Plasma levels of apolipoproteins C-III, A-IV, and E are independently associated with stable atherosclerotic cardiovascular disease

Atherosclerosis. 2019 Feb:281:17-24. doi: 10.1016/j.atherosclerosis.2018.11.006. Epub 2018 Nov 9.

Abstract

Background and aims: Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). As key regulators of lipoprotein metabolism, apolipoproteins (apos) are discussed as vascular risk factors. This study aimed to analyze associations of major plasma apos with coronary artery disease (CAD), peripheral artery disease (PAD) and carotid artery plaque (CAP) to elucidate their diagnostic potential in risk assessment.

Methods: ApoA-I, apoA-II, apoA-IV, apoB-100, apoC-I, apoC-III, apoE, and apoJ were simultaneously quantified in 3 μL EDTA-plasma by LC-MS/MS in a case-control subgroup of the Leipziger LIFE-Heart Study (N = 911). Confounder analysis with demographic, clinical covariates and serum lipids, cardiac, inflammatory, and hepatic markers were performed. Apos were associated with CAD, CAP, and PAD in a multivariate regression model.

Results: Fasting and statin therapy showed strongest effects on apo concentrations. Inverse correlations of HDL-related apos A-I, A-II, A-IV, and C-I were observed for troponin T and interleukin 6. Concentrations of apos A-II, B-100, C-I, and E were decreased under statin therapy. After adjustment for influencing factors and related lipids, only apoB-100 (odds ratio per one SD [OR], 1.39; 95% confidence interval [CI], 1.05-1.84) was independently associated with CAD while apoA-IV (OR, 0.74; 95% CI 0.58-0.95) indicated PAD. ApoB-100 (OR, 1.55; 95% CI, 1.18-2.04), apoC-III (OR, 1.30; 95% CI, 1.06-1.58), and apoE (OR, 1.34; 95% CI, 1.13-1.58) were associated with CAP.

Conclusions: Triglyceride rich lipoproteins (TRLs) associated apos A-IV, B-100, C-III, and E are independently associated with stable ASCVD, providing further evidence for a potential role of TRLs in atherogenesis.

Keywords: ASCVD; Apolipoproteins; Carotid artery plaque; Coronary artery disease; Peripheral artery disease; Targeted proteomics; Vascular risk assessment.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apolipoprotein C-III / blood*
  • Apolipoproteins A / blood*
  • Apolipoproteins E / blood*
  • Biomarkers / blood
  • Carotid Stenosis / blood*
  • Carotid Stenosis / diagnosis
  • Carotid Stenosis / drug therapy
  • Carotid Stenosis / epidemiology
  • Case-Control Studies
  • Coronary Stenosis / blood*
  • Coronary Stenosis / diagnosis
  • Coronary Stenosis / drug therapy
  • Coronary Stenosis / epidemiology
  • Dyslipidemias / blood*
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy
  • Dyslipidemias / epidemiology
  • Germany / epidemiology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Middle Aged
  • Peripheral Arterial Disease / blood*
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / drug therapy
  • Peripheral Arterial Disease / epidemiology
  • Prognosis
  • Protective Factors
  • Risk Assessment
  • Risk Factors

Substances

  • APOC3 protein, human
  • ApoE protein, human
  • Apolipoprotein C-III
  • Apolipoproteins A
  • Apolipoproteins E
  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • apolipoprotein A-IV