In hospital prevalence and mortality associated with individual and combined cardiovascular–kidney–metabolic (CKM) syndrome components: analysis of the national inpatient sample (NIS)

Background Cardiovascular-Kidney-Metabolic Syndrome (CKM) encompasses the shared origins and intertwined pathophysiology of metabolic dysfunction, cardiovascular disease (CVD), and chronic kidney disease (CKD). The overall prevalence and clinical burden of CKM continues to rise globally and within the US. Globally, age-adjusted CVD and DM mortality has declined over recent decades; within the U.S., this trend has reversed over the past decade. There remains limited U.S. data characterizing the relative prevalence and mortality of CKM components, as well as the burden posed by its multi-morbidity disease-states. Purpose The purpose of the study is to describe the prevalence of three core CKM components: diabetes mellitus (DM), congestive heart failure (CHF), and chronic kidney disease (CKD). We seek to characterize the burden of different overlapping combinations (DM+CHF, DM+CKD, CHF+CKD, DM+CHF+CKD) and in-hospital mortality as it differs across these groups, among hospitalized US. adults. We hypothesize that each dual CKM combination will be associated with a stepwise increase in mortality, with the greatest mortality among those with triple CKM multi-morbidity (CKD+CHF+DM). Methods This is a retrospective cohort analysis of adults > 18 years old from the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) between 2016-2021. ICD-10 codes were used for each group: DM (E11.x), CHF (I50.x, I25.5, I42.0), and CKD (N18.x, I12.x). Weighted discharge estimates were applied to generate national prevalence estimates. Univariate logistic regression models estimated unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality by CKM category relative to the DM group. All p-values were two-sided with significance at p<0.05. Analyses were conducted using STATA 17. Results The total weighted hospital discharges for CKM were 148,767,786. The prevalence of CKM hospitalizations was as follows: DM = 22,331,659 (15.01%); CHF = 6,638,078 (4.46%); CKD = 8,233,038 (5.53%), representing a total of 37,202,775 hospitalizations (25% of weighted national discharges). Dual multi-morbidity hospitalizations were as follows: DM+CHF = 4,134,139 (2.78%), CHF+CKD = 4,123,674 (2.77%), DM+CKD = 8,454,103 (5.68%). The total number of hospitalizations with full CKM multi-morbidity was 5,595,484 (3.76%). Odds of in-hospital mortality (DM group as reference) were as follows: CKD = 1.95 (1.93-1.98), CHF = 2.36 (2.32-2.38), DM+CKD = 1.62 (1.60-1.64), DM+CHF = 1.77 (1.75-1.80), CKD+CHF = 2.86 (2.82-2.90), DM+CKD+CHF = 2.22 (2.19-2.25). All comparisons p<0.001. Conclusions Compared to DM alone, CKD+CHF had the highest in-hospital mortality, even higher than DM+CKD+CHF. Patients with DM may receive earlier, more structured therapies than those with cardiorenal disease without DM. Alternatively, patients with triple CKM multi-morbidity may face disproportionately high rates of hospital readmissions.