Remnant Cholesterol, Not LDL Cholesterol, Explains Peripheral Artery Disease Risk Conferred by apoB: A Cohort Study

Benjamin N. Wadström, Kasper M. Pedersen, Anders B. Wulff, Børge G. Nordestgaard*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

2 Citationer (Scopus)

Abstract

BACKGROUND:
Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction.

METHODS:
apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003–2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004–2010).

RESULTS:
In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5–2.4) and 1.1 (95% CI, 1.0–1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4–2.1) and 0.9 (95% CI, 0.9–1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%–100%) and 8% (0%–46%), respectively; corresponding results were 63% (30%–100%) and 0% (0%–33%) for risk of chronic limb-threatening ischemia and 41% (27%–55%) and 54% (38%–70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings.

CONCLUSIONS:
PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.
OriginalsprogEngelsk
TidsskriftArteriosclerosis, Thrombosis, and Vascular Biology
Vol/bind44
Udgave nummer5
Sider (fra-til)1144-1155
Antal sider12
ISSN1079-5642
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
The authors thank the Independent Research Fund Denmark (grant 1030-00168B), Novo Nordisk Foundation (grant NNF21OC0071977), Johan and Lise Boserup Fund, Aase and Ejnar Danielsen Fund, and Herlev and Gentofte Hospital for providing funding. The funders had no role in the design of the study or collection, analysis, interpretation of data, or in writing the manuscript.

Publisher Copyright:
© 2024 American Heart Association, Inc.

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