Association of low muscle mass and obesity with increased all-cause and cardiovascular disease mortality in US adults

Abstract

Background: Sarcopenic obesity, defined as the coexistence of low muscle mass and high adiposity, is associated with cardiovascular disease (CVD) and mortality. However, to what extent sarcopenia contributes to these risks independently or in conjunction with other cardiovascular risk factors remains unclear. This study aimed to investigate the association of low muscle mass, central obesity (COB), metabolic abnormalities, and their combinations with CVD and mortality risk.

Methods: This cross-sectional analysis used data from the National Health and Nutrition Examination Survey 1999-2006 and 2011-2018. Participants aged >20 years and with reported whole-body dual X-ray absorptiometry data were included. Participants were divided into eight groups based on low muscle mass, metabolic abnormalities, and COB status.

Results: The mean age of participants was 55 years, and 50.4% of participants were male. Low muscle mass was observed in 2472 (14.6%) out of 16 839 participants. Among the eight groups, the metabolically unhealthy COB group with low muscle mass had the highest hazard ratio (HR) for all-cause mortality (HR, 2.00; 95% CI, 1.56-2.56; P < 0.001), whereas the metabolically healthy COB group with low muscle mass had the highest HR for CVD mortality (HR, 3.18; 95% CI, 1.53-6.65; P = 0.001). The mediation analysis showed that low muscle mass directly increased the risk of both all-cause mortality (HR, 1.56; 95% CI, 1.35-1.79; P < 0.001) and CVD mortality (HR, 1.80; 95% CI, 1.40-2.31; P < 0.001). Additionally, subgroup analysis revealed that low muscle mass significantly increased the risk of all-cause and CVD mortality in participants without a prior CVD history and those with diabetes mellitus.

Conclusions: Low muscle mass is an independent risk factor for all-cause and CVD mortality, especially in individuals with metabolic abnormalities and COB.

Keywords: Cardiovascular disease; Central obesity; Metabolic syndrome; Sarcopenia.

Figure 1

Hazard ratio according to the continuous value of ASMI. (A) ASMI and HR of total participants, (B) ASMI and HR according to sex, (C) ASMI and HR according to presence of COB, (D) ASMI and HR according to presence of metabolic abnormalities, (E) ASMI and HR according to presence of CVD, (F) ASMI and HR according to presence of DM adjusted for age, sex, race, smoking status, alcohol consumption, eGFR, COB, history of cancer, HTN, DM, dyslipidaemia, and past CVD events. Abbreviations: ASMI, appendicular skeletal muscle index; COB, central obesity; CVD, cardiovascular disease; HR, hazard ratio.

Figure 2

Hazard ratios for all‐cause and CVD mortality according to the low muscle mass. Adjusted for age, sex, race, smoking status, alcohol consumption, eGFR, COB, history of cancer, HTN, DM, dyslipidaemia, and past CVD events.

Figure 3

Effects of low muscle mass on mortality risk according to central obesity and metabolic abnormalities. Adjusted for age, sex, race, smoking status, alcohol consumption, eGFR, COB, and history of cancer. Abbreviations: COB, central obesity; CVD, cardiovascular disease; MU, metabolically unhealthy status; MU_COB, metabolically unhealthy status with central obesity.

Figure 4

Mediation analysis of effect of low muscle mass and central obesity through metabolically unhealthy status on all‐cause and CVD mortality. (A) Low muscle mass, (B) central obesity. Adjusted for age, sex, race, smoking status, alcohol consumption, eGFR, low muscle mass, and central obesity. Abbreviations: PNDE, pure natural direct effect; PNIE, pure natural indirect effect; TE, total effect; TNDE, total natural direct effect; TNIE, total natural indirect effect.

Figure 5

Mediation analysis of effect of low muscle mass and central obesity through frailty status on all‐cause and CVD mortality. (A) Low muscle mass, (B) central obesity. Adjusted for age, sex, race, smoking status, alcohol consumption, eGFR, low muscle mass, and central obesity. Abbreviations: PNDE, pure natural direct effect; PNIE, pure natural indirect effect; TE, total effect; TNDE, total natural direct effect; TNIE, total natural indirect effect.

Figure 6

Mediation analysis of effect of low muscle mass through ASCVD risk in individuals without previous CVD on all‐cause and CVD mortality. Adjusted for alcohol consumption, eGFR, central obesity, and history of cancer. Abbreviations: PNDE, pure natural direct effect; PNIE, pure natural indirect effect; TE, total effect; TNDE, total natural direct effect; TNIE, total natural indirect effect.

Figure 7

Mediation analysis of effect of low muscle mass through HbA1c and microvascular complications in patients with DM on all‐cause and CVD mortality. Adjusted for age, sex, race, smoking status, alcohol consumption, central obesity, history of cancer, HTN, dyslipidaemia, previous CVD events, duration of DM, microvascular complications and haemoglobin A1c (HbA1c). Abbreviations: PNDE, pure natural direct effect; PNIE, pure natural indirect effect; TE, total effect; TNDE, total natural direct effect; TNIE, total natural indirect effect.