Associations of cardiovascular–kidney–metabolic syndrome stages with premature mortality and the role of social determinants of health

Objectives: The American Heart Association defined cardiovascular–kidney–metabolic (CKM) syndrome as a novel multi-stage disorder. We examined the associations of CKM stages with premature mortality and the role of social determinants of health (SDOHs). Design: A prospective cohort study. Setting and participants: A nationally representative sample of US adults from NHANES 1999–2018. Measurements: CKM included 5 stages (stages 0–4), reflecting progressive pathophysiology. Premature mortality (deaths before 75 years) were ascertained via linkage to the National Death Index with follow-up until 2019. Cox proportional-hazards models adjusted for age, sex, race/ethnicity, medical history, and other confounding factors were used to calculate the hazard ratios (HR) and 95% CIs for CKM-mortality associations. Results: Among 27,909 participants (mean age 49.7 years, 49.0% females), 1762 premature deaths occurred over a median follow-up of 8.3 years. Compared with stage 0, the adjusted HRs for all-cause premature mortality at CKM stages 1–4 were 0.88 (95% CI 0.66–1.17), 1.31 (0.99–1.73), 1.94 (1.31–2.87), and 2.19 (1.61–2.98), respectively. For CVD premature mortality, the adjusted HRs for CKM stages 1–4 were 1.12 (0.46–2.72), 1.74 (0.71–4.28), 3.93 (1.53–10.12), and 6.48 (2.95–14.20), respectively. Among adults at CKM stages 3–4, unfavorable SDOHs, particularly not living with a partner, low family income, lack of private health insurance, unemployment, or ≥2 cumulative SDOHs (4.16, 95% CI 3.35–5.18) were associated with increased all-cause premature mortality. Among those at CKM stages 0–2, unfavorable SDOHs were also related to increased premature mortality. Conclusion: CKM stages 3–4, but not stages 1–2, were associated with increased risks of premature mortality compared with stage 0. The risks were increased by unfavorable SDOHs across CKM stages.