D. Bainton

Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies.

BackgroundRecent studies have suggested that hemostatic factors and white blood cell count are predictive of ischemic heart disease (IHD). The relations of fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. Methods and ResultsThe two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count. Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count. Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both. Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors. Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index. Conclusion. Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD. (Circulation 1991;83:836–844)

Plasma triglyceride and high density lipoprotein cholesterol as predictors of ischaemic heart disease in British men: The Caerphilly and Speedwell Collaborative Heart Disease Studies

Objective—To assess the roles of plasma triglyceride and high density lipoprotein (HDL) cholesterol concentrations in predicting ischaemic heart disease. Design—Two prospective cohort studies with common core protocols. Setting and participants—Both cohorts are 100% samples of middle aged men. In Caerphilly the 2512 men were living within a defined area. In Speedwell the 2348 men were registered with local general practitioners. Main outcome measures—Fasting blood samples were taken at initial examination and plasma lipid concentrations were measured. Major ischaemic heart disease events were assessed from hospital notes, death certificates, and electrocardiograms. Results—At first follow up, after an average of 5·1 years in Caerphilly and 3·2 years in Speedwell, 251 major ischaemic heart disease events had occurred. Men with triglyceride concentrations in the top 20% of the distribution had a relative odds value for ischaemic heart disease of 2·3 (95% confidence interval (95% CI) 1·3 to 4·1) compared with men in the bottom 20%, after adjusting for both plasma total and HDL cholesterol, and non-lipid risk factors. Men in the lowest 20% of the distribution of HDL cholesterol concentration had a relative odds value of 1·7 (95% CI 1·0 to 2·8) compared with the top 20%, after adjustment was made for total cholesterol and triglyceride concentrations, and non-lipid risk factors. These relations were not caused by β blockers, which were being taken by 5% of the men. Conclusions—Plasma triglyceride concentration predicts major ischaemic events after allowance is made for total and HDL cholesterol concentrations and other risk factors. In these populations, triglyceride is a more important predictor than total cholesterol concentration.

C-Reactive Protein, Fibrin D-Dimer, and Incident Ischemic Heart Disease in the Speedwell Study Are Inflammation and Fibrin Turnover Linked in Pathogenesis?

Abstract— 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.

Peripheral vascular disease: consequence for survival and association with risk factors in the Speedwell prospective heart disease study.

OBJECTIVE--To measure the prevalence and incidence of intermittent claudication, to describe the mortality associated wtih the condition, and to assess the relevance of risk factors for vascular disease. DESIGN--A standard questionnaire on calf pain when walking was given in the prospective Speedwell study, and a range of risk factors were measured. The men were re-examined at intervals of three years, and deaths over 11 years were identified. SETTING--The general population. PARTICIPANTS--All men aged 45 to 59 registered with 16 general practitioners. RESULTS--The prevalence of intermittent claudication increased from almost nil at ages 45-49 to 2.9% at ages 60-64. The annual incidence increased from 0.3% in the youngest men to 0.5% in those in their early 60s. Intermittent claudication was related to the existence of ischaemic heart disease, particularly angina, at the first examination. The relative odds of men with angina developing intermittent claudication was 6.7 (95% confidence interval (95% CI) 3.6 to 12.4). The risk of death in men with intermittent claudication was substantially raised. After standardisation for age and smoking the relative odds of death was 3.8 (95% CI 2.2 to 6.5). The excess was entirely from circulatory causes. Systolic blood pressure, fasting plasma glucose, triglycerides, and white cell count were all independently associated with the development of intermittent claudication, but the most striking association was with smoking. CONCLUSIONS--Intermittent claudication is an indicator for a very high risk of death. This is only partly explained by its strong association with ischaemic heart disease.

Some long term effects of smoking on the haemostatic system: a report from the Caerphilly and Speedwell Collaborative Surveys

Data from two community studies on men from South Wales and the west of England suggest that the effects of smoking on the haemostatic system remain for many years after giving up. Long term correlations between several variables, including plasma fibrinogen and white cell count, and the length of time after giving up were seen in ex-smokers. Dose response relations were apparent in current smokers in terms of the white cell count and two haematological variables, the packed and mean cell volumes. These long term correlations probably reflect the toxicity of other agents in tobacco smoke besides nicotine and carbon monoxide, which act only in the short term. Identification of these agents may further our understanding of the mechanism by which cigarette smoking is associated with atherosclerotic disease.

Temperature and risk factors for ischaemic heart disease in the Caerphilly prospective study.

OBJECTIVE--To examine the associations between air temperature and risk factors for ischaemic heart disease. METHOD--Data on risk factors are available from up to 2036 men in the Caerphilly Prospective Heart Disease Study. Daily temperatures were obtained from the Meteorological Office. Relations between these were examined by regression. RESULTS--The coldest month of the year has a mean temperature that is 16 degrees C lower than that in the warmest month. A fall in temperature of this magnitude is associated with higher blood pressures (by 3-5 mm Hg) and a lower concentration of high density lipoprotein cholesterol (by 0.08 mmol/l). The most important effects however, seem to be on the haemostatic system. Fibrinogen is 0.34 g/l higher in the coldest month than in the warmest (p < 0.001) and alpha 2 macroglobulin, a protein that inhibits fibrinolysis, is also raised. Platelet count is increased by 30% of a standard deviation and the sensitivity of platelets in whole blood to adenosine diphosphate is increased by cold. CONCLUSIONS--These effects on haemostasis, together with the effect on blood pressure, could explain a large part of the increase in ischaemic heart disease in the winter but are unlikely to explain much of the difference in mortality within different areas of England and Wales.

C-Reactive Protein, Fibrin D-Dimer, and Risk of Ischemic Heart Disease The Caerphilly and Speedwell Studies

Background—There is increasing interest in the predictive value of C-reactive protein (CRP) and fibrin D-dimer in the prediction of ischemic heart disease (IHD). We assessed their joint and independent associations with IHD in a large combined analysis of 2 population cohorts. Methods and Results—Men aged 49 to 66 years from the general populations of Caerphilly and Speedwell were studied between 1982 and 1988 and re-examined for new IHD events at fixed intervals of ≈105 months (Caerphilly) and 75 months (Speedwell). 3213 men had CRP and D-dimer measured at baseline and 351 (11%) had a new IHD event. Mean levels of CRP and D-dimer were significantly higher among men in whom IHD developed. The relative odds of IHD in men in the top 20% of the distribution of CRP was 2.97 (95% CI, 2.04, 4.32) and for D-dimer was 2.40 (95% CI, 1.69, 3.40); CRP and D-dimer had additive effects on risk of IHD. Multivariate analysis reduced the size of the relative odds, which remained significant for D-dimer. Conclusions—Both inflammatory and thrombogenic markers are important (and potentially additive) predictors of coronary risk.

Is metabolic syndrome a discrete entity in the general population? Evidence from the Caerphilly and Speedwell population studies

Objective To examine the clinical and epidemiological utility of the concepts of metabolic syndrome and insulin resistance syndrome in two prospective cohort studies of white men. Methods Men aged 45–63 years were screened for evidence of ischaemic heart disease (IHD) between 1979 and 1982 and followed up at regular intervals thereafter. Non-fatal coronary events were validated from hospital records and fatal coronary events from death certificates. Results Analysis of serum insulin concentrations in non-diabetic individuals measured at entry to the study showed no independent contribution to the prediction of subsequent IHD at 10 year follow up. Blood glucose concentrations, however, showed a small independent contribution in the combined cohort in the upper fifth of the distribution. Three different models of metabolic syndrome among non-diabetic individuals were defined based on tertiles, medians, and clusters. The predictive value of each model was assessed using logistic regression before and after adjustment for conventional and metabolic risk factors. After adjustment the odds were non-significant and close to unity. Conclusions This study did not detect any complex relation among the five variables defining metabolic syndrome; the excess risk seems to be no greater than can be explained by individual effects of the defining variables in a multiple logistic model.

Prevalence of ischaemic heart disease: the Caerphilly and Speedwell surveys

Mortality from ischaemic heart disease remains high in the United Kingdom, and the present report describes the prevalence of the various epidemiological manifestations of the disease in two recent community studies with a common core protocol, each containing samples of over 2000 men, carried out in South Wales (Caerphilly) and the West of England (Speedwell, Bristol). The prevalence of electrocardiographic evidence of ischaemia was similar in the two communities--8.7% of men aged 45-49 years rising to 18.6% in men aged 55-59 years in the samples from South Wales, and 8.0% and 17.2% respectively in the Bristol population. The overall prevalence of angina was 7.7% in Caerphilly and 7.8% in Speedwell in men aged 45-59 years, but symptoms of severe chest pain were more commonly reported in South Wales than in Speedwell (10.1% compared with 6.3%). The data, however, suggested that the overall prevalence of ischaemic heart disease was very similar in the two areas. The prevalence of ischaemic heart disease was compared with that found in other population studies carried out in the United Kingdom and was higher than that found when employed men only were studied. There were substantial differences in mortality between the two areas; possible reasons for this are differences in community or medical services, smoking habit, or unemployment rates.

A comparison of two preparation regimens for oral cholecystography

The increase in uric acid excretion produced by contrast agents used in cholecystography may be responsible for the acute renal failure that may rarely complicate this procedure. Encouragement of fluids as part of the preparation would be expected to reduce this risk. It is possible that this might affect the usefulness of the cholecystogram as a diagnostic procedure — although there is no evidence to suggest this. This report concerns a trial in which two regimens for oral cholecystography were compared — one in which fluid was prohibited and the other in which fluid (as two pints of water) was encouraged. The allocation to either preparation regimen was random. There was little difference in terms of quality of radiographs or detection of pathology between the two groups.