Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis are Associated with Advanced Cardiovascular-Kidney-Metabolic Syndrome in Chinese and US Populations

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Purpose: Despite the pathophysiologic overlap between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular-kidney-metabolic (CKM) syndrome, MASLD has not been incorporated into the current CKM framework. This study examined the associations of MASLD and MASLD-related fibrosis with advanced CKM syndrome in Chinese and US populations. Patients and Methods: We enrolled 6186 participants in a community-based cross-sectional study conducted in China, with validation utilizing the National Health and Nutrition Examination Survey (NHANES). Advanced CKM syndrome was defined as stages 3 and 4. Hepatic steatosis and fibrosis were assessed via vibration-controlled transient elastography. Multivariable logistic regression and restricted cubic spline (RCS) analyses were employed. Results: Advanced CKM syndrome was present in 8.8% of the Chinese and 14.9% of the US populations. MASLD participants exhibited a significantly higher prevalence of advanced CKM than those without (China: 12.6% vs 6.4%; US: 21.5% vs 9.9%). In addition, participants with MASLD were associated with increased odds of advanced CKM (China: OR 2.06, 95% CI: 1.64– 2.58; US: OR 1.60, 95% CI: 1.22– 2.10; both P < 0.01). Among participants with MASLD, advanced CKM syndrome was more prevalent in participants with fibrosis than without (China: 17.1% vs 11.2%; US: 28.4% vs 20.1%). MASLD-related fibrosis was also independently linked to higher odds of advanced CKM compared to non-fibrotic MASLD (China: OR 1.55, 95% CI: 1.09– 2.18; US: OR 1.44, 95% CI: 1.01– 2.05; both P < 0.05). Furthermore, RCS analysis revealed a positive linear relationship of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) values with the prevalence of advanced CKM syndrome ( P non-linear > 0.05). Conclusion: MASLD and MASLD-related fibrosis were significantly associated with a higher prevalence of advanced CKM syndrome, and higher CAP/LSM levels showed linear associations with advanced CKM syndrome in both Chinese and US populations. These findings support evaluating liver health (eg, CAP/LSM) when risk-stratifying CKM syndrome. Keywords: advanced cardiovascular-kidney-metabolic syndrome, controlled attenuation parameter, fibrosis, liver stiffness measurement, metabolic dysfunction-associated steatotic liver disease

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