Elsevier

Atherosclerosis

Volume 140, Issue 2, October 1998, Pages 349-356
Atherosclerosis

Homocysteine and ischaemic heart disease in the Caerphilly cohort

https://doi.org/10.1016/S0021-9150(98)00139-7Get rights and content

Abstract

Elevated circulating total homocyst(e)ine concentrations are associated with a higher prevalence of ischaemic heart disease (IHD). We utilized data from the Caerphilly Prospective Cohort Study to assess the predictive power of the serum total homocyst(e)ine concentration for future IHD. Serum total homocyst(e)ine concentrations were measured in 2290 men in the Caerphilly cohort, a representative population sample of men aged 50–64 years. During a 5-year follow-up period, 56 men suffered fatal IHD, 77 had a non-fatal myocardial infarction, while 21 were found to have ECG evidence of myocardial infarction (MI) when examined at follow-up. The mean serum total homocyst(e)ine concentration in the total of 154 men who experienced an incident IHD event was 12.4 μmol/l, whereas the 2136 men who experienced no such event had a mean level of 11.7 μmol/l. The difference between these means, examined by logistic regression and standardising for the effects of differences in age, social class, smoking, BMI, diabetes, HDL-cholesterol and prevalent IHD is 0.47 μmol/l (95% CI=−0.13 to 1.11 μmol/l). The mean difference for the 56 men who died, and whose death was attributed to IHD, is 0.81 μmol/l (95% CI=−0.17 to 1.88 μmol/l) after correction for confounding factors. Vitamin nutritional status and alcohol intake were significant negative determinants of serum total homocyst(e)ine concentrations; the effect of alcohol is explained by the folic acid content of beer, which is the preferred alcoholic beverage in Caerphilly. It is concluded that the serum total homocyst(e)ine concentration is weakly predictive of IHD events, though in the present data adjustments for other factors attenuated the relationship and it became not statistically significant (P>0.05).

Introduction

In the rare inherited disorder homocyst(e)inuria there is impaired clearance of circulating homocyst(e)ine1 leading to grossly elevated serum and urine levels of homocyst(e)ine [1]and such patients show markedly accelerated atherosclerosis and thrombosis [2]. Although the evidence is not entirely consistent, lesser degrees of homocyst(e)ine accumulation in the circulation appear to carry an increased risk of death and clinical events consequent upon coronary 3, 4, 5, 6, cerebral [7]and peripheral [8]atherosclerosis. Furthermore, positive correlations between the circulating total homocyst(e)ine (tHcy) level and the degree of atherosclerosis judged from coronary angiography have been described 3, 9, and mild hyperhomocyst(e)inemia is not infrequently seen in patients with premature vascular disease 10, 11. A meta-analysis of 27 studies has been reported and this has summarised the overall risk in terms of an increase in the odds ratio for coronary heart disease of 1.6 for every 5 μmol/l increase in circulating tHcy concentrations in men [12].

A number of mechanisms have been suggested by which elevated tHcy concentrations may relate to cardiovascular disease. These include damage to endothelium cells [13], enhancement of thrombosis 5, 11and stimulation of lipid peroxidation 14, 15.

The Caerphilly Prospective Study of cardiac and cerebral ischaemia gives opportunity to further examine the relevance of serum tHcy levels to incident cardiovascular disease in a representative male population sample in the UK. In this report we present data on the predictive power of the serum tHcy concentration for ischaemic heart disease (IHD) during 5 years following the serum tHcy estimations, while evidence on dietary and other ‘determinants’ of serum tHcy concentrations is also presented.

Section snippets

The population sample

The Caerphilly cohort consists of a total sample of men within the defined area of the town of Caerphilly in South Wales and several surrounding villages. A total of 2818 men were identified, and 2512 (89%) co-operated in a population survey in 1979–1983. Five years later, in 1984–88 a further private census was conducted and all the men in the original cohort who were still resident in the area, together with men aged 50–64 years who had moved into the area, were seen again. The present study

Results

Serum tHcy concentrations were available for 2290 men. Serum tHcy concentrations of the 90 men who reported that they were non-fasting did not differ significantly from serum tHcy concentrations of the fasting men. This is in agreement with observations tHcy concentrations showed only small variations after breakfast [22]and the non-fasting subjects were therefore retained in the statistical analyses reported below. The frequency distribution for serum tHcy concentrations is skewed to the

Discussion

The data presented here come from a large representative population cohort of older men within which estimations of tHcy were made on almost every member of the cohort. Although the association between serum tHcy concentration and the risk of an incident IHD event is significant, this relation is weakened when the data is standardised for the usual confounding factors including age, social class, body mass index, smoking and prevalent IHD (Table 2). In addition, our data revealed significant

Acknowledgements

The skilful technical assistance of L. Goddard and A. Schnell is gratefully acknowledged. Janet Pickering, statistician, is supported by the Mental Health Foundation.

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