Increased mortality risk with more severe form of CKM syndrome

In a Chinese prospective cohort study among ~98,000 adults, a higher stage of cardiovascular-kidney-metabolic (CKM) syndrome was associated with an increased risk of all-cause mortality, especially in younger participants.

This summary is based on the publication of Li N, Li Y, Cui L, et al. - Association between different stages of cardiovascular-kidney-metabolic syndrome and the risk of all-cause mortality. Atherosclerosis. 2024 Oct:397:118585. doi: 10.1016/j.atherosclerosis.2024.118585

Introduction and methods

Background

Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic health disorder characterized by pathophysiological interactions among obesity, diabetes, CKD, and CVD [1]. Poor CKM health is a major determinant of all-cause mortality [2]. However, the association between different stages of CKM syndrome and the risk of all-cause mortality is still unknown.

Aim of the study

The authors examined the association between different stages of CKM syndrome and risk of all-cause mortality.

Methods

The Kailuan Study was a large-scale, prospective, observational, community-based cohort study in which 97,777 adults (79.9% males) with baseline data on, among others, BMI, fasting blood glucose levels, lipid profile, and blood pressure were enrolled at 11 hospitals in northern China in the period June 2006–October 2007. All participants were subjected to questionnaires, physical examinations, and laboratory tests. Median follow-up duration was 15.0 years (IQR: 14.7–15.2).

CKM syndrome was classified into the following stages:

• Stage 0 – absence of CKM risk factors
• Stage 1 – presence of excess weight (BMI ≥23 kg/m²), abdominal obesity (waist circumference ≥80 cm in women and ≥90 cm in men), or dysfunctional adipose tissue, with no additional metabolic risk factors or CKD
• Stage 2 – presence of metabolic risk factors (hypertriglyceridemia, dyslipidemia, hypertension, metabolic syndrome, diabetes), moderate-to high-risk CKD, or both
• Stage 3 – subclinical CVD
• Stage 4 – clinical CVD, with or with no kidney failure

Outcome

The endpoint was the incidence of all-cause mortality.

Main results

• During follow-up, 14,805 participants died due to any cause (incidence rate: 10.8 per 1000 person-years).

• The cumulative risk of all-cause mortality increased with higher CKM syndrome stages (log-rank P<0.001). The incidence rate ranged from 3.0 per 1000 person-years for participants with Stage 0 to 37.9 per 1000 person-years for participants with Stage 4.

• In Cox proportional hazards regression model analysis adjusted for age, sex, and baseline variables such as smoking status, physical activity, and educational level, the CKM syndrome stage was positively associated with the risk of all-cause mortality: Compared with Stage 0, the multivariable-adjusted HR of all-cause mortality was 1.24 (95%CI: 1.06–1.45) for Stage 1, 1.72 (95%CI: 1.48–2.00) for Stage 2, 2.58 (95%CI: 2.22–3.01) for Stage 3, and 3.73 (95%CI: 3.19–4.37) for Stage 4 (P for trend<0.001).

• Subgroup analyses showed the association between CKM syndrome stage and all-cause mortality was stronger in participants aged <60 years (adjusted HR for Stage 4 vs. Stage 0: 8.07; 95%CI: 6.38–10.21) compared with older adults (adjusted HR for Stage 4 vs. Stage 0: 3.44; 95%CI: 2.77–4.26; P for interaction<0.001).

Conclusion

In the Chinese Kailuan Study, a higher CKM syndrome stage was associated with an increased risk of all-cause mortality, especially in participants aged <60 years. According to the authors, “[t]he CKM staging approach facilitates identifying individuals at different levels of syndromic severity, thereby providing windows for preventive action to halt or reverse disease progression.”

Find this article online at Atherosclerosis.

References

1. C.E. Ndumele, J. Rangaswami, S.L. Chow, et al., Cardiovascular-kidney-metabolic health: a presidential advisory from the American heart association, Circulation 148 (20) (2023) 1606–1635.
2. C.E. Ndumele, I.J. Neeland, K.R. Tuttle, et al., A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: a scientific statement from the American heart association, Circulation 148 (20) (2023) 1636–1664.