Global trends and the case of China in Cardio-Kidney-Metabolic multimorbidity: development and validation of a...

The syndemic burden of cardiovascular disease (CVD), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM) represents a growing global health challenge, yet standardized tools for quantifying integrated disease burden remain lacking. We developed and preliminarily evaluated a novel Cardio-Kidney-Metabolic (CKM) Index to assess multimorbidity trends and to explore its potential to inform evidence-based policy interventions.

Using Global Burden of Disease Study 2021 data spanning 204 countries and territories from 1990 to 2021, we extracted age-standardized disability-adjusted life years (DALYs) for CVD, CKD, and T2DM. The CKM Index was constructed through logarithmic transformation (log[x + 1]), min-max normalization, and weighted integration based on global burden proportions and clinical significance (CVD = 0.5, CKD = 0.2, T2DM = 0.3) to generate a standardized 0-100 scale. We analyzed temporal trends using estimated annual percentage change (EAPC), performed joinpoint regression to identify trajectory inflection points, and conducted forecasting through 2030 using ARIMA and Bayesian ridge regression models. Sensitivity analyses evaluated index robustness across alternative weighting schemes, and clustering analysis identified distinct country trajectory patterns across socio-demographic index (SDI) regions.

Global CKM-related DALYs increased dramatically by 60% from 343 million person-years in 1990 to 548 million in 2021 (EAPC + 1.51%). T2DM demonstrated the most explosive growth (EAPC + 3.57%), followed by CKD (+ 2.46%) and CVD (+ 1.18%). The CKM Index revealed marked global health inequalities, with high-SDI countries exhibiting the highest burden (70.7 in 2021) despite advanced healthcare systems, while middle-SDI regions showed concerning acceleration (reaching 77.1). Low-SDI regions demonstrated lower absolute burden (22.7) but concerning stagnation since 2005. China's CKM Index rose substantially from 27.7 in 1990 to 67.6 in 2021, with joinpoint analysis revealing acceleration phases in 1998 and 2006, reflecting rapid epidemiological transition during economic development. Age-stratified analysis revealed 35% of total burden concentrated in individuals aged 60-74 years, with consistent male predominance. Pairwise comorbidity analysis showed CVD + T2DM combinations increasing fastest globally (EAPC + 1.45%), while CKD + T2DM burden nearly tripled. Forecasting models projected continued escalation through 2030, with middle-SDI regions reaching 86.6-87.5 and China plateauing at 66.7-77.5, though COVID-19 highlighted forecasting limitations under structural disruptions.

The CKM Index provides a promising methodological prototype for quantifying multimorbidity burden and reveals alarming global escalation trends with pronounced health inequalities. The syndemic nature of CKM diseases demands paradigmatic shifts from specialty-siloed to integrated chronic disease management. Countries achieving burden reductions within similar development contexts demonstrate the potential for coordinated policy interventions. Urgent global action is required to address the growing CKM crisis through enhanced surveillance, integrated care delivery, and targeted interventions addressing social determinants of health.