Baseline clinical characteristics of patients
The baseline demographics and laboratory parameters of patients according to physical performance status are shown in Table 1. The prevalence rates of low GS and HS were 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, higher prescription rate of statins was observed in patients with low GS than in those with normal GS.
Association between physical performance, comorbidity index, and mental health
We performed 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 coefficient was weak (R2 = 0.070 and p < 0.001; Figure 1). We next evaluated the relationship between physical performance, comorbidity indexes, 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 3.4±1.2 vs. 4.0±1.5 vs. 4.4±1.3 vs. 4.7±1.2 and Liu comorbidity scores of 3.9±2.1 vs. 4.6±2.8 vs. 5.1±2.4 vs. 6.1±2.7 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 functions as assessed by the MMSE and the KDQOL-SF (27.4±2.7, 25.8±4.2, 26.4±3.6, and 25.2±4.8; and 86.1±14.3, 80.8±18.0, 73.3±23.8, and 73.5±22.1 for the normal GS and HS, normal GS and low HS, low GS and normal HS, and low GS and HS groups; p = 0.010 and 0.001, respectively). The social activity index was relatively maintained in the low GS and HS group. Notably, the comorbidity scores, depression index, and the quality of life scores were mostly worse in patients with low GS and normal HS compared to those with normal GS and low HS, although statistical significance was only observed in 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 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 HS. On the other hand, low HS, but not low GS, was significantly associated with low body mass index (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 groups. Among measued 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 2A and B). In contrast, 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 2C-E).
Impact 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 3).
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 risk for major adverse events (adjusted HR of 2.72, 95% CI of 1.14 – 6.46; p = 0.024) compared to the risks of those with normal GS and HS after multivariate adjustments of possible confounders. Patients with normal HS but low GS also exhibited an increasing trends in the 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 increased risk for adverse outcomes, although the adjusted HRs were slightly elevated. There was a significant interaction between GS and HS for the major adverse events (p = 0.019).