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

Abstract

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.

Keywords: Cardiovascular disease; Cardiovascular–kidney–metabolic health; Diabetes; Health disparities; Obesity.

Fig. 1

Adjusted hazard ratios for risk of premature mortality from all causes and cardiovascular disease according to cardiovascular–kidney–metabolic syndrome stages by cumulative unfavorable social determinants of health. Abbreviations: SDOHs, social determinants of health; CKM, cardiovascular–kidney–metabolic syndrome; HR, hazard ratio; CI, confidence interval. Points represent HRs and error bars represent 95% CIs. No adjustments of multiple comparisons were applied. All estimates accounted for complex survey designs. Models were adjusted for baseline age, sex, race/ethnicity, alcohol consumption, smoking status, physical activity, and medical history of cancer at baseline.

Fig. 2

Adjusted hazard ratios for risk of all-cause premature mortality according to cardiovascular–kidney–metabolic syndrome stages by social determinants of health. Abbreviations: SDOHs, social determinants of health; CKM, cardiovascular–kidney–metabolic syndrome; HR, hazard ratio; CI, confidence interval. Points represent HRs and error bars represent 95% CIs. No adjustments of multiple comparisons were applied. All estimates accounted for complex survey designs. Models were adjusted for baseline age, sex, race/ethnicity, education, marital status, family income-to-poverty ratio, food security, type of health insurance, employment status, home ownership, regular health-care access, alcohol consumption, smoking status, physical activity, and medical history of cancer at baseline if applicable.

Fig. 3

Adjusted hazard ratios for risk of premature mortality from cardiovascular disease according to cardiovascular–kidney–metabolic syndrome stages by social determinants of health. Abbreviations: SDOHs, social determinants of health; CKM, cardiovascular–kidney–metabolic syndrome; HR, hazard ratio; CI, confidence interval. Points represent HRs and error bars represent 95% CIs. No adjustments of multiple comparisons were applied. All estimates accounted for complex survey designs. Models were adjusted for baseline age, sex, race/ethnicity, education, marital status, family income-to-poverty ratio, food security, type of health insurance, employment status, home ownership, regular health-care access, alcohol consumption, smoking status, physical activity, and medical history of cancer at baseline if applicable.