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Association of remnant cholesterol with frailty: findings from observational and Mendelian randomization analyses

BACKGROUND: Recent insights suggest that remnant cholesterol (RC) plays a role in cellular senescence, yet its specific contribution to frailty remains indeterminate. Through the integration of observational and mendelian randomization (MR) studies, this research explores the impact of elevated seru...

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Autores principales: Hu, Yuanlong, Wang, Xiaojie, Lin, Lin, Huan, Jiaming, Li, Yuan, Zhang, Lei, Li, Yunlun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399004/
https://www.ncbi.nlm.nih.gov/pubmed/37537564
http://dx.doi.org/10.1186/s12944-023-01882-4
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author Hu, Yuanlong
Wang, Xiaojie
Lin, Lin
Huan, Jiaming
Li, Yuan
Zhang, Lei
Li, Yunlun
author_facet Hu, Yuanlong
Wang, Xiaojie
Lin, Lin
Huan, Jiaming
Li, Yuan
Zhang, Lei
Li, Yunlun
author_sort Hu, Yuanlong
collection PubMed
description BACKGROUND: Recent insights suggest that remnant cholesterol (RC) plays a role in cellular senescence, yet its specific contribution to frailty remains indeterminate. Through the integration of observational and mendelian randomization (MR) studies, this research explores the impact of elevated serum RC levels on frailty susceptibility. METHODS: A dual-method approach, combining an observational study with an MR study, was employed to investigate the connection between RC and frailty. The observational study included 11,838 participants from the National Health and Nutrition Examination Survey. Multivariable logistic regression and propensity score matching were employed to control for potential confounders. The non-linear relationship was assessed using restricted cubic splines. To circumvent observational study limitations, a two-sample MR analysis was conducted using the inverse-variance weighted method, leveraging genome-wide association studies (GWAS) data. RESULTS: After adjusting for potential confounding variables, the observational study identified a significant association between high serum RC levels and frailty in middle-aged and older adults (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.20 to 2.33, P = 0.003), exhibiting a non-linear dose–response correlation (non-linear P = 0.011). This association persisted after propensity score matching (OR = 1.53, 95% CI = 1.14 to 2.06, P = 0.005). The MR study echoed these results, demonstrating a causal association of RC with the frailty index (β = 0.059, 95% CI = 0.033 to 0.085, P = 1.05E-05), consistent with the observational findings (β = 0.017, 95% CI = 0.008 to 0.026, P = 4.51E-04). CONCLUSION: This study provides evidence that higher RC levels amplify frailty risk in middle-aged and older adults, implying that the reduction of RC levels may present a promising strategy for frailty prevention and management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-023-01882-4.
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spelling pubmed-103990042023-08-04 Association of remnant cholesterol with frailty: findings from observational and Mendelian randomization analyses Hu, Yuanlong Wang, Xiaojie Lin, Lin Huan, Jiaming Li, Yuan Zhang, Lei Li, Yunlun Lipids Health Dis Research BACKGROUND: Recent insights suggest that remnant cholesterol (RC) plays a role in cellular senescence, yet its specific contribution to frailty remains indeterminate. Through the integration of observational and mendelian randomization (MR) studies, this research explores the impact of elevated serum RC levels on frailty susceptibility. METHODS: A dual-method approach, combining an observational study with an MR study, was employed to investigate the connection between RC and frailty. The observational study included 11,838 participants from the National Health and Nutrition Examination Survey. Multivariable logistic regression and propensity score matching were employed to control for potential confounders. The non-linear relationship was assessed using restricted cubic splines. To circumvent observational study limitations, a two-sample MR analysis was conducted using the inverse-variance weighted method, leveraging genome-wide association studies (GWAS) data. RESULTS: After adjusting for potential confounding variables, the observational study identified a significant association between high serum RC levels and frailty in middle-aged and older adults (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.20 to 2.33, P = 0.003), exhibiting a non-linear dose–response correlation (non-linear P = 0.011). This association persisted after propensity score matching (OR = 1.53, 95% CI = 1.14 to 2.06, P = 0.005). The MR study echoed these results, demonstrating a causal association of RC with the frailty index (β = 0.059, 95% CI = 0.033 to 0.085, P = 1.05E-05), consistent with the observational findings (β = 0.017, 95% CI = 0.008 to 0.026, P = 4.51E-04). CONCLUSION: This study provides evidence that higher RC levels amplify frailty risk in middle-aged and older adults, implying that the reduction of RC levels may present a promising strategy for frailty prevention and management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-023-01882-4. BioMed Central 2023-08-03 /pmc/articles/PMC10399004/ /pubmed/37537564 http://dx.doi.org/10.1186/s12944-023-01882-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hu, Yuanlong
Wang, Xiaojie
Lin, Lin
Huan, Jiaming
Li, Yuan
Zhang, Lei
Li, Yunlun
Association of remnant cholesterol with frailty: findings from observational and Mendelian randomization analyses
title Association of remnant cholesterol with frailty: findings from observational and Mendelian randomization analyses
title_full Association of remnant cholesterol with frailty: findings from observational and Mendelian randomization analyses
title_fullStr Association of remnant cholesterol with frailty: findings from observational and Mendelian randomization analyses
title_full_unstemmed Association of remnant cholesterol with frailty: findings from observational and Mendelian randomization analyses
title_short Association of remnant cholesterol with frailty: findings from observational and Mendelian randomization analyses
title_sort association of remnant cholesterol with frailty: findings from observational and mendelian randomization analyses
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399004/
https://www.ncbi.nlm.nih.gov/pubmed/37537564
http://dx.doi.org/10.1186/s12944-023-01882-4
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