Homocysteine and ischaemic heart disease in the Caerphilly cohort
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.
References (36)
- et al.
Homocysteinemia—association of a metabolic disorder with vascular disease and Thrombosis
Thromb Res
(1993) - et al.
Hyperhomocysteinemia in patients operated for lower extremity ischaemia below the age of 50—effect of smoking and extent of disease
Eur J Vasc Surg
(1993) - et al.
Oxidation of low density lipoprotein by thiols-superoxide-dependent and superoxide-independent mechanism
J Lip Res
(1993) - et al.
Determination of free and total homocysteine in human plasma by HPLC with fluorescence detection
J Chromatogr
(1987) - et al.
Rapid high-performance liquid chromatographic assay for total homocysteine levels in human serum
J Chromatogr
(1991) - et al.
Human arterial endothelial cell detachment in vitro: its promotion by homocysteine and cysteine
Atherosclerosis
(1991) - et al.
Vitamin B-12, vitamin B-6 and folate nutritional status in men with hyperhomocysteinemia
Am J Clin Nutr
(1993) - et al.
Vitamin requirements for the treatment of hyperhomocysteinemia in humans
J Nutr
(1994) - et al.
Disorders of transsulfuration
- et al.
The prevalence of homocysteinemia and hypercholesterolemia in angiographically defined coronary heart disease
Klin Wochenschr
(1991)
Hyperhomocysteinemia: an independent risk factor for vascular disease
N Engl J Med
Plasma homocysteine assay in the exploration of thrombosis in young subjects
Presse Med (Paris)
A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians
J Am Med Assoc
Elevated plasma homocyst(e)ine concentration as a possible independent risk factor for stroke
Stroke
Effects of age, lipoproteins, and hemostatic parameters on the role of homocyst(e)inemia as a cardiovascular risk factor in men
Arterioscler Thromb
Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology
Arterioscler Thromb
Homocysteine, a risk factor for premature vascular disease and thrombosis, induces tissue factor activity in endothelial cells
Arterioscler Thromb
A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes
J Am Med Assoc
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