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Cited by 175Genetic Associations and EpidemiologyLipoproteins and Cardiovascular HealthNutrition, Genetics, and Disease

Genetic Risk Prediction and a 2-Stage Risk Screening Strategy for Coronary Heart Disease

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Tikkanen, Emmi, Havulinna, Aki S., Palotie, Aarno, Salomaa, Veikko, Ripatti, Samuli·2013·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/atvbaha.112.301120PMC PMC4210840
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Abstract

Objective—: Genome-wide association studies have identified several genetic variants associated with coronary heart disease (CHD). The aim of this study was to evaluate the genetic risk discrimination and reclassification and apply the results for a 2-stage population risk screening strategy for CHD. Approach and Results—: We genotyped 28 genetic variants in 24 124 participants in 4 Finnish population-based, prospective cohorts (recruitment years 1992–2002). We constructed a multilocus genetic risk score and evaluated its association with incident cardiovascular disease events. During the median follow-up time of 12 years (interquartile range 8.75–15.25 years), we observed 1093 CHD, 1552 cardiovascular disease, and 731 acute coronary syndrome events. Adding genetic information to conventional risk factors and family history improved risk discrimination of CHD (C-index 0.856 versus 0.851; P =0.0002) and other end points (cardiovascular disease: C-index 0.840 versus 0.837, P =0.0004; acute coronary syndrome: C-index 0.859 versus 0.855, P =0.001). In a standard population of 100 000 individuals, additional genetic screening of subjects at intermediate risk for CHD would reclassify 2144 subjects (12%) into high-risk category. Statin allocation for these subjects is estimated to prevent 135 CHD cases over 14 years. Similar results were obtained by external validation, where the effects were estimated from a training data set and applied for a test data set. Conclusions—: Genetic risk score improves risk prediction of CHD and helps to identify individuals at high risk for the first CHD event. Genetic screening for individuals at intermediate cardiovascular risk could help to prevent future cases through better targeting of statins.

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  • Integrated models of PRS together with other lifestyle and clinical factors have enabled clinicians to more accurately quantify the risk of heart attack.

    “Additionally, integrated models of PRS together with other lifestyle and clinical factors have enabled clinicians to more accurately quantify the risk of heart attack for patients;”

    From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [9]

    The Methods and Results show that adding a genetic risk score to models with traditional factors, including smoking and clinical measures, improved coronary heart disease risk prediction and reclassification. The Discussion describes potential clinical value, but the paper models screening rather than showing that clinicians used these models to quantify patients’ heart-attack risk in practice. (LLM, conf=0.82)

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Research works printed but not linked: 31

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Authors
Tikkanen, E., Havulinna, A. S., Palotie, A., Salomaa, V., & Ripatti, S.
Affiliations
Broad Institute (US)
ORCID
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2013-09
Volume
33
Issue
9
Pages
2261-2266
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/atvbaha.112.301120
PMC
PMC4210840
OpenAlex
W2165670510
Cited by
175
References
4
Citations by year
2026: 2 · 2025: 8 · 2024: 10 · 2023: 13 · 2022: 20 · 2021: 13 · 2020: 15 · 2019: 9 · 2018: 14 · 2017: 16 · 2016: 21 · 2015: 17 · 2014: 13 · 2013: 2 · 2012: 2
FWCI
11.72
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
  • WOS
Funders
Wellcome Trust (098051)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
Keywords
coronary artery disease, polygenic risk score, genetic risk prediction, risk reclassification, risk discrimination, cardiovascular disease, acute coronary syndrome, genetic screening, intermediate cardiovascular risk, family history (medicine), genetic variants
MeSH terms
Adult, Coronary Disease, Female, Finland, Gene Frequency, Genetic Testing, Humans, Male, Mass Screening, Middle Aged, Phenotype, Predictive Value of Tests, Preventive Health Services, Prognosis, Prospective Studies, Risk Factors, Time Factors, Prevalence, Linear Models, Proportional Hazards Models, Molecular Epidemiology, Disease Progression, Risk Assessment, Patient Selection, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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