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European Heart Journal 2002 23(20):1580-1586; doi:10.1053/euhj.2002.3172
Copyright © 2002 by the European Society of Cardiology.
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Smoking and plasma homocysteine

P. O'Callaghan, R. Meleady, T. Fitzgerald and I. Grahamf2 European COMAC groupf1

The Adelaide and Meath Hospital Dublin, incorporating the National Childrens Hospital and Trinity College, Dublin, Ireland

revised January 21, 2002; accepted January 23, 2002

Abstract

Background Smoking is known to be associated with an increased plasma homocysteine level. Both are associated with an increased risk of cardiovascular disease. B-vitamins modulate plasma homocysteine levels.

Aims To investigate the relationships between smoking, plasma homocysteine, nutrient levels and risk of cardiovascular disease.

Methods The European Concerted Action Project case control study of 750 cases and 800 age- and sex-matched controls aged less than 60 years from 19 centres in 10 European countries.

Results Smokers were at increased risk of vascular disease. This risk was greatly increased in the presence of a raised plasma homocysteine; cigarette smokers with a plasma homocysteine above 12µmol.l–1 had a 12-fold increased risk of cardiovascular disease (OR 12·4 95% CI 7·3 to 21·2) compared with non-smokers with a normal plasma homocysteine. In both cases and controls the current smokers had a higher plasma homocysteine level than the never smokers (11·7µmol.l–1 vs 10·07µmol.l–1, P<0·05 cases; 9·90µmol.l–1 vs 9·53µmol.l–1P value non significant controls). Current smokers tended to have lower levels of folate, and vitamin B6 and vitamin B12 than never smokers. The risk of cardiovascular disease associated with smoking was not significantly altered by adjustment for levels of B-vitamins using a conditional regression model (OR for current smoker >20.day–1 8·19, after adjustment for B6, B12, folate OR 7·09).

Conclusions This case control study suggests that smokers with high plasma homocysteine are at greatly increased risk of cardiovascular disease and should therefore be offered intensive advice to help them cease smoking. They also have reduced levels of those B-vitamins (folate, vitamin B6 and vitamin B12) that modulate homocysteine metabolism. While this finding may reflect a direct effect of smoking or reduced B-vitamin intake, supplementation of these nutrients may be appropriate in smokers with high homocysteine levels.

Key Words: Homocysteine, smoking, vitamins, cardiovascular disease

f2 Correspondence: Professor Ian Graham, Cardiology Department, The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland.

f1 Members of The European Concerted Action Project: ‘Homocysteine and vascular disease: from natural history to therapy’. Project members are listed in the Appendix.

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