Development and Evaluation of a Comprehensive Prediction Model for Incident Coronary Heart Disease Using Genetic, Social, and Lifestyle-Psychological Factors: A Prospective Analysis of the UK Biobank.

IF 19.6 1区医学 Q1 MEDICINE, GENERAL & INTERNAL

Annals of Internal Medicine Pub Date : 2024-12-10 DOI:10.7326/ANNALS-24-00716

Mohammadreza Naderian, Kristjan Norland, Daniel J Schaid, Iftikhar J Kullo

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引用次数: 0

Abstract

Background: Clinical risk calculators for coronary heart disease (CHD) do not include genetic, social, and lifestyle-psychological risk factors.

Objective: To improve CHD risk prediction by developing and evaluating a prediction model that incorporated a polygenic risk score (PRS) and a polysocial score (PSS), the latter including social determinants of health and lifestyle-psychological factors.

Design: Cohort study.

Setting: United Kingdom.

Participants: UK Biobank participants recruited between 2006 and 2010.

Measurements: Incident CHD (myocardial infarction and/or coronary revascularization); 10-year clinical risk based on pooled cohort equations (PCE), Predicting Risk of cardiovascular disease EVENTs (PREVENT), and QRISK3; PRS (Polygenic Score Catalog identification: PGS000018) for CHD (PRS_CHD); and PSS_CHD from 100 related covariates. Machine-learning and time-to-event analyses and model performance indices.

Results: In 388 224 participants (age, 55.5 [SD, 8.1] years; 42.5% men; 94.9% White), the hazard ratio for 1 SD increase in PSS_CHD for incident CHD was 1.43 (95% CI, 1.38 to 1.49; P < 0.001) and for 1 SD increase in PRS_CHD was 1.59 (CI, 1.53 to 1.66, P < 0.001). Non-White persons had higher PSS_CHD than White persons. The effects of PSS_CHD and PRS_CHD on CHD were independent and additive. At a 10-year CHD risk threshold of 7.5%, adding PSS_CHD and PRS_CHD to PCE reclassified 12% of participants, with 1.86 times higher CHD risk in the up- versus down-reclassified persons and showed superior performance compared with PCE as reflected by improved net benefit while maintaining good calibration relative to the clinical risk calculators. Similar results were seen when incorporating PSS_CHD and PRS_CHD into PREVENT and QRISK3.

Limitation: A predominantly White cohort; possible healthy participant effect and ecological fallacy.

Conclusion: A PSS_CHD was associated with incident CHD and its joint modeling with PRS_CHD improved the performance of clinical risk calculators.

Primary funding source: National Human Genome Research Institute.

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来源期刊

Annals of Internal Medicine 医学-医学：内科

CiteScore

23.90

自引率

1.80%

发文量

1136

审稿时长

3-8 weeks

期刊介绍： Established in 1927 by the American College of Physicians (ACP), Annals of Internal Medicine is the premier internal medicine journal. Annals of Internal Medicine’s mission is to promote excellence in medicine, enable physicians and other health care professionals to be well informed members of the medical community and society, advance standards in the conduct and reporting of medical research, and contribute to improving the health of people worldwide. To achieve this mission, the journal publishes a wide variety of original research, review articles, practice guidelines, and commentary relevant to clinical practice, health care delivery, public health, health care policy, medical education, ethics, and research methodology. In addition, the journal publishes personal narratives that convey the feeling and the art of medicine.