Mohammadreza Naderian, Marwan E Hamed, Ali A Vaseem, Kristjan Norland, Ozan Dikilitas, Azin Teymourzadeh, Kent R Bailey, Iftikhar J Kullo
{"title":"披露冠心病多基因风险评分对不良心血管事件的影响","authors":"Mohammadreza Naderian, Marwan E Hamed, Ali A Vaseem, Kristjan Norland, Ozan Dikilitas, Azin Teymourzadeh, Kent R Bailey, Iftikhar J Kullo","doi":"10.1161/CIRCGEN.124.004968","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In the MI-GENES clinical trial (URL: https://www.clinicaltrials.gov; Unique identifier: NCT01936675), participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (Framingham risk score group, n=103) or an integrated risk score (integrated risk score group [IRS<sub>g</sub>], n=104) that additionally included a polygenic risk score. After 6 months, IRS<sub>g</sub> participants had higher statin initiation and lower low-density lipoprotein cholesterol. We conducted a post hoc 10-year follow-up analysis to investigate whether disclosure of a polygenic risk score for CHD was associated with a reduction in major adverse cardiovascular events (MACE).</p><p><strong>Methods: </strong>Participants were followed from randomization in October 2013 to September 2023 to ascertain MACE, testing for CHD, and changes in risk factors. The primary outcome was time to first MACE, defined as cardiovascular death, nonfatal myocardial infarction, coronary revascularization, and nonfatal stroke. Statistical analyses included Cox proportional hazards regression and linear mixed-effects models.</p><p><strong>Results: </strong>We followed all participants who completed the trial, 100 in Framingham risk score group and 103 in IRS<sub>g</sub> (mean age at the end of follow-up, 68.2±5.2; 48% male). During a median follow-up of 9.5 years, 9 MACEs occurred in Framingham risk score group and 2 in IRS<sub>g</sub> (hazard ratio, 0.20 [95% CI, 0.04-0.94]; <i>P</i>=0.042). In Framingham risk score group, 47 (47%) underwent at least 1 diagnostic test for CHD, compared with 30 (29%) in IRS<sub>g</sub> (hazard ratio, 0.51 [95% CI, 0.32-0.81]; <i>P</i>=0.004). A higher proportion of IRS<sub>g</sub> participants were on statin therapy during the first 4 years postrandomization and had a greater reduction in low-density lipoprotein cholesterol for up to 3 years postrandomization. No significant differences were observed between 2 groups in other traditional cardiovascular risk factors during follow-up.</p><p><strong>Conclusions: </strong>Disclosure of an integrated risk score that included a polygenic risk score to individuals at intermediate risk for CHD was associated with lower MACE incidence after 10 years, likely due to higher statin initiation, leading to lower low-density lipoprotein cholesterol levels.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004968"},"PeriodicalIF":6.0000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of Disclosing a Polygenic Risk Score for Coronary Heart Disease on Adverse Cardiovascular Events.\",\"authors\":\"Mohammadreza Naderian, Marwan E Hamed, Ali A Vaseem, Kristjan Norland, Ozan Dikilitas, Azin Teymourzadeh, Kent R Bailey, Iftikhar J Kullo\",\"doi\":\"10.1161/CIRCGEN.124.004968\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In the MI-GENES clinical trial (URL: https://www.clinicaltrials.gov; Unique identifier: NCT01936675), participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (Framingham risk score group, n=103) or an integrated risk score (integrated risk score group [IRS<sub>g</sub>], n=104) that additionally included a polygenic risk score. After 6 months, IRS<sub>g</sub> participants had higher statin initiation and lower low-density lipoprotein cholesterol. We conducted a post hoc 10-year follow-up analysis to investigate whether disclosure of a polygenic risk score for CHD was associated with a reduction in major adverse cardiovascular events (MACE).</p><p><strong>Methods: </strong>Participants were followed from randomization in October 2013 to September 2023 to ascertain MACE, testing for CHD, and changes in risk factors. The primary outcome was time to first MACE, defined as cardiovascular death, nonfatal myocardial infarction, coronary revascularization, and nonfatal stroke. Statistical analyses included Cox proportional hazards regression and linear mixed-effects models.</p><p><strong>Results: </strong>We followed all participants who completed the trial, 100 in Framingham risk score group and 103 in IRS<sub>g</sub> (mean age at the end of follow-up, 68.2±5.2; 48% male). During a median follow-up of 9.5 years, 9 MACEs occurred in Framingham risk score group and 2 in IRS<sub>g</sub> (hazard ratio, 0.20 [95% CI, 0.04-0.94]; <i>P</i>=0.042). In Framingham risk score group, 47 (47%) underwent at least 1 diagnostic test for CHD, compared with 30 (29%) in IRS<sub>g</sub> (hazard ratio, 0.51 [95% CI, 0.32-0.81]; <i>P</i>=0.004). A higher proportion of IRS<sub>g</sub> participants were on statin therapy during the first 4 years postrandomization and had a greater reduction in low-density lipoprotein cholesterol for up to 3 years postrandomization. No significant differences were observed between 2 groups in other traditional cardiovascular risk factors during follow-up.</p><p><strong>Conclusions: </strong>Disclosure of an integrated risk score that included a polygenic risk score to individuals at intermediate risk for CHD was associated with lower MACE incidence after 10 years, likely due to higher statin initiation, leading to lower low-density lipoprotein cholesterol levels.</p>\",\"PeriodicalId\":10326,\"journal\":{\"name\":\"Circulation: Genomic and Precision Medicine\",\"volume\":\" \",\"pages\":\"e004968\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-03-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation: Genomic and Precision Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCGEN.124.004968\",\"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.124.004968","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Effect of Disclosing a Polygenic Risk Score for Coronary Heart Disease on Adverse Cardiovascular Events.
Background: In the MI-GENES clinical trial (URL: https://www.clinicaltrials.gov; Unique identifier: NCT01936675), participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (Framingham risk score group, n=103) or an integrated risk score (integrated risk score group [IRSg], n=104) that additionally included a polygenic risk score. After 6 months, IRSg participants had higher statin initiation and lower low-density lipoprotein cholesterol. We conducted a post hoc 10-year follow-up analysis to investigate whether disclosure of a polygenic risk score for CHD was associated with a reduction in major adverse cardiovascular events (MACE).
Methods: Participants were followed from randomization in October 2013 to September 2023 to ascertain MACE, testing for CHD, and changes in risk factors. The primary outcome was time to first MACE, defined as cardiovascular death, nonfatal myocardial infarction, coronary revascularization, and nonfatal stroke. Statistical analyses included Cox proportional hazards regression and linear mixed-effects models.
Results: We followed all participants who completed the trial, 100 in Framingham risk score group and 103 in IRSg (mean age at the end of follow-up, 68.2±5.2; 48% male). During a median follow-up of 9.5 years, 9 MACEs occurred in Framingham risk score group and 2 in IRSg (hazard ratio, 0.20 [95% CI, 0.04-0.94]; P=0.042). In Framingham risk score group, 47 (47%) underwent at least 1 diagnostic test for CHD, compared with 30 (29%) in IRSg (hazard ratio, 0.51 [95% CI, 0.32-0.81]; P=0.004). A higher proportion of IRSg participants were on statin therapy during the first 4 years postrandomization and had a greater reduction in low-density lipoprotein cholesterol for up to 3 years postrandomization. No significant differences were observed between 2 groups in other traditional cardiovascular risk factors during follow-up.
Conclusions: Disclosure of an integrated risk score that included a polygenic risk score to individuals at intermediate risk for CHD was associated with lower MACE incidence after 10 years, likely due to higher statin initiation, leading to lower low-density lipoprotein cholesterol levels.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
