Kasen Culler, Leila R Zelnick, Rupal C Mehta, Giselle R de Sosa, Mayank Kansal, Panduranga S Rao, Zeenat Bhat, Jonathan Taliercio, Edward Horwitz, Jing Chen, Jiang He, Sanjiv J Shah, Tamara Isakova, Ravi B Patel
{"title":"慢性肾脏病患者ICAM1 p.K56M变异与心衰风险：慢性肾功能不全队列研究","authors":"Kasen Culler, Leila R Zelnick, Rupal C Mehta, Giselle R de Sosa, Mayank Kansal, Panduranga S Rao, Zeenat Bhat, Jonathan Taliercio, Edward Horwitz, Jing Chen, Jiang He, Sanjiv J Shah, Tamara Isakova, Ravi B Patel","doi":"10.1136/heartjnl-2024-325205","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein that facilitates inflammation through leucocyte adhesion. Approximately 35% of Black individuals carry at least one copy of an <i>ICAM1</i> missense variant (rs5491; p.K56M), which has been associated with increased risk of heart failure (HF) with preserved ejection fraction (HFpEF). Whether the risk of HFpEF conferred by rs5491 extends to individuals with chronic kidney disease (CKD), a cohort at high risk for HF, is unknown.</p><p><strong>Aims: </strong>We investigated the association between rs5491 and the incidence of HF in CKD.</p><p><strong>Methods: </strong>We estimated associations of rs5491 with incident HF and HF subtypes among Black individuals who were free from HF at baseline in the Chronic Renal Insufficiency Cohort (CRIC). The CRIC study recruited individuals who were 21-74 years old with estimated glomerular filtration rate (eGFR) of 20-70 mL/min/1.73 m<sup>2</sup> at baseline.</p><p><strong>Results: </strong>Among 1267 Black participants (mean age 57±11 years, 51% female, mean eGFR 45±15 mL/min/1.73 m<sup>2</sup>), 464 (37%) had at least one copy of rs5491. During a median follow-up of 10.3 years (IQR: 4.7-15.0 years), there were 309 incident overall HF hospitalisations (160 HFpEF, 111 HF with reduced ejection fraction (HFrEF) and 38 HF with unknown ejection fraction). Each additional rs5491 allele was significantly associated with incident HFpEF (HR 1.35, 95% CI 1.03 to 1.76, p=0.029). The rs5491 variant was not associated with incident overall HF (HR 1.14, 95% CI 0.93 to 1.39, p=0.20) or incident HFrEF (HR 0.76, 95% CI 0.53 to 1.10, p=0.15).</p><p><strong>Conclusion: </strong>The <i>ICAM1</i> p.K56M variant is specifically associated with increased risk of incident HFpEF among individuals with CKD.</p>","PeriodicalId":12835,"journal":{"name":"Heart","volume":" ","pages":"441-444"},"PeriodicalIF":5.1000,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048245/pdf/","citationCount":"0","resultStr":"{\"title\":\"The <i>ICAM1</i> p.K56M variant and risk of heart failure in chronic kidney disease: the Chronic Renal Insufficiency Cohort study.\",\"authors\":\"Kasen Culler, Leila R Zelnick, Rupal C Mehta, Giselle R de Sosa, Mayank Kansal, Panduranga S Rao, Zeenat Bhat, Jonathan Taliercio, Edward Horwitz, Jing Chen, Jiang He, Sanjiv J Shah, Tamara Isakova, Ravi B Patel\",\"doi\":\"10.1136/heartjnl-2024-325205\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein that facilitates inflammation through leucocyte adhesion. Approximately 35% of Black individuals carry at least one copy of an <i>ICAM1</i> missense variant (rs5491; p.K56M), which has been associated with increased risk of heart failure (HF) with preserved ejection fraction (HFpEF). Whether the risk of HFpEF conferred by rs5491 extends to individuals with chronic kidney disease (CKD), a cohort at high risk for HF, is unknown.</p><p><strong>Aims: </strong>We investigated the association between rs5491 and the incidence of HF in CKD.</p><p><strong>Methods: </strong>We estimated associations of rs5491 with incident HF and HF subtypes among Black individuals who were free from HF at baseline in the Chronic Renal Insufficiency Cohort (CRIC). The CRIC study recruited individuals who were 21-74 years old with estimated glomerular filtration rate (eGFR) of 20-70 mL/min/1.73 m<sup>2</sup> at baseline.</p><p><strong>Results: </strong>Among 1267 Black participants (mean age 57±11 years, 51% female, mean eGFR 45±15 mL/min/1.73 m<sup>2</sup>), 464 (37%) had at least one copy of rs5491. During a median follow-up of 10.3 years (IQR: 4.7-15.0 years), there were 309 incident overall HF hospitalisations (160 HFpEF, 111 HF with reduced ejection fraction (HFrEF) and 38 HF with unknown ejection fraction). Each additional rs5491 allele was significantly associated with incident HFpEF (HR 1.35, 95% CI 1.03 to 1.76, p=0.029). The rs5491 variant was not associated with incident overall HF (HR 1.14, 95% CI 0.93 to 1.39, p=0.20) or incident HFrEF (HR 0.76, 95% CI 0.53 to 1.10, p=0.15).</p><p><strong>Conclusion: </strong>The <i>ICAM1</i> p.K56M variant is specifically associated with increased risk of incident HFpEF among individuals with CKD.</p>\",\"PeriodicalId\":12835,\"journal\":{\"name\":\"Heart\",\"volume\":\" \",\"pages\":\"441-444\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2025-05-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048245/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Heart\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/heartjnl-2024-325205\",\"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":"Heart","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/heartjnl-2024-325205","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
The ICAM1 p.K56M variant and risk of heart failure in chronic kidney disease: the Chronic Renal Insufficiency Cohort study.
Background: Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein that facilitates inflammation through leucocyte adhesion. Approximately 35% of Black individuals carry at least one copy of an ICAM1 missense variant (rs5491; p.K56M), which has been associated with increased risk of heart failure (HF) with preserved ejection fraction (HFpEF). Whether the risk of HFpEF conferred by rs5491 extends to individuals with chronic kidney disease (CKD), a cohort at high risk for HF, is unknown.
Aims: We investigated the association between rs5491 and the incidence of HF in CKD.
Methods: We estimated associations of rs5491 with incident HF and HF subtypes among Black individuals who were free from HF at baseline in the Chronic Renal Insufficiency Cohort (CRIC). The CRIC study recruited individuals who were 21-74 years old with estimated glomerular filtration rate (eGFR) of 20-70 mL/min/1.73 m2 at baseline.
Results: Among 1267 Black participants (mean age 57±11 years, 51% female, mean eGFR 45±15 mL/min/1.73 m2), 464 (37%) had at least one copy of rs5491. During a median follow-up of 10.3 years (IQR: 4.7-15.0 years), there were 309 incident overall HF hospitalisations (160 HFpEF, 111 HF with reduced ejection fraction (HFrEF) and 38 HF with unknown ejection fraction). Each additional rs5491 allele was significantly associated with incident HFpEF (HR 1.35, 95% CI 1.03 to 1.76, p=0.029). The rs5491 variant was not associated with incident overall HF (HR 1.14, 95% CI 0.93 to 1.39, p=0.20) or incident HFrEF (HR 0.76, 95% CI 0.53 to 1.10, p=0.15).
Conclusion: The ICAM1 p.K56M variant is specifically associated with increased risk of incident HFpEF among individuals with CKD.
期刊介绍：
Heart is an international peer reviewed journal that keeps cardiologists up to date with important research advances in cardiovascular disease. New scientific developments are highlighted in editorials and put in context with concise review articles. There is one free Editor’s Choice article in each issue, with open access options available to authors for all articles. Education in Heart articles provide a comprehensive, continuously updated, cardiology curriculum.
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