Plasma homocysteine concentration predicts mortality in non-insulin-dependent diabetic patients with and without albuminuria

Background. A high plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease in the nondiabetic population and in nondiabetic patients with end-stage renal disease. Methods. We prospectively evaluated the impact of tHcy concentrations on mortality in 211 white non-insulin-dependent diabetic (NIDDM) patients of less than 70 years of age at entry (61 with microalbuminuria and 44 with macroalbuminuria). They were followed for a median of 6.4 (range 0.2 to 7.1) years. Results. At the end of the follow-up period, 49 of 211 (23%) patients had died, 30 (61%) from cardiovascular disease. Univariate Cox sur vival analysis revealed that baseline tHcy level (1 mu mol/liter) was associated with an increased all-cause mortality risk of 1.11 [95% confidence interval (CI) 1.08 to 1.15, P < 0.0001], and a cardiovascular mortality risk of 1.09 (CI 1.03 to 1.16, P < 0.01). The six-year cumulative all-cause mortality hazard was 44%, 14%, and 25% in the high (tHcy greater than or equal to 8.2 mu mol/liter), the middle (tHcy 6.2-8.1 mu mol/liter), and the low (tHcy less than or equal to 6.1 mu mol/liter) tertile of tHcy levels, respectively (P < 0.001 high vs. middle; P < 0.001 high vs. low; and P = 0.88 middle vs. low). Cox proportional hazards regression analysis revealed significant predictors of air-cause mortality to be tHcy level (per 1 mu mol/liter), relative risk 1.09 (1.03 to 1.14); pre-existing coronary heart disease (yes vs. no), relative risk 1.98 (1.09 to 3.61); log(10) albumin excretion rate (AER; factor 10), relative risk 1.89 (1.31 to 2.74); and age (per 1 year), relative risk 1.08 (1.03 to 1.13). Predictors of cardiovascular mortality were pre-existing coronary heart disease, log(10) AER, and age. tHcy level did not predict cardiovascular mortality independently of these risk factors. Conclusion. Plasma tHcy concentration is a significant predictor of mortality in NIDDM patients with or without albuminuria.