Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus

Abstract

Background: High plasma homocysteine level has been associated with increased risk for coronary heart disease (CHD) events in nondiabetic individuals, especially in those with previously diagnosed CHD. In persons with type 2 diabetes mellitus, the association between homocysteine level and cardiovascular disease may be stronger than that in nondiabetic individuals, but no large prospective studies have examined the relationship between homocysteine level and CHD mortality in persons with type 2 diabetes.

Objective: To investigate whether moderately elevated plasma homocysteine levels are independently related to increased incidence of fatal and nonfatal CHD events in persons with type 2 diabetes.

Design: Prospective study.

Setting: Finnish sample of patients with type 2 diabetes.

Patients: 462 men and 368 women who were 45 to 64 years of age at baseline.

Measurements: Coronary heart disease mortality and incidence of nonfatal myocardial infarction during the 7-year follow-up.

Results: Participants with plasma homocysteine levels of 15 micromol/L or more at baseline had a higher risk for CHD death than those with plasma homocysteine levels less than 15 micromol/L (26.1% and 13.5%, respectively; P = 0.005). The risks for all CHD events were 36.2% and 22.6%, respectively (P = 0.011). In Cox regression analyses, elevated plasma homocysteine level was significantly associated with CHD mortality (P < 0.001) and all CHD events (P = 0.002) even after adjustment for confounding variables, including creatinine clearance. In participants without myocardial infarction at baseline, moderate hyperhomocysteinemia was also associated with CHD mortality and all CHD events in univariate (P < 0.001 and P = 0.006, respectively) and multivariate Cox regression analyses (P < 0.001 and P = 0.004, respectively).

Conclusions: In this large cohort of patients with type 2 diabetes, plasma homocysteine level was a strong and independent risk factor for CHD events.