Objective: This study aimed to resolve the paradoxical associations of limb circumference—inversely with mortality but positively with cardiovascular risk factors (CVRFs)—by systematically comparing the predictive value of the ratio of combined arm and thigh circumference to waist circumference (ATC/WC) against that of the sum of arm and thigh circumference (ATC) for all-cause and cardiovascular mortality and key CVRFs. Design and method: We analyzed data from 17,276 participants in the 1999-2006 NHANES. Cox proportional hazards, generalized linear, and restricted cubic spline models were used, with comprehensive adjustment for confounders including adiposity. Outcomes were all-cause and cardiovascular mortality, hypertension, diabetes, and resting tachycardia. Results: During median 18.04-year follow-up (3,927 deaths, 1,047 cardiovascular deaths), the highest versus lowest ATC/WC quartile showed consistently protective associations: all-cause mortality (HR=0.47, 95%CI:0.38-0.57), cardiovascular mortality (HR=0.32, 0.21-0.49), hypertension (OR=0.49, 0.41-0.59), diabetes (OR=0.26, 0.18-0.37), and resting tachycardia (OR=0.28, 0.19-0.39; all P<0.001). Conversely, ATC exhibited adiposity-dependent paradoxical associations: protective for mortality but harmful for CVRFs when unadjusted for adiposity. After adiposity adjustment, ATC's harmful CVRF associations were attenuated or reversed, while mortality benefits persisted. ATC/WC demonstrated superior linearity in dose-response relationships compared to ATC. Conclusions: The ATC/WC ratio consistently demonstrates protective associations with both mortality and cardiovascular risk factors, effectively resolving the limb circumference paradox through integration of peripheral muscle mass and central adiposity into a single, clinically applicable metric. This waist-standardized approach overcomes the adiposity-related confounding that limits the utility of absolute limb measurements.
Zuo et al. (Fri,) studied this question.