Hyperhomocysteinemia Is Associated With an Increased Risk of Cardiovascular Disease, Especially in Non–Insulin-Dependent Diabetes Mellitus

A Population-Based Study

From the Institute for Research in Extramural Medicine (E.K.H., P.J.K., P.J.B., L.M.B., R.J.H., C.D.A.S.) and the Department of Epidemiology and Biostatistics (P.J.K., L.M.B.), Vrije Universiteit; and the Departments of Internal Medicine (R.J.H., C.D.A.S.), Surgery (A.J.C.M.), and Clinical Chemistry (C.J.), University Hospital Vrije Universiteit, Amsterdam, The Netherlands.

Correspondence to Ellen K. Hoogeveen, MD, Institute for Research in Extramural Medicine, Vrije Universiteit, Van der Boechorststraat 7, NL-1081 BT Amsterdam, Netherlands. E-mail ellen.hoogeveen{at}paradigm.nl

Abstract—A high serum total homocysteine (tHcy) level is an independent risk factor for cardiovascular disease. Because it is not known whether the strength of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease, we compared the three separate risk estimates in an age-, sex-, and glucose tolerance–stratified random sample (n=631) from a 50- to 75-year-old general white population. Furthermore, we investigated the combined effect of hyperhomocysteinemia and diabetes mellitus with regard to cardiovascular disease. The prevalence of fasting hyperhomocysteinemia (>14.0 µmol/L) was 25.8%. After adjustment for age, sex, hypertension, hypercholesterolemia, diabetes, and smoking, the odds ratios (ORs; 95% confidence intervals) per 5 -µmol/L increment in tHcy were 1.44 (1.10 to 1.87) for peripheral arterial, 1.25 (1.03 to 1.51) for coronary artery, 1.24 (0.97 to 1.58) for cerebrovascular, and 1.39 (1.15 to 1.68) for any cardiovascular disease. After stratification by glucose tolerance category and adjustment for the classic risk factors and serum creatinine, the ORs per 5 -µmol/L increment in tHcy for any cardiovascular disease were 1.38 (1.03 to 1.85) in normal glucose tolerance, 1.55 (1.01 to 2.38) in impaired glucose tolerance, and 2.33 (1.11 to 4.90) in non–insulin-dependent diabetes mellitus (P=.07 for interaction). We conclude that the magnitude of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease in a 50- to 75-year-old general population. High serum tHcy may be a stronger (1.6-fold) risk factor for cardiovascular disease in subjects with non–insulin-dependent diabetes mellitus than in nondiabetic subjects.

Key Words: homocysteine • non–insulin-dependent diabetes mellitus • cardiovascular disease • epidemiology

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