Relationship of apolipoprotein C-III proteoform composition with ankle-brachial index and peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis (MESA)

Juraj Koska, Spencer Hansen, Yueming Hu, Majken C. Jensen, Dean Billheimer, Dobrin Nedelkov, Matthew J. Budoff, Matthew Allison, Robyn L. McClelland, Peter D. Reaven

Research output: Contribution to journalArticlepeer-review

Abstract

Background and aims: Apolipoprotein C-III (apoC-III) proteoform composition shows distinct relationships with plasma lipids and cardiovascular risk. The present study tested whether apoC-III proteoforms are associated with risk of peripheral artery disease (PAD). Methods: ApoC-III proteoforms, i.e., native (C-III0a), and glycosylated with zero (C-III0b), one (C-III1) or two (C-III2) sialic acids, were measured by mass spectrometry immunoassay on 5,734 Multi-Ethnic Study of Atherosclerosis participants who were subsequently followed for clinical PAD over 17 years. Ankle-brachial index (ABI) was also assessed at baseline and then 3 and 10 years later in 4,830 participants. Results: Higher baseline C-III0b/C-III1 and lower baseline C-III2/C-III1 were associated with slower decline in ABI (follow-up adjusted for baseline) over time, independently of cardiometabolic risk factors, and plasma triglycerides and HDL cholesterol levels (estimated difference per 1 SD was 0.31 % for both, p < 0.01). The associations between C-III2/C-III1 and changes in ABI were stronger in men (−1.21 % vs. −0.27 % in women), and in Black and Chinese participants (−0.83 % and −0.86 % vs. 0.12 % in White). Higher C-III0b/C-III1 was associated with a trend for lower risk of PAD (HR = 0.84 [95%CI: 0.67–1.04]) that became stronger after excluding participants on lipid-lowering medications (0.73 [95%CI: 0.57–0.94]). Neither change in ABI nor clinical PAD was related to total apoC-III levels. Conclusions: We found associations of apoC-III proteoform composition with changes in ABI that were independent of other risk factors, including plasma lipids. Our data further support unique properties of apoC-III proteoforms in modulating vascular health that go beyond total apoC-III levels.

Original languageEnglish (US)
Article number117584
JournalAtherosclerosis
Volume395
DOIs
StatePublished - Aug 2024

Keywords

  • Ankle-brachial index
  • Apolipoproteins
  • Lipids
  • Peripheral artery disease
  • Posttranslational proteoforms

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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