AUTHOR=Wang Xinyi , Chen Zhuo , Tian Wende , Zhang Jie , Li Qiuyi , Ju Jianqing , Xu Hao , Chen Keji 

TITLE=Plasma homocysteine levels and risk of congestive heart failure or cardiomyopathy: A Mendelian randomization study

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1030257

DOI=10.3389/fcvm.2023.1030257

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Although observational studies have demonstrated associations between elevated plasma homocysteine levels and the risk of cardiovascular diseases, controversy remains.</p></sec><sec><title>Objective</title><p>This study investigated the causal association of plasma homocysteine levels with congestive heart failure and cardiomyopathy risk.</p></sec><sec><title>Methods</title><p>We performed a two-sample Mendelian randomization (MR) study of congestive heart failure (<italic>n</italic> = 218,792), cardiomyopathy (<italic>n</italic> = 159,811), and non-ischemic cardiomyopathy (<italic>n</italic> = 187,152). Genetic summary data on the association of single-nucleotide polymorphisms with homocysteine were extracted from the most extensive genome-wide association study of 44,147 individuals. MR analyses, including the random-effect inverse variance-weighted (IVW) meta-analysis, weighted median, simple median, maximum likelihood, penalized weighted median, MR-PRESSO, and MR-Egger regression, were used to estimate the associations between the selected single-nucleotide polymorphisms and congestive heart failure or cardiomyopathy.</p></sec><sec><title>Results</title><p>The MR analyses revealed no causal role of higher genetically predicted plasma homocysteine levels with congestive heart failure risk (random-effect IVW, odds ratio [OR] per standard deviation (SD) increase in homocysteine levels = 1.753, 95% confidence interval [CI] = 0.674–4.562, <italic>P</italic> = 0.250), cardiomyopathy (random-effect IVW, OR per SD increase in homocysteine levels = 0.805, 95% CI = 0.583 to 1.020, <italic>P</italic> = 0.189), or non-ischemic cardiomyopathy (random-effect IVW, OR per SD increase in homocysteine levels = 1.064, 95% CI = 0.927–1.222, <italic>P</italic> = 0.379). The results were consistent with other analytical methods and sensitivity analyses.</p></sec><sec><title>Conclusion</title><p>Genetically predicted homocysteine level was not associated with congestive heart failure or cardiomyopathy risk. It is unlikely that homocysteine-lowering therapy decreases the incidence or improves the outcomes of congestive heart failure and cardiomyopathy.</p></sec>