Cited by 117Diabetes, Cardiovascular Risks, and LipoproteinsLipoproteins and Cardiovascular HealthChronic Disease Management Strategies

Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity

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Zhao, Yimin, Zhuang, Zhenhuang, Li, Yueying, Xiao, Wendi, Song, Zimin, Huang, Ninghao, Wang, Wenxiu, Dong, Xue +3 more·2024·Nature Communications

Abstract

The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.

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  • Mendelian randomization analyses confirm a causal relationship between lifelong TRL elevation and ASCVD.

    “Observational cohorts demonstrate that higher TG and remnant cholesterol predict cardiovascular events independently of LDL-C, while Mendelian randomization analyses confirm a causal relationship between lifelong TRL elevation and ASCVD.”

    From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [58]

    The Results (Mendelian randomization analysis) report causal associations of genetically predicted remnant cholesterol and triglycerides with ischemic heart disease, supporting the claim for that cardiovascular outcome. The Discussion says MR estimates may indicate life-course effects, but the Results report no causal association with stroke; the paper therefore does not establish the broader claim about ASCVD as a whole. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Zhao, Y., Zhuang, Z., Li, Y., Xiao, W., Song, Z., Huang, N., Wang, W., Dong, X., Jia, J., Clarke, R., & Huang, T.
Affiliations
  • Peking University (CN)
  • University of Oxford (GB)
  • Ministry of Education of the People's Republic of China (CN)
Corresponding author
Huang, Tao
Venue
Nature Communications
Published
2024-03-19
Volume
15
Issue
1
Pages
2451-2451
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4392954776
Cited by
117
References
53
Citations by year
2026: 52 · 2025: 47 · 2024: 17
FWCI
38.20
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (82173499, 82204026)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Epidemiology › Chronic Disease Management Strategies
Keywords
remnant cholesterol, triglycerides, cardiometabolic multimorbidity, type 2 diabetes, ischemic heart disease, stroke, triglyceride-rich lipoproteins, disease progression, multi-state models, Mendelian randomization, genetic instruments, causal inference
MeSH terms
Multimorbidity, Cholesterol, Diabetes Mellitus, Type 2, Humans, Hypercholesterolemia, Risk Factors, Triglycerides, Myocardial Ischemia

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