CBS - The 17th Left Main & Coronary Bifurcation Summit, CBS2025

科学研究

Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or with Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights from the AUGUSTUS Trial Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients How Will the Transition to hs-cTn Affect the Diagnosis of Type 1 and 2 MI? Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes: The Rapid Assessment of Possible ACS In the Emergency Department with High Sensitivity Troponin T (RAPID-TnT) Study Cutoff Value and Long-Term Prediction of Clinical Events by FFR Measured Immediately After Implantation of a Drug-Eluting Stent in Patients With Coronary Artery Disease: 1- to 3-Year Results From the DKCRUSH VII Registry Study 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC) Fourth Universal Definition of Myocardial Infarction (2018) Progression of Device-Detected Subclinical Atrial Fibrillation and the Risk of Heart Failure Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study

Sort by hits |<< 1 2 3 4 5 6 7 ...>>|

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