Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome: Results of the ATHEROREMO-IVUS study
Introduction
In current clinical practice, the concentration of low-density lipoprotein (LDL) cholesterol is often used for risk stratification in coronary artery disease (CAD). However, LDL cholesterol represents merely one aspect of lipid metabolism. Lipidomic analyses have demonstrated that hundreds of molecular lipid species are present in human plasma [1]. It is reasonable to assume that some of these molecular lipid species are also directly involved in the development of atherosclerosis [2], [3], [4]. Assessment of such 'high risk' molecular lipids may further improve our understanding of the development of atherosclerosis and may also improve CAD risk stratification. In fact, we have recently identified several molecular lipid species that are associated with fatal outcome in patients with CAD by performing lipidomic analysis in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study [5].
So far, lipidomics studies in CAD have mostly examined associations with clinical cardiovascular outcomes. Investigations using sophisticated imaging techniques may provide further insight into the pathophysiological role of lipid species in CAD. Intravascular ultrasound virtual histology (IVUS-VH) is an in-vivo imaging technique that analyzes radiofrequency backscatter [6]. IVUS-VH imaging allows for accurate measurement of the extent of coronary atherosclerosis and of the composition of atherosclerotic plaque, including necrotic core tissue [6], [7], [8], [9]. Previous studies have demonstrated that the amount of necrotic core tissue on IVUS-VH predicts cardiovascular outcome [7], [8], [9]. Near-infrared spectroscopy (NIRS) is another in-vivo imaging technique that analyzes tissue scattering and absorption of light in the near-infrared wavelength region. NIRS allows for identification of plaques with lipid cores in coronary atherosclerosis [10]. We have recently demonstrated that the lipid core burden assessed by NIRS predicts cardiovascular outcome [11].
This study aims to investigate the associations of high risk molecular lipids, previously identified in the LURIC study, with coronary plaque characteristics assessed by IVUS-VH imaging, with coronary lipid core burden assessed by NIRS imaging, and with 1 year cardiovascular outcome in patients with CAD.
Section snippets
Study population
The design of The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis – Intravascular Ultrasound (ATHEROREMO-IVUS) study has been described in detail elsewhere [7], [12]. In brief, 581 patients who underwent diagnostic coronary angiography or percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) or stable angina pectoris were included between 2008 and 2011 in the Erasmus MC, Rotterdam, the Netherlands. The ATHEROREMO-IVUS study was
Baseline characteristics
Mean age of the patients was 61.5 ± 11.3 years, 75% were men, and 55% were admitted with ACS (Table 1). ACS patients had higher concentrations of CE 14:0, CE 18:3, CE 22:5, Cer(d18:1/16:0), Cer(d18:1/24:0), LacCer(d18:1/18:0) and Cer(d18:1/16:0)/Cer(d18:1/24:0) than patients with stable CAD (Table 2). Patients who used statins at hospital admission had lower concentrations of the majority of the molecular lipids compared to patients who did not used statins (Supplemental Table 1).
Association between molecular lipids and coronary plaque characteristics
Patients whose
Discussion
This study investigated the association of eight previously identified high risk cholesteryl ester, ceramide and lactosylceramide lipids and three ceramide ratios with coronary plaque characteristics on IVUS-VH and NIRS imaging, as well as with 1-year clinical outcome in patients with established CAD undergoing coronary angiography. The main finding is that higher plasma concentrations of several of these molecular lipid species are associated with more vulnerable plaque morphology, reflected
Funding sources
The ATHEROREMO-IVUS study was funded by the European Commission, Seventh Framework Programme (grant number FP7-HEALTH-2007-2.4.2-1). Jin M. Cheng was supported by the Netherlands Heart Foundation (grant number NHS2009B091).
Disclosures
Matti Suoniemi, Terhi Vihervaara, Marko Sysi-Aho, Kim Ekroos and Reijo Laaksonen are employed by Zora Biosciences, Espoo, Finland. Other authors declare no conflict of interest.
Acknowledgments
We would like to thank the following interventional cardiologists and technical staff for their contribution to this study: Eric Duckers, MD, PhD; Jurgen M.R. Ligthart; Nicolas van Mieghem, MD; Carl Schultz, MD, PhD; Karen T. Witberg and Felix Zijlstra, MD, PhD. We are indebted to professor Willem van der Giessen, who made a valuable contribution to the design and completion of the study, but passed away before finalization of this work.
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Contributed equally to this work.