The association of plasma lactate with incident cardiovascular outcomes: the ARIC Study.

We examined the association of plasma lactate at rest, a marker of oxidative capacity, with incident cardiovascular outcomes in 10,006 participants in the Atherosclerosis Risk in Communities (ARIC) Study visit 4 (1996-1998). We used Cox proportional-hazards models to estimate hazard ratios of incident coronary heart disease, stroke, heart failure, and all-cause mortality by quartiles of plasma lactate (Q1, ≤5.3 mg/dL; Q2, 5.4-6.6; Q3, 6.7-8.6; and Q4 ≥8.7). During a median follow-up time of 10.7 years, there were 1,105 coronary heart disease cases, 379 stroke cases, 820 heart failure cases, and 1,408 deaths. A significant graded relation between lactate level and cardiovascular events was observed in the demographically adjusted model (all P for trend < 0.001). After further adjustment for traditional and other potential confounders, the association remained significant for heart failure (Q4 vs. Q1: hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.07, 1.71) and all-cause mortality (HR = 1.27, 95% CI: 1.07, 1.51) (P for trend < 0.02 for these outcomes) but not for coronary heart disease (HR = 1.02, 95% CI: 0.84, 1.24) and stroke (HR = 1.26, 95% CI: 0.91, 1.75). The results for heart failure were robust across multiple subgroups, after further adjustment for N-terminal pro-B-type natriuretic peptide and after exclusion of participants with incident heart failure within 3 years. The independent associations of plasma lactate with heart failure and all-cause mortality suggest an important role for low resting oxidative capacity.