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Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study

Renato Quispe1,2, Seth Shay Martin1,2, Erin Donelly Michos1,2

  • 1Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA.

European Heart Journal
|July 22, 2021
PubMed

Insights

Remnant cholesterol (RC) increases atherosclerotic cardiovascular disease (ASCVD) risk, even beyond LDL-C and apoB. Elevated RC is linked to ASCVD in individuals without prior ASCVD, suggesting a need for further investigation into its role in primary prevention.

Area of Science:

  • Cardiovascular Medicine
  • Lipid Metabolism
  • Preventive Cardiology

Background:

  • Emerging evidence implicates remnant cholesterol (RC) in promoting atherosclerotic cardiovascular disease (ASCVD).
  • Traditional lipid markers like low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) are established ASCVD risk factors.
  • The independent contribution of RC to ASCVD risk in individuals without diagnosed ASCVD requires further elucidation.

Purpose of the Study:

  • To quantify the risk of incident ASCVD associated with remnant cholesterol (RC) levels.
  • To determine if RC confers additional risk beyond established markers like LDL-C and apoB in an ASCVD-free population.
  • To explore discordant risk profiles, specifically high RC with low LDL-C, and their association with ASCVD.

Main Methods:

  • Pooled data from 17,532 individuals across three large cohort studies (ARIC, MESA, YOUTH).
  • Remnant cholesterol calculated as non-HDL-C minus calculated LDL-C.
  • Adjusted Cox proportional hazards models and discordance analyses were employed to assess ASCVD risk.

Main Results:

  • After multivariable adjustment including LDL-C and apoB, elevated log RC levels were significantly associated with increased ASCVD risk (HR 1.65, 95% CI 1.45-1.89).
  • Individuals with high RC and low LDL-C demonstrated increased ASCVD risk compared to a concordant group (HR 1.21, 95% CI 1.08-1.34).
  • This association persisted even when discordance was evaluated against clinical LDL-C targets.

Conclusions:

  • Elevated remnant cholesterol (RC) is an independent predictor of ASCVD in individuals without prior ASCVD, beyond traditional risk factors, LDL-C, and apoB.
  • The findings suggest RC may play a significant role in ASCVD pathogenesis, potentially through mechanisms not fully captured by apoB.
  • Further research is warranted to investigate the biological mechanisms underlying RC's association with ASCVD and its potential utility in primary prevention strategies.
Abstract

Keywords:
Apolipoprotein BLDL-cholesterolPrimary preventionRemnant cholesterol

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