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. 2017 Jan;63(1):288-296.
doi: 10.1373/clinchem.2016.261636. Epub 2016 Nov 3.

A Novel Protein Glycan-Derived Inflammation Biomarker Independently Predicts Cardiovascular Disease and Modifies the Association of HDL Subclasses With Mortality

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A Novel Protein Glycan-Derived Inflammation Biomarker Independently Predicts Cardiovascular Disease and Modifies the Association of HDL Subclasses With Mortality

Robert W McGarrah et al. Clin Chem. .
Free PMC article

Abstract

Background: Evidence suggests that systemic inflammation may adversely impact HDL function. In this study we sought to evaluate the independent and incremental predictive performance of GlycA-a novel serum inflammatory biomarker that is an aggregate measure of enzymatically glycosylated acute phase proteins-and HDL subclasses on adverse events in a retrospective observational study of a secondary prevention population and to understand a priori defined potential interactions between GlycA and HDL subclasses.

Methods: GlycA and HDL subclasses were measured using proton nuclear magnetic resonance spectroscopy in 7617 individuals in the CATHGEN (CATHeterization GENetics) cardiac catheterization biorepository.

Results: GlycA was associated with presence [odds ratio (OR) 1.07 (1.02-1.13), P = 0.01] and extent [OR 1.08 (1.03, 1.12) P < 0.0005] of coronary artery disease and with all-cause mortality [hazard ratio (HR) 1.34 (1.29-1.39), P < 0.0001], cardiovascular mortality [1.37 (1.30-1.45), P < 0.0001] and noncardiovascular mortality [1.46 (1.39-1.54) P < 0.0001] in models adjusted for 10 cardiovascular risk factors. GlycA and smaller HDL subclasses had independent but opposite effects on mortality risk prediction, with smaller HDL subclasses being protective [HR 0.69 (0.66-0.72), P < 0.0001]. There was an interaction between GlycA and smaller HDL subclasses-increasing GlycA concentrations attenuated the inverse association of smaller HDL subclasses with mortality. Adding GlycA and smaller HDL subclasses into the GRACE (Global Registry of Acute Coronary Events) and Framingham Heart Study Risk Scores improved mortality risk prediction, discrimination and reclassification.

Conclusions: These findings highlight the interaction of systemic inflammation and HDL with clinical outcomes and may increase precision for clinical risk assessment in secondary prevention populations.

Conflict of interest statement

Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:

Employment or Leadership: None declared.

Consultant or Advisory Role: None declared.

Stock Ownership: None declared.

Honoraria: None declared.

Research Funding: J.P. Kelly, grant T32HL7101–39 from the NIH; W.E. Kraus, Institutional support from Liposcience, Incorporated; S.H. Shah, Sponsored research agreement between BMS and Duke.

Expert Testimony: None declared.

Patents: None declared.

Figures

Fig. 1
Fig. 1
GlycA and all-cause mortality. Adjusted Kaplan-Meier curve demonstrating the relationship between GlycA quartiles and all-cause mortality in fully adjusted models. HRs when compared to quartile 1 were as follows: quartile 2 HR 1.19 [1.05–1.35], P = 0.007; quartile 3 HR 1.42 [1.26–1.61], P = 0.004; quartile 4 HR 2.13 [1.89–2.40] P < 0.0001.
Fig. 2
Fig. 2
GlycA and all-cause mortality according to diabetes status. Adjusted Kaplan–Meier curves demonstrating the relationship between GlycA quartiles and all-cause mortality in fully adjusted models, stratified by diabetes status. DM, diabetes mellitus.
Fig. 3
Fig. 3
Effect of GlycA on the relationship between MS-HDL-P and mortality risk for a representative individual from CATHGEN. Mortality risk for a 62 year-old white male with hypertension, hyperlipidemia, CAD, and a BMI of 30 according to MS-HDL-P and GlycA concentrations. The curves are the probability of death at the median quartile values of MS-HDL-P estimated at GlycA concentrations.

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