CBS 2019
CBSMD教育中心
中 文

科学研究

Abstract

Recommended Article

Robustness of Fractional Flow Reserve for Lesion Assessment in Non-Infarct-Related Arteries of Patients With Myocardial Infarction Impact of an optical coherence tomography guided approach in acute coronary syndromes: A propensity matched analysis from the international FORMIDABLE-CARDIOGROUP IV and USZ registry Diagnostic accuracy of fractional flow reserve from anatomic CT angiography Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment Optical Coherence Tomography-Guided Percutaneous Coronary Intervention in ST-Segment-Elevation Myocardial Infarction: A Prospective Propensity-Matched Cohort of the Thrombectomy Versus Percutaneous Coronary Intervention Alone Trial Exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and pulmonary vascular disease Left main coronary artery compression in pulmonary hypertension Rotational Atherectomy in acute STEMI with heavily calcified culprit lesion is a rule breaking solution
|<<... 185 186 187 188 189 190 191 ...>>|

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)
>CBS CBS 2019

> CBS 2019 REGISTRATION

> CBS 2019 PROGRAM

> CBS 2019 CALL FOR SCIENCE

> CBS 2019 SPOTLIGHTS

 CBSMD

> CBSMD WEBSITE REGISTRATION

> EDUCATION CENTER

> RECOMMANDED PAPER

> TOP 10 RESEARCH PAPER

> PRE-READING

CBS 2019 CBS 2019 FACULTY Education Resource CBSMD Scientific Library
Copyright ⓒ CBS MD Nanjing China. All rights reserved. 京ICP备16025898号-11
联系我们| Top