Kraler, Simon; Wenzl, Florian A; Vykoukal, Jody; Fahrmann, Johannes F; Shen, Ming-Yi; Chen, Der-Yuan; Chang, Kuan-Cheng; Chang, Ching-Kun; von Eckardstein, Arnold; Räber, Lorenz; Mach, François; Nanchen, David; Matter, Christian M; Liberale, Luca; Camici, Giovanni G; Akhmedov, Alexander; Chen, Chu-Huang; Lüscher, Thomas F (2023). Low-density lipoprotein electronegativity and risk of death after acute coronary syndromes: A case-cohort analysis. Atherosclerosis, 376, pp. 43-52. Elsevier 10.1016/j.atherosclerosis.2023.05.014
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BACKGROUND AND AIMS
Low-density lipoprotein (LDL)-cholesterol (LDL-C) promotes atherosclerotic cardiovascular disease (ASCVD), with changes in LDL electronegativity modulating its pro-atherogenic/pro-thrombotic effects. Whether such alterations associate with adverse outcomes in patients with acute coronary syndromes (ACS), a patient population at particularly high cardiovascular risk, remains unknown.
METHODS
This is a case-cohort study using data from a subset of 2619 ACS patients prospectively recruited at four university hospitals in Switzerland. Isolated LDL was chromatographically separated into LDL particles with increasing electronegativity (L1-L5), with the L1-L5 ratio serving as a proxy of overall LDL electronegativity. Untargeted lipidomics revealed lipid species enriched in L1 (least) vs. L5 (most electronegative subfraction). Patients were followed at 30 days and 1 year. The mortality endpoint was reviewed by an independent clinical endpoint adjudication committee. Multivariable-adjusted hazard ratios (aHR) were calculated using weighted Cox regression models.
RESULTS
Changes in LDL electronegativity were associated with all-cause mortality at 30 days (aHR, 2.13, 95% CI, 1.07-4.23 per 1 SD increment in L1/L5; p=.03) and 1 year (1.84, 1.03-3.29; p=.04), with a notable association with cardiovascular mortality (2.29; 1.21-4.35; p=.01; and 1.88; 1.08-3.28; p=.03). LDL electronegativity superseded several risk factors for the prediction of 1-year death, including LDL-C, and conferred improved discrimination when added to the updated GRACE score (area under the receiver operating characteristic curve 0.74 vs. 0.79, p=.03). Top 10 lipid species enriched in L1 vs. L5 were: cholesterol ester (CE) (18:2), CE (20:4), free fatty acid (FA) (20:4), phosphatidyl-choline (PC) (36:3), PC (34:2), PC (38:5), PC (36:4), PC (34:1), triacylglycerol (TG) (54:3), and PC (38:6) (all p < .001), with CE (18:2), CE (20:4), PC (36:3), PC (34:2), PC (38:5), PC (36:4), TG (54:3), and PC (38:6) independently associating with fatal events during 1-year of follow-up (all p < .05).
CONCLUSIONS
Reductions in LDL electronegativity are linked to alterations of the LDL lipidome, associate with all-cause and cardiovascular mortality beyond established risk factors, and represent a novel risk factor for adverse outcomes in patients with ACS. These associations warrant further validation in independent cohorts.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology |
UniBE Contributor: |
Räber, Lorenz |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1879-1484 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
08 Jun 2023 11:20 |
Last Modified: |
08 Jun 2023 11:28 |
Publisher DOI: |
10.1016/j.atherosclerosis.2023.05.014 |
PubMed ID: |
37285778 |
Uncontrolled Keywords: |
Lipidomics Low-density lipoprotein Residual cardiovascular risk Risk prediction modelling |
BORIS DOI: |
10.48350/183252 |
URI: |
https://boris.unibe.ch/id/eprint/183252 |
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