Dataset Information

Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank.

ABSTRACT: Background The "healthy obese" hypothesis suggests the risks associated with excess adiposity are reduced in those with higher muscle quality (mass/strength). Alternative possibilities include loss of muscle quality as people become unwell (reverse causality) or unmeasured confounding. Methods and Results We conducted a cohort study using the UK Biobank (n=452 931). Baseline body mass index ( BMI) was used to quantify adiposity and handgrip strength ( HGS ) used for muscle quality. Outcomes were fatal and non-fatal cardiovascular disease, and mortality. As a secondary analysis we used waist-hip-ratio or fat mass percentage instead of BMI , and skeletal muscle mass index instead of HGS . In a subsample, we used gene scores for BMI , waist-hip-ratio and HGS in a Mendelian randomization ( MR ). BMI defined obesity was associated with an increased risk of all outcomes (hazard ratio [ HR ] range 1.10-1.82). Low HGS was associated with increased risks of cardiovascular and all-cause mortality ( HR range 1.39-1.72). HR s for the association between low HGS and cardiovascular disease events were smaller ( HR range 1.05-1.09). There was no suggestion of an interaction between HGS and BMI to support the healthy obese hypothesis. Results using other adiposity metrics were similar. There was no evidence of an association between skeletal muscle mass index and any outcome. Factorial Mendelian randomization confirmed no evidence for an interaction. Low genetically predicted HGS was associated with an increased risk of mortality ( HR range 1.08-1.19). Conclusions Our analyses do not support the healthy obese concept, with no evidence that the adverse effect of obesity on outcomes was reduced by improved muscle quality. Lower HGS was associated with increased risks of mortality in both observational and MR analyses, suggesting reverse causality may not be the sole explanation.

SUBMITTER: Farmer RE

PROVIDER: S-EPMC6662360 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank.

Farmer Ruth E RE Mathur Rohini R Schmidt A Floriaan AF Bhaskaran Krishnan K Fatemifar Ghazaleh G Eastwood Sophie V SV Finan Chris C Denaxas Spiros S Smeeth Liam L Chaturvedi Nish N

Journal of the American Heart Association 20190621 13

Background The "healthy obese" hypothesis suggests the risks associated with excess adiposity are reduced in those with higher muscle quality (mass/strength). Alternative possibilities include loss of muscle quality as people become unwell (reverse causality) or unmeasured confounding. Methods and Results We conducted a cohort study using the UK Biobank (n=452 931). Baseline body mass index ( BMI) was used to quantify adiposity and handgrip strength ( HGS ) used for muscle quality. Outcomes were ...[more]

PMID: 31221000

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Project description:(1) Background: Observational studies associate vitamin D deficiency with muscle disorders, while some clinical trial data support a minor association between the vitamin and skeletal muscle performance in healthy subjects. Vitamin D receptor knockout mice studies confirm the relationship between vitamin D and skeletal muscle; however, causal inference in humans is challenging due to the ethical implications of including vitamin D-deficient participants in randomized trials. This study uses genetic methods to safely explore causal underpinnings for the relationship between 25(OH)D concentrations and skeletal muscle-related traits, including grip strength and combined arm skeletal muscle mass, and extends this analysis to suspected pathophysiology in the form of probable sarcopenia and sarcopenic obesity. (2) Methods: We conducted Mendelian randomization (MR) analyses in up to 307,281 participants from the UK Biobank of whom 25,414 had probable sarcopenia and 16,520 had sarcopenic obesity. In total, 35 variants were used to instrument 25(OH)D and MR analyses conducted using multiple approaches. (3) Results: Genetic analyses provided support for a relationship between genetically predicted higher 25(OH)D and skeletal muscle traits, with linear MR analyses for grip strength showing 0.11 kg (95% CI 0.04, 0.19) greater contractile force per 10 unit higher 25(OH)D, while there was a modest association with skeletal muscle mass (0.01 kg (95% CI 0.003, 0.02) greater muscle mass). For probable sarcopenia risk, there was suggestive evidence for lower odds by higher 25(OH)D (OR 0.96 (95% CI 0.92, 1.00)); however, this did not reflect an association with sarcopenic obesity (OR 0.97 (95% CI 0.93, 1.02)), but was seen in probable sarcopenia cases who were not obese (OR 0.92 (95% CI 0.86, 0.98)). Results were similar across multiple MR approaches. (4) Conclusions: Our study supports a causal relationship between 25(OH)D and skeletal muscle health. While evidence for benefit did not extend to lower risk of sarcopenic obesity, effective vitamin D-deficiency prevention strategies may help reduce age-related muscle weakness.

Dataset Information

Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank.

Publications

Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank.

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