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Hyperhomocysteinemia was found to be uniformly associated with the development of heart failure (HF) and HF mortality; however, it is uncertain whether this relation is causative or not. We used Mendelian randomization to examine the associations of the methylene tetrahydrofolate gene (MTHFR) and paraoxonase 1 gene (PON1) variants as a proxy for lifelong exposure to high Hcy and Hcy-thiolactone concentrations with the development of HF in men aged ≤ 60 years and the occurrence of adverse effects at one–year follow–up.

The study enrolled 172 men with HF: 117 with ischemic etiology (iHF) related to coronary artery disease (CAD) and 55 with non-ischemic etiology (niHF) related to dilated cardiomyopathy (DCM). The reference group of 329 CAD patients without HF and the control group of 384 men were also analyzed.

Hyperhomocysteinemia (OR = 2.0, P < 0.05) and the …