Plasma Lactate and Incident Hypertension in the Atherosclerosis Risk in Communities Study

BACKGROUND: Recent evidence suggests that insufficient oxidative capacity or mitochondrial dysfunction may play a causal role in the development of high blood pressure. However, this hypothesis has not been tested in the general population. We hypothesized that lactate, a measure of oxidative capacity, would be positively associated with incident hypertension even after accounting for traditional hypertension risk factors. METHODS: Plasma lactate was measured in 5,554 participants from the Atherosclerosis Risk in Communities (ARIC) Study with no subclinical or diagnosed hypertension at baseline (1996-1998). Incident hypertension was defined by self-report or hypertension medication use. Analyses were performed with Cox proportional hazards models. RESULTS: The mean age was 61.9 years, and the mean lactate was 0.8 mmol/L. During a median follow-up period of 11.9 years (range = 26.9 days to 13.4 years), there were 3,849 new cases of hypertension. The fourth quartile of lactate (compared with the first quartile) was associated with an elevated risk of hypertension (hazard ratio (HR) = 1.18; 95% confidence interval (CI) = 1.07-1.31) even after adjustment for traditional risk factors, including baseline systolic and diastolic blood pressure. This association was stronger when the population was restricted to participants with normal blood pressure (<120mm Hg/<80mm Hg; HR = 1.42; 95% CI = 1.23-1.63). In strata of sex, the association was strong in women vs. null in men (P interaction = 0.01). CONCLUSIONS: Plasma lactate is associated with incident hypertension in women, especially with a normal blood pressure (<120mm Hg/<80mm Hg). Future studies should elucidate the mechanisms underlying these observations.