ArticleEuropean heart journal. Cardiovascular pharmacotherapy2025
Emerging antihypertensive therapies and cardiovascular, kidney, and metabolic outcomes: a Mendelian randomization study.
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 7 papers.
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Who cites it
7 citing papers in PubMed.
- Challenges of Biomarker Application in Patients with Cardiorenal Syndrome.Biomedicines · 2026Review
- Article
- Editorial: Exploring molecular mechanisms and novel diagnostics in cardiovascular disease treatment.Frontiers in cardiovascular medicine · 2026Article
- An integrated multi-omics study of key mediators and therapeutic targets for doxorubicin-induced atrial fibrillation.PloS one · 2026Article
- Trandolapril Attenuates Pro-Arrhythmic Downregulation of Cx43 and Cx40 in Atria of Volume Overloaded Hypertensive and Normotensive Rats.Biomolecules · 2025Article
- Unveiling the global impact of hypertensive heart disease among individuals aged ≥ 65 years: metabolic risk factors and future projections for 2050.Frontiers in nutrition · 2025Article
- Review
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Authors and funding
5 authors.
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Abstract
aimsEmerging antihypertensive drug classes offer new opportunities to manage hypertension; however, their long-term effects on cardiovascular, kidney, and metabolic (CKM) outcomes remain to be elucidated. This study aims to explore the effects of phosphodiesterase type 5 inhibitors (PDE5i), soluble guanylate cyclase stimulators (sGCs), endothelin receptor antagonists (ERAs), and angiotensinogen inhibitors (AGTis) on a range of CKM outcomes. METHODS AND
resultsMendelian randomization (MR), summary-based MR (SMR), and colocalization analyses were applied to assess the drug effect on coronary artery disease (CAD), myocardial infarction (MI), ischaemic stroke, atrial fibrillation (AF), heart failure (HF), type 2 diabetes (T2D), and chronic kidney disease (CKD). Genetic association and gene expression summary data were obtained from the largest European-ancestry genome-wide association studies (GWAS) and the genotype-tissue expression version 8 for 29 tissues relevant to the outcomes' pathophysiology.Genetically predicted systolic blood pressure (SBP) reduction was associated with reduced risks of all outcomes. PDE5i was associated with reduced risks of CAD (OR per 10-mmHg decrease in SBP: 0.348[95% confidence interval (CI): 0.199-0.607]) and ischaemic stroke (0.588[0.453-0.763]). sGCs showed protective effects against CAD (0.332[0.236-0.469]), MI (0.238[0.168-0.337]), and CKD (0.55[0.398-0.761]). ERA and AGTi showed protective effects against CAD and ischaemic stroke. SMR and colocalization supported the association of gene expression levels of GUCY1A3 and PDE5A with CAD and MI risk.
conclusionOur study highlights the potential of PDE5i, sGCs, ERA, and AGTi in reducing cardiovascular and renal risks. These findings underscore the necessity for targeted clinical trials to validate the efficacy and safety of these therapies.
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