AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Body Mass Index-Anchored Cardiovascular-Kidney-Metabolic Biomarker Discordance and Stage Progression: Evidence from the ChinaHEART Cohort
By ZHENG S, Xin F
Background: Cardiovascular-kidney-metabolic (CKM) syndrome emphasizes the systemic links among adiposity, metabolic dysfunction, kidney disease, and cardiovascular risk. However, BMI alone may not capture CKM biomarker heterogeneity or progression risk among individuals with similar BMI and baseline CKM stage. Hypothesis: BMI-anchored CKM biomarker profiles identify clinically interpretable phenotypes associated with subsequent CKM stage progression. Methods: We included 21,892 adults with baseline CKM stage 0-3 from the CHINA HEART cohort, with a median follow-up of 4.21 years. BMI-based expected models were fitted for CKM biomarkers, including heart rate, blood pressure, glycemic markers, lipids, kidney function, and liver metabolism markers. Standardized residuals were derived to quantify deviations from BMI-expected biomarker levels. Gaussian mixture modeling was used to identify BMI-anchored CKM subtypes. The primary outcome was CKM progression, defined as an increase of at least 1 CKM stage during follow-up. Cox models evaluated associations between subtypes and CKM progression using the BMI-concordant subtype as reference, with adjustment for age, sex, BMI, smoking, alcohol use, and baseline CKM stage. Landmark, stratified, and interaction analyses were also performed. Results: Five BMI-anchored CKM subtypes were identified. After multivariable adjustment, the renal-risk subtype showed the highest risk of CKM progression (HR, 1.50; 95% CI, 1.34-1.69). The hyperglycemic-liver enzyme-triglyceride discordant subtype was also associated with increased risk (HR, 1.14; 95% CI, 1.03-1.26), whereas the renal-favorable subtype was associated with lower risk (HR, 0.84; 95% CI, 0.75-0.95). After excluding events within the first year, findings remained consistent, with the renal-risk subtype showing the strongest association (HR, 1.55; 95% CI, 1.33-1.80). The renal-risk subtype was associated with higher progression risk across normal-weight, overweight, and obese groups. Significant interaction by baseline CKM stage was observed, with the strongest association among participants with baseline CKM stage 3 (HR, 2.46; 95% CI, 1.49-4.07). Conclusions: BMI-anchored CKM biomarker profiles identified discordant phenotypes with differential CKM progression risk. The renal-risk subtype was the most robust high-risk phenotype, particularly in baseline CKM stage 3. BMI-anchored CKM biomarker discordance may provide clinically interpretable information beyond BMI and support refined CKM risk stratification. These findings may inform population-level strategies to identify individuals at elevated CKM progression risk who may be missed by BMI-based assessment alone.