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Lancet. 1995 Nov 25;346(8987):1395-8.

Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men.

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Department of Public Health, Royal Free Hospital School of Medicine, London, UK.


Moderate hyperhomocysteinaemia is common in the general population and has been linked with cardiovascular disease. However, there are no data from prospective, population-based studies. We examined the association between serum total homocysteine (tHcy) concentration and stroke in a nested case-control study within the British Regional Heart Study cohort. Between 1978 and 1980 serum was saved from 5661 men, aged 40-59 years, randomly selected from the population of one general practice in each of 18 towns in the UK. During follow-up to December, 1991, there were 141 incident cases of stroke among men with no history of stroke at screening. Serum tHcy was measured in 107 cases and 118 control men (matched for age-group and town, without a history of stroke at screening, who did not develop a stroke or myocardial infarction during follow-up). tHcy concentrations were significantly higher in cases than controls (geometric mean 13.7 [95% CI 12.7-14.8] vs 11.9 [11.3-12.6] mumol/L; p = 0.004). There was a graded increase in the relative risk of stroke in the second, third, and fourth quarters of the tHcy distribution (odds ratios 1.3, 1.9, 2.8; trend p = 0.005) relative to the first. Adjustment for age-group, town, social class, body-mass index, hypertensive status, cigarette smoking, forced expiratory volume, packed-cell volume, alcohol intake, diabetes, high-density-lipoprotein cholesterol, and serum creatinine did not attenuate the association. These findings suggest that tHcy is a strong and independent risk factor for stroke.

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