Xinhang Pan,1,* Aowen Tian,1,* Jin Tan,1,2 Yuyang Miao,1,2 Qiang Zhang1,2 

1Department of Geriatrics, Tianjin Medical University General Hospital; Tianjin Key Laboratory of Elderly Health; Tianjin Geriatrics Institute, Tianjin, People’s Republic of China; 2Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in the Central Nervous System, Ministry of Education; State Key Laboratory of Experimental Hematology, Tianjin, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Qiang Zhang, Department of Geriatrics, Tianjin Medical University General Hospital, Anshan Road No. 154, Tianjin, 300052, People’s Republic of China, Tel/Fax +86 022 6036 3659, Email zhangqiangyulv@163.com

Background: Sleep and frailty are established influencing factors for cardiometabolic diseases (CMDs). However, their joint effects on cardiometabolic multimorbidity (CMM) in older adults remain poorly understood. This study aimed to assess the joint effect of sleep health and frailty on CMD prevalence and severity, with an emphasis on subgroup-specific health risk profiles.
Methods: This study analyzed 8944 adults aged ≥ 60 years from the National Health and Nutrition Examination Survey (NHANES, 2007– 2018). Weighted Logistic and quasi-Poisson regression models were used to assess the associations between sleep health, frailty, and CMD/CMM burden. Mediation analyses were used to examine the indirect effects of frailty index (FI) on the associations between sleep and CMM. Further cross-stratification of the population was conducted to evaluate the differences in characteristic indicators of health risks and biological aging.
Results: Poor sleep and frailty exhibited dose-dependent joint effects on CMD risk. After full adjustment, poor sleep combined with frailty had an incidence rate ratio (IRR) of 2.01 (95% CI: 1.78, 2.27) for existing cumulative number of CMDs (p for interaction = 0.006). The indirect effect of the FI explained 57.80% of the relationship between sleep health and the cumulative number of CMDs. Frailty was mainly manifested as differences in individual inflammation and aging indicators (eg, Systemic inflammation response index, Phenoage acceleration), while poor sleep was more reflected in changes in metabolic indicators (eg, Metabolic score for insulin resistance).
Conclusion: Poor sleep and frailty jointly amplified associations with CMM in older US adults. The relationship between sleep and CMM could be partially explained by FI. Elderly individuals with poor sleep should focus on changes on metabolic indicators, while those combined with frailty need to pay extra attention to aging and inflammation indicators.

Keywords: sleep, frailty, cardiometabolic diseases, multimorbidity