Cardiovascular-Kidney-Metabolic Syndrome Among US Adults, 1999–2023: National Trends and Projections Through 2050
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Background
Cardiovascular-kidney-metabolic (CKM) syndrome places adiposity, metabolic risk, kidney dysfunction, and cardiovascular disease within a single prevention-oriented framework. After publication of the American Heart Association framework, nationally representative estimates remain incomplete for the full 1999–2023 NHANES interval and for future burden under plausible population scenarios.
Methods
We analyzed US adults aged 20 years or older from 11 NHANES cycles, beginning with 1999–2000 and ending with August 2021–August 2023. CKM stage 0 to stage 4 was derived from harmonized examination findings, laboratory measures, medication information, and questionnaire items. Prevalence was estimated with survey weights and directly standardized to the 2010 US Census adult population. Decade trends were assessed using survey-weighted logistic regression adjusted for age, sex, and race and ethnicity. For 2040 and 2050, exploratory projections linked NHANES prevalence models to US Census population projections under population-aging-only, trend-continuation, and risk-improvement assumptions.
Results
Among 62,890 eligible adults, 62,888 had sufficient information for CKM staging. In 2021–2023, the age-standardized prevalence of CKM stage 1 or higher was 87.9% (95% CI, 86.5%–89.4%), and the prevalence of CKM stages 2–4 was 62.0% (95% CI, 60.1%–63.8%). Stage 2 represented 50.1% (95% CI, 48.2%–51.9%) of adults, while stages 3–4 represented 11.9% (95% CI, 11.0%–12.7%). Between 1999–2000 and 2021–2023, any CKM increased by 4.6 percentage points (95% CI, 2.4 to 6.9; P<0.001), but CKM stages 2–4 changed by −2.1 percentage points (95% CI, −5.1 to 0.8; P=0.156). In adjusted decade models, any CKM increased (odds ratio [OR], 1.28; 95% CI, 1.19–1.38; P<0.001), whereas CKM stages 2–4 did not show a significant linear trend (OR, 0.95; 95% CI, 0.89–1.01; P=0.084). Excess adiposity and diabetes became more common, dyslipidemia declined, and hypertension, chronic kidney disease, and clinical cardiovascular disease showed no significant adjusted decade trend. With population aging alone, the projected CKM stages 2–4 burden rose from 164.8 million adults in 2023 to 193.7 million in 2050; under sustained risk improvement, the 2050 projection was 147.7 million.
Conclusions
In a 25-year NHANES surveillance series, CKM syndrome remained a major population health state among US adults. The distribution moved toward earlier CKM risk without a significant increase in stages 2–4, yet population aging could still enlarge the absolute number of adults requiring CKM-oriented prevention and care unless risk improves broadly.
Clinical Perspective
What Is Known
Cardiovascular, kidney, and metabolic abnormalities frequently develop in the same adults, and the American Heart Association has proposed the cardiovascular-kidney-metabolic (CKM) staging framework to describe this overlap as a prevention continuum.
Although recent US estimates show that CKM stages are common, most reports have centered on 2011–2020 NHANES data and do not yet describe the reopened August 2021–August 2023 public cycle within the longer modern NHANES record.
What the Study Adds
Using harmonized data from 62,890 adults in 11 NHANES cycles spanning 1999–2000 to 2021–2023, we found persistently high CKM burden; by 2021–2023, 87.9% of adults were classified as stage 1 or higher and 62.0% as stages 2–4.
Across the study period, any CKM rose by 4.6 percentage points and stage 1 rose by 6.8 percentage points, whereas CKM stages 2–4 did not have a statistically significant absolute increase; adjusted component models pointed to growing early metabolic risk despite a marked decline in dyslipidemia.
In scenario analyses, population aging alone raised the estimated number of US adults with CKM stages 2–4 from about 165 million in 2023 to 194 million in 2050, while a sustained risk-improvement scenario lowered the corresponding 2050 estimate to about 148 million.
