Yuting Liu,1 Yanting Liang,1 Huan Ma,2 Hengyuan Gao,3,4 Xinzhou Zhang1,5 

1Department of Nephrology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 2Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Thyroid Surgery, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, People’s Republic of China; 4Department of Thyroid and Breast Surgery,Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 5Shenzhen Key Laboratory of Kidney Diseases, The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China

Correspondence: Hengyuan Gao, Email geland136@163.com Xinzhou Zhang, Email xinzhouzhang1946@163.com

Objective: The American Heart Association has recently emphasized the significance of the cardiovascular-kidney-metabolic (CKM) syndrome. However, the cumulative impact of these factors on cardiorespiratory fitness remains inadequately characterized. This study aimed to examine the responses observed during cardiopulmonary exercise testing (CPET) of CKM syndrome patients and explore the potential correlation between cardiorespiratory fitness and hemoglobin concentration in this cohort.
Design: Cross-sectional study.
Methods: We retrospectively collected medical data of 8206 patients who underwent CPET from 2012– 2022. Among the 878 individuals enrolled, 12 were healthy controls, 809 had isolated CVD, and 57 were in CKM stage 4. After propensity score matching, 112 patients were included in the matched cohort analysis, with 56 each in the CVD and CKM groups. CPET responses were compared between the groups using propensity matched analysis. Additionally, simple mediation models were employed to investigate the potential mediating role of hemoglobin concentration in the association between CKM syndrome and peak VO2.
Results: After propensity score-matching, CKM stage 4 was associated with diminished cardiorespiratory fitness compared to the other two groups. This included diminished exercise capacity, reflected by shorter exercise time, lower maximum workload (and its percent predicted value), and reduced peak VO2 (including its percent predicted value and peak VO2/kg). Additionally, cardiac autonomic function was impaired, as evidenced by decreased heart rate recovery (HRR) and a reduced slope of HR recovery (all p< 0.05). Mediation model regression analysis indicated a significant and direct detrimental effect of CKM syndrome on peak VO2 (β = − 228.502; P = 0.003), and a significant indirect partial effect of hemoglobin concentration on the direct effect (β = − 335.718; P < 0.001), with the percentage mediated through hemoglobin concentration of 46.9%.
Conclusion: Individuals with CKM syndrome demonstrate compromised responses to CPET manifested by diminished exercise capacity and cardiac autonomic function. While diminished peak oxygen uptake can be partly explained by hemoglobin concentration as we found, further research is necessary to understand other underlying mechanisms.

Keywords: cardiovascular-kidney-metabolic, cardiovascular disease, diabetes, chronic kidney disease, cardiorespiratory fitness, Cardiopulmonary Exercise Testing