The global burden of heart failure (HF) remains a significant challenge for healthcare systems.² While clinical risk factors are well-established, the utility of genetic information in predicting incident HF has been less certain. A recent study investigated the ability of a heart failure polygenic risk score (HF PRS) to predict new-onset HF in individuals across the full spectrum of cardiovascular risk.¹

This analysis utilised data from 74,897 patients without pre-existing HF, drawn from seven distinct clinical studies. An HF PRS, incorporating over one million single nucleotide variations, was used to stratify participants into low (quintile 1), intermediate (quintiles 2–4), or high (quintile 5) genetic risk categories.

The cohort was divided into two main groups for analysis:

• An elevated-risk group of 51,627 patients (median age 65 years; 71% men) from six clinical trials, with a median follow-up of 2.5 years.
• A low-risk group of 23,270 individuals from a separate dataset, with a follow-up period of 20 years.

The primary endpoint was the risk of hospitalisation for new-onset HF. Cox proportional-hazards models were used to calculate hazard ratios, adjusted for established clinical risk factors.

In the elevated cardiovascular risk cohort, the HF PRS was a significant predictor of incident HF, independent of clinical factors. Compared to the low-risk genetic group, individuals with an intermediate HF PRS had a twofold increased rate of new-onset HF (adjusted HR: 2.01; 95% CI: 1.62–2.49; p<0.001). Those in the high-risk genetic group had a fivefold increased rate (adjusted HR: 5.00; 95% CI: 3.99–6.27; p<0.001).

The addition of the HF PRS to a standard clinical risk model improved its predictive ability, increasing the area under the curve (AUC) from 0.787 (95% CI: 0.775–0.798) to 0.822 (95% CI: 0.811–0.832). The study noted that these results were consistent in the low-risk cohort over the 20-year follow-up period.

The findings demonstrate that a genome-wide PRS can identify individuals at higher risk for developing HF, across diverse populations with both high and low baseline cardiovascular risk. The authors concluded that, “An HF PRS is a strong and independent predictor for new-onset HF in individuals across the spectrum of cardiovascular risk. The polygenic contribution to HF is complementary to established clinical risk assessment.”¹ This suggests that genetic information could be integrated with clinical data to enhance risk stratification and potentially guide preventative strategies for HF.

References

1. Haller PM, Melloni GEM, Berg DD, et al. A Polygenic Risk Score to Predict Incident Heart Failure Across the Spectrum of Cardiovascular Risk. J Am Coll Cardiol. 2025;86(12):860-873. https://doi.org/10.1016/j.jacc.2025.06.050

2. Savarese G, Becher PM, Lund LH, et al. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res. 2023;118(17):3272-3287. https://doi.org/10.1093/cvr/cvac013

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