Limitations of Contemporary Guidelines for Managing Patients at High Genetic Risk of Coronary Artery Disease.
Adult
Aged
Aged, 80 and over
Coronary Artery Disease
/ epidemiology
Databases, Factual
/ standards
Delivery of Health Care
/ methods
Disease Management
Electronic Health Records
/ standards
Female
Genetic Predisposition to Disease
/ epidemiology
Humans
Male
Middle Aged
Multifactorial Inheritance
/ genetics
Practice Guidelines as Topic
/ standards
Risk Factors
coronary artery disease
genetic risk
primary prevention
statin
Journal
Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365
Informations de publication
Date de publication:
09 06 2020
09 06 2020
Historique:
received:
15
01
2020
revised:
31
03
2020
accepted:
07
04
2020
entrez:
6
6
2020
pubmed:
6
6
2020
medline:
6
1
2021
Statut:
ppublish
Résumé
Polygenic risk scores (PRS) for coronary artery disease (CAD) identify high-risk individuals more likely to benefit from primary prevention statin therapy. Whether polygenic CAD risk is captured by conventional paradigms for assessing clinical cardiovascular risk remains unclear. This study sought to intersect polygenic risk with guideline-based recommendations and management patterns for CAD primary prevention. A genome-wide CAD PRS was applied to 47,108 individuals across 3 U.S. health care systems. The authors then assessed whether primary prevention patients at high polygenic risk might be distinguished on the basis of greater guideline-recommended statin eligibility and higher rates of statin therapy. Of 47,108 study participants, the mean age was 60 years, and 11,020 (23.4%) had CAD. The CAD PRS strongly associated with prevalent CAD (odds ratio: 1.4 per SD increase in PRS; p < 0.0001). High polygenic risk (top 20% of PRS) conferred 1.9-fold odds of developing CAD (p < 0.0001). However, among primary prevention patients (n = 33,251), high polygenic risk did not correspond with increased recommendations for statin therapy per the American College of Cardiology/American Heart Association (46.2% for those with high PRS vs. 46.8% for all others, p = 0.54) or U.S. Preventive Services Task Force (43.7% vs. 43.7%, p = 0.99) or higher rates of statin prescriptions (25.0% vs. 23.8%, p = 0.04). An additional 4.1% of primary prevention patients may be recommended for statin therapy if high CAD PRS were considered a guideline-based risk-enhancing factor. Current paradigms for primary cardiovascular prevention incompletely capture a polygenic susceptibility to CAD. An opportunity may exist to improve CAD prevention efforts by integrating both genetic and clinical risk.
Sections du résumé
BACKGROUND
Polygenic risk scores (PRS) for coronary artery disease (CAD) identify high-risk individuals more likely to benefit from primary prevention statin therapy. Whether polygenic CAD risk is captured by conventional paradigms for assessing clinical cardiovascular risk remains unclear.
OBJECTIVES
This study sought to intersect polygenic risk with guideline-based recommendations and management patterns for CAD primary prevention.
METHODS
A genome-wide CAD PRS was applied to 47,108 individuals across 3 U.S. health care systems. The authors then assessed whether primary prevention patients at high polygenic risk might be distinguished on the basis of greater guideline-recommended statin eligibility and higher rates of statin therapy.
RESULTS
Of 47,108 study participants, the mean age was 60 years, and 11,020 (23.4%) had CAD. The CAD PRS strongly associated with prevalent CAD (odds ratio: 1.4 per SD increase in PRS; p < 0.0001). High polygenic risk (top 20% of PRS) conferred 1.9-fold odds of developing CAD (p < 0.0001). However, among primary prevention patients (n = 33,251), high polygenic risk did not correspond with increased recommendations for statin therapy per the American College of Cardiology/American Heart Association (46.2% for those with high PRS vs. 46.8% for all others, p = 0.54) or U.S. Preventive Services Task Force (43.7% vs. 43.7%, p = 0.99) or higher rates of statin prescriptions (25.0% vs. 23.8%, p = 0.04). An additional 4.1% of primary prevention patients may be recommended for statin therapy if high CAD PRS were considered a guideline-based risk-enhancing factor.
CONCLUSIONS
Current paradigms for primary cardiovascular prevention incompletely capture a polygenic susceptibility to CAD. An opportunity may exist to improve CAD prevention efforts by integrating both genetic and clinical risk.
Identifiants
pubmed: 32498804
pii: S0735-1097(20)34939-1
doi: 10.1016/j.jacc.2020.04.027
pmc: PMC7346975
mid: NIHMS1592979
pii:
doi:
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2769-2780Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL139731
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL105780
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM124836
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL092577
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139865
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148565
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142711
Pays : United States
Organisme : CSRD VA
ID : IK2 CX001780
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008685
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148050
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 American College of Cardiology Foundation. All rights reserved.
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