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Sex Differences in Cardiovascular-Kidney-Metabolic Syndrome: 30-Year US Trends and Mortality Risks-Brief Report
Hongwei Ji1,2, Charumathi Sabanayagam3,4, Kunihiro Matsushita5
1Tsinghua Medicine, Tsinghua University, Beijing, China (H.J., T.Y.W.).
Insights
Cardiovascular-kidney-metabolic (CKM) syndrome prevalence increased in both sexes, but women face higher mortality risks despite lower prevalence. Further research is needed to address sex disparities in CKM disease.
Area of Science:
- Cardiology
- Nephrology
- Metabolic Health
- Public Health
- Epidemiology
Background:
- Recent American Heart Association guidelines define clinical identification of cardiovascular-kidney-metabolic (CKM) syndrome.
- Significant gaps exist in understanding sex-based differences in CKM syndrome prevalence and prognosis.
- This study investigates the impact of sex on CKM syndrome trends and long-term mortality in the US.
Purpose of the Study:
- To analyze sex-specific prevalence trends of CKM syndrome over three decades (1988-2018).
- To evaluate the association between CKM syndrome severity and all-cause mortality, stratified by sex.
- To identify potential sex disparities in CKM syndrome outcomes.
Main Methods:
- Utilized data from 33,868 US adults (≥20 years) from the National Health and Nutrition Examination Survey (1988-2018).
- Monitored all-cause mortality through December 31, 2019.
- Employed multivariable Cox regression to assess sex-specific associations between CKM syndrome and mortality.
Main Results:
- Overall CKM syndrome prevalence increased in both men and women from 1988 to 2018.
- Men showed a larger increase in prevalent stage 3 CKM compared to women.
- Worsening CKM severity was linked to increased all-cause and cardiovascular mortality in both sexes, with a significantly higher risk magnitude observed in women.
Conclusions:
- Women with CKM syndrome experience a disproportionately higher mortality risk compared to men, despite lower prevalence.
- Findings highlight the need to explore underlying pathophysiological mechanisms driving sex disparities in CKM disease.
- Addressing these sex differences is crucial to mitigate multiorgan disease risks and close the health equity gap.
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 remains unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and the long-term prognosis of CKM syndrome in the United States.
Methods:
We analyzed nationally representative National Health and Nutrition Examination Survey 1988 to 2018 data collected from 33 868 US adults (aged ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined the 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% women 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 men (from 18.9% to 22.4%) compared with women (from 13.9% to 15.2%). Over a median follow-up of 13.3 years, there were 8745 deaths. In the 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 women (hazards ratio, 1.24-3.33) compared with men (hazards ratio, 0.85-2.60) across all stages (likelihood ratio test χ2, 19.0; Pinteraction<0.001); results were similar for cardiovascular mortality (likelihood ratio test χ2, 22.3; Pinteraction<0.001).
Conclusions:
Women, compared with men, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multisystem CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, kidney, and metabolic system pathophysiology to close a potentially widening sex disparities gap in multiorgan disease risk.
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