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. 2021 Nov 7;42(42):4324-4332.
doi: 10.1093/eurheartj/ehab432.

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

Renato Quispe  1   2 , Seth Shay Martin  1   2 , Erin Donelly Michos  1   2 , Isha Lamba  3 , Roger Scott Blumenthal  1   2 , Anum Saeed  4 , Joao Lima  2   5 , Rishi Puri  6 , Sarah Nomura  7 , Michael Tsai  7 , John Wilkins  8 , Christie Mitchell Ballantyne  9 , Stephen Nicholls  10 , Steven Richard Jones  1   2 , Mohamed Badreldin Elshazly  1   6
Affiliations

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

Renato Quispe et al. Eur Heart J. .

Abstract

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.

Keywords: Apolipoprotein B; LDL-cholesterol; Primary prevention; Remnant cholesterol.

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Figures

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Graphical abstract
Figure 1
Figure 1
Proportions of discordance among individuals with LDL-C below clinical cutpoints.
See this image and copyright information in PMC

Comment in

  • Keeping remnants in perspective.
    Borén J, Packard CJ. Borén J, et al. Eur Heart J. 2021 Nov 7;42(42):4333-4335. doi: 10.1093/eurheartj/ehab531. Eur Heart J. 2021. PMID: 34352097 No abstract available.

References

    1. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670–1681. - PMC - PubMed
    1. Wong ND, Zhao Y, Quek RGW, Blumenthal RS, Budoff MJ, Cushman M, Garg P, Sandfort V, Tsai M, Lopez JAG. Residual atherosclerotic cardiovascular disease risk in statin-treated adults: the Multi-Ethnic Study of Atherosclerosis. J Clin Lipidol 2017;11:1223–1233. - PMC - PubMed
    1. Sirimarco G, Labreuche J, Bruckert E, Goldstein LB, Fox KM, Rothwell PM, Amarenco P; PERFORM and SPARCL Investigators and Committees. Atherogenic dyslipidemia and residual cardiovascular risk in statin-treated patients. Stroke 2014;45:1429–1436. - PubMed
    1. Fruchart JC, Sacks FM, Hermans MP, Assmann G, Brown WV, Ceska R, Chapman MJ, Dodson PM, Fioretto P, Ginsberg HN, Kadowaki T, Lablanche JM, Marx N, Plutzky J, Reiner Z, Rosenson RS, Staels B, Stock JK, Sy R, Wanner C, Zambon A, Zimmet P; Residual Risk Reduction Initiative (R3I). The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patient. Diabetes Vasc Dis Res 2008;5:319–335. - PubMed
    1. Joshi PH, Martin SS, Blumenthal RS. The remnants of residual risk. J Am Coll Cardiol 2015;65:2276–2278. - PubMed

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