Weiqiang Ruan MD , Xiaoqin Zhou MD , Huizhen Liu MS , Ting Wang MS , Guiying Zhang MS , Ke Lin MD
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引用次数: 0
Abstract
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.