{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:47:03Z","timestamp":1790304423669,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Internal Medicine, University of Michigan","award":["R01 HL124266"],"award-info":[{"award-number":["R01 HL124266"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Elevated C-reactive protein (CRP) levels are an indicator of inflammation, a major risk factor for cardiovascular disease (CVD). However, this potential association in observational studies remains inconclusive. We performed a two-sample bidirectional Mendelian randomization (MR) study using publicly available GWAS summary statistics to evaluate the relationship between CRP and CVD. Instrumental variables (IVs) were carefully selected, and multiple approaches were used to make robust conclusions. Horizontal pleiotropy and heterogeneity were evaluated using the MR-Egger intercept and Cochran\u2019s Q-test. The strength of the IVs was determined using F-statistics. The causal effect of CRP on the risk of hypertensive heart disease (HHD) was statistically significant, but we did not observe a significant causal relationship between CRP and the risk of myocardial infarction, coronary artery disease, heart failure, or atherosclerosis. Our primary analyses, after performing outlier correction using MR-PRESSO and the Multivariable MR method, revealed that IVs that increased CRP levels also increased the HHD risk. However, after excluding outlier IVs identified using PhenoScanner, the initial MR results were altered, but the sensitivity analyses remained congruent with the results from the primary analyses. We found no evidence of reverse causation between CVD and CRP. Our findings warrant updated MR studies to confirm the role of CRP as a clinical biomarker for HHD.<\/jats:p>","DOI":"10.3390\/ijms24119129","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T08:14:28Z","timestamp":1684829668000},"page":"9129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study"],"prefix":"10.3390","volume":"24","author":[{"given":"Annapurna","family":"Kuppa","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himi","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Al-Darraji","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadea M.","family":"Tarhuni","sequence":"additional","affiliation":[{"name":"Canadian Cardiac Research Center, Department of Internal Medicine, Division of Cardiology, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abdel-Latif","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Ann Arbor VA Healthcare System, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"ref_1","first-page":"e596","article-title":"2019 ACC\/AHA guideline on the primary prevention of cardiovascular disease: A report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"140","author":"Arnett","year":"2019","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jacc.2022.05.033","article-title":"Cardiovascular Disease Projections in the United States Based on the 2020 Census Estimates","volume":"80","author":"Mohebi","year":"2022","journal-title":"J. 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