Table 1
Age, body composition, physical parameters, and plasma profile of healthy controls (n = 92) and patients with CHF (n = 89). Based on EF, CHF patients were divided into moderate (EF = 26.4–32.9%) and mild (33-39.9%) CHF. The numbers in parenthesis indicate the percentage of total participants for that category. Values are expressed as mean ± SD; *p < 0.05 vs. healthy controls, #p < 0.05 vs. moderate CHF. (BMI; body mass index, ASM; appendicular skeletal mass, HGS; handgrip strength, HDL; high-density lipoproteins, HbA1c; glycosylated hemoglobin, CRP; C – reactive protein).
| Healthy controls | CHF | |||
|---|---|---|---|---|
| n = 92 | All (n = 89) | Mild (n = 63) | Moderate (n =26) | |
| Age at baseline (years) | 67.7 ± 5.3 | 64.4 ± 6.5 | 63.5 ± 6.1 | 66.5 ± 7.1 |
| Body composition | ||||
| BMI (Kg/m2) | 24.8 ± 2.8 | 22.2 ± 2.9* | 22.5 ± 3.1* | 21.5 ± 2.6* |
| ASM (Kg) | 22.4 ± 3.1 | 21.1 ± 2.3 | 21.5 ± 2.6 | 20 ± 2.1* |
| Percent fat | 29.8 ± 2.7 | 25.4 ± 3.1* | 25.5 ± 3.2* | 25.1 ± 3.3* |
| ASMI (Kg/m2) | 6.8 ± 1.8 | 6.2 ± 1.4* | 6.3 ± 1.44 | 6.1 ± 1.31 |
| Physical capacity | ||||
| HGS (Kg) | 23.5 ± 3.2 | 18.6 ± 3.3* | 19.5 ± 3* | 16.4 ± 3.6*# |
| HGS/ASM | 1.05 ± 0.21 | 0.88 ± 0.18* | 0.90 ± 0.15* | 0.81 ± 0.21*# |
| 4-meter walking Speed (m/s) | 1.18 ± 0.17 | 0.97 ± 0.13* | 1.01 ± 0.11* | 0.87 ± 0.19* |
| Daily steps count | 5,211 ± 1113 | 3,427 ± 838* | 3,708 ± 813* | 2,746 ± 928* |
| SPPB score | ||||
| 12 | 44 (47.8) | 4 (4.4)* | 4 (6.3)* | 0 |
| 11 | 18 (19.5) | 8 (8.9)* | 6 (9.5)* | 2 (7.7) |
| 10 | 15 (16.3) | 22 (24.7)* | 17 (27) | 5 (19.2) |
| 9 | 7 (7.6) | 33 (37.1)* | 24 (38)* | 9 (34.6)* |
| 8 | 5 (5.4) | 17 (19.1)* | 11 (17.5)* | 6 (23.1)* |
| 7 | 3 (3.2) | 4 (4.5) | 1 (1.6) | 3 (11.5) |
| 6 | 0 | 1 (1.1) | 0 | 1 (3.8) |
| Plasma profile | ||||
| Total Cholesterol | 187.4 ± 25.4 | 236.3 ± 39.8* | 232.4 ± 40.5* | 246.5 ± 37.9* |
| HDL-C (mg/dl) | 40.2 ± 2.8 | 37.1 ± 2.7* | 37.4 ± 2.8 | 36.4 ± 2.2* |
| LDL-C (mg/dl) | 97.8 ± 14.9 | 149.8 ± 29.2* | 146.3 ± 24.9* | 154.4 ± 33.5* |
| Triglycerides (mg/dl) | 144.3 ± 26.3 | 197.6 ± 39.3* | 189.4 ± 35.5* | 216.5 ± 42.3* |
| HbA1c (%) | 5.81 ± 0.11 | 5.93 ± 0.17 | 5.89 ± 0.15 | 6.04 ± 0.19 |
| 8-isoprostanes (pg/ml) | 51.6 ± 9.7 | 106.9 ± 28.5* | 102.4 ± 26.2* | 116.7 ± 32.6*# |
| CRP (mg/dl) | 0.15 ± 0.03 | 0.32 ± 0.08* | 0.31 ± 0.07* | 0.34 ± 0.07* |
| Creatine kinase (IU/L) | 182.3 ± 19.7 | 291.4 ± 38.7 | 281.7 ± 34.6 | 315.3 ± 37.4* |
Figure 1
Relative expressions of the plasma miRs (A) and the markers of inflammation and oxidative stress (B) in the healthy controls (n = 92) and the patients with CHF (n = 89). Values are expressed as mean ± SEM, *p < 0.05 vs. the healthy controls. (Interleukin-10, IL-10; Transforming growth factor-beta 1, TGF-b1; c-c motif chemokine receptor 5, CCR5; c-x-c motif chemokine ligand 8, CXCL-8; Interleukin-6, IL-6; c-x-c motif chemokine ligand 2, CXCL2; adrenomedullin, ADM; superoxide dismutase-1, SOD1; glutathione synthetase, glutathione peroxidase-1 GPX1).
Figure 2
Linear regression analysis of the relationships of plasma miRs with hand-grip strength (HGS) in healthy controls (n = 92) and patients with the CHF (n = 89).
Table 2
Correlations coefficients (r2) of circulating mi-RNAs with absolute and adjusted (for anti-coagulant therapy and daily step count) HGS, ASM, ASMI and 4MWS in healthy controls (n = 92) and participants with CHF (n = 89), * p < 0.05.
| MiR-21 | MiR-181a | miR-133a | MiR-424-5p | MiR-434-3p | MiR-455-3p | |
|---|---|---|---|---|---|---|
| HGS | ||||||
| Healthy | 0.184* | 0.129* | 0.203* | 0.098* | 0.112* | 0.124* |
| CHF | 0.126* | 0.122* | 0.167* | 0.157* | 0.115* | 0.139* |
| ASM | ||||||
| Healthy | 0.126 | 0.204* | 0.136* | 0.116* | 0.098 | 0.321* |
| CHF | 0.246* | 0.171 | 0.15* | 0.112 | 0.204* | 0.24* |
| ASMI | ||||||
| Healthy | 0.086 | 0.059 | 0.095 | 0.058 | 0.118* | 0.128* |
| CHF | 0.034 | 0.018 | 0.273* | 0.104* | 0.081 | 0.094* |
| 4MWS | ||||||
| Healthy | 0.065 | 0.049 | 0.083* | 0.067 | 0.096 | 0.113* |
| CHF | 0.089 | 0.177* | 0.095* | 0.137* | 0.128* | 0.098 |
| Adjusted HGS | ||||||
| Healthy | 0.131* | 0.103* | 0.184* | 0.075* | 0.063 | 0.103* |
| CHF | 0.109* | 0.128* | 0.181* | 0.139* | 0.078 | 0.164* |
| Adjusted ASM | ||||||
| Healthy | 0.107 | 0.225* | 0.124* | 0.096 | 0.109* | 0.285* |
| CHF | 0.155* | 0.104 | 0.157* | 0.135* | 0.188* | 0.256* |
| Adjusted ASMI | ||||||
| Healthy | 0.075 | 0.068 | 0.064 | 0.086 | 0.129* | 0.155* |
| CHF | 0.046 | 0.024 | 0.183* | 0.169* | 0.108* | 0.109* |
| Adjusted 4MWS | ||||||
| Healthy | 0.098* | 0.055 | 0.074 | 0.075 | 0.122* | 0.205* |
| CHF | 0.084 | 0.205* | 0.108* | 0.103* | 0.187* | 0.129* |
Figure 3
ROC curve illustrating sensitivity and specificity of the plasma miRs in discriminating healthy controls (n = 92) from the patients with CHF (n = 89).
Table 3
Correlations coefficients (r2) of circulating mi-RNAs with absolute and adjusted (for anti-coagulant therapy and daily stem count) plasma 8-isoprostanes and CRP levels in healthy controls (n = 92) and participants with CHF (n = 89), * p < 0.05.
| MiR-21 | MiR-181a | miR-133a | MiR-424-5p | MiR-434-3p | MiR-455-3p | |
|---|---|---|---|---|---|---|
| 8-isoprostanes | ||||||
| Healthy | 0.094 | 0.105 | 0.095 | 0.239* | 0.053 | 0.079* |
| CHF | 0.079 | 0.185* | 0.119 | 0.179* | 0.076 | 0.068 |
| CRP | ||||||
| Healthy | 0.134 | 0.046 | 0.149* | 0.028 | 0.071 | 0.139* |
| CHF | 0.169* | 0.108* | 0.253* | 0.131* | 0.105* | 0.261* |
| Plasma CK | ||||||
| Healthy | 0.085 | 0.103* | 0.187* | 0.379* | 0.158* | 0.141* |
| CHF | 0.129* | 0.094 | 0.353* | 0.413* | 0.224* | 0.178* |
| Adjusted 8-isoprostanes | ||||||
| Healthy | 0.081 | 0.129* | 0.071 | 0.204* | 0.059 | 0.097* |
| CHF | 0.098 | 0.151* | 0.089 | 0.191* | 0.071 | 0.074 |
| Adjusted CRP | ||||||
| Healthy | 0.155* | 0.053 | 0.163* | 0.036 | 0.084 | 0.128* |
| CHF | 0.188* | 0.094* | 0.204* | 0.152* | 0.118* | 0.218* |
| Adjusted Plasma CK | ||||||
| Healthy | 0.104 | 0.129* | 0.166* | 0.398* | 0.144* | 0.166* |
| CHF | 0.144* | 0.104 | 0.308* | 0.367* | 0.219* | 0.152* |