Low handgrip strength as a potential indicator of 2-year mortality in older Chinese inpatients: A multicenter prospective cohort study

To the Editor: With the advancements in the global economy and the increase in human life expectancy, many nations are transitioning to aging societies. China currently has the most extensive elderly population in the world.[1] Consequently, healthcare for older people has become of paramount importance in China. A primary characteristic of aging is the decline in skeletal muscle mass, resulting in diminished muscle strength. Muscle strength is crucial for daily activities and independence during healthy aging. Previous research has overlooked the impact of handgrip strength on mortality among older hospitalized patients in China. This study seeks to fill this gap by analyzing the association between low handgrip strength and 2-year mortality risk in this population through a detailed cohort study. The data were acquired by a joint effort between Peking Union Medical College Hospital and five tertiary hospitals across China from October 31, 2018 to February 21, 2019 [Supplementary Table 1, https://links.lww.com/CM9/C418]. This study received approval from the Peking Union Medical College Hospital (No. S-K540) and was registered in the Chinese Clinical Trials Registry (No. ChiCTR1800017682, http://www.chictr.org.cn/). All participants provided written informed consent. A total of 9474 participants were included who were enrolled and underwent a follow-up process in our study. We included patients who were assessed at least once (at any of the designated follow-up points of 30 days, 90 days, 1 year, and 2 years after enrollment) in Cox proportional risk model as censored data. The handgrip strength assessment followed a specific protocol. First, the individual stood naturally with feet shoulder-width apart and arms hanging freely. Second, the participant squeezed the handgrip dynamometer with maximum force. This procedure was repeated three times, and the highest value was recorded in kilograms (kg) to two decimal places for precision. This measurement aligns with the Asian Working Group for Sarcopenia guidelines, wherein low handgrip strength is defined as below 28 kg for men and 18 kg for women.[2] We also analyzed handgrip strength as a continuous variable, assessing the impact of every 5 kg increase in strength. The demographic variables of inpatients were obtained within 48 h of admission and included sex, age, education, marital status, and ethnicity. Additionally, we gathered other significant covariates, such as the Charlson Comorbidity Index (CCI), history of smoking and alcohol consumption, depression status, nutritional status, and frailty. This study evaluated multimorbidity using the diagnoses listed at admission, with reference to the 10th Revision of the International Classification of Diseases (ICD-10).[3] The CCI was utilized as a measure to reflect the chronic disease status of the participants. This index applies a scoring system to effectively assess comorbidities in patients. We categorized educational status into four groups: illiterate, primary school, middle school, and university. Smoking and alcohol use were categorized as non-use, current, and former for both activities. The Geriatric Depression Scale was used to evaluate the mental well-being of older individuals.[4] The mini-nutritional assessment-short form (MNA-SF) is a reliable tool for evaluating the nutritional status of older individuals.[5] The total score of the MNA-SF is 14, with scores ranging from 0 to 11 indicating abnormal nutritional status and scores from 12 to 14 indicating normal nutritional status. The frailty condition was assessed using the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) scale, which comprises five items: fatigue, endurance, power, presence of illness, and body weight.[6] Each item is scored as 1, and a total score of 0–2 indicates the absence of frailty, while a score of 3–5 indicates the presence of frailty. The categorical data were described using frequencies (percentages), and differences between the two groups were determined using the chi-squared test. The log-rank test was employed to assess differences in the survival curves between the low handgrip strength group and the normal handgrip strength group. Low handgrip strength was incorporated into the Cox proportional hazards regression model as both a binary variable and a continuous variable to examine its relationship with 2-year mortality. Cox models that were both unadjusted and adjusted for potential confounding factors were assessed. We stratified potential confounders for subgroup analyses and explored the interaction between these variables and low handgrip strength. A significance level of two-tailed P <0.05 was utilized for all statistical analyses, which were conducted using SAS 9.4 software (SAS Institute Inc.,Cary, USA). Following the 2-year follow-up period, a total of 9474 older hospitalized patients were included in the analysis, after excluding those with missing baseline data and unknown survival time. The findings revealed that 58.04% (5499/9474) of the older hospitalized patients were men, while individuals aged over 75 years constituted 29.39% (2784/9474) of the cohort. Moreover, 94.07% (8912/9474) of the patients identified as Han ethnicity. Additionally, 88.68% (8402/9474) of the patients were married and had a living partner. The Kaplan–Meier method revealed that patients with normal handgrip strength had higher 2-year survival rates than those with low handgrip strength (P <0.01). Further analysis found that women had statistically significant stronger handgrip strength ( P = 0.03) but a lower risk of 2-year mortality (P <0.01) than men. Compared with those in the 65–74 years age group, the proportion of individuals with low handgrip strength and the proportion of deaths were higher in the group aged 75 and older (both P <0.01). Individuals with higher levels of education exhibited lower rates of low handgrip strength and experienced fewer deaths in a 2-year period compared with those with lower levels of education (both P <0.01). In addition, abnormal nutritional status, depression, and frailty increased the risk of mortality in older adults (all P <0.01) . Considering the potential clinical heterogeneity among participants and its impact on inpatient mortality rates, we employed the CCI to characterize comorbidities, the results indicated that as the CCI score increased, there was a higher proportion of individuals with low handgrip strength and greater mortality (P <0.01) [Supplementary Table 2, https://links.lww.com/CM9/C418]. We conducted a collinearity check on the covariates and found variance inflation factor (VIF) values near 1. Given that VIF <10 suggests minimal collinearity, we confirmed that there were no significant concerns regarding these covariates. The Cox proportional hazard regression models demonstrated a statistically significant positive association between low handgrip strength and an increased 2-year risk of mortality in unadjusted model (hazard ratio [HR] = 2.08, 95% confidence interval [CI]: 1.84–2.35; P <0.01). This association remained statistically significant even after adjusting for sex and age in model 2 (HR = 2.02, 95% CI: 1.79–2.28; P <0.01) and even further adjustment for ethnicity, education, and marital status in model 3 (HR = 1.94, 95% CI: 1.71–2.19; P <0.01). In model 4, which included additional adjustments for the CCI, smoking status, alcohol consumption, depression, MNA-SF, and frailty, the association remained statistically significant (HR = 1.58, 95% CI: 1.40–1.80; P <0.01) [Supplementary Table 3, https://links.lww.com/CM9/C418]. We also analyzed handgrip strength as a continuous variable, assessing the impact of every 5 kg increase in strength, and after adjusting for all potential confounding factors, the negative correlation remained. We performed subgroup analyses stratified by several demographic and correlated factors. The risk of mortality associated with low handgrip strength varied across different subgroups [Supplementary Figure 1, https://links.lww.com/CM9/C418]. To account for the increased risk of a Type I error (α) due to multiple comparisons, we applied the Bonferroni correction. Even after adjustment, the findings remained statistically significant across all subgroups, further reinforcing the robustness of our results. Cox regression models were employed to examine the association between handgrip strength and the risk of mortality in hospitalized patients. After comprehensive adjustment for confounding factors, the analysis revealed that older patients with reduced handgrip strength had a 1.51-fold higher risk of mortality over a 2-year period compared with patients with normal handgrip strength. Given these results, it is imperative to explore the potential underlying mechanisms linking handgrip strength to mortality risk. Reduced handgrip strength is indicative of bodily and muscular weakness, which is often associated with muscle-related disorders.[7] Sarcopenia is widely recognized as an independent risk factor contributing to increased mortality rates.[8] The influence of muscle strength on mortality may be intricately linked to its role in the deterioration of functional capacity. People with less physical strength often struggle with daily activities, and their limited movement flexibility can make them less likely to exercise. This lack of muscle endurance and strength can lead to less activity and motivation, thereby increasing the risk of accidents and illnesses. Confounding factors were categorized into distinct subgroups for sensitivity analyses. The findings consistently revealed a robust positive correlation between low handgrip strength and an increased 2-year mortality risk across all subgroups (all HR >1.50, P <0.05). These results underscore the robustness of our analytical outcomes. Our study showed a strong link between low handgrip strength and increased 2-year mortality risk in hospitalized older Chinese patients, even after accounting for other factors. Handgrip strength could be a key indicator of mortality risk in this group. This study supports the importance of assessing handgrip strength in clinical settings. Early screening and interventions, such as nutritional modifications and exercise protocols, are crucial for improving outcomes and reducing mortality. Funding This study was support by grants from the National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-C-058), Capital’s Funds for Health Improvement and Research (No. 2024-2G-4211), the CAMS Innovation Fund for Medical Sciences (No. 2018-I2M-AI-009), and the Special Research Fund for Central Universities, Peking Union Medical College (No. 2018PT33001). Acknowledgments The authors thank the inpatients, nurses, clinicians, and management staff of the research hospitals involved in the study. Conflicts of interest None.