Abstract
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic disorder characterized by pathophysiological interactions among metabolic risk factors. We aimed to determine the prevalence of CKM syndrome and investigate the association between CKM stages and mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We extracted data on patients with MASLD from NHANES III and the Chinese Kailuan cohort, enrolling a total of 2159 and 22,865 patients, respectively. Hepatic steatosis was assessed by liver ultrasound. Participants were categorized into three groups according to CKM stages: 1, 2, and 3-4. Mortality was evaluated using the Cox proportional hazards model with or without inverse probability of treatment weighting (IPTW). RESULTS: In NHANES III cohort, 84.5% MASLD patients meet the criteria for CKM stage 2 or higher, and 36.9% deaths are observed. CKM stages 3-4 is an independent risk factor for liver fibrosis after adjusting for confounding factors (aOR 2.24 95% CI: 1.14-4.40, P = 0.019). By using stage 1 as a reference, an increasing trend in all-cause mortality is shown in patients with higher stages (stage 2: aHR 1.55, 95% CI 1.17-2.07, P = 0.003; stages 3-4: aHR 2.69, 95% CI 1.92-3.76, P < 0.001), as well as for cardiovascular mortality during a follow-up of 50,895.4 person-years. Moreover, patients with stages 3-4 have the highest mortality risk among different stages across most subgroups. Similar results are validated in Kailuan cohort. CONCLUSIONS: The majority of MASLD patients also have CKM syndrome. A significant increase in all-cause and cardiovascular mortality is associated with advancing CKM stages.