Weiqiang Ruan MD , Xiaoqin Zhou MD , Huizhen Liu MS , Ting Wang MS , Guiying Zhang MS , Ke Lin MD
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Inverse-variance weighted analysis was undertaken as the primary analysis, with several sensitivity analyses applied.</p></div><div><h3>Results</h3><p>Hepatocyte growth factor (HGF) demonstrated a causal relationship with increased susceptibility to both any stroke (OR 1.111; 95 % CI 1.044 - 1.183; <em>P</em> = 9.50e-04) and ischemic stroke (OR 1.121; 95 % CI 1.047 - 1.200; <em>P</em> = 1.04e-03). Programmed cell death 1 ligand 1 (PD-L1) was negatively associated with atrial fibrillation risk (OR 0.936, 95 % CI 0.901 - 0.973; <em>P</em> = 7.69e-04). CCL20, CDCP1, Flt3L and IL-10RA were identified as causal coronary artery disease risk factors, while LIF and ST1A1 had protective effects. IL-4 and LIF-R demonstrated causal links with right heart functional changes.</p></div><div><h3>Conclusions</h3><p>Our MR study nominates specific circulating inflammatory cytokines as potential targets for CVD treatment and prevention. Further research into mechanisms and clinical translation are warranted.</p></div>","PeriodicalId":55064,"journal":{"name":"Heart & Lung","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Causal role of circulating inflammatory cytokines in cardiac diseases, structure and function\",\"authors\":\"Weiqiang Ruan MD , Xiaoqin Zhou MD , Huizhen Liu MS , Ting Wang MS , Guiying Zhang MS , Ke Lin MD\",\"doi\":\"10.1016/j.hrtlng.2024.04.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Inflammation is implicated in cardiovascular disease (CVD) pathogenesis, but causal roles of specific circulating inflammatory cytokines remain unclear. Mendelian randomization (MR) studies are well-poised to provide etiological insights beyond constraints of conventional research.</p></div><div><h3>Methods</h3><p>We conducted a large-scale MR study to investigate potential causal relationships of 91 inflammatory proteins with CVD outcomes and cardiac remodeling using summary-level genetic data. Outcomes included coronary artery disease, myocardial infarction, stroke, atrial fibrillation, heart failure, abdominal aortic aneurysm, deep vein thrombosis of lower extremities, pulmonary embolism, cardiac structure and functional parameters. Inverse-variance weighted analysis was undertaken as the primary analysis, with several sensitivity analyses applied.</p></div><div><h3>Results</h3><p>Hepatocyte growth factor (HGF) demonstrated a causal relationship with increased susceptibility to both any stroke (OR 1.111; 95 % CI 1.044 - 1.183; <em>P</em> = 9.50e-04) and ischemic stroke (OR 1.121; 95 % CI 1.047 - 1.200; <em>P</em> = 1.04e-03). Programmed cell death 1 ligand 1 (PD-L1) was negatively associated with atrial fibrillation risk (OR 0.936, 95 % CI 0.901 - 0.973; <em>P</em> = 7.69e-04). CCL20, CDCP1, Flt3L and IL-10RA were identified as causal coronary artery disease risk factors, while LIF and ST1A1 had protective effects. IL-4 and LIF-R demonstrated causal links with right heart functional changes.</p></div><div><h3>Conclusions</h3><p>Our MR study nominates specific circulating inflammatory cytokines as potential targets for CVD treatment and prevention. Further research into mechanisms and clinical translation are warranted.</p></div>\",\"PeriodicalId\":55064,\"journal\":{\"name\":\"Heart & Lung\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Heart & Lung\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0147956324000827\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Heart & Lung","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0147956324000827","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
背景炎症与心血管疾病(CVD)的发病机制有关,但特定循环炎性细胞因子的因果作用仍不清楚。方法我们开展了一项大规模的孟德尔随机化研究,利用汇总级遗传数据调查 91 种炎症蛋白与心血管疾病结局和心脏重塑的潜在因果关系。结果包括冠心病、心肌梗塞、中风、心房颤动、心力衰竭、腹主动脉瘤、下肢深静脉血栓、肺栓塞、心脏结构和功能参数。结果肝细胞生长因子(HGF)与任何中风(OR 1.111; 95 % CI 1.044 - 1.183; P = 9.50e-04)和缺血性中风(OR 1.121; 95 % CI 1.047 - 1.200; P = 1.04e-03)的易感性增加有因果关系。程序性细胞死亡 1 配体 1 (PD-L1) 与心房颤动风险呈负相关(OR 0.936,95 % CI 0.901 - 0.973;P = 7.69e-04)。CCL20、CDCP1、Flt3L和IL-10RA被确定为冠状动脉疾病的致病风险因素,而LIF和ST1A1则具有保护作用。IL-4和LIF-R与右心功能变化有因果关系。 结论:我们的磁共振研究发现,特定的循环炎性细胞因子是治疗和预防心血管疾病的潜在靶点。我们的磁共振研究发现,特定的循环炎症细胞因子是治疗和预防心血管疾病的潜在靶点。
Causal role of circulating inflammatory cytokines in cardiac diseases, structure and function
Background
Inflammation is implicated in cardiovascular disease (CVD) pathogenesis, but causal roles of specific circulating inflammatory cytokines remain unclear. Mendelian randomization (MR) studies are well-poised to provide etiological insights beyond constraints of conventional research.
Methods
We conducted a large-scale MR study to investigate potential causal relationships of 91 inflammatory proteins with CVD outcomes and cardiac remodeling using summary-level genetic data. Outcomes included coronary artery disease, myocardial infarction, stroke, atrial fibrillation, heart failure, abdominal aortic aneurysm, deep vein thrombosis of lower extremities, pulmonary embolism, cardiac structure and functional parameters. Inverse-variance weighted analysis was undertaken as the primary analysis, with several sensitivity analyses applied.
Results
Hepatocyte growth factor (HGF) demonstrated a causal relationship with increased susceptibility to both any stroke (OR 1.111; 95 % CI 1.044 - 1.183; P = 9.50e-04) and ischemic stroke (OR 1.121; 95 % CI 1.047 - 1.200; P = 1.04e-03). Programmed cell death 1 ligand 1 (PD-L1) was negatively associated with atrial fibrillation risk (OR 0.936, 95 % CI 0.901 - 0.973; P = 7.69e-04). CCL20, CDCP1, Flt3L and IL-10RA were identified as causal coronary artery disease risk factors, while LIF and ST1A1 had protective effects. IL-4 and LIF-R demonstrated causal links with right heart functional changes.
Conclusions
Our MR study nominates specific circulating inflammatory cytokines as potential targets for CVD treatment and prevention. Further research into mechanisms and clinical translation are warranted.
期刊介绍:
Heart & Lung: The Journal of Cardiopulmonary and Acute Care, the official publication of The American Association of Heart Failure Nurses, presents original, peer-reviewed articles on techniques, advances, investigations, and observations related to the care of patients with acute and critical illness and patients with chronic cardiac or pulmonary disorders.
The Journal''s acute care articles focus on the care of hospitalized patients, including those in the critical and acute care settings. Because most patients who are hospitalized in acute and critical care settings have chronic conditions, we are also interested in the chronically critically ill, the care of patients with chronic cardiopulmonary disorders, their rehabilitation, and disease prevention. The Journal''s heart failure articles focus on all aspects of the care of patients with this condition. Manuscripts that are relevant to populations across the human lifespan are welcome.