Evidence map›Paper›PMID 39424597›Full record

ArticleEuropean heart journal. Cardiovascular pharmacotherapy2025

Phosphodiesterase 5 and its inhibitors with ischaemic heart disease: a Mendelian randomization analysis and a real-world study.

Jun Xiao, Naiqi Zhang, Ziting Gao, Yajing Wei, Hongye Wei, Ziyi Qiu, Kristina Sundquist, Jan Sundquist, Jianguang Ji, Wuqing Huang

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Article in European heart journal. Cardiovascular pharmacotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Jun XiaoDepartment of Cardiovascular Surgery, Fujian Medical University, Union Hospital, Fuzhou, Fujian, China.
Naiqi ZhangCenter for Primary Health Care Research, Department of Clinical Sciences Malmö, Lund University, Sweden.
Ziting GaoDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
Yajing WeiDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
Hongye WeiDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
Ziyi QiuDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
Kristina SundquistCenter for Primary Health Care Research, Department of Clinical Sciences Malmö, Lund University, Sweden.ORCID 0000-0001-8031-279X
Jan SundquistCenter for Primary Health Care Research, Department of Clinical Sciences Malmö, Lund University, Sweden.ORCID 0000-0001-7228-5015
Jianguang JiCenter for Primary Health Care Research, Department of Clinical Sciences Malmö, Lund University, Sweden.
Wuqing HuangDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.ORCID 0000-0002-7616-8622

Funding

National Natural Science Foundation of China 82304213Natural Science Foundation of Fujian Province 2022J01706
6 · The paper itself

Abstract

backgroundAccumulating studies reported that several phosphodiesterases (PDEs) inhibitors might have cardiovascular benefits.

objectivesThis study aimed to explore the relationship between genetically-predicted PDEs and ischaemia heart disease via drug target Mendelian randomization (MR) approach, and then examine the effect of inhibitors of identified target on the outcomes by using real-world data. METHODS AND

resultsIn the two-sample MR study, the expression of genes encoding PDEs was used to proxy the level of PDEs and available expression quantitative trait loci (eQTLs) for each target gene were identified as the genetic instruments. The outcomes included coronary heart disease (CHD) and myocardial infarction (MI). In the real-world study, a retrospective cohort was conducted to compare the incidence of outcomes between PDE5 inhibitors and alprostadil use by linking Swedish nationwide registers. MR analyses identified two types of PDEs, PDE5, and PDE8, genetically-predicted expression in blood of the encoded genes was significantly associated with the risk of CHD [odds ratio (OR)PDE5A = 1.22,95% confidence interval (CI) = 1.06-1.40; ORPDE8A = 1.26,95% CI = 1.07-1.49] and MI (ORPDE5A = 1.27,95% CI = 1.09-1.48; ORPDE8A = 1.24,95% CI = 1.04-1.48). Notably, the highest expression of PDE5A was observed in artery aorta, which was also positively related to CHD (OR = 1.17,95% CI = 1.05-1.32) and MI (OR = 1.15,95% CI = 1.02-1.30). Real-world study provided supportive evidence that as compared to alprostadil use, PDE5 inhibitors use significantly reduced the incidence of CHD (adjusted HR = 0.70,95% CI = 0.66-0.73) and MI (adjusted HR = 0.79,95% CI = 0.73-0.84).

conclusionThis study provided observational and genetic evidence about the protective role of PDE5 inhibition against ischaemic heart disease, indicating the potential of these drugs to be repurposed for ischemia heart disease prevention and treatment.

Indexed as

Cyclic Nucleotide Phosphodiesterases, Type 5Myocardial InfarctionMyocardial IschemiaPharmacogenomic VariantsPhosphodiesterase 5 InhibitorsAgedFemaleGenetic Predisposition to DiseaseHumansIncidenceMaleMendelian Randomization AnalysisMiddle AgedPhenotypeQuantitative Trait LociRegistriesCyclic Nucleotide Phosphodiesterases, Type 5PDE5A protein, humanPhosphodiesterase 5 InhibitorsDrug target Mendelian randomizationEpidemiologyIschaemic heart diseasePhosphodiesterasesReal-world study

Identifiers

PMID39424597
PMCPMC11805687

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.