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, B 6 , B 12 , 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 mol/L tCys used as the reference category, the adjusted risk of vascular disease at low (Յ225 mol/L) tCys levels was 2.1 (95% CI 1.2 to 3.6), and the risk at high (Ͼ300 mol/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.

Plasma tCys is strongly related to several factors that constitute the cardiovascular disease risk profile. This should be an incentive to determine the role of tCys in cardiovascular disease.

High tCys concentrations were associated with risks of preeclampsia, premature delivery, and low birth weight.

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