The association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques assessed by near-infrared spectroscopy

Julie Caroline Sæther; Elisabeth Kleivhaug Vesterbekkmo; Bruna Gigante; Guro Fanneløb Giskeødegård; Tone Frost Bathen; Turid Follestad; Rune Wiseth; Erik Madssen; Anja Bye

doi:10.1016/j.ijcha.2023.101215

The association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques assessed by near-infrared spectroscopy

Int J Cardiol Heart Vasc. 2023 May 4:46:101215. doi: 10.1016/j.ijcha.2023.101215. eCollection 2023 Jun.

Authors

Julie Caroline Sæther^{1

2}, Elisabeth Kleivhaug Vesterbekkmo^{1

2

3}, Bruna Gigante⁴, Guro Fanneløb Giskeødegård⁵, Tone Frost Bathen¹, Turid Follestad^{6

7}, Rune Wiseth^{1

2}, Erik Madssen^{1

2}, Anja Bye^{1

2}

Affiliations

¹ Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
² Clinic of Cardiology, St. Olavs Hospital, Trondheim, Norway.
³ National Advisory Unit on Exercise Training as Medicine for Cardiopulmonary Conditions, Trondheim, Norway.
⁴ Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
⁶ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
⁷ Clinical Research Unit Central Norway, St. Olavs Hospital, Trondheim Norway.

Abstract

Background: Lipid content in coronary atheromatous plaques, measured by near-infrared spectroscopy (NIRS), can predict the risk of future coronary events. Biomarkers that reflect lipid content in coronary plaques may therefore improve coronary artery disease (CAD) risk assessment.

Purpose: We aimed to investigate the association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques in statin-treated patients with stable CAD undergoing percutaneous coronary intervention.

Methods: 56 patients with stable CAD underwent three-vessel imaging with NIRS when feasible. The coronary artery segment with the highest lipid content, defined as the maximum lipid core burden index within any 4 mm length across the entire lesion (maxLCBI_4mm), was defined as target segment. Lipoprotein subfractions and Lipoprotein a (Lp(a)) were analyzed in fasting serum samples by nuclear magnetic resonance spectroscopy and by standard in-hospital procedures, respectively. Penalized linear regression analyses were used to identify the best predictors of maxLCBI_4mm. The uncertainty of the lasso estimates was assessed as the percentage presence of a variable in resampled datasets by bootstrapping.

Results: Only modest evidence was found for an association between lipoprotein subfractions and maxLCBI_4mm. The lipoprotein subfractions with strongest potential as predictors according to the percentage presence in resampled datasets were Lp(a) (78.1 % presence) and free cholesterol in the smallest high-density lipoprotein (HDL) subfractions (74.3 % presence). When including established cardiovascular disease (CVD) risk factors in the regression model, none of the lipoprotein subfractions were considered potential predictors of maxLCBI_4mm.

Conclusion: In this study, serum levels of Lp(a) and free cholesterol in the smallest HDL subfractions showed the strongest potential as predictors for lipid content in coronary atheromatous plaques. Although the evidence is modest, our study suggests that measurement of lipoprotein subfractions may provide additional information with respect to coronary plaque composition compared to traditional lipid measurements, but not in addition to established risk factors. Further and larger studies are needed to assess the potential of circulating lipoprotein subfractions as meaningful biomarkers both for lipid content in coronary atheromatous plaques and as CVD risk markers.

Keywords: Coronary atherosclerosis; HDL subfractions; Lasso regression; Lp(a); NIRS; NMR spectroscopy; maxLCBI4mm.