Associations of Skeletal Muscle Mass and Fat Mass With Incident Cardiovascular Disease and All-Cause Mortality: A Prospective Cohort Study of UK Biobank Participants

Abstract

Background There is debate whether body mass index is a good predictor of health outcomes because different tissues, namely skeletal muscle mass (SMM) and fat mass (FM), may be differentially associated with risk. We investigated the association of appendicular SMM (aSMM) and FM with fatal and nonfatal cardiovascular disease (CVD) and all-cause mortality. We compared their prognostic value to that of body mass index. Methods and Results We studied 356 590 UK Biobank participants aged 40 to 69 years with bioimpedance analysis data for whole-body FM and predicted limb muscle mass (to calculate aSMM). Associations between aSMM and FM with CVD and all-cause mortality were examined using multivariable Cox proportional hazards models. Over 3 749 501 person-years of follow-up, there were 27 784 CVD events and 15 844 all-cause deaths. In men, aSMM was positively associated with CVD incidence (hazard ratio [HR] per 1 SD 1.07; 95% CI, 1.06-1.09) and there was a curvilinear association in women. There were stronger positive associations between FM and CVD with HRs per SD of 1.20 (95% CI, 1.19-1.22) and 1.25 (95% CI, 1.23-1.27) in men and women respectively. Within FM tertiles, the associations between aSMM and CVD risk largely persisted. There were J-shaped associations between aSMM and FM with all-cause mortality in both sexes. Body mass index was modestly better at discriminating CVD risk. Conclusions FM showed a strong positive association with CVD risk. The relationship of aSMM with CVD risk differed between sexes, and potential mechanisms need further investigation. Body fat and SMM bioimpedance measurements were not superior to body mass index in predicting population-level CVD incidence or all-cause mortality.

Keywords: all‐cause mortality; cardiovascular disease; cohort study; fat mass; skeletal muscle mass.

Figure 1. Adjusted hazard ratios (HRs) of incident cardiovascular disease associated with appendicular skeletal muscle mass (aSMM) and fat mass (FM).

A, HRs of incident CVD associated with aSMM in men, 1 SD=5.66 kg. B, HRs of incident CVD associated with aSMM in women, 1 SD=1.45 kg. C, HRs of incident CVD associated with FM in men, 1 SD=6.75 kg. D, HRs of incident CVD associated with FM in women, 1 SD=8.28 kg. For all panels, likelihood ratio tests were used to estimate nonlinearity (aSMM in men, P=0.04; aSMM in women, P<0.001; FM in men, P=0.09; FM in women, P=0.09). Adjusted HRs and CIs obtained using the floated absolute risk method of Cox proportional hazards regression, number of cases shown above each estimate and HRs shown below. Adjusted for age (underlying timescale variable), height (as a continuous variable in FM and included by regression out of variation due to height for aSMM), Townsend index of deprivation, education, smoking status, alcohol intake, physical activity, oily fish intake, fruit and vegetable intake, saturated fat intake, diabetes mellitus, cancer history, menopause (women), and mutually adjusted for FM (in the aSMM models) and aSMM (in the FM models). HRs are plotted at the mean of the resurvey values for the baseline‐defined quintiles (“usual” values) to correct for measurement error. HRs per 1 SD given where there was no evidence of departure from linearity. CVD indicates cardiovascular disease.

Figure 2. Adjusted hazard ratios (HRs) of all‐cause mortality associated with appendicular skeletal muscle mass (ASMM) and fat mass (FM).

A, HRs of all‐cause mortality associated with aSMM in men, 1 SD=5.66 kg. B, HRs of all‐cause mortality associated with aSMM in women, 1 SD=1.45 kg. C, HRs of all‐cause mortality associated with FM in men, 1 SD=6.75 kg. D, HRs of all‐cause mortality associated with FM in women, 1 SD=8.28 kg. For all panels, likelihood ratio tests were used to estimate nonlinearity P values (aSMM in men, P=0.002; aSMM in women, P=0.008; FM in men, P<0.001; FM in women, P<0.001). Adjusted HRs and CIs obtained using the floated absolute risk method of Cox proportional hazards regression, number of cases shown above each estimate and HRs shown below. Adjusted for age (underlying timescale variable), height (as a continuous variable in FM and included by regression out of variation due to height for aSMM), Townsend index of deprivation, education, smoking status, alcohol intake, physical activity, oily fish intake, fruit and vegetable intake, saturated fat intake, diabetes mellitus, cancer history, menopause (women), and mutually adjusted for FM (in the aSMM models) and aSMM (in the FM models). HRs are plotted at the mean of the resurvey values for the baseline‐defined quintiles (“usual” values) to correct for measurement error.

Figure 3. Adjusted hazard ratios (HRs) of cardiovascular disease and all‐cause mortality associated with appendicular skeletal muscle mass (aSMM) when participants are stratified into fat mass (FM) tertiles.

A, HRs of cardiovascular disease (CVD) associated with aSMM in low fat men. B, HRs of CVD associated with aSMM in moderate fat men. C, HRs of CVD associated with aSMM in high fat men. D, HRs of CVD associated with aSMM in low fat women. E, HRs of CVD associated with aSMM in moderate fat women. F, HRs of CVD associated with aSMM in high fat women. G, HRs of all‐cause mortality associated with aSMM in low fat men. H, HRs of all‐cause mortality associated with aSMM in moderate fat men. I, HRs of all‐cause mortality associated with aSMM in high fat men. J, HRs of all‐cause mortality associated with aSMM in low fat women. K, HRs of all‐cause mortality associated with aSMM in moderate fat women. L, HRs of all‐cause mortality associated with aSMM in high fat women. For all panels, adjusted hazard ratios (HR) and CIs obtained using Cox proportional hazards regression, number of cases shown above each estimate and HRs shown below. Adjusted for age (underlying timescale variable), height (included by regression out of variation due to height), Townsend index of deprivation, education, smoking status, alcohol intake, physical activity, oily fish intake, fruit and vegetable intake, saturated fat intake, diabetes mellitus, cancer history, menopause (women), and mutually adjusted for FM (in the aSMM models) and aSMM (in the FM models). HRs are plotted at the mean of the resurvey values for the baseline‐defined quintiles (“usual” values) to correct for measurement error.

Figure 4. Independent effects of body mass index (BMI), fat mass (FM), waist circumference, appendicular skeletal muscle mass (aSMM), and grip strength on cardiovascular disease (CVD) subtypes and all‐cause mortality. Adjusted hazard ratios (HRs) per SD change.

A, The independent effects of BMI, FM, waist circumference, aSMM and grip strength on CVD subtypes and all‐cause mortality in men. B, The independent effects of BMI, FM, waist circumference, aSMM, and grip strength on CVD subtypes and all‐cause mortality in women. Range excludes outliers. Adjusted hazard ratios (HR) and CIs obtained using Cox proportional hazard regression. Adjusted for age (underlying timescale variable), height (as a continuous variable in all models except aSMM where it was included by regression out of variation due to height for aSMM), Townsend index of deprivation, education, smoking status, alcohol intake, physical activity, oily fish intake, fruit and vegetable intake, saturated fat intake, diabetes mellitus, cancer history, menopause (women), and mutually adjusted for FM (in the aSMM models) and aSMM (in the FM models). HRs are corrected for regression dilution bias by the MacMahon‐Peto method.