Baseline clinical characteristics of patients
The baseline demographics and laboratory parameters of patients stratified by physical performance status are shown in Table 1. The prevalence of low GS and HS was 78 (28.2%) and 124 (44.8%), respectively. Patients with low GS and HS were older and had a lower body mass index and a shorter duration of dialysis than those in the other groups. The prevalence of previous cardiovascular events and diabetes was also higher in these patients. The predialysis serum albumin and creatinine levels were significantly lower in patients with poor physical performance, while spKt/V was inversely correlated with GS and HS. Mid-arm muscle circumference (MAMC) was positively correlated with GS and HS, although the statistical significance was marginal. Finally, a higher rate of the prescription of statins was observed in patients with low GS than in those with normal GS.
Associations among physical performance, comorbidity index scores, and mental health
We performed a correlation analysis to determine the relationship between GS and HS and found that the two parameters were significantly correlated with each other, but the correlation was weak (R2 = 0.070 and p < 0.001; Figure 2). We next evaluated the relationships among physical performance, comorbidity index scores, and mental health. As shown in Table 2, GS and HS were significantly associated with comorbidity scores and poor physical status (Charlson comorbidity scores of 4 [2, 4] vs. 4 [3, 5] vs. 5 [3, 5] vs. 5 [4, 5] and Liu comorbidity scores of 4 [3, 5] vs. 4 [3, 6] vs. 6 [4, 7] vs. 6 [4, 7] for the normal GS and HS, normal GS and low HS, low GS and normal HS, and low GS and HS groups, respectively; p < 0.001 for both comparisons). In addition, patients with low GS and HS showed profoundly impaired cognitive functioning as assessed by the MMSE and the KDQOL-SF (28 [26, 29] vs. 27 [24, 28] vs. 27 [25, 30] vs. 27 [23, 29] and 87 [80, 100] vs. 87 [67, 100] vs. 80 [60, 93] vs. 73 [60, 93], normal GS and HS vs. normal GS and low HS vs. low GS and normal HS vs. low GS and HS groups; p = 0.030 and 0.007, respectively). The social activity index was relatively maintained in the low GS and HS groups. Notably, the comorbidity scores, depression index scores, and quality of life scores were generally worse in patients with low GS and normal HS compared to those with normal GS and low HS, although statistical significance was only observed for the physical functioning status.
Risk factors for low gait speed and poor handgrip strength
Logistic regression analysis was performed to identify the determining factors of poor physical performance (Table 3). Older age was the only common risk factor for both low GS (adjusted odds ratio [OR] of 1.51, 95% confidence interval [CI] of 1.20 – 1.91; p < 0.001) and low HS (adjusted OR of 1.30, 95% CI of 1.07 – 1.57; p = 0.008). The presence of diabetes and low serum albumin levels were risk factors for low GS (adjusted OR of 2.12, 95% CI of 1.16 – 43.86 and adjusted OR of 3.37, 95% CI of 1.32 – 8.62, respectively) but not for low HS. On the other hand, low HS but not low GS was significantly associated with low BMI (adjusted OR of 0.92, 95% CI of 0.86 – 0.99; p = 0.022) and a previous history of cardiovascular events (adjusted OR of 1.73, 95% CI of 1.02 – 2.95; p = 0.043).
The relationship between plasma inflammatory markers and physical performance
We next measured various plasma inflammatory markers and compared their levels across the groups. Among the cytokines and chemokines, the levels of plasma endocan and MMP-7 were significantly higher in patients with low GS and HS than in those with normal GS and HS (Figure 3A and B). In contrast, the levels of traditional inflammatory markers, including TNF-α, IL-6, and high sensitivity C-reactive protein (hs-CRP), were not associated with physical performance (Figure 3C-E).
Impacts of gait speed and handgrip strength on all-cause mortality and cardiovascular events
The mean duration of follow-up since the recruitment of patients was 25.3 months, and a total of 19 deaths (6.9%) and 30 (10.8%) cardiovascular events occurred during this period. Patients with low GS and HS showed the highest cumulative incidence rate for major adverse events (11.8%, 15.0%, 17.6%, and 29.5% for the normal GS and HS, normal GS and low HS, low GS and normal HS, and low GS and HS groups, respectively, p = 0.004 for overall comparisons; Figure 4).
The observed hazard ratios (HRs) for major adverse events are shown in Table 4. Multivariate Cox regression analysis revealed that patients with low GS and HS had the highest level of risk for major adverse events (adjusted HR of 2.72, 95% CI of 1.14 – 6.46; p = 0.024) compared to the risk levels of those with normal GS and HS after multivariate adjustments of possible confounders. Patients with normal HS but low GS also exhibited a tendency toward an increase in major adverse events (adjusted HR of 2.38, 95% CI of 0.86 – 6.53; p = 0.084). In contrast, isolated low HS was not related to an increased risk of adverse outcomes, although the adjusted HRs were slightly elevated. Notably, low GS and HS was associated with significantly increased composite event rate even after adjustment with patient’ comorbidity scores (adjusted HR of 2.30, 95% CI of 1.02 – 5.21; p = 0.045). There was a significant interaction between GS and HS for major adverse events (p = 0.019). Finally, we performed a subgroup analysis of enrolled patients according to their age. As shown in Figure 5, physical performance was not associated with composite outcomes in hemodialysis patients under 65 years of age. In contrast, the risk of major adverse events was significantly increased in elderly patients with low GS and HS (adjusted HR of 5.76, 95% CI of 1.78 – 18.62; p = 0.012).