Heart failure & cardiomyopathiesCohort study

A Polygenic Risk Score to Predict Incident Heart Failure Across the Spectrum of Cardiovascular Risk

J Am Coll CardiolPublished

  • Pooled cohort analysis of 7 clinical studies
  • 6 trials of patients at elevated CV risk
  • separate low-risk data set

Authors' conclusion

An HF PRS is a strong and independent predictor for new-onset HF in individuals across the spectrum of cardiovascular risk.

Study context

Population
Individuals without heart failure (HF) across the spectrum of CV risk51,627 at elevated CV risk
Participants
74,897 individuals
Exposure
HF polygenic risk score (PRS) intermediate or high vs low genetic risk
Outcome
Hospitalization for HF (new-onset HF)
Follow-up
Median 2.5 years

Main finding

As reported in the abstract

New-onset HF (elevated CV risk)
adjusted for clinical factors
Each group vs lowAdjusted hazard ratio (95% CI)P value
Intermediate
2.01(1.62–2.49)
P < 0.001
High
5.00(3.99–6.27)
P < 0.001

Observational data: associations, not effects.

Further findings

Discrimination: AUC of clinical model vs clinical model + HF PRS

AUC clinical model
0.787 [95% CI: 0.775-0.798]
AUC clinical model + HF PRS
0.822 [95% CI: 0.811-0.832]

Low CV risk data set · 20-year follow-up

Results consistent in individuals at low CV risk
23,270

Original publication

A Polygenic Risk Score to Predict Incident Heart Failure Across the Spectrum of Cardiovascular Risk. J Am Coll Cardiol. Published 27 August 2025. doi:10.1016/j.jacc.2025.06.050

Summarised from the published abstract; every number is checked against it