Homocysteine Metabolism, Subclinical Myocardial Injury, and Cardiovascular Mortality in the General Population

Abstract

BackgroundHomocysteine (Hcy) is a recognized cardiovascular disease (CVD) risk factor linked with atherosclerosis. However, the association between Hcy and myocardial injury is little known. ObjectivesThis study aimed to examine the associations between Hcy metabolism, subclinical myocardial injury, and cardiovascular mortality. MethodsWe 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 B12, 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–B-type natriuretic peptide [NT-proBNP]). ResultsAmong 10,871 participants, the weighted mean levels for tHcy, folate, and vitamin B12 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 B12 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; P < 0.001) and 1.58 (95% CI: 1.20-2.08; P < 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. ConclusionsPlasma tHcy, not folate or vitamin B12, 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.