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

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.