Associations of Serum Folate and Homocysteine Concentrations with All-Cause, Cardiovascular Disease, and Cancer Mortality in Men and Women in Korea: the Cardiovascular Disease Association Study

Abstract

Background: Evidence on the association of serum folate and homocysteine concentrations with risk of mortality in the general population is unclear.

Objectives: This study aimed to examine the associations of serum folate and homocysteine concentrations with all-cause, CVD, and cancer mortality risk in Korean men and women aged ≥40 y.

Methods: In this population-based prospective cohort study, serum folate and homocysteine concentrations were measured in a subset of participants enrolled between 2005 and 2012. A total of 21,260 participants were linked to mortality data from the survey date to 31 December 2019. Cox proportional hazards models and restricted cubic splines were used to identify the associations of serum folate and homocysteine concentrations with mortality.

Results: During a median follow-up of 12.3 y, 2501, 549, and 842 deaths were attributed to all-cause, CVD, and cancer, respectively. The prevalence of folate deficiency and hyperhomocysteinemia were higher in men than in women. In men, a nonlinear inverse association was observed between serum folate concentrations and all-cause mortality. Men in the third quartile of serum folate concentrations exhibited a lower risk of all-cause mortality (HR: 0.85; 95% CI: 0.73, 0.99) than those in the lowest quartile. Serum homocysteine concentration was positively associated with all-cause and CVD mortality. Men and women in the highest compared with those in the lowest serum homocysteine quartile showed a higher risk of CVD mortality (HR: 1.60; 95% CI: 1.07, 2.39; and HR: 1.79; 95% CI: 1.11, 2.89, respectively). Hyperhomocysteinemia combined with folate deficiency was associated with increased all-cause, CVD, and cancer-related mortality rates.

Conclusions: Higher serum homocysteine and lower serum folate concentrations were associated with an increased risk of all-cause, CVD, and cancer-related mortality in Korean adults. The finding of a nonlinear inverse relationship between serum folate concentration and mortality in men warrants further investigation.

Keywords: cohort study; epidemiology; homocysteine; mortality; serum folate.