The present study, to our knowledge, is the first attempt to investigate the association between grip strength and frailty in RA patients, with a specific focus on finger/wrist joint symptoms (i.e., swollen and tender joints) and disease activity (DAS28-CRP). Frailty was significantly associated with grip strength independently of age and disease activity, which were previously reported to be factors related to frailty 24, as well as finger/wrist joint symptoms (Table 3). While the cut-off score of grip strength corresponding to frailty in RA patients without finger/wrist joint symptoms was 17 kg, which was similar to one of the CHS criteria for diagnosing frailty (i.e., < 18 kg for females) 3,14 (Fig. 1a), the cut-off score of grip strength in RA patients with finger/wrist joint symptoms was 14 kg, which was lower than that in those without finger/wrist joint symptoms (Fig. 1b). Furthermore, the upper limit of 95% CI for mean grip strength in subjects with frailty and no finger/wrist joint symptoms was 17.3 kg, and that for those with frailty and finger/wrist joint symptoms was 14.7 kg (Fig. 2), indicating that RA patients with no finger/wrist joint symptoms having a grip strength less than 18 kg or RA patients with finger/wrist joint symptoms having a grip strength less than 15 kg are frailty. These findings suggest that grip strength in RA patients reflects frailty regardless of finger/wrist joint symptoms and disease activity. The cut-off score of grip strength corresponding to frailty is < 18 kg (equivalent to CHS criteria) when RA patients have no finger/wrist joint symptoms. However, when RA patients have finger/wrist joint symptoms and a grip strength greater than 15 kg but less than 18 kg, it is important to look at other measures, such as lower limb function.
Finger/wrist joint symptoms were significantly associated with DAS28-CRP (Table 2). In daily clinical practice, compared to DAS28-CRP which requires complicated calculations, information on finger/wrist joint symptoms can be obtained simply and intuitively. We also found that grip strength was significantly associated with HAQ-DI (Table 2). Based on the results of this study, we propose a screening method for evaluating frailty that uses grip strength in combination with finger/wrist joint symptoms. Actually, it is better to calculate DAS28-CRP and HAQ-DI to evaluate the condition of RA patients in detail. Moreover, since RA patients often have finger/wrist joint symptoms, it is reasonable to use knee extension strength instead of grip strength in such patients to evaluate frailty, as was done in a previous report 25. However, an understanding of the characteristics of each measurement method is important. For instance, grip strength and knee extension strength were reported to be affected by height and weight, respectively 11, suggesting that knee extension strength is not an appropriate evaluation method for all patients. Moreover, according to one report, grip strength of RA patients in remission of disease activity was almost equivalent to that of the healthy population 26. Nonetheless, grip strength can be measured more easily than lower limb muscle strength, and finger/wrist joint symptoms can be identified immediately. Accordingly, it will be important to clarify which RA patients can be evaluated for frailty using grip strength, and when necessary, to lower the grip strength cut-off score when the patients have finger/wrist joint symptoms. The significance of our present findings is that it reveals the need to reduce the cut-off score of grip strength, or use an evaluation method other than grip strength, to predict frailty in RA patients with finger/wrist joint symptoms.
Cut-off scores of grip strength corresponding to clinical remission (DAS28-CRP < 2.3) and functional remission (HAQ-DI ≤ 0.5) were 16 kg (without finger/wrist joint symptoms) and 14 kg (with finger/wrist joint symptoms), respectively, which were similar to the cut-off score of grip strength corresponding to frailty. It was reported that frailty had significant association with disease activity 24 and HAQ 27. Notably, maintaining grip strength from the perspective of preventing frailty may lead to also aiming for clinical and functional remission.
Factors that may influence grip strength in RA patients include age 28 and disease activity 29. In this study, even when adjusting for these factors, grip strength was significantly associated with frailty (Table 3). Higher grip strength is reportedly associated with lower levels of inflammation, leading to lower mortality 30. Furthermore, hand involvement in early inflammatory arthritis has been shown to be a strong predictor of a poor long-term disease outcome 31. These results suggest that regular follow-up of grip strength and finger/wrist joint symptoms in RA patients may allow for the determination that disease activity is changing (worsening) and the prevention of the negative health outcomes of frailty. Adequate exercise can reduce pain in RA patients 32 and improve grip strength 33. From the perspective of preventing frailty, exercise may have a synergistic effect when performed in combination with RA drug therapy.
This study has several limitations. First, radiographic evaluations were not performed. However, we believe our findings are valid because tender and swollen joints could lead to reduced grip strength even without radiographic changes (e.g., early RA). Second, this study targeted only female RA patients. Cut-off scores of CHS criteria for males and females differ (i.e., < 18 kg for females and < 28 kg for males) 3,14. Since this study aimed to confirm the validity of the cut-off score of grip strength, we first targeted females given the small number of male patients in the source population. It will be important to conduct a study with a larger male RA patient population to confirm the cut-off score for males. Third, we did not obtain information regarding the history of upper limb surgery, which can affect grip strength. Finally, physical factors of lower limb function such as walking time and psychosocial factors such as depression, anxiety, and social support, which are related to frailty 34, were not evaluated in detail. Since some RA patients do not have frailty despite having poor grip strength, evaluating frailty based only on upper limb function is insufficient. Nonetheless, upper limb function measurements are simple to perform and may serve as a screening index for evaluating frailty in daily clinical practice.
In conclusion, we investigated the association between grip strength and frailty in RA patients. Frailty was significantly associated with grip strength, independently of age, disease activity, and finger/wrist joint symptoms. Measuring grip strength and checking finger/wrist joint symptoms offer a useful and simple way to assess frailty in daily clinical practice. Our findings serve as a foundation for the development of methods to detect and screen for frailty, as well as interventions.