Michael Weyrich, Sebastian Cremer, Martin Gerster, Tamim Sarakpi, Tina Rasper, Stephen Zewinger, Sammy R Patyna, David M Leistner, Gunnar H Heine, Christoph Wanner, Winfried März, Danilo Fliser, Stefanie Dimmeler, Andreas M Zeiher, Thimoteus Speer
{"title":"慢性肾脏病患者的 Y 染色体缺失与心血管事件","authors":"Michael Weyrich, Sebastian Cremer, Martin Gerster, Tamim Sarakpi, Tina Rasper, Stephen Zewinger, Sammy R Patyna, David M Leistner, Gunnar H Heine, Christoph Wanner, Winfried März, Danilo Fliser, Stefanie Dimmeler, Andreas M Zeiher, Thimoteus Speer","doi":"10.1161/CIRCULATIONAHA.124.069139","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease.</p><p><strong>Methods: </strong>LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study, n=279) and dialysis patients (4D study, n=544). The association between LOY and mortality, combined cardiovascular and heart failure-specific end points, and echocardiographic measures was assessed.</p><p><strong>Results: </strong>In CARE for HOMe, the frequency of LOY increased with age. LOY >17% was associated with increased mortality (heart rate, 2.58 [95% CI, 1.33-5.03]) and risk for cardiac decompensation or death (heart rate, 2.30 [95% CI, 1.23-4.27]). Patients with LOY >17% showed a significant decline of ejection fraction and an increase of E/E' within 5 years. Consistently, in the 4D study, LOY >17% was significantly associated with increased mortality (heart rate, 2.76 [95% CI, 1.83-4.16]), higher risk of death due to heart failure and sudden cardiac death (heart rate, 4.11 [95% CI, 2.09-8.08]), but not atherosclerotic events. Patients with LOY >17% showed significantly higher plasma levels of soluble interleukin 1 receptor-like 1, a biomarker for myocardial fibrosis. Mechanistically, intermediate monocytes from patients with LOY >17% showed significantly higher C-C chemokine receptor type 2 expression and higher plasma levels of the C-C chemokine receptor type 2 chemokine (C-C motif) ligand 2, which may have contributed to increased heart failure events.</p><p><strong>Conclusions: </strong>LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361358/pdf/","citationCount":"0","resultStr":"{\"title\":\"Loss of Y Chromosome and Cardiovascular Events in Chronic Kidney Disease.\",\"authors\":\"Michael Weyrich, Sebastian Cremer, Martin Gerster, Tamim Sarakpi, Tina Rasper, Stephen Zewinger, Sammy R Patyna, David M Leistner, Gunnar H Heine, Christoph Wanner, Winfried März, Danilo Fliser, Stefanie Dimmeler, Andreas M Zeiher, Thimoteus Speer\",\"doi\":\"10.1161/CIRCULATIONAHA.124.069139\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease.</p><p><strong>Methods: </strong>LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study, n=279) and dialysis patients (4D study, n=544). The association between LOY and mortality, combined cardiovascular and heart failure-specific end points, and echocardiographic measures was assessed.</p><p><strong>Results: </strong>In CARE for HOMe, the frequency of LOY increased with age. LOY >17% was associated with increased mortality (heart rate, 2.58 [95% CI, 1.33-5.03]) and risk for cardiac decompensation or death (heart rate, 2.30 [95% CI, 1.23-4.27]). Patients with LOY >17% showed a significant decline of ejection fraction and an increase of E/E' within 5 years. Consistently, in the 4D study, LOY >17% was significantly associated with increased mortality (heart rate, 2.76 [95% CI, 1.83-4.16]), higher risk of death due to heart failure and sudden cardiac death (heart rate, 4.11 [95% CI, 2.09-8.08]), but not atherosclerotic events. Patients with LOY >17% showed significantly higher plasma levels of soluble interleukin 1 receptor-like 1, a biomarker for myocardial fibrosis. Mechanistically, intermediate monocytes from patients with LOY >17% showed significantly higher C-C chemokine receptor type 2 expression and higher plasma levels of the C-C chemokine receptor type 2 chemokine (C-C motif) ligand 2, which may have contributed to increased heart failure events.</p><p><strong>Conclusions: </strong>LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.</p>\",\"PeriodicalId\":10331,\"journal\":{\"name\":\"Circulation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":35.5000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361358/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCULATIONAHA.124.069139\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCULATIONAHA.124.069139","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/15 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
背景：慢性肾脏病是心血管疾病，尤其是心力衰竭的最大风险因素之一。尽管药物治疗有所改善，但死亡率仍然很高。最近，实验研究表明，Y 染色体（LOY）的镶嵌缺失与雄性小鼠的心脏纤维化有关。由于弥漫性心脏纤维化是各种形式心力衰竭进展的共同点，我们确定了 LOY 与慢性肾脏病患者死亡率和心血管疾病预后的关系：我们对慢性肾脏病稳定期男性患者（CARE for HOMe 研究 [XXX]，n=279）和透析患者（4D 研究，n=544）的 LOY 进行了量化。评估了LOY与死亡率、心血管和心衰特异性综合终点以及超声心动图测量之间的关系：结果：在 HOMe CARE 中，LOY 的频率随年龄增长而增加。LOY>17%与死亡率（心率，2.58 [95% CI，1.33-5.03]）和心脏失代偿或死亡风险（心率，2.30 [95% CI，1.23-4.27]）增加有关。LOY>17%的患者在5年内射血分数显著下降，E/E'增加。同样，在4D研究中，LOY>17%与死亡率增加（心率，2.76 [95% CI，1.83-4.16]）、心力衰竭和心脏性猝死导致的死亡风险增加（心率，4.11 [95% CI，2.09-8.08]）显著相关，但与动脉粥样硬化事件无关。LOY>17%的患者血浆中可溶性白细胞介素1受体样1的水平明显更高，这是心肌纤维化的生物标志物。从机制上讲，LOY>17%患者的中间单核细胞显示出明显更高的C-C趋化因子受体2型表达和更高的C-C趋化因子受体2型趋化因子（C-C motif）配体2血浆水平，这可能是导致心衰事件增加的原因：结论：LOY能识别慢性肾脏病男性患者的高死亡率和心衰事件风险。
Loss of Y Chromosome and Cardiovascular Events in Chronic Kidney Disease.
Background: Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease.
Methods: LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study, n=279) and dialysis patients (4D study, n=544). The association between LOY and mortality, combined cardiovascular and heart failure-specific end points, and echocardiographic measures was assessed.
Results: In CARE for HOMe, the frequency of LOY increased with age. LOY >17% was associated with increased mortality (heart rate, 2.58 [95% CI, 1.33-5.03]) and risk for cardiac decompensation or death (heart rate, 2.30 [95% CI, 1.23-4.27]). Patients with LOY >17% showed a significant decline of ejection fraction and an increase of E/E' within 5 years. Consistently, in the 4D study, LOY >17% was significantly associated with increased mortality (heart rate, 2.76 [95% CI, 1.83-4.16]), higher risk of death due to heart failure and sudden cardiac death (heart rate, 4.11 [95% CI, 2.09-8.08]), but not atherosclerotic events. Patients with LOY >17% showed significantly higher plasma levels of soluble interleukin 1 receptor-like 1, a biomarker for myocardial fibrosis. Mechanistically, intermediate monocytes from patients with LOY >17% showed significantly higher C-C chemokine receptor type 2 expression and higher plasma levels of the C-C chemokine receptor type 2 chemokine (C-C motif) ligand 2, which may have contributed to increased heart failure events.
Conclusions: LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.
期刊介绍：
Circulation is a platform that publishes a diverse range of content related to cardiovascular health and disease. This includes original research manuscripts, review articles, and other contributions spanning observational studies, clinical trials, epidemiology, health services, outcomes studies, and advancements in basic and translational research. The journal serves as a vital resource for professionals and researchers in the field of cardiovascular health, providing a comprehensive platform for disseminating knowledge and fostering advancements in the understanding and management of cardiovascular issues.
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