Elevated Plasma Homocysteine Level Is an Independent Predictor of Coronary Heart Disease Events in Patients with Type 2 Diabetes Mellitus

20 January 2004 | Volume 140 Issue 2 | Pages 94-100

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 µmol/L or more at baseline had a higher risk for CHD death than those with plasma homocysteine levels less than 15 µmol/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.

Editors' Notes Context Previous studies have not assessed the relationship between homocysteine level and coronary heart disease mortality in diabetic patients. Contribution This prospective, 7-year study of 830 middle-aged patients with type 2 diabetes mellitus found that plasma homocysteine level of 15 µmol/L or more was independently associated with increased risk for coronary heart disease events, including death. Implications Homocysteine level is an independent risk factor for coronary heart disease in patients with type 2 diabetes mellitus. Caution The study did not assess folate or vitamin B12 intake or whether lowering homocysteine level with folate supplementation would reduce the risk for coronary artery disease. –The Editors

 

Author and Article Information

From University of Turku, Turku, Finland; The Social Insurance Institution of Finland, Turku, Finland; and University of Kuopio, Kuopio, Finland.

Grant Support: By the Turku University Central Hospital Research Fund, Turku University Foundation.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Minna Soinio, MD, Department of Medicine, Turku University Central Hospital, PO Box 52, FIN-20521 Turku, Finland; e-mail, minna.soinio{at}tyks.fi.

Current Author Addresses: Drs. Soinio and Rönnemaa: Department of Medicine, Turku University Central Hospital, PO Box 52, FIN-20521 Turku, Finland.

Dr. Marniemi: The Social Insurance Institution of Finland, Research Department, Peltolantie 3, FIN-20720 Turku, Finland.

Drs. Laakso and Lehto: Department of Medicine, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland.

Author Contributions: Conception and design: M. Laakso, T. Rönnemaa.

Analysis and interpretation of the data: M. Soinio, T. Rönnemaa.

Drafting of the article: M. Soinio, T. Rönnemaa.

Critical revision of the article for important intellectual content: M. Soinio, J. Marniemi, M. Laakso, T. Rönnemaa.

Final approval of the article: M. Soinio, J. Marniemi, M. Laakso, S. Lehto, T. Rönnemaa.

Provision of study materials or patients: M. Laakso, T. Rönnemaa.

Statistical expertise: M. Soinio, S. Lehto.

Collection and assembly of data: J. Marniemi, S. Lehto.