CBS 2019
CBSMD教育中心
English

科学研究

科研文章

荐读文献

Comparison of 2 Different Drug-Coated Balloons in In-Stent Restenosis: The RESTORE ISR China Randomized Trial Long-term clinical outcomes after treatment of stent restenosis with two drug-coated balloons Pulmonary hypertension is associated with an increased incidence of NAFLD: A retrospective cohort study of 18,910 patients Outcomes After Orbital Atherectomy of Severely Calcified Left Main Lesions: Analysis of the ORBIT II Study Healed coronary plaque rupture as a cause of rapid lesion progression: a case demonstrated with in vivo histopathology by directional coronary atherectomy Drug-Coated Balloon for De Novo Coronary Artery Disease: JACC State-of-the-Art Review Orbital atherectomy for the treatment of small (2.5mm) severely calcified coronary lesions: ORBIT II sub-analysis A Notch3-Marked Subpopulation of Vascular Smooth Muscle Cells Is the Cell of Origin for Occlusive Pulmonary Vascular Lesions. Intravascular ultrasound enhances the safety of rotational atherectomy In vivo comparison of lipid-rich plaque on near-infrared spectroscopy with histopathological analysis of coronary atherectomy specimens
|<<... 161 162 163 164 165 166 167 ...>>|

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

> CBS 2019 注册

> CBS 2019 会议日程

> CBS 2019 学术征集

> CBS 2019 热点

 CBSMD

> CBSMD 网站注册

> 教育中心

> 荐读文献

> Top 10 阅读文献

> 文献导读
CBS 2019 CBS 2019 主席团 教育中心 科研动态
Copyright ⓒ CBS MD Nanjing China. All rights reserved. 京ICP备16025898号-11
联系我们| Top