Non-linear associations of serum and red blood cell folate with risk of cardiovascular and all-cause mortality in hypertensive adults

Hypertens Res. 2023 Jun;46(6):1504-1515. doi: 10.1038/s41440-023-01249-3. Epub 2023 Mar 10.

Abstract

This study aims to assess the associations of serum and red blood cell (RBC) folate with cardiovascular and all-cause mortality in hypertensive adults. Data on serum and RBC folate from the 1999-2014 National Health and Nutrition Examination Survey were included. Through December 31, 2015, cardiovascular and all-cause mortality were identified from the National Death Index. Multiple Cox regression and restricted cubic spline analyses were used to determine the relationship between folate concentrations and outcomes. A total of 13,986 hypertensive adults were included in the analysis (mean age, 58.5 ± 16.1 years; 6898 [49.3%] men). At a median of 7.0 years of follow-up, 548 cardiovascular deaths and 2726 all-cause deaths were identified. After multivariable adjustment, the fourth quartile of serum folate was associated with cardiovascular (HR = 1.32 [1.02-1.70]) and all-cause (HR = 1.20 [1.07-1.35]) mortality compared to the second quartile, whereas the first quartile was only linked with increased all-cause (HR = 1.29 [1.15-1.46]) mortality. The inflection points for the non-linear associations of serum folate with cardiovascular and all-cause mortality were 12.3 ng/mL and 20.5 ng/mL, respectively. In addition, the highest quartile of RBC folate was associated with cardiovascular (HR = 1.68 [1.30-2.16]) and all-cause (HR = 1.30 [1.16-1.46]) mortality compared to the second quartile, but the lowest quartile was not associated with either outcome. The inflection points for the non-linear associations of RBC folate with cardiovascular and all-cause mortality were 819.7 and 760.1 ng/mL, respectively. The findings suggest non-linear associations between serum and RBC folate levels and the risk of cardiovascular and all-cause mortality in hypertensive adults.

Keywords: All-cause mortality; Cardiovascular mortality; Folate; Hypertension; NHANES.

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases*
  • Erythrocytes
  • Female
  • Folic Acid
  • Humans
  • Hypertension* / complications
  • Male
  • Middle Aged
  • Nutrition Surveys
  • Risk Factors

Substances

  • Folic Acid