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

Abstract

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.

Keywords: cardiovascular disease; epidemiology; heart failure; oxidative capacity; plasma lactate.

Figure 1.

Adjusted hazard ratios of incident heart failure for top quartile of lactate (quartile 4, ≥8.7 mg/dL) compared with bottom quartile (quartile 1, ≤5.3 mg/dL) in subgroups, Atherosclerosis Risk in Communities Study, 1996–2008. The hazard ratios were adjusted for the same covariates as Model 3 in Table 2 (i.e., age, sex, race, level of education, systolic and diastolic blood pressure, antihypertensive medication, smoking, total cholesterol, high-density lipoprotein cholesterol, diabetes, body mass index, waist circumference, homeostasis model assessment of insulin resistance, physical activity, history of lung disease, heart rate, high-sensitivity C-reactive protein, alanine aminotransferase, aspartate aminotransferase, alcohol intake, and estimated glomerular filtration rate). Body mass index was defined as weight in kilograms divided by the square of height in meters. CI, confidence interval; eGFR, estimated glomerular filtration rate.