Abstract Body (Do not enter title and authors here): Background: Cardiovascular-Kidney-Metabolic (CKM) syndrome reflects the interrelatedness of cardiovascular, kidney, and metabolic disease, with excess/dysfunctional adiposity as the predominant etiology. The CKM staging framework facilitates assessment of progression, as well as regression, of CKM syndrome stages. However, the impact of intentional weight loss on CKM stage regression has not been quantified.

Methods: We prospectively evaluated 360 bariatric surgery patients in the Geisinger Obesity Institute Registry free of cardiovascular disease. Data were collected pre-operatively, and 6-18 months post-operatively. CKM syndrome stage was defined as Stage 0: no CKM risk factors; Stage 1: excess/dysfunctional adiposity (body mass index >= 25kg/m² or fasting blood glucose [FBG] 100-125mg/dL); Stage 2: metabolic risk factors (high blood pressure [>= 130/80mmHg], diabetes [FBG >= 126mg/dL], hypertriglyceridemia [>= 135mg/dL]), or chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] 30 - <60mL/min/1.73m²); and Stage 3: moderate-to-severely elevated high-sensitivity cardiac troponin I levels (>= 4 ng/L in women or >= 6 ng/L in men) or very high-risk CKD (eGFR < 30 mL/min/1.73m²). We compared the distribution of CKM stages pre- and post-surgery, and used logistic regression and cubic splines to assess the association of weight loss with odds of regressing to a lower CKM syndrome stage over time.

Results: The mean age was 46 years (83% women, 95% White, mean BMI 46 kg/m²). On average, participants lost 28% of their baseline weight. During follow-up, there was a decrease in the proportion with CKM stage 3 (20% to 12%) and stage 2 (65% to 41%), with an increase in stage 1 (15% to 42%). CKM Stage 0, non-existent pre-surgery, was seen in 5% of participants post-surgery. Overall, 45% regressed in CKM syndrome stage (Panel A). In logistic regression, there was a linear relationship between weight loss and odds of CKM stage regression (Panel B), with each 10% greater weight loss associated with an OR of 1.91 (95% CI 1.45-2.50) for CKM stage regression.

Conclusion: Weight loss is strongly linked to CKM stage regression, underscoring the role of intentional weight loss in improving CKM health.