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. 2022 Jun 21;79(24):2383-2397.
doi: 10.1016/j.jacc.2022.03.384.

Elevated Remnant Cholesterol Reclassifies Risk of Ischemic Heart Disease and Myocardial Infarction

Takahito Doi  1 , Anne Langsted  2 , Børge G Nordestgaard  3
Affiliations

Elevated Remnant Cholesterol Reclassifies Risk of Ischemic Heart Disease and Myocardial Infarction

Takahito Doi et al. J Am Coll Cardiol. .

Abstract

Background: Elevated remnant cholesterol causes ischemic heart disease.

Objectives: We tested the hypothesis that the inclusion of elevated remnant cholesterol will lead to appropriate reclassification of individuals who later experience myocardial infarction and ischemic heart disease.

Methods: For >10 years we followed up 41,928 white Danish individuals from the Copenhagen General Population Study without a history of ischemic cardiovascular disease, diabetes, and statin use. Using predefined cut points for elevated remnant cholesterol, we calculated net reclassification index (NRI) from below to above 5%, 7.5%, and/or 10% 10-year occurrence of myocardial infarction and ischemic heart disease defined as a composite of death from ischemic heart disease, myocardial infarction, and coronary revascularization.

Results: For individuals with remnant cholesterol levels ≥95th percentile (≥1.6 mmol/L, 61 mg/dL), 23% (P < 0.001) of myocardial infarction and 21% (P < 0.001) of ischemic heart disease were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly. Consequently, the addition of remnant cholesterol levels yielded NRI of 10% (95% CI: 1%-20%) for myocardial infarction and 5% (95% CI: -3% to 13%) for ischemic heart disease. Correspondingly, when reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% (P < 0.001) of individuals with myocardial infarction and 41% (P < 0.001) with ischemic heart disease were reclassified appropriately, leading to NRI of respectively 20% (95% CI: 9%-31%) and 11% (95% CI: 2%-21%).

Conclusions: Elevated remnant cholesterol levels considerably improve myocardial infarction and ischemic heart disease risk prediction.

Keywords: atherosclerotic cardiovascular disease; primary prevention; reclassification; triglyceride-rich lipoproteins; very-low-density lipoprotein.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by the Global Excellence Programme (to Dr Nordestgaard) and by the Research Fund for the Capital Region of Denmark (to Drs Doi and Langsted), by the Japanese College of Cardiology Overseas Research Fellowship (to Dr Doi) and by Scandinavia-Japan Sasakawa Foundation (to Dr Doi). Dr Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr Doi has reported talks sponsored by MSD. Dr Langsted has reported that she has no relationships relevant to the contents of this paper to disclose.

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