Imaging-Derived Sarcopenic Obesity and Cardiovascular Outcomes: Insights Into Heart Failure Risk and Muscle Biology.
Authors
Affiliations (10)
Affiliations (10)
- William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Charterhouse Square, London, United Kingdom; Barts Heart Centre, Barts Health NHS Trust, West Smithfield, London, United Kingdom. Electronic address: [email protected].
- William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Charterhouse Square, London, United Kingdom.
- William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Charterhouse Square, London, United Kingdom; Barts Heart Centre, Barts Health NHS Trust, West Smithfield, London, United Kingdom.
- William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Charterhouse Square, London, United Kingdom; Aragon Institute of Engineering Research, University of Zaragoza, c/Mariano Esquillor s/n, Zaragoza, Spain; Centro de Investigación Biomédica en Red, Biomedicina, Bioingeniería y Nanomedicina, c/Mariano Esquillor s/n, Zaragoza, Spain.
- Faculty of Medicine, Mississauga Academy of Medicine, University of Toronto, Mississauga, Ontario, Canada.
- Faculty of Medical Sciences, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
- Faculty of Science, School of Kinesiology and Health Studies, Queens University, Kingston, Ontario, Canada.
- Faculty of Science, Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
- School of Medicine, University of Nottingham, Derby, United Kingdom.
- William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Charterhouse Square, London, United Kingdom; Barts Heart Centre, Barts Health NHS Trust, West Smithfield, London, United Kingdom. Electronic address: [email protected].
Abstract
The prognostic value of obesity in cardiovascular disease is complex. Measures such as body mass index and waist-to-height ratio show differing associations with outcomes, especially in heart failure. Assessing sarcopenic obesity, the coexistence of excess fat and low muscle mass, may clarify this relationship; however, quantifying sarcopenia in clinical practice remains challenging. The goal was to establish a translatable method of assessing sarcopenic obesity from cardiovascular imaging and assess its clinical relevance using long-term follow-up, genomic, and transcriptomic data. We developed a deep learning pipeline to quantify pectoralis major muscle mass from 55,768 cardiovascular magnetic resonance examinations and combined this with body weight to derive a novel sarcopenic obesity index. Associations with cardiac remodeling phenotypes and adverse cardiovascular and mortality outcomes were tested in multivariable models. Genome-wide association analysis, colocalization, and polygenic risk score evaluation were performed for the sarcopenic obesity index. Transcriptomic profiling of skeletal muscle across 7 pathophysiological states assessed differential gene expression. A higher sarcopenic obesity index was associated with adverse cardiac remodeling, and with increased risk of incident heart failure (HR: 1.31; 95% CI: 1.16-1.49), cardiovascular death (HR: 1.51; 95% CI: 1.25-1.81), and all-cause mortality (HR: 1.37; 95% CI: 1.26-1.49). Genome-wide association analysis identified 16 loci for sarcopenic obesity. Loci included genes associated with heart failure and nonischemic cardiomyopathy, with colocalization implicating shared causal variants in heart failure. Transcriptomic profiling demonstrated that sarcopenic obesity loci were specifically modulated during muscle atrophy. Analyses identified ACVR2B, the target of bimagrumab, which is being tested with semaglutide to enhance fat loss while maintaining lean mass. These results establish sarcopenic obesity as a clinically meaningful cardiovascular risk phenotype and point to viable therapeutic targets.