Results from the intermountain heart collaborative study Both the Novel NMR Biomarker of Inflammation, GlycA and HS-CRP, Are Independent and Additive Predictors of Future Cardiovascular Events Among Patients Undergoing Coronary Angiography Results from the intermountain heart collaborative study joseph b. muhlestein *† • Heidi t. may* • Oxana galenko* • kirk u. knowlton* ‡ • james d. otvos • margery a. connelly • donald l. lappé * • Jeffrey l anderson*† *Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, UT; † Cardiology Division, Department of Internal Medicine University of Utah, Salt Lake City, UT., ‡Cardiology Division, Department of Internal Medicine, University of California San Diego, San Diego, CA; §LipoScience, Laboratory Corporation of America ® Holdings FIGURES. MULTIVARIABLE HAZARD RATIOS (HR) FOR THE ASSOCIATION OF CATEGORIES OF GLYCA AND HSCRP TO MACE AND ITS COMPONENTS. BACKGROUND NMR spectroscopy has been very successful in analyzing various lipoprotein sub- particles. It has also revealed a variety of other biomarkers of potential interest, including one called GlycA. Plasma GlycA signals arise from mobile carbohydrate side-chains on circulating glycoproteins (including fibrinogen, α1- antichymotrypsin, haptoglobin-1, α1-1-antitrypsin, complement C3 and α1-acid glycoprotein), many of which are acute phase reactants associated with inflammation. GlycA has been associated with future cardiovascular (CV) risk among patients with or without pre-existing coronary artery disease (CAD). However, whether GlycA is an independent and additive risk predictor from other known inflammatory markers, such as high sensitivity C-reactive protein (hsCRP) needs further study. METHODS Patients (N=2,996) in the Intermountain Heart Collaborative Study who were >18 years of age, underwent angiography for coronary artery disease (CAD) determination, and had plasma levels of GlycA and hsCRP were studied. Baseline GlycA was determined by nuclear magnetic resonance (NMR) spectroscopy. Baseline hsCRP testing was performed with hsCRP Elisa by Sigma Aldrich (Cat #SE120041). GlycA and hsCRP concentrations were stratified into high and low categories by their median values: GlycA: median = 339 µmol/L (<339, n=1,053; >340, n=1,493; IQR: <281, >408) hsCRP: median = 6.25 mg/L (<6.25, n=1,499; >6.26, n=1,499; IQR: <2.32, >11.57) Categories of low and high GlycA and hsCRP were made to determine associations to endpoints: LowGlycA/low hsCRP, n=1,004 Low GlycA/high hsCRP, n=499 High GlycA/low hsCRP, n=493 High GlycA/high hsCRP, n= 1,000 Multivariable Cox hazard regression was utilized to determine the association of the high and low categories to major adverse cardiovascular events (MACE). MACE was defined as the first occurrence of death, follow-up myocardial infarction (MI), follow-up heart failure (HF) hospitalization, and stroke. Patients were followed for a mean of 7.0±2.8 (median: 7.9) years. GlycA and hsCRP were moderately correlated: spearman r=0.463, p<0.0001 MACE DEATH RESULTS TABLE 1. BASELINE CHARACTERISTICS Low GlycA/ Low hsCRP Low GlycA /high hsCRP High GlycA/ low hsCRP high hsCRP p-value Age (years) 63.9±11.7 63.1±12.2 64.5±12.1 63.1±12.3 0.12 Sex (male) 75.4% 66.3% 63.9% 56.5% <0.0001 Hypertension 63.0% 67.1% 70.4% 68.9% 0.01 Hyperlipidemia 66.7% 60.5% 70.6% 63.7% 0.004 Diabetes 20.8% 24.0% 26.2% 32.6% Family history 46.1% 47.3% 44.2% 44.0% 0.58 Smoking 17.1% 19.8% 13.8% 17.7% 0.09 HF 10.6% 14.6% 16.6% 22.6% 0.02 Renal failure 1.0% 1.6% 2.8% Prior MI 12.3% 12.6% 13.4% 15.1% 0.28 Prior stroke 2.4% 3.0% 4.5% 4.4% 0.05 Prior CAD 50.2% 46.3% 54.0% 47.7% 0.06 PVD 1.5% 2.2% 2.7% 0.18 Atrial fibrillation 28.0% 29.3% 25.4% 29.7% 0.34 Depression history 6.4% 7.6% 8.5% 11.6% BMI (kg/m2) Presentation Stable angina 53.3% 62.5% 53.0% USA 33.3% 33.7% 28.7% MI 3.7% 3.9% 18.3% CAD 65.6% 63.5% 66.5% 65.0% 0.78 MI HF HOSPITALIZATION TABLE 2. BASELINE LIPOPROTEIN PARTICLE LEVELS Low GlycA/ Low hsCRP Low GlycA /high hsCRP High GlycA/ low hsCRP high hsCRP p-value LDL-P (nmol/L) 994.3±325.6 996.1±310.9 1251.5±417.7 1236.4±411.6 <0.0001 HDL-P (µmol/L) 26.4±6.1 24.4±6.3 33.9±7.7 29.3±8.4 Small HDL-P 15.3±5.7 13.2±5.4 19.3±7.3 14.9±7.5 Medium HDL-P 7.9±5.4 8.0±5.4 10.6±6.7 11.2±7.3 Large HDL-P 3.2±2.1 4.0±2.5 3.8±2.4 STROKE CONCLUSIONS Baseline levels of both GlycA and hsCRP were found to be independent and additive markers of risk for future MACE, especially death and HF hospitalization. Further studies are need to determine the differential pathophysiology of these two markers. TABLE 3. FREQUENCY OF OUTCOMES Low GlycA/ Low hsCRP Low GlycA /high hsCRP High GlycA/ low hsCRP high hsCRP p-value MACE 33.5% 41.3% 35.7% 49.1% <0.0001 Death 17.1% 27.1% 22.5% 32.8% MI 16.1% 18.0% 17.4% 18.8% 0.47 HF hospitalization 4.4% 6.4% 6.3% 10.6% Stroke 6.0% 5.3% 6.8% 0.69 Conflicts of Interest: JDO and MAC are employees of LipoScience, Laboratory Corporation of America ® Holdings