Romit Bhattacharya, Christopher S Marnell, So Mi Jemma Cho, Aniruddh Patel, Yunfeng Ruan, Satoshi Koyama, Amanda Jowell, Mark Trinder, Sara Haidermota, Kim Lannery, Michael C Honigberg, Seyedeh M Zekevat, Ida Surakka, Gina M Peloso, Pradeep Natarajan
{"title":"临床、实验室和遗传因素对冠心病的重要性。","authors":"Romit Bhattacharya, Christopher S Marnell, So Mi Jemma Cho, Aniruddh Patel, Yunfeng Ruan, Satoshi Koyama, Amanda Jowell, Mark Trinder, Sara Haidermota, Kim Lannery, Michael C Honigberg, Seyedeh M Zekevat, Ida Surakka, Gina M Peloso, Pradeep Natarajan","doi":"10.1161/CIRCGEN.124.004937","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Prior work suggests modifiable cardiovascular risk factors (CRFs) account for 80% to 90% of the risk for incident myocardial infarction. The contributions of genetic and other novel CRFs have not been simultaneously assessed in contemporary data sets.</p><p><strong>Methods: </strong>In the United Kingdom Biobank, CRFs were identified and Cox proportional hazards models with traditional CRFs (hypertension, diabetes, dyslipidemia, waist-to-hip ratio, diet, exercise, alcohol, and socioeconomic deprivation) and contemporary/genetic CRFs (Lp(a) [lipoprotein(a)], hsCRP [high-sensitivity C-reactive protein], familial hypercholesterolemia variants, and polygenic risk score for coronary artery disease) were constructed for coronary artery disease. Coronary artery disease was defined as a first-time myocardial infarction diagnosis or coronary revascularization. R<sup>2</sup> was calculated for each model, and the percent contribution of each individual CRF was calculated by the R<sup>2</sup> percent decrease after its removal.</p><p><strong>Results: </strong>Among 299 707 individuals, the mean (SD) age was 56.2 (8.1) years, and 166 533 (55.6%) were women. Over a median (interquartile range) follow-up of 11.0 (9.6-12.5) years, 17 409 (5.8%) of participants developed myocardial infarction. R<sup>2</sup> increased from the base model (R<sup>2</sup>, 0.021 [0.020-0.022]), to the clinical model (R<sup>2</sup>, 0.045 [0.043-0.046]), to the contemporary/genetic model (R<sup>2</sup>, 0.053 [0.052-0.055]). The most powerful individual CRFs were hypertension (R<sup>2</sup> loss, 15.2% [14.5-17.1]) and polygenic risk score for coronary artery disease (R<sup>2</sup> loss, 12.4% [10.8-13.3]), followed by dyslipidemia (R<sup>2</sup> loss, 3.4% [2.6-3.5]), diabetes (R<sup>2</sup> loss, 2.2% [1.5-2.0]), hsCRP (R<sup>2</sup> loss, 1.8% [1.5-2.0]), and Lp(a) (R<sup>2</sup> loss, 1.5% [1.2-1.8]).</p><p><strong>Conclusions: </strong>Novel CRFs like polygenic risk score for coronary artery disease, hsCRP, and Lp(a) have similar importance, comparable to traditional CRFs such as hypertension, dyslipidemia, and diabetes, for incident myocardial infarction, highlighting important identifiable residual risk factors.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004937"},"PeriodicalIF":5.5000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240475/pdf/","citationCount":"0","resultStr":"{\"title\":\"Importance of Clinical, Laboratory, and Genetic Risk Factors for Incident CAD.\",\"authors\":\"Romit Bhattacharya, Christopher S Marnell, So Mi Jemma Cho, Aniruddh Patel, Yunfeng Ruan, Satoshi Koyama, Amanda Jowell, Mark Trinder, Sara Haidermota, Kim Lannery, Michael C Honigberg, Seyedeh M Zekevat, Ida Surakka, Gina M Peloso, Pradeep Natarajan\",\"doi\":\"10.1161/CIRCGEN.124.004937\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Prior work suggests modifiable cardiovascular risk factors (CRFs) account for 80% to 90% of the risk for incident myocardial infarction. The contributions of genetic and other novel CRFs have not been simultaneously assessed in contemporary data sets.</p><p><strong>Methods: </strong>In the United Kingdom Biobank, CRFs were identified and Cox proportional hazards models with traditional CRFs (hypertension, diabetes, dyslipidemia, waist-to-hip ratio, diet, exercise, alcohol, and socioeconomic deprivation) and contemporary/genetic CRFs (Lp(a) [lipoprotein(a)], hsCRP [high-sensitivity C-reactive protein], familial hypercholesterolemia variants, and polygenic risk score for coronary artery disease) were constructed for coronary artery disease. Coronary artery disease was defined as a first-time myocardial infarction diagnosis or coronary revascularization. R<sup>2</sup> was calculated for each model, and the percent contribution of each individual CRF was calculated by the R<sup>2</sup> percent decrease after its removal.</p><p><strong>Results: </strong>Among 299 707 individuals, the mean (SD) age was 56.2 (8.1) years, and 166 533 (55.6%) were women. Over a median (interquartile range) follow-up of 11.0 (9.6-12.5) years, 17 409 (5.8%) of participants developed myocardial infarction. R<sup>2</sup> increased from the base model (R<sup>2</sup>, 0.021 [0.020-0.022]), to the clinical model (R<sup>2</sup>, 0.045 [0.043-0.046]), to the contemporary/genetic model (R<sup>2</sup>, 0.053 [0.052-0.055]). The most powerful individual CRFs were hypertension (R<sup>2</sup> loss, 15.2% [14.5-17.1]) and polygenic risk score for coronary artery disease (R<sup>2</sup> loss, 12.4% [10.8-13.3]), followed by dyslipidemia (R<sup>2</sup> loss, 3.4% [2.6-3.5]), diabetes (R<sup>2</sup> loss, 2.2% [1.5-2.0]), hsCRP (R<sup>2</sup> loss, 1.8% [1.5-2.0]), and Lp(a) (R<sup>2</sup> loss, 1.5% [1.2-1.8]).</p><p><strong>Conclusions: </strong>Novel CRFs like polygenic risk score for coronary artery disease, hsCRP, and Lp(a) have similar importance, comparable to traditional CRFs such as hypertension, dyslipidemia, and diabetes, for incident myocardial infarction, highlighting important identifiable residual risk factors.</p>\",\"PeriodicalId\":10326,\"journal\":{\"name\":\"Circulation: Genomic and Precision Medicine\",\"volume\":\" \",\"pages\":\"e004937\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240475/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation: Genomic and Precision Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCGEN.124.004937\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation: Genomic and Precision Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCGEN.124.004937","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Importance of Clinical, Laboratory, and Genetic Risk Factors for Incident CAD.
Background: Prior work suggests modifiable cardiovascular risk factors (CRFs) account for 80% to 90% of the risk for incident myocardial infarction. The contributions of genetic and other novel CRFs have not been simultaneously assessed in contemporary data sets.
Methods: In the United Kingdom Biobank, CRFs were identified and Cox proportional hazards models with traditional CRFs (hypertension, diabetes, dyslipidemia, waist-to-hip ratio, diet, exercise, alcohol, and socioeconomic deprivation) and contemporary/genetic CRFs (Lp(a) [lipoprotein(a)], hsCRP [high-sensitivity C-reactive protein], familial hypercholesterolemia variants, and polygenic risk score for coronary artery disease) were constructed for coronary artery disease. Coronary artery disease was defined as a first-time myocardial infarction diagnosis or coronary revascularization. R2 was calculated for each model, and the percent contribution of each individual CRF was calculated by the R2 percent decrease after its removal.
Results: Among 299 707 individuals, the mean (SD) age was 56.2 (8.1) years, and 166 533 (55.6%) were women. Over a median (interquartile range) follow-up of 11.0 (9.6-12.5) years, 17 409 (5.8%) of participants developed myocardial infarction. R2 increased from the base model (R2, 0.021 [0.020-0.022]), to the clinical model (R2, 0.045 [0.043-0.046]), to the contemporary/genetic model (R2, 0.053 [0.052-0.055]). The most powerful individual CRFs were hypertension (R2 loss, 15.2% [14.5-17.1]) and polygenic risk score for coronary artery disease (R2 loss, 12.4% [10.8-13.3]), followed by dyslipidemia (R2 loss, 3.4% [2.6-3.5]), diabetes (R2 loss, 2.2% [1.5-2.0]), hsCRP (R2 loss, 1.8% [1.5-2.0]), and Lp(a) (R2 loss, 1.5% [1.2-1.8]).
Conclusions: Novel CRFs like polygenic risk score for coronary artery disease, hsCRP, and Lp(a) have similar importance, comparable to traditional CRFs such as hypertension, dyslipidemia, and diabetes, for incident myocardial infarction, highlighting important identifiable residual risk factors.
期刊介绍：
Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations.
Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
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