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

• Published in: Nature communications Vol. 15; no. 1; p. 2451
• Main Authors: Zhao, Yimin, Zhuang, Zhenhuang, Li, Yueying, Xiao, Wendi, Song, Zimin, Huang, Ninghao, Wang, Wenxiu, Dong, Xue, Jia, Jinzhu, Clarke, Robert, Huang, Tao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.03.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308/174; 692/4019/592/75; 692/53; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Comorbidity; Diabetes; Diabetes mellitus (non-insulin dependent); Health risks; Heart diseases; Humanities and Social Sciences; Ischemia; Lipoproteins; multidisciplinary; Multimorbidity; Risk factors; Risk sharing; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Triglycerides
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46686-x

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. Dysmetabolism of triglyceride-rich lipoproteins is considered a shared risk factor for cardiometabolic diseases, but their associations with cardiometabolic multimorbidity have not been fully understood. Here, the authors show that elevated levels of remnant cholesterol and triglycerides were observationally and genetically associated with a higher risk of cardiometabolic multimorbidity.