Biomedical consequences of elevated cholesterol-containing lipoproteins and apolipoproteins on cardiovascular and non-cardiovascular outcomes
Issued Date
2023-12-01
Resource Type
eISSN
2730664X
Scopus ID
2-s2.0-85150765579
Journal Title
Communications Medicine
Volume
3
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Communications Medicine Vol.3 No.1 (2023)
Suggested Citation
Schmidt A.F., Joshi R., Gordillo-Marañón M., Drenos F., Charoen P., Giambartolomei C., Bis J.C., Gaunt T.R., Hughes A.D., Lawlor D.A., Wong A., Price J.F., Chaturvedi N., Wannamethee G., Franceschini N., Kivimaki M., Hingorani A.D., Finan C. Biomedical consequences of elevated cholesterol-containing lipoproteins and apolipoproteins on cardiovascular and non-cardiovascular outcomes. Communications Medicine Vol.3 No.1 (2023). doi:10.1038/s43856-022-00234-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98099
Title
Biomedical consequences of elevated cholesterol-containing lipoproteins and apolipoproteins on cardiovascular and non-cardiovascular outcomes
Author's Affiliation
Amsterdam Cardiovascular Sciences
Faculty of Tropical Medicine, Mahidol University
Bristol Medical School
NIHR Bristol Biomedical Research Centre
Edinburgh Medical School
Istituto Italiano di Tecnologia
University Medical Center Utrecht
University of Washington School of Medicine
University College London
Brunel University London
UNC Gillings School of Global Public Health
Mahidol University
Faculty of Tropical Medicine, Mahidol University
Bristol Medical School
NIHR Bristol Biomedical Research Centre
Edinburgh Medical School
Istituto Italiano di Tecnologia
University Medical Center Utrecht
University of Washington School of Medicine
University College London
Brunel University London
UNC Gillings School of Global Public Health
Mahidol University
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Higher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increase the risk of cardiovascular disease (CVD). The association of LDL-C with non-CVD traits remains unclear, as are the possible independent contributions of other cholesterol-containing lipoproteins and apolipoproteins. Methods: Nuclear magnetic resonance spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), as well as low-density lipoprotein fractions, the apolipoproteins Apo-A1 and Apo-B, as well as total triglycerides (TG), remnant-cholesterol (Rem-Chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 outcomes using univariable and multivariable Mendelian randomization (MR). Results: The majority of cholesterol containing lipoproteins and apolipoproteins affect coronary heart disease (CHD), carotid intima-media thickness, carotid plaque, C-reactive protein (CRP) and blood pressure. Multivariable MR indicated that many of these effects act independently of HDL-C, LDL-C and TG, the most frequently measured lipid fractions. Higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B increased heart failure (HF) risk; often independently of LDL-C, HDL-C or TG. Finally, a subset of these exposures associated with non-CVD traits such as Alzheimer’s disease (AD: HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (T2DM: VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (IBD: LDL-C, IDL-C). Conclusions: The cholesterol content of a wide range of lipoprotein and apolipoproteins associate with measures of atherosclerosis, blood pressure, CRP, and CHD, with a subset affecting HF, T2DM, AD and IBD risk. Many of the observed effects appear to act independently of LDL-C, HDL-C, and TG, supporting the targeting of lipid fractions beyond LDL-C for disease prevention.