{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:43:48Z","timestamp":1792622628189,"version":"4.5.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005892","name":"China Academy of Chinese Medical Sciences","doi-asserted-by":"publisher","award":["CI2021B004"],"award-info":[{"award-number":["CI2021B004"]}],"id":[{"id":"10.13039\/501100005892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Although observational studies have demonstrated associations between elevated plasma homocysteine levels and the risk of cardiovascular diseases, controversy remains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study investigated the causal association of plasma homocysteine levels with congestive heart failure and cardiomyopathy risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a two-sample Mendelian randomization (MR) study of congestive heart failure (<jats:italic>n<\/jats:italic> = 218,792), cardiomyopathy (<jats:italic>n<\/jats:italic> = 159,811), and non-ischemic cardiomyopathy (<jats:italic>n<\/jats: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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats: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\u20134.562, <jats:italic>P<\/jats:italic> = 0.250), cardiomyopathy (random-effect IVW, OR per SD increase in homocysteine levels = 0.805, 95% CI = 0.583 to 1.020, <jats:italic>P<\/jats:italic> = 0.189), or non-ischemic cardiomyopathy (random-effect IVW, OR per SD increase in homocysteine levels = 1.064, 95% CI = 0.927\u20131.222, <jats:italic>P<\/jats:italic> = 0.379). The results were consistent with other analytical methods and sensitivity analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats: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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1030257","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T05:39:36Z","timestamp":1674711576000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Plasma homocysteine levels and risk of congestive heart failure or cardiomyopathy: A Mendelian randomization 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