Homocysteine Metabolism, Subclinical Myocardial Injury, and Cardiovascular Mortality in the General Population
Overview
Affiliations
Background: Homocysteine (Hcy) is a recognized cardiovascular disease (CVD) risk factor linked with atherosclerosis. However, the association between Hcy and myocardial injury is little known.
Objectives: This study aimed to examine the associations between Hcy metabolism, subclinical myocardial injury, and cardiovascular mortality.
Methods: We included 10,871 participants without diagnosed CVD. Generalized linear regression was used to investigate the relationship between Hcy-related indicators (plasma total Hcy [tHcy], vitamin B, and folate) and myocardial injury biomarkers (high-sensitivity troponin T [hs-cTnT], high-sensitivity troponin I [hs-cTnI] measured using 3 assays [Abbott, Siemens, and Ortho], and N-terminal pro-Btype natriuretic peptide [NT-proBNP]).
Results: Among 10,871 participants, the weighted mean levels for tHcy, folate, and vitamin B were 8.58 μmol/L, 32.43 nmol/L, and 447.08 pmol/L, respectively. Plasma tHcy levels were positively associated with elevated hs-cTnT, hs-cTnI, and NT-proBNP, whereas folate and vitamin B were not inversely related to myocardial injury biomarkers. Multivariable-adjusted odds ratios for elevated hs-cTnT (19 ng/L) and NT-proBNP (125 pg/mL) per doubling of tHcy were 2.80 (95% CI: 1.17-6.73; < 0.001) and 1.58 (95% CI: 1.20-2.08; < 0.001), respectively. The associations of tHcy levels with elevated hs-cTnI (Abbott: 28 ng/L; Siemens: 46.5 ng/L; Ortho: 11 ng/L) were consistent. Indirect effects of tHcy on cardiovascular mortality risk via hs-cTnT and NT-proBNP explained up to 26.6% and 12.3% of the total effect, respectively.
Conclusions: Plasma tHcy, not folate or vitamin B, is significantly associated with elevated hs-cTnT, hs-cTnI, and NT-proBNP in adults without CVD. Subclinical myocardial injury may substantially mediate Hcy-related cardiovascular mortality risk.