Association between serum folate and cardiovascular deaths among adults with hypertension

Background: A significant shift toward high folate concentrations has been taking place following the mandatory folate fortification. Yet the relationship between folate and health outcomes beyond neural tube defects remains understudied. We longitudinally examined relationships between serum folate and risk of cardiovascular death. Methods: We analyzed data of 3116 adults aged ≥19 who participated in the Third National Health and Nutrition Examination Survey, 1991–1994 and were diagnosed with hypertension. Vital status was followed through December 31, 2010. Cox regression was used to estimate hazard ratios (HRs) of cardiovascular deaths for individuals with serum folate in the first quartile and fourth quartile compared with the patients with interquartile folate. Results: After 33627 person years (p*ys) of follow-up, 1298 deaths were recorded with 638 cardiovascular disease (CVD) deaths (109 strokes and 529 heart diseases). A U-shaped association appeared after multivariable adjustment for heart disease, acute myocardial infarction, and overall CVD deaths. The mortality rate for heart disease in patients with low, moderate, and high folate were 12.18/1000 p*ys, 14.12/1000 p*ys, and 23.80/1000 p*ys, respectively, and the corresponding adjusted HRs were 1.79 (95% confidence interval, CI = 1.63–1.98), 1.00 (reference), and 1.31 (1.17–1.46). The HRs of acute myocardial infarction were 2.28 (1.80–2.88), 1.00 (reference), and 1.77 (1.42–2.20) for hypertensive patients with serum folate in low quartile, interquartile, and high quartile, respectively. Conclusions: Among hypertensive adults, both low and high folate were associated with an elevated risk of dying from cardiovascular diseases compared with adults with moderate serum folate concentration.