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(Circulation. 2001;103:2544.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Plasma Total Cysteine as a Risk Factor for Vascular Disease

The European Concerted Action Project

Lina El-Khairy, MPhil; Per M. Ueland, MD; Helga Refsum, MD; Ian M. Graham, FRCPI; Stein E. Vollset, MD, DrPH

From LOCUS for Homocysteine and Related Vitamins (L.E., P.M.U., H.R, S.E.V.), University of Bergen, Bergen, Norway; and the Department of Cardiology (I.M.G.), Adelaide-Meath Hospital, Incorporating the National Children’s Hospital, Tallaght, Dublin, Ireland.

Correspondence to Lina El-Khairy, Section for Medical Statistics, Department of Public Health and Primary Health Care, University of Bergen, Armauer Hansens Hus, N-5021 Bergen, Norway. E-mail lina.el-khairy{at}smis.uib.no

Background—Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease. Although cysteine is structurally similar and metabolically linked to tHcy, its relation to the risk of cardiovascular disease has received little attention. We studied the relation between plasma total cysteine (tCys) levels and the risk of vascular disease in the coronary, cerebral, and peripheral vessels.

Methods and Results—This case-control study included 750 patients with vascular disease and 800 age- and sex-matched control subjects recruited from 19 centers in 9 European countries. Conventional risk factors for cardiovascular disease were recorded. In addition, plasma levels of tCys, tHcy, folate, B₆, B₁₂, and creatinine were measured. Overall, a U-shaped relationship was observed between tCys and risk of vascular disease. With the middle range of 250 to 275 µmol/L tCys used as the reference category, the adjusted risk of vascular disease at low (225 µmol/L) tCys levels was 2.1 (95% CI 1.2 to 3.6), and the risk at high (>300 µmol/L) tCys levels was 1.6 (95% CI 1.1 to 2.3). Different shapes of the dose-response relationship were seen for the 3 vascular disease categories. The relation with peripheral vascular and cerebrovascular disease was U-shaped, whereas a weak positive relation was observed with coronary heart disease.

Conclusions—Our data show a significant U-shaped relationship between tCys and cardiovascular disease after adjustment for tHcy, creatinine, and other cardiovascular disease risk factors.

Key Words: cardiovascular diseases • amino acids • risk factors

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