Red blood cell folate and cardiovascular deaths among hypertensive adults, an 18-year follow-up of a national cohort

A shift towards high folate concentration has emerged following folate fortification. However, the association between folate and health outcomes beyond neural tube defects remains inconclusive. To assess the relationship between red blood cell (RBC) folate and the risk of cardiovascular death among hypertensive patients, we analyzed the data of 2,986 adults aged 19 or older with hypertension who participated in the National Health and Nutrition Examination Survey (1991-1994) as the baseline examination and were followed up through December 31, 2010. After 32,743 person-years of follow-up with an average of 11.7 (standard error = 0.03) years, 1192 deaths were recorded with 579 cardiovascular deaths. The median survival time was significantly shorter in adults in the high folate quartile than in patients in the low folate quartile: 11.97 vs. 13.85 years for heart diseases and 13.37 vs. 14.82 years for myocardial infarction deaths. The cardiovascular mortality was 13.04, 16.95, and 26.61/1,000 person-years for the groups with low, intermediate and high folate quartiles, respectively. After adjustment for age, sex and other factors, a J-shaped association emerged. The hazard ratios (HRs) of all cardiovascular deaths in patients with low, intermediate, and high folate quartiles were 1.09 (0.94, 1.27), 1.00 (reference), and 1.44 (1.31, 1.58), respectively. The corresponding HRs of acute myocardial infarction were 1.13 (0.86, 1.50), 1.00, and 2.13 (1.77, 2.57), respectively. The estimates remained significant after adjustment for BMI and medication use. Compared to moderate RBC folate levels, high folate levels were significantly associated with an increased risk of cardiovascular deaths, especially acute myocardial infarction.