Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kuppa, Annapurna, Tripathi, Himi, Al-Darraji, Ahmed, Tarhuni, Wadea M., Abdel-Latif, Ahmed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785056241061462016
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
work_keys_str_mv AT kuppaannapurna creactiveproteinlevelsandriskofcardiovasculardiseasesatwosamplebidirectionalmendelianrandomizationstudy
AT tripathihimi creactiveproteinlevelsandriskofcardiovasculardiseasesatwosamplebidirectionalmendelianrandomizationstudy
AT aldarrajiahmed creactiveproteinlevelsandriskofcardiovasculardiseasesatwosamplebidirectionalmendelianrandomizationstudy
AT tarhuniwadeam creactiveproteinlevelsandriskofcardiovasculardiseasesatwosamplebidirectionalmendelianrandomizationstudy
AT abdellatifahmed creactiveproteinlevelsandriskofcardiovasculardiseasesatwosamplebidirectionalmendelianrandomizationstudy