Genetic, sociodemographic, lifestyle, and clinical risk factors of recurrent coronary artery disease events: a population-based cohort study

Author:

Cho So Mi Jemma123ORCID,Koyama Satoshi12ORCID,Honigberg Michael C1245ORCID,Surakka Ida16ORCID,Haidermota Sara12ORCID,Ganesh Shriienidhie12,Patel Aniruddh P1245ORCID,Bhattacharya Romit1245ORCID,Lee Hokyou7ORCID,Kim Hyeon Chang378ORCID,Natarajan Pradeep1245ORCID

Affiliation:

1. Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard , 415 Main St., Cambridge, MA 02142 , USA

2. Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital , 185 Cambridge St., Boston, MA 02114 , USA

3. Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Yonsei University College of Medicine , 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea

4. Cardiology Division, Department of Medicine, Massachusetts General Hospital , 55 Fruit St., Boston, MA 02114 , USA

5. Department of Medicine, Harvard Medical School , 25 Shattuck St., Boston, MA 02114 , USA

6. Division of Cardiology, Department of Internal Medicine, University of Michigan , 1500 E Medical Center Dr., Ann Arbor, MI 48109 , USA

7. Department of Preventive Medicine, Yonsei University College of Medicine , 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea

8. Institute for Innovation in Digital Healthcare, Yonsei University Health System , 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea

Abstract

Abstract Aims Complications of coronary artery disease (CAD) represent the leading cause of death among adults globally. This study examined the associations and clinical utilities of genetic, sociodemographic, lifestyle, and clinical risk factors on CAD recurrence. Methods and results Data were from 7024 UK Biobank middle-aged adults with established CAD at enrolment. Cox proportional hazards regressions modelled associations of age at enrolment, age at first CAD diagnosis, sex, cigarette smoking, physical activity, diet, sleep, Townsend Deprivation Index, body mass index, blood pressure, blood lipids, glucose, lipoprotein(a), C reactive protein, estimated glomerular filtration rate (eGFR), statin prescription, and CAD polygenic risk score (PRS) with first post-enrolment CAD recurrence. Over a median [interquartile range] follow-up of 11.6 [7.2–12.7] years, 2003 (28.5%) recurrent CAD events occurred. The hazard ratio (95% confidence interval [CI]) for CAD recurrence was the most pronounced with current smoking (1.35, 1.13–1.61) and per standard deviation increase in age at first CAD (0.74, 0.67–0.82). Additionally, age at enrolment, CAD PRS, C-reactive protein, lipoprotein(a), glucose, low-density lipoprotein cholesterol, deprivation, sleep quality, eGFR, and high-density lipoprotein (HDL) cholesterol also significantly associated with recurrence risk. Based on C indices (95% CI), the strongest predictors were CAD PRS (0.58, 0.57–0.59), HDL cholesterol (0.57, 0.57–0.58), and age at initial CAD event (0.57, 0.56–0.57). In addition to traditional risk factors, a comprehensive model improved the C index from 0.644 (0.632–0.654) to 0.676 (0.667–0.686). Conclusion Sociodemographic, clinical, and laboratory factors are each associated with CAD recurrence with genetic risk, age at first CAD event, and HDL cholesterol concentration explaining the most.

Funder

Korea Health Technology

Korea Health Industry Development Institute

Ministry of Health & Welfare

National Heart, Lung, and Blood Institute

American Heart Association

Harvard Catalyst Medical Research

National Human Genetics Research Institute

National Institute of Diabetes and Digestive and Kidney Diseases

Massachusetts General Hospital

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

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