Abstract Body (Do not enter title and authors here): Background. The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remain unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and long-term prognosis of the CKM syndrome in the US.
Methods. We analyzed nationally representative NHANES 1988-2018 data collected from 33,868 US adults (age ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined sex-specific prevalence of CKM syndrome, and sex-specific CKM associations with all-cause mortality.
Results. Of the 33,868 adults studied, the mean±SD age was 48.4±18.3 years with 52% female and 56% non-White. Overall prevalence of CKM syndrome increased steadily from 1988 to 2018 in both sexes, with a larger temporal rise in prevalent Stage 3 CKM seen for males (from 18.9% to 22.4%) compared to females (from 13.9% to 15.2%) (Figure 1). Over a median follow-up of 13.3 years, there were 8745 deaths. In multivariable cox-regression analysis, worsening CKM severity was associated with all-cause mortality (P<0.001 for both sexes), with greater magnitudes of risk seen in females (HR=1.24 to 3.33) compared to males (HR=0.85 to 2.60) across all stages (LRT χ²=19.0, P_interaction <0.001); results were similar for cardiovascular mortality (LRT χ²=22.3, P_interaction <0.001) (Table 1).
Conclusions. Females, compared with males, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multi-system CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, renal, and metabolic systems pathophysiology to close a potentially widening sex disparities gap in multi-organ disease risk.