Exploring the mechanisms mediating the inverse association between heart failure and prostate cancer risk: a nested case-control study

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2026
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Ranked #274 of 282 articles by views in European heart journal supplements : journal of the European Society of Cardiology

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Abstract
Abstract Background Heart failure (HF) has been paradoxically associated with reduced prostate cancer (PCa) risk, yet the mechanisms remain unclear. Purpose We aimed to identify biomarker and pharmacological pathways potentially mediating this inverse association. Methods We conducted a nested case-control study within the UK Biobank, including 11,070 incident PCa cases and 33,208 matched controls. HF was identified through self-report and hospital records. Causal mediation analysis examined cardiovascular medications and circulating biomarkers spanning glycemic, lipid, hormonal, renal, and inflammatory pathways. Sub-distribution hazard ratios with bootstrap confidence intervals were calculated. Results After multivariate adjustment by relevant confounders, baseline HF (n=2,136; 4.8%) was associated with 14.4% reduced PCa odds (OR 0.856, 95% CI 0.764-0.966, p=0.011). Beta-blocker use emerged as the dominant mediator, accounting for 25.7% of the protective effect (ACME -0.00802, 95% CI -0.01476 to -0.00159, p=0.016). Glycemic markers (HbA1c/HDL ratio: 13.6%; HbA1c: 9.0%; glucose: 3.3%) and lipid markers (LDL cholesterol: 12.2%; total cholesterol: 12.0%) demonstrated modest mediation. Testosterone showed no mediation despite established HF-associated hypogonadism. SHBG and creatinine demonstrated suppression effects. Conclusion Beta-blockers mediate approximately one-quarter of the HF-PCa protective association, supporting the emerging "reverse cardio-oncology" paradigm. These hypothesis-generating findings warrant replication and mechanistic investigation.
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Authors S A Gomez Ochoa, S Stahl-Toyota, R T Levinson
Journal European heart journal supplements : journal of the European Society of Cardiology
Year 2026
DOI
10.1093/eurheartjsupp/suag097.226
URL
https://doi.org/10.1093/eurheartjsupp/suag097.226
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