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C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study
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 publicl...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252732/ https://www.ncbi.nlm.nih.gov/pubmed/37298077 http://dx.doi.org/10.3390/ijms24119129 |
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author | Kuppa, Annapurna Tripathi, Himi Al-Darraji, Ahmed Tarhuni, Wadea M. Abdel-Latif, Ahmed |
author_facet | Kuppa, Annapurna Tripathi, Himi Al-Darraji, Ahmed Tarhuni, Wadea M. Abdel-Latif, Ahmed |
author_sort | Kuppa, Annapurna |
collection | PubMed |
description | 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’s 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. |
format | Online Article Text |
id | pubmed-10252732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102527322023-06-10 C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study Kuppa, Annapurna Tripathi, Himi Al-Darraji, Ahmed Tarhuni, Wadea M. Abdel-Latif, Ahmed Int J Mol Sci Article 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’s 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. MDPI 2023-05-23 /pmc/articles/PMC10252732/ /pubmed/37298077 http://dx.doi.org/10.3390/ijms24119129 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kuppa, Annapurna Tripathi, Himi Al-Darraji, Ahmed Tarhuni, Wadea M. Abdel-Latif, Ahmed C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study |
title | C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study |
title_full | C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study |
title_fullStr | C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study |
title_full_unstemmed | C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study |
title_short | C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study |
title_sort | c-reactive protein levels and risk of cardiovascular diseases: a two-sample bidirectional mendelian randomization study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252732/ https://www.ncbi.nlm.nih.gov/pubmed/37298077 http://dx.doi.org/10.3390/ijms24119129 |
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