Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Xiao, Jun LU ; Zhang, Naiqi LU orcid ; Gao, Ziting ; Wei, Yajing ; Wei, Hongye ; Qiu, Ziyi ; Sundquist, Kristina LU ; Sundquist, Jan LU ; Ji, Jianguang LU orcid and Huang, Wuqing LU orcid (2025) In European heart journal. Cardiovascular pharmacotherapy 11(1). p.75-83
Abstract

BACKGROUND: Accumulating studies reported that several phosphodiesterases (PDEs) inhibitors might have cardiovascular benefits.

OBJECTIVES: This study aimed to explore the relationship between genetically-predicted PDEs and ischemia 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: In 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... (More)

BACKGROUND: Accumulating studies reported that several phosphodiesterases (PDEs) inhibitors might have cardiovascular benefits.

OBJECTIVES: This study aimed to explore the relationship between genetically-predicted PDEs and ischemia 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: In 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.

RESULTS: 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 (ORPDE5A = 1.22,95% 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).

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

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European heart journal. Cardiovascular pharmacotherapy
volume
11
issue
1
pages
75 - 83
publisher
Oxford University Press
external identifiers
  • scopus:85217639940
  • pmid:39424597
ISSN
2055-6837
DOI
10.1093/ehjcvp/pvae081
language
English
LU publication?
yes
additional info
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
id
8ec1cd05-93d9-4596-a85e-3f7f0712126e
date added to LUP
2024-10-20 15:08:22
date last changed
2025-07-11 12:50:48
@article{8ec1cd05-93d9-4596-a85e-3f7f0712126e,
  abstract     = {{<p>BACKGROUND: Accumulating studies reported that several phosphodiesterases (PDEs) inhibitors might have cardiovascular benefits.</p><p>OBJECTIVES: This study aimed to explore the relationship between genetically-predicted PDEs and ischemia 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.</p><p>METHODS: In 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.</p><p>RESULTS: 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 (ORPDE5A = 1.22,95% 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).</p><p>CONCLUSION: This study provided observational and genetic evidence about the protective role of PDE5 inhibition against ischemic heart disease, indicating the potential of these drugs to be repurposed for ischemia heart disease prevention and treatment.</p>}},
  author       = {{Xiao, Jun and Zhang, Naiqi and Gao, Ziting and Wei, Yajing and Wei, Hongye and Qiu, Ziyi and Sundquist, Kristina and Sundquist, Jan and Ji, Jianguang and Huang, Wuqing}},
  issn         = {{2055-6837}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{75--83}},
  publisher    = {{Oxford University Press}},
  series       = {{European heart journal. Cardiovascular pharmacotherapy}},
  title        = {{Phosphodiesterase 5 and its inhibitors with ischemic heart disease : a Mendelian randomization analysis and a real-world study}},
  url          = {{http://dx.doi.org/10.1093/ehjcvp/pvae081}},
  doi          = {{10.1093/ehjcvp/pvae081}},
  volume       = {{11}},
  year         = {{2025}},
}