Impact of Cardiovascular-Kidney-Metabolic Burden on Echocardiographic Remodeling and Cardiovascular Outcomes in Hypertension

Aims Cardiovascular-kidney-metabolic (CKM) syndrome highlights the interrelationship between metabolic, renal, and cardiovascular disorders. However, whether CKM burden influences longitudinal cardiac structural and functional recovery and subsequent cardiovascular outcomes remains unclear. Methods We studied 1,600 patients from the STRATS-HHD registry who underwent echocardiography at baseline and 6–18 months after treatment initiation. CKM burden was defined by obesity, diabetes, chronic kidney disease, and severe hypertension (0–1, 2, or ≥3 components). The primary outcome was cardiovascular death or heart failure hospitalization (HHF). Results CKM burden was 0–1 in 973 patients (60.8%), 2 in 440 (27.5%), and ≥3 in 187 (11.7%). Higher burden was associated with worse baseline cardiac abnormalities and increased primary outcome risk (adjusted HR, 3.09; 95% CI, 1.92–4.98 for ≥3 vs 0–1; adjusted HR, 1.53; 95% CI, 1.27–1.84 per +1 CKM component). The prognostic association persisted after additional adjustment for hepatic steatosis index-defined metabolic dysfunction-associated steatotic liver disease. Despite overall improvement in most echocardiographic parameters after treatment, patients with CKM burden ≥3 showed less favorable E/e′, LV global longitudinal strain (GLS), and LA stiffness index at follow-up. Normalization of these parameters at follow-up was associated with substantially lower subsequent cardiovascular risk. Mediation analyses suggested that echocardiographic abnormalities partially mediated the association between high CKM burden and the primary outcome. Conclusion CKM burden identifies hypertensive patients with less favorable cardiac function after treatment and increased cardiovascular risk. These findings highlight the association of CKM burden with cardiac functional recovery and prognosis in patients with hypertension. Graphical Abstract In patients with hypertension, higher CKM burden was associated with more pronounced cardiac abnormalities, less favorable cardiac functional status after antihypertensive treatment, and increased cardiovascular risk. Normalization of functional echocardiographic parameters was associated with lower subsequent cardiovascular risk.