In:
European Journal of Preventive Cardiology, Oxford University Press (OUP), Vol. 30, No. 13 ( 2023-09-20), p. 1382-1390
Abstract:
Mortality risk assessment in patients with heart failure (HF) with preserved ejection fraction (HFpEF) presents a major challenge. We sought to construct a polygenic risk score (PRS) to accurately predict the mortality risk of HFpEF. Methods and results We first carried out a microarray analysis of 50 HFpEF patients who died and 50 matched controls who survived during 1-year follow-up for candidate gene selection. The HF-PRS was developed using the independent common (MAF & gt; 0.05) genetic variants that showed significant associations with 1-year all-cause death (P & lt; 0.05) in 1442 HFpEF patients. Internal cross-validation and subgroup analyses were performed to evaluate the discrimination ability of the HF-PRS. In 209 genes identified by microarray analysis, 69 independent variants (r & lt; 0.1) were selected to develop the HF-PRS model. This model yielded the best discrimination capability for 1-year all-cause mortality with an area under the curve (AUC) of 0.852 (95% CI 0.827–0.877), which outperformed the clinical risk score consisting of 10 significant traditional risk factors for 1-year all-cause mortality (AUC 0.696, 95% CI 0.658–0.734, P = 4 × 10−11), with net reclassification improvement (NRI) of 0.741 (95% CI 0.605–0.877; P & lt; 0.001) and integrated discrimination improvement (IDI) of 0.181 (95% CI 0.145–0.218; P & lt; 0.001). Individuals in the medium and the highest tertile of the HF-PRS had nearly a five-fold (HR = 5.3, 95% CI 2.4–11.9; P = 5.6 × 10−5) and 30-fold (HR = 29.8, 95% CI 14.0–63.5; P = 1.4 × 10−18) increased risk of mortality compared to those in the lowest tertile, respectively. The discrimination ability of the HF-PRS was excellent in cross validation and throughout the subgroups regardless of comorbidities, gender, and patients with or without a history of heart failure. Conclusion The HF-PRS comprising 69 genetic variants provided an improvement of prognostic power over the contemporary risk scores and NT-proBNP in HFpEF patients.
Type of Medium:
Online Resource
ISSN:
2047-4873
,
2047-4881
DOI:
10.1093/eurjpc/zwad209
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2023
detail.hit.zdb_id:
2646239-4
