Integrating polygenic and classical risk factors for cardiovascular risk stratification in a polish primary-care cohort

Banach, M ORCID: 0000-0001-6690-6874, Stempor, P ORCID: 0000-0002-9464-7475, Osadnik, T ORCID: 0000-0002-3202-6972, Gach, A ORCID: 0000-0002-6590-5797, Strapagiel, D ORCID: 0000-0001-9752-4270, Słomka, M ORCID: 0000-0002-7906-5549, Skóra, M ORCID: 0000-0002-7047-2279, Fronczek, M ORCID: 0000-0003-3669-1416, Lejawa, M ORCID: 0000-0002-1228-7534, Goc, A ORCID: 0000-0003-4271-1954, Boniewska-Bernacka, E ORCID: 0000-0002-4424-8409, Pańczyszyn, A ORCID: 0000-0003-1580-3925, Lip, GYH ORCID: 0000-0002-7566-1626, Mikhailidis, DP ORCID: 0000-0002-5802-0528, Toth, PP ORCID: 0000-0001-5810-5460, Penson, PE ORCID: 0000-0001-6763-1489, Viigimaa, M ORCID: 0000-0001-5575-5978 and Jóźwiak, J ORCID: 0000-0002-2645-7274 (2026) Integrating polygenic and classical risk factors for cardiovascular risk stratification in a polish primary-care cohort. Progress in Cardiovascular Diseases. ISSN 0033-0620

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Abstract

Background: Polygenic risk scores (PRS) promise improved cardiovascular risk stratification, but most validation derives from UK or Nordic biobanks. The transferability of these scores to Central European populations and their incremental value over classical risk factors in routine care remain unestablished. Objectives: To determine whether a coronary PRS derived from external European data transfers to a Polish primary-care population and adds discrimination for prevalent cardiovascular disease beyond classical risk factors. Methods: In the nationwide Polish LIPIDOGEN2015 primary-care cohort, we derived PRS for coronary heart disease, myocardial infarction (MI) and stroke from FinnGen data with continuous shrinkage priors and applied them to imputed genotypes. We compared allele frequencies of 1,397 unrelated participants with a non-Finnish European (NFE) reference and, in 1,328 participants with clinical data, related the PRS to coronary artery disease (CAD), MI and stroke recorded at baseline and to a composite including death during follow-up, with and without classical risk factors or SCORE2. Results: Allele frequencies correlated with the NFE reference (r=0.97). Per standard deviation (SD), the coronary PRS was associated with prevalent CAD (odds ratio 1.36, 95% CI 1.11 to 1.67) and the composite endpoint (1.26, 95% CI 1.04 to 1.51), as were two validated genomewide scores. Adding it to classical risk factors changed the area under the curve (AUC) for the composite endpoint by 0.0017 (95% CI −0.0005 to 0.0076), from 0.860 to 0.861; results with SCORE2 were similar. The study had 80% power for odds ratios per SD of 1.31 (CAD) and 1.27 (composite). Conclusions: A coronary PRS derived from external European data retains its association with prevalent CAD without re-derivation in this Polish primary-care cohort but, in this crosssectional, event-limited sample, adds little discrimination to classical risk factors. Its value for predicting future events in this setting remains to be tested against incident outcomes.

Item Type:	Article
Uncontrolled Keywords:	1102 Cardiorespiratory Medicine and Haematology; Cardiovascular System & Hematology; 3201 Cardiovascular medicine and haematology
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	Elsevier
Date of acceptance:	3 November 2026
Date of first compliant Open Access:	11 November 2026
Date Deposited:	10 Nov 2026 14:05
Last Modified:	11 Nov 2026 00:50
DOI or ID number:	10.1016/j.pcad.2026.11.006
URI:	https://researchonline.ljmu.ac.uk/id/eprint/29858

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