Diverging trajectories of cardiorenal protection: from early benefit to late attenuation with multifactorial target achievement across cardiovascular- kidney-metabolic syndrome stages

BackgroundThe extent to which achieving multiple metabolic treatment targets confers sustained cardiorenal protection across all stages of cardiovascular - kidney - metabolic (CKM) syndrome remains uncertain. MethodsThis multicenter retrospective cohort study used data from the China Renal Data System (CRDS). Participants were classified into CKM stages 1-4. Metabolic target achievement was defined as simultaneous control of blood pressure (BP<130/80 mmHg), fasting blood glucose (FBG<5.6 mmol/L), and low-density lipoprotein cholesterol (LDL-C<1.8 mmol/L). A metabolic score (0-3) reflected the number of targets met. Outcomes included a composite cardiovascular-renal endpoint and all-cause mortality. Cox and restricted cubic spline regression models were used to assess associations between metabolic control and outcomes in CKM patients. ResultsThe proportion of patients meeting all three metabolic targets decreased markedly with advancing CKM stage. Kaplan-Meier curves showed increasing risks of cardiovascular-renal events and mortality across higher stages (P<0.001). After adjustment, higher metabolic scores were linked to lower risks: for cardiovascular-renal outcomes, HR 0.82 (95% CI 0.77-0.87) for score 1, 0.72 (0.68-0.77) for score 2, and 0.65 (0.57-0.73) for score 3; for mortality, HR 0.73 (0.62-0.87) for score 1 and 0.68 (0.47-1.00) for score 2 (both P<0.05). However, achieving all three targets did not reduce mortality risk (HR 1.04, 95% CI 0.64-1.68). Stratified analysis showed significant risk reduction in early CKM stages but not in advanced stages. Restricted cubic spline models indicated nonlinear associations between LDL-C and both outcomes, and between FBG, systolic BP, and mortality, after full adjustment (all P<0.05). ConclusionWhile multifactorial metabolic target attainment shows strong protective associations with cardiovascular-renal outcomes in early CKM stages, this relationship diminishes in advanced disease. These findings highlight the need for stage-specific management strategies in CKM syndrome.