Famine Exposure Affects Cardiovascular-Kidney-Metabolic Health Transitions in Adults

Introduction: Cardiovascular-kidney-metabolic (CKM) syndrome represents a progressive pathophysiological continuum. While early-life famine exposure has been associated with cardiometabolic outcomes, its impact on transitions across CKM stages remains unknown. Methods: We utilized data from the Kailuan Study, an ongoing, prospective cohort study in China. We included 24,190 participants with complete baseline anthropometric and biochemical data. Eligible participants had a baseline CKM syndrome stage between 0 and 3 and at least two CKM syndrome stage assessments (through Dec 31, 2022). Famine exposure was classified by birth year into fetal-exposed (1959–1961), early-childhood-exposed (1956–1958), and unexposed (1962–1964). Multistate models estimated associations between famine exposure and stage-specific transitions—CKM progression (within stages 0–3), recovery, clinical cardiovascular disease (CVD), and mortality—stratified by baseline CKM stage. Results: Over a median follow-up of 15.9 years, 2,611 participants developed CVD and 1,645 died. Among those with baseline stage 0, famine exposure was not significantly associated with adverse progression. Among those in stage 1, fetal famine was associated with higher risks of progression (hazard ratio [HR] 1.10; 95% CI, 1.00–1.21) and death after progression (HR 1.78; 95% CI, 1.01–3.14); early-childhood famine showed similar patterns: progression (HR 1.09; 95% CI, 1.00–1.18) and death after progression (HR 1.88; 95% CI, 1.12–3.14). For stage 2, fetal and early-childhood famine were associated with increased risks of progression (HR 1.42; 95% CI, 1.22–1.66 and HR 1.89; 95% CI, 1.66–2.16, respectively), clinical CVD (HR 1.19; 95% CI, 1.05–1.34 and HR 1.30; 95% CI, 1.18–1.45), and death (early-childhood HR 1.65; 95% CI, 1.42–1.92). In addition, early-childhood famine was associated with reduced probability of recovery (HR 0.79; 95% CI 0.71-0.87). No statistically significant associations were detected in participants with stage 3 at baseline (n = 196), likely due to limited power. Conclusion: Early-life famine exposure does not raise CVD or mortality risk among metabolically healthy adults, but it markedly accelerates CKM progression once metabolic dysfunction emerges. This underscores two priorities: (1) sustain metabolic health in famine exposed populations, and (2) implementing proactive interventions at the earliest CKM stages (0-1) to prevent progression to more severe stages.