HDL 3 -C is a marker of coronary artery disease severity and inflammation in patients on statin therapy Rahul Chaudhary a , Marija Kinderytė b , Rohit Chaudhary c , Ajaypaul Sukhi a , Kevin Bliden b , Udaya Tantry d , Paul Gurbel b, ⁎ a Sinai Hospital of Baltimore, Baltimore, MD, USA b Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Falls Church FVA, USA c Peter Lee Associates, Sydney, Australia d Platelet and Thrombosis Research, Baltimore, MD, USA abstract article info Article history: Received 5 November 2018 Accepted 20 December 2018 Available online xxxx Introduction: Low high-density lipoprotein (HDL-C) and inflammation are risk factors for coronary artery disease (CAD). However, limited data are available determining the role of HDL-C sub-particles HDL 2 -C and HDL 3 -C for assessing CAD severity in patients on statin therapy. Methods: Blood samples were obtained prior to cardiac catheterization in 304 consecutive patients with suspected CAD on statin therapy in this sub-analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Detailed lipid profiling and oxidized LDL (ox-LDL) were ana- lyzed. CAD severity was angiographically defined as severe CAD (N75% luminal diameter stenosis [LDS]) and non-severe CAD (≤75% LDS). Multi-regression analysis was performed to test for statistical significance. Receiver operator curve (ROC) analysis was performed to determine cut-point for predicting severe CAD. Results: Patients with severe CAD had a significantly lower total-HDL-C, lower HDL 3 -C and higher lipoprotein (a) levels. HDL 3 -C and lipoprotein(a) cholesterol [Lp(a)-C] retained statistical significance on multiple regression analysis. ROC analysis showed HDL 3 -C to have a C-statistic of 0.60 (p = 0.003) and Lp(a)-C to have a C-statistic of 0.61 (p = 0.0007). Patients with HDL 3 -C ≤ 33 mg/dL and Lp(a)-C N 7 mg/dL were found to have significantly el- evated ox-LDL levels. Conclusion: In patients on statin therapy, HDL 3 -C and Lp(a)-C improve prediction of severe CAD compared to a traditional lipid panel. In addition, patients with HDL 3 -C ≤ 33 mg/dL and Lp(a)-C N 7 mg/dL have greater inflam- mation marked by ox-LDL. Further studies are needed to evaluate the utility of these novel biomarkers in predicting CAD severity. © 2018 Published by Elsevier Inc. Keywords: HDL 3 -C HDL sub-particles Lp(a)-C Coronary artery disease Inflammation Cholesterol 1. Introduction Coronary artery disease (CAD) is the leading cause of death and loss of disability-adjusted life years (DALYs) according to the World Health Or- ganization. The global projected rise in DALYs has been estimated to be from 47 million in 1990 up to 82 million by 2020 [1,2]. Due to the vast burden of the disease, much research has been focused on early detection and risk stratification of asymptomatic individuals for appropriate utiliza- tion of health care resources and improving mortality outcomes. In an effort to estimate the risk of developing atherosclerotic cardio- vascular disease (ASCVD), several risk calculators have been devised. The most recent update by the American College of Cardiology/ American Heart Association (ACC/AHA) recommended the use of the Pooled Cohort risk calculator for assessment of 10 year ASCVD risk. However, the risk calculator utilizes only total cholesterol and total high-density lipoprotein (HDL-C) from the lipid panel. It does not take into account potential contributions of lipoprotein subfractions to ASCVD risk. Recent reports have shown the utility of lipoprotein sub- particles in predicting CAD severity and adverse cardiovascular out- comes [3,4]. Multiple studies have shown a strong inverse correlation between HDL-C levels and risk of ASCVD [5,6]. Low levels of HDL-C and HDL-C subtype HDL 3 -C have been shown to be independent risk factors for CAD and cardiovascular events respectively [7–10]. With the introduc- tion of the ACC/AHA cholesterol management guidelines, it is estimated that approximately 13 million additional individuals became eligible for statin therapy [11]. Statins have also been shown to have an anti- inflammatory action which contributes to their beneficial effects be- yond low-density lipoprotein (LDL-C) lowering [12]. Several theories Cardiovascular Revascularization Medicine xxx (xxxx) xxx ⁎ Corresponding author at: Interventional Cardiology and Cardiovascular Medicine Research, Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, 3300 Gallows Road, Falls Church, VA 22042, USA. E-mail address: Paul.Gurbel@inova.org (P. Gurbel). CARREV-01467; No of Pages 6 https://doi.org/10.1016/j.carrev.2018.12.019 1553-8389/© 2018 Published by Elsevier Inc. Contents lists available at ScienceDirect Cardiovascular Revascularization Medicine Please cite this article as: R. Chaudhary, M. Kinderytė, R. Chaudhary, et al., HDL3-C is a marker of coronary artery disease severity and inflammation in patients on statin therap..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2018.12.019