The association of appendicular lean mass and grip strength with low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein particle diameter: a Mendelian randomization study of the UK Biobank cohort

Richard Kirwan; Mohsen Mazidi; Tom Butler; Fatima Perez de Heredia; Gregory Y H Lip; Ian G Davies

doi:10.1093/ehjopen/oeae019

The association of appendicular lean mass and grip strength with low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein particle diameter: a Mendelian randomization study of the UK Biobank cohort

Eur Heart J Open. 2024 Mar 14;4(2):oeae019. doi: 10.1093/ehjopen/oeae019. eCollection 2024 Mar.

Authors

Richard Kirwan^{1

2}, Mohsen Mazidi^{2

3

4}, Tom Butler⁵, Fatima Perez de Heredia⁶, Gregory Y H Lip^{2

7}, Ian G Davies^{1

2}

Affiliations

¹ Research Institute of Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK.
² Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, Liverpool Heart and Chest Hospital, Liverpool, UK.
³ Clinical Trial Service Unit, Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Roosevelt Dr., Doll Bldg, Oxford, OX3 7LF, UK.
⁴ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
⁵ School of Applied Health and Social Care and Social Work, Faculty of Health, Social Care and Medicine, Edge Hill University, Ormskirk, UK.
⁶ School of Biological and Environmental Sciences, Liverpool John Moores University, Liverpool, UK.
⁷ Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

Abstract

Aims: Reduced muscle mass and reduced strength are frequently associated with both alterations in blood lipids and poorer cardiometabolic outcomes in epidemiological studies; however, a causal association cannot be determined from such observations. Two-sample Mendelian randomization (MR) was applied to assess the association of genetically determined appendicular lean mass (ALM) and handgrip strength (HGS) with serum lipid particle diameter.

Methods and results: Mendelian randomization was implemented using summary-level data from the largest genome-wide association studies on ALM (n = 450 243), HGS (n = 223 315), and lipoprotein [low-density lipoprotein (LDL), very LDL (VLDL), and high-density lipoprotein (HDL)] particle diameters (n = 115 078). Inverse variance-weighted (IVW) method was used to calculate the causal estimates. Weighted median-based method, MR-Egger, and leave-one-out method were applied as sensitivity analysis. Greater ALM had a statistically significant positive effect on HDL particle diameter (MR-Egger: β = 0.055, SE = 0.031, P = 0.081; IVW: β = 0.068, SE = 0.014, P < 0.001) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β = -0.114, SE = 0.039, P = 0.003; IVW: β = -0.081, SE = 0.017, P < 0.001). Similarly, greater HGS had a statistically significant positive effect on HDL particle diameter (MR-Egger: β = 0.433, SE = 0.184, P = 0.019; IVW: β = 0.121, SE = 0.052, P = 0.021) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β = -0.416, SE = 0.163, P = 0.011; IVW: β = -0.122, SE = 0.046, P = 0.009). There was no statistically significant effect of either ALM or HGS on LDL particle diameter.

Conclusion: There were potentially causal associations between both increasing ALM and HGS and increasing HDL particle size and decreasing VLDL particle size. These causal associations may offer possibilities for interventions aimed at improving cardiovascular disease risk profile.

Keywords: High-density lipoprotein; Lean mass; Lipoprotein diameter; Low-density lipoprotein; Mendelian randomization; Muscle mass; Sarcopenia.