Plasma total cysteine as a risk factor for vascular disease - The EuropeanConcerted Action project

Background-Elevated plasma total homocysteine (tHcy) is a risk factor for c ardiovascular disease. Although cysteine is structurally similar and metabo lically 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, c erebral, and peripheral vessels. Methods and Results-This case-control study included 750 patients with vasc ular disease and 800 age- and sex-matched control subjects recruited from 1 9 centers in 9 European countries. Conventional risk factors for cardiovasc ular disease were recorded. In addition, plasma levels of tCys, tHcy, folat e, B-6, B-12, and creatinine were measured. Overall, a U-shaped relationshi p was observed between tCys and risk of vascular disease. With the middle r ange of 250 to 275 mu mol/L tCys used as the reference category, the adjust ed risk of vascular disease at low (less than or equal to 225 mu mol/L) tCy s levels was 2.1 (95% CI 1.2 to 3.6), and the risk at high (>300 mu mol/L) tCys levels was 1.6 (95% CI 1.1 to 2.3). Different shapes of the dose-respo nse relationship were seen for the 3 vascular disease categories. The relat ion with peripheral vascular and cerebrovascular disease was U-shaped, wher eas 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.