The limb-to-waist ratio: resolving the divergence between mortality and cardiovascular risk

Aim: We aimed to resolve the paradoxical associations of limb circumference—inverse with mortality but positive with cardiovascular risk factors (CVRFs)—by systematically comparing the predictive value of the ratio of combined arm and thigh circumference (ATC) to waist circumference (WC) against that of the sum of ATC for mortality and key CVRFs. Methods: Our analysis utilized data from 17,276 U.S. participants in the 1999-2006 NHANES (National Health and Nutrition Examination Survey). We utilized Cox proportional hazards, generalized linear, and restricted cubic spline models, with comprehensive adjustment for confounders including adiposity. The outcomes assessed 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 (hazard ratio (HR) = 0.47, 95% confidence interval (95%CI): 0.38-0.57), cardiovascular mortality (HR = 0.32, 0.21-0.49), hypertension (OR = 0.49, 0.41-0.59), diabetes (odds ratio (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 CVRFs associations were attenuated or reversed, while mortality benefits persisted. ATC/WC demonstrated superior linearity in dose-response relationships compared to ATC. Conclusion: The ATC/WC ratio consistently demonstrates protective associations with both mortality and CVRFs. The waist standardization approach clarifies the relationship between limb measurements, cardiovascular health, and mortality by adjusting for central adiposity-related confounding that limits the utility of absolute rather than relative peripheral limb measurements.