Abstract WE422: Prognostic Value of Cardiovascular-Kidney-Metabolic Syndrome Stage 3 Components: Dallas Heart Study

Background: The Cardiovascular-Kidney Metabolic (CKM) Syndrome Stages are associated with heightened risk of cardiovascular diseases (CVD). However, the individual and additive impact of CKM Stage 3 (subclinical CVD) criteria on risk of incident clinical CVD is unclear. Methods: We included participants in the Dallas Heart Study, a population-sampled cohort from Dallas County, who attended study Visit 1 (2000-2002) and were categorized as Stage 2 or 3 CKM based on the presence of CVD risk factors or abnormal subclinical CVD biomarkers, respectively. CKM Stage 3 criteria included coronary artery calcium by cardiac CT (CAC) > 100 HU, abnormal left ventricular ejection fraction (< 50%) or mass (> 89 g/m 2 in women&> 112 g/m 2 in men) by cardiac MRI (CMR), elevated NT-proBNP (≥125 pg/mL), elevated high sensitive-troponin T or I (≥14 ng/L and ≥10 ng/L women; ≥22 ng/L and ≥12 ng/L in men, respectively) despite normal kidney function (eGFR> 90 mL/min/1.73 m 2 ), and high CVD risk based on very high risk by KDIGO HeatMap or PREVENT score > 20%. Participants were followed for incident coronary heart disease (CHD), heart failure (HF), stroke, or death through December 31, 2018. Multivariable Cox proportional hazard models adjusting for age, sex, and race/ethnicity were used to assess the association of Stage CKM 3 criteria with incident CVD using CKM Stage 2 as reference. Results: The study included 1,995 participants (1,568 CKM Stage 2, 427 CKM Stage 3) with a mean age of 45±10 years, 54% were female, and 50% reported Black race. Over a median follow-up of 17 years, 405 (20%) had incident CHD, HF, stroke, or died. Compared to Stage 2 participants, those who met two or three CKM Stage 3 criterion demonstrated higher risk of incident CVD compared to those who only met one Stage 3 criterion (Hazard Ratios 3.5 [95% CI 2.3-5.3] and 3.0 [95% CI 1.6-5.7] vs. 2.0 [95% CI 1.6-2.5], respectively; Figure 1A ). Among those with only 1 Stage 3 criterion (n=364), the most common was CAC (46%), followed by NT-proBNP (24%), troponin (15%), CMR (11%), and PREVENT score (5%). Those with elevated troponin alone were not at higher risk compared to Stage 2 (HR 1.3, 0.7-2.5, p=0.44), while the others were ( Figure 1B ). Conclusion: Within the CKM Syndrome framework, a greater number of Stage 3 criteria met is associated with greater risk of incident CVD compared to Stage 2. The prognostic value of isolated elevation of Tn to define Stage 3 requires further study.