration, and the DD genotype contributes to a moderate increase in homocysteine levels across the homocysteine distribution (OR = 1.58, DD genotype in the upper half of the homocysteine distribution, P = 0.006). Unlike thermolabile MTHFR, the homocysteine-elevating effects of the methionine synthase polymorphism are independent of folate and B(12) levels; however, the DD genotype has a larger homocysteine-elevating effect in individuals with low B(6) levels. This polymorphism may, therefore, make a moderate, but significant, contribution to clinical conditions that are associated with elevated homocysteine.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Homocysteine and B-group vitamins in renal transplant patients.

Increased plasma homocysteine is an independent risk factor for cardiovascular disease. We have investigated homocysteine and B-group vitamin levels in renal transplant patients. Fasting blood was collected from 55 renal transplant recipients with good renal function and 32 age/sex matched control subjects. Total homocysteine was increased in transplant recipients in comparison to controls (10.9+/-1.5 vs. 6.7+/-1.3 micromol/l, P < 0.001). There was no difference in homocysteine between patients receiving cyclosporin (n = 39, homocysteine 11.0+/-1.5 micromol/l) and patients receiving prednisolone + azathioprine (n = 16, 10.8+/-1.6 micromol/l, mean+/-S.D.), although there was a significant correlation between homocysteine and serum cyclosporin concentration in the sub-group of patients receiving that immunosuppressive regimen (r = 0.42, P < 0.05). Levels of B-group vitamins were similar in patients and controls. Plasma homocysteine is increased in renal transplant recipients even in the presence of minor degrees of renal impairment and normal levels of B-group vitamins.

Adolescent↗

Antioxidants, but not B-group vitamins increase the resistance of low-density lipoprotein to oxidation: a randomized, factorial design, placebo-controlled trial.

We have conducted an intervention trial to assess the effects of antioxidants and B-group vitamins on the susceptibility of low-density lipoprotein (LDL) to oxidation. A total of 509 men aged 30-49 from a local workforce were screened for total plasma homocysteine. The 132 selected (homocysteine concentration > or = 8.34 mumol/l) men were randomly assigned, using a factorial design, to one of four groups receiving supplementation with B group vitamins alone (1 mg folic acid, 7.2 mg pyridoxine, 0.02 mg cyanocobalamin), antioxidant vitamins (150 mg ascorbic acid, 67 mg alpha-tocopherol, 9 mg beta-carotene), B vitamins with antioxidant vitamins, or placebo. Intervention was double-blind. A total of 101 men completed the 8-week study. The lag time of LDL isolated ex vivo to oxidation (induced by 2 mumol/l cupric chloride) was increased in the two groups receiving antioxidants whether with (6.88 +/- 1.65 min) or without (8.51 +/- 1.77 min) B-vitamins, compared with placebo (-2.03 +/- 1.50) or B-vitamins alone (-3.34 +/- 1.08) (Mean +/- S.E., P < 0.001). Antibodies to malondialdehyde (MDA) modified LDL were also measured, but there were no significant changes in titers of these antibodies in any group of subjects whether receiving antioxidants or not. Contrast analysis showed that there was no interaction between antioxidants and B-group vitamins. This study indicates that while B-group vitamins lower plasma homocysteine they do not have an antioxidant effect. Thus B-group vitamins and antioxidants appear to have separate, independent effects in reducing cardiovascular risk.

Adult↗

Fasting plasma glucose and subsequent macrovascular disease after 10 years follow-up: a collaborative study on two populations.

The American Diabetes Association recently proposed a new, lower, cut-point of 7.0 mmol/l for diagnosis of diabetes mellitus. We examined data from the Caerphilly and Speedwell cohorts to determine possible cut-points of fasting plasma glucose for increased risk of subsequent ischaemic heart disease (IHD). Men (n = 4860) from the general population of a town in South Wales and a practice-based population in Bristol aged 45-63 years were first examined in 1979-83, and re-examined at intervals, and these data relate to follow-up at about 10 years (120 months, Caerphilly) (112 months, Speedwell). Clinically recognized diabetics (n = 94) experienced a higher mortality rate and an excess number of major IHD events. Among non-diabetics, mean blood glucose was 5.0 mmol/l and a significant excess of major IHD events occurred above this point even when the data were fully adjusted for all other IHD risk factors. Risk of major IHD was greatest for non-diabetic men with plasma glucose levels between 7.0 and 7.7 mmol/l. Under 7.0 mmol/l, the excess event rate was modest, however. Glucose levels were not associated with excess all-cause mortality among these non-diabetic men. These data, based on the excess risk of macrovascular disease experienced by a British cohort of non-diabetic men, accord with the proposals to base the diagnosis of diabetes on a cut point of 7.0 rather than 7.8 mmol/l.

Blood Glucose↗

Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study.

The relationships of three measurements of the factor VIII/von Willebrand factor (VWF) complex (factor VIII activity, FVIIIc (one-stage assay); VWF antigen, VWF Ag (ELISA); and VWF activity, VWF act, measured by a recently-developed ELISA) to major ischaemic heart disease (IHD) events were studied in 1997 men aged 49-65 years, in the second phase of the Caerphilly Heart Study. These variables were related using logistic regression analysis to myocardial infarction or IHD death, which occurred in 129 men during an average follow-up period of 61 months. All three measurements were highly correlated (r = 0.63-0.77), and each was significantly associated with incident major IHD on univariate analyses (relative odds in highest fifth compared to lowest fifth, 1.68-1.90; P = 0.028-0.006) and on multivariate analyses adjusting for major IHD risk factors and for baseline IHD. Neither FVIIIc nor VWF act was significantly related to incident IHD following adjustment for VWF Ag. We therefore suggest that the associations between these three measurements of the factor VIII/VWF complex and incident IHD might have at least three explanations: VWF Ag is a marker of arterial endothelial disturbance; VWF act promotes platelet adhesion/aggregation and hence the platelet component of arterial thrombosis; and FVIIIc promotes fibrin formation and hence the fibrin component of arterial thrombosis.

Enzyme-Linked Immunosorbent Assay↗

Relation of Helicobacter pylori infection to 13-year mortality and incident ischemic heart disease in the caerphilly prospective heart disease study.

BACKGROUND: Associations have been suggested between Helicobacter pylori seropositivity, cardiovascular risk factors, and ischemic heart disease (IHD). The effect of this common infection on mortality is uncertain. METHODS AND RESULTS: Plasma specimens collected during 1979 to 1983 from 1796 men in Caerphilly, South Wales, were analyzed for IgG antibodies to H pylori. Cause of death and occurrence of incident IHD events were ascertained over an average of 13.7 years from death certificates, hospital records, and ECG changes at 5-yearly follow-up examinations. Seventy percent of men were seropositive. The prevalence of IHD at entry was similar in men with and without H pylori antibodies (odds ratio [OR], 1.10; 95% CI, 0.87 to 1.40). Seropositivity was significantly (P<0.05) associated with poorer socioeconomic status currently and in childhood, shorter stature, and poorer ventilatory function at entry but not with age, smoking, body mass index, blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, fibrinogen, plasma viscosity, or heat shock protein antibodies. Thirteen-year incidence of IHD was not significantly associated with H pylori (OR, 1.05; 95% CI, 0.80 to 1.39), but there was a stronger relationship with all-cause mortality (OR, 1.46; 95% CI, 1.12 to 1.92) and fatal IHD (OR, 1.54; 95% CI, 1.03 to 2.30). After adjustment for cardiovascular risk factors and both adult and childhood socioeconomic status, ORs were slightly reduced and lost statistical significance (OR=1.32 [95% CI, 0.99 to 1.78] for all-cause mortality and OR=1.52 [95% CI, 0.99 to 2.34] for fatal IHD). CONCLUSIONS: H pylori infection is unlikely to be as strong a risk factor for IHD as some previous studies have suggested, but its relationship to mortality, including fatal IHD, deserves further investigation. The mechanism underlying these associations is unlikely to involve hypertension, circulating lipid profile, fibrinogen, or cross-reacting antibodies to bacterial heat shock proteins.

Helicobacter Infections↗