Hyperhomocysteinemia is a risk factor for coronary arteriosclerosis in Japanese patients with type 2 diabetes

An increased plasma homocysteine level is an important risk factor for vascular disease, including coronary atherosclerosis, in the general population. However, the role of hyperhomocysteinemia in the development of coronary artery disease (CAD) in patients with type 2 diabetes is unknown. Therefore, we have endeavored to determine the relationship between plasma homocysteine levels and the presence of coronary arteriosclerosis in patients with type 2 diabetes.

The study group consisted of 145 Japanese patients (95 men and 50 women) who underwent routine coronary angiography to assess chest pain or suspected CAD. Plasma total homocysteine level, lipid level, and parameters of fibrinolytic activity were measured. All patients were identified as diabetic or nondiabetic by the new American Diabetes Association (ADA) criteria. The diagnoses of all patients studied were confirmed by coronary angiography. The severity of coronary artery stenosis was quantified using CAD scoring on the basis of prior reports, and subjects were graded as nonstenotic, stenotic single-vessel, stenotic two-vessel, or stenotic three-vessel based on the number of stenotic coronary arteries. Patients were classified into two groups: those with stenotic vessels and those without stenotic vessels.

The plasma homocysteine level was significantly higher in patients with than in patients without stenotic vessels (13.8 +/- 3.9 vs. 11.7 +/- 3.9 mumol/l, respectively; P = 0.0009). The number of stenotic coronary arteries, which was used to grade each case as nonstenotic, stenotic single-vessel, stenotic two-vessel, or stenotic three-vessel, was related only to the total homocysteine level in the diabetic (diabetes mellitus [DM]) group, but it was associated with lipoprotein(a) in the nondiabetic (non-diabetes mellitus [non-DM]) group. Spearman's rank correlation test demonstrated that the plasma homocysteine level was strongly correlated with CAD score, both in the entire study group and in the DM group (P = 0.003 for the entire group and P = 0.011 for the DM group). Hyperhomocysteinemia, which was defined as total homocysteine level > 14.0 mumol/l, was seen in 57 (39.3%) of the patients. The CAD score was highest in diabetic patients with hyperhomocysteinemia (P < 0.05).

There seems to be a clear relationship between hyperhomocysteinemia and an increased risk of coronary arteriosclerosis in Japanese patients with type 2 diabetes.