Voutilainen, S., J.K. Virtanen, T.H. Rissanen, G. Alfthan, J. Laukkanen, K. Nyyssonen, J. Mursu, V.P. Valkonen, T.P. Tuomainen, George A. Kaplan, and J.T. Salonen. 2004. "Serum Folate and Homocysteine and the Incidence of Acute Coronary Events: the Kuopio Ischaemic Heart Disease Risk Factor Study." American Journal of Clinical Nutrition, 80(2): 317-323.
Background: Several, but not all, prospective studies have shown that low folate intakes, low circulating folate concentrations, or high plasma total homocysteine (tHcy) concentrations are associated with an increased risk of coronary artery disease (CAD). Objective: We examined the relations of both serum folate and serum tHy concentrations with acute coronary events in middle-aged men from eastern Finland who had no CAD at baseline. Design: In a population-based prospective cohort study, 1027 men aged 46-64 y were examined in 1991-1993 as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 7.7 y (7900 person-years of follow-up), 114 acute coronary events were observed in 61 men who had no previous history of CAD (n = 8 10). Results: In a Cox model, compared with men whose serum folate concentrations were in the lowest tertile, those whose concentrations were in the hi-hest tertile had a risk factor-adjusted relative risk of acute coronary events of 0.35 (95% Cl: 0.17, 0.73; P = 0.005). Serum tHcy concentrations were not significantly associated with the risk of acute coronary events (for the highest tertile compared with the lowest, adjusted relative risk = 1.03; 95% Cl: 0.57, 1.87; P = 0.932). Conclusions: The results of this prospective cohort study do not support the hypothesis that a high circulating tHcy concentration is a risk factor for acute coronary events in a male population free of prior heart disease. However, they do suggest that moderate-to-high serum folate concentrations are associated with a greatly reduced incidence of acute coronary events.