Elevated Lp(a) Levels Correlate with Severe and Multiple Coronary Artery Stenotic Lesions

Cynthia Al Hageh,1,* Stephanie Chacar,1,2,* Michella Ghassibe-Sabbagh,3 Daniel E Platt,4 Andreas Henschel,5 Hamdan Hamdan,1,2 Dominique Gauguier,6,7 Yara El Murr,3 Eman Alefishat,8,9 Elie Chammas,10 Siobhán O’Sullivan,1 Antoine Abchee,11 Moni Nader,2,9 Pierre A Zalloua1,9,12 1Department of Molecular Biology and Genetics, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 2Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 3Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon; 4Computational Biology Center, IBM TJ Watson Research Centre, Yorktown Hgts, NY, USA; 5Department of Electrical Engineering and Computer, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 6Université Paris Cité, INSERM UMR 1124, Paris, 75006, France; 7McGill University and Genome Quebec Innovation Centre, Montreal, QC, H3A 0G1, Canada; 8Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 9Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, 127788, United Arab Emirates; 10School of Medicine, Lebanese University, Beirut, Lebanon; 11Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates; 12Harvard T.H. Chan School of Public Health, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Pierre A Zalloua; Moni Nader, College of Medicine and Health Sciences, Khalifa University for Science and Technology, PO Box 127788, Abu Dhabi, United Arab Emirates, Email pierre.zalloua@ku.ac.ae; moni.nader@ku.ac.aeBackgrounds and Aims: The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis.Methods: Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries.Results: Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥ 35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with > 50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the LPA gene was significantly associated with CAD.Conclusion: Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis.Keywords: lipoprotein(a), cardiovascular diseases, stenosis