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

Renato Quispe, Seth Shay Martin, Erin Donelly Michos, Isha Lamba, Roger Scott Blumenthal, Anum Saeed, Joao Lima, Rishi Puri, Sarah Nomura, Michael Tsai, John Wilkins, Christie Mitchell Ballantyne, Stephen Nicholls, Steven Richard Jones, Mohamed Badreldin Elshazly

Research output: Contribution to journalArticlepeer-review

145 Scopus citations


Aims: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. Methods and results: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.34). Similar results were shown when examining discordance across clinical cutpoints. Conclusions: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.

Original languageEnglish (US)
Pages (from-to)4324-4332
Number of pages9
JournalEuropean heart journal
Issue number42
StatePublished - Nov 7 2021

Bibliographical note

Publisher Copyright:
© 2021 Published on behalf of the European Society of Cardiology. All rights reserved.


  • Apolipoprotein B
  • LDL-cholesterol
  • Primary prevention
  • Remnant cholesterol


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