Weight-adjusted waist index is positively and linearly associated with all-cause and cardiovascular mortality in metabolic dysfunction-associated steatotic liver disease: findings from NHANES 1999-2018

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Body mass index (BMI) is the most used obesity index but has important limitations. The weight-adjusted waist index (WWI) is a novel obesity metric and accurately reflects body composition. We explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in MASLD.

Methods: Adult participants with MASLD were included from NHANES 1999-2018. WWI was calculated by dividing the waist circumference (WC) by the square root of body weight. MASLD was diagnosed by the presence of hepatic steatosis and at least one cardiometabolic risk factor in the absence of other causes of steatosis. A fatty liver index ≥60 suggested the presence of hepatic steatosis. Mortality data was obtained by prospectively linking to the National Death Index. Multivariate Cox proportional hazards regression analyses were used to explore these associations and multiple adjustment models were constructed including crude, partial, and fully adjusted models.

Results: After adjusting for all covariates including BMI, WWI remained positively and linearly associated with all-cause and CVD mortality in MASLD (hazard ratios [HR] 1.247 and 1.218, respectively). Higher WWI was associated with a significantly increased risk of mortality (both p for trend <0.05). There was an "obesity paradox" between BMI and all-cause mortality in MASLD, with significantly lower all-cause mortality in those with overweight/obesity compared to normal BMI (HR 0.625 and 0.596, respectively, p for trend = 0.024), and no association between BMI and CVD mortality. Interaction analyses indicated that these associations were influenced by several demographic variables and disease status. Time-dependent receiver operating characteristic curves indicated that the predictive value of WWI for mortality in MASLD was higher than that of BMI, WC, and waist-to-height ratio across all follow-up durations.

Conclusions: WWI was positively and linearly associated with all-cause and CVD mortality in MASLD, whereas BMI did not accurately reflect mortality risk. WWI provided the optimal predictive value for mortality compared to traditional obesity indicators. These findings emphasize the potential use of WWI as a novel obesity indicator for mortality risk assessment, stratification, and prevention in MASLD.

Keywords: body mass index; metabolic dysfunction-associated steatotic liver disease; mortality; obesity; weight-adjusted waist index.

Figure 1

Flowchart of study population selection, NHANES 1999-2018.

Figure 2

KM survival analysis of WWI and all-cause and CVD mortality in people with MASLD, NHANES 1999-2018. (A) All-cause; (B) CVD.

Figure 3

RCS analysis of the association of WWI with all-cause and CVD mortality in the MASLD population, NHANES 1999-2018. (A) All-cause; (B) CVD.

Figure 4

Stratified analysis of the association between WWI and all-cause mortality in the MASLD population.

Figure 5

Stratified analysis of the association between WWI and CVD mortality in the MASLD population.

Figure 6

ROC curves for mortality prediction in the MASLD population by the WWI and other traditional obesity indicators. (A) Time-dependent ROC for all-cause mortality; (B) Time-dependent ROC for CVD mortality; (C) ROC for all-cause mortality at 75% follow-up duration; (D) ROC for CVD mortality at 75% follow-up duration.