左主干暨冠状动脉分叉病变峰会，CBS2019 - CBS 2019

推荐文献

Discharge Against Medical Advice After Percutaneous Coronary Intervention in the United States Randomized Comparison of Ridaforolimus-Eluting and Zotarolimus-Eluting Coronary Stents 2-Year Clinical Outcomes: From the BIONICS and NIREUS Trials Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity Burden of 30-Day Readmissions After Percutaneous Coronary Intervention in 833,344 Patients in the United States: Predictors, Causes, and Cost Coronary Angiography after Cardiac Arrest without ST-Segment Elevation 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC) 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Hs-cTroponins for the prediction of recurrent cardiovascular events in patients with established CHD - A comparative analysis from the KAROLA study Validation of High-Risk Features for Stent-Related Ischemic Events as Endorsed by the 2017 DAPT Guidelines A Randomized Trial Comparing the NeoVas Sirolimus-Eluting Bioresorbable Scaffold and Metallic Everolimus-Eluting Stents

Sort by hits |<<... 6 7 8 9 10 11 12 ...>>|

Original ResearchVolume 72, Issue 3, July 2018

JOURNAL：J Am Coll Cardiol. Article Link

Blood CSF1 and CXCL12 as Causal Mediators of Coronary Artery Disease

J Sjaarda, H Gerstein, M Chong et al. Keywords: biomarker; coronary artery disease; CSF1; CXCL12; genetics; Mendelian randomization;

ABSTRACT

BACKGROUND - Identification of biomarkers that cause coronary artery disease (CAD) has led to important advances in prevention and treatment. Epidemiological analyses have identified many biomarker-CAD relationships; however, these associations may arise from reverse causation and/or confounding and therefore may not represent true causal associations. Mendelian randomization (MR) analyses overcome these limitations.

OBJECTIVES - This study sought to identify causal mediators of CAD through a comprehensive screen of 237 biomarkers using MR.

METHODS - MR was performed by identifying genetic determinants of 227 biomarkers in ORIGIN (Outcome Reduction With Initial Glargine Intervention) trial participants (N = 4,147) and combining these with genetic effects on CAD from the CARDIoGRAM consortium (60,801 cases and 123,504 controls). Blood concentrations of novel biomarkers identified by MR were then tested for association with incident major adverse cardiovascular events in ORIGIN.

RESULTS - Six biomarkers were found to be causally linked to CAD after adjustment for multiple hypothesis testing. The causal role of 4 of these is well documented, whereas macrophage colony-stimulating factor 1 (CSF1) and stromal cell–derived factor 1 (CXCL12) have not previously been reported, to the best of our knowledge. MR analysis predicted an 18% higher risk of CAD per SD increase in CSF1 (odds ratio: 1.18; 95% confidence interval: 1.08 to 1.30; p = 2.1 × 10−4) and epidemiological analysis identified a 16% higher risk of major adverse cardiovascular events per SD (hazard ratio: 1.16; 95% confidence interval: 1.09 to 1.23; p < 0.001). Elevated CXCL12 levels were also identified as a causal risk factor for CAD with consistent epidemiological results. Furthermore, genetically predicted CSF1 and CXCL12 levels were associated with CAD in the UK Biobank (n = 343,735).

CONCLUSIONS - The study identified CSF1 and CXCL12 as causal mediators of CAD in humans. Understanding the mechanism by which these markers mediate CAD will provide novel insights into CAD and could lead to new approaches to prevention. These results support targeting inflammatory processes and macrophages, in particular, to prevent CAD, consistent with the recent CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study). (Outcome Reduction With Initial Glargine Intervention [ORIGIN]; NCT00069784)

科研文章

荐读文献

Blood CSF1 and CXCL12 as Causal Mediators of Coronary Artery Disease

ABSTRACT