Comparison of baseline data between the NTIS and non-NTIS groups
To minimize research bias, PSM was used to match the two groups according to two major factors that influence metabolic indicators and mortality: age and BMI. After matching, statistically significant differences in age and BMI were not observed (see Additional file 1). And after matching by age and BMI, the triiodothyronine, free T3, total T4 (all P < 0.001), and TSH levels (P = 0.001) were significantly lower in the NTIS group than in the non-NTIS group, moreover, the percentage of patients with primary care was much more in the NTIS group than in the non-NTIS group (P < 0.001), and that for patients admitted with respiratory disease and accompanied by respiratory disease and chronic kidney disease were more in the NTIS group than in the non-NTIS group (P < 0.001, Table 1).
Table 1 Comparison of baseline characteristics between the NTIS and non-NTIS groups (`x ± SD)
|
Total
(n=852)
|
NTIS group
(n=192)
|
Non-NTIS group
(n=660)
|
t/Z/c2
|
P
|
Age (y)
|
87.63±6.11
|
87.84±5.96
|
87.56±6.16
|
0.56
|
0.57
|
BMI
|
23.85±3.23
|
23.72±3.56
|
23.88±3.13
|
−0.57
|
0.57
|
Triiodothyronine
(µmol/L)
|
1.27±0.31
|
0.90±0.16
|
1.38±0.25
|
−25.21
|
<0.001
|
Free T3
(pmol/L)
|
3.63±0.83
|
2.63±0.54
|
3.92±0.66
|
−24.78
|
<0.001
|
Total T4
(µmol/L)
|
86.34±16.31
|
75.10±16.38
|
89.60±14.78
|
−11.67
|
<0.001
|
Free T4
(pmol/L)
|
15.99±2.73
|
15.62±2.99
|
16.10±2.63
|
−2.17
|
0.31
|
TSH
(uIU/mL)
|
1.88(1.30, 2.88)
|
1.68(1.04, 2.74)
|
1.95(1.36, 2.93)
|
−3.37
|
0.001
|
Nursing degree
|
|
|
|
|
|
Primary
|
60
|
42(21.88%)
|
18(2.73%)
|
83.30
|
<0.001
|
Secondary
or tertiary
|
792
|
150(78.12%)
|
642(97.27%)
|
|
|
Reason for hospital admission
|
|
|
|
|
CVD
|
434
|
51(26.56%)
|
383 (58.03%)
|
111.24
|
<0.001
|
RD
|
282
|
110 (57.29%)
|
172 (26.06%)
|
|
|
NSD
|
60
|
13 (6.77%)
|
47 (7.12%)
|
|
|
CKD
|
10
|
10 (5.21%)
|
0 (0.00%)
|
|
|
Others
|
66
|
8 (4.17%)
|
58 (8.79%)
|
|
|
Comorbidities
|
|
|
|
|
|
RD
|
282
|
110(57.29%)
|
172(26.06%)
|
65.51
|
<0.001
|
NSD
|
82
|
24(12.50%)
|
58(8.79%)
|
2.36
|
0.13
|
CVD
|
759
|
174(90.63%)
|
585(88.64%)
|
0.61
|
0.44
|
CKD
|
112
|
45(23.44%)
|
67(10.15%)
|
22.99
|
<0.001
|
Tumour
|
180
|
30(15.63%)
|
150(22.73%)
|
4.50
|
0.03
|
RD respiratory disease, NSD nervous system disease, CVD cardiovascular disease, CKD chronic kidney disease, T3 triiodothyronine, T4 thyroxine, TSH thyroid-stimulating hormone.
After matching by age and BMI, TP, Alb, PA, Hb, UA, TG, and HDLC levels were significantly lower, while UN and FBG levels were higher, in the NTIS group than in the non-NTIS group (Table 2).
Table 2 Comparison of other baseline biochemical indicators between the NTIS and non-NTIS groups (`x ± SD)
|
Total
(n=852)
|
NTIS group
(n=192)
|
Non-NTIS group
(n=660)
|
t/Z
|
P
|
TP
(g/L)
|
66.37±6.34
|
64.48±6.67
|
66.92±6.14
|
−4.78
|
<0.001
|
Alb
(g/L)
|
38.06±4.57
|
34.82±4.43
|
39.01±4.17
|
−12.08
|
<0.001
|
PA
(mg/dL)
|
23.19±7.52
|
21.86±9.18
|
23.58±6.93
|
−2.79
|
0.005
|
Hb
(g/L)
|
119.10±18.99
|
111.46±18.30
|
121.32±18.63
|
−6.48
|
<0.001
|
UA
(µmol/L)
|
335.25±100.74
|
320.34±120.80
|
339.58±93.78
|
−2.34
|
0.02
|
FBG
(mmol/L)
|
5.88±1.88
|
6.68±2.28
|
5.65±1.68
|
6.83
|
<0.001
|
TC
(mmol/L)
|
3.99±0.88
|
4.07±1.06
|
3.97±0.82
|
1.48
|
0.14
|
TG
(mmol/L)
|
1.20(0.87, 1.65)
|
1.05(0.79, 1.65)
|
1.21(0.90, 1.65)
|
−2.09
|
0.04
|
HDLC
(mmol/L)
|
1.19±0.37
|
1.13±0.42
|
1.20±0.35
|
−2.37
|
0.02
|
LDLC
(mmol/L)
|
2.30±0.75
|
2.34±0.91
|
2.28±0.69
|
0.94
|
0.35
|
ALT
(U/L)
|
13.00(10.00, 20.00)
|
13.00(9.00, 22.00)
|
13.00(10.00, 20.00)
|
−0.54
|
0.59
|
AST
(U/L)
|
15.00(18.00, 23.00)
|
19.00(14.00, 26.83)
|
18.00(15.00, 22.00)
|
−0.90
|
0.37
|
UN
(mmol/L)
|
6.40(5.20, 8.90)
|
7.80(5.90, 11.30)
|
6.20(5.10, 8.30)
|
−5.95
|
<0.001
|
Cr
(µmol/L)
|
82.00(69.00, 99.00)
|
82.00(66.25, 121.75)
|
82.00(70.25, 97.00)
|
−1.07
|
0.285
|
TP total protein, Alb albumin, PA prealbumin, Hb haemoglobin, UA uric acid, FBG fasting blood glucose, TC total cholesterol, TG triglyceride, HDLC high-density lipoprotein cholesterol, LDLC low-density lipoprotein cholesterol, ALT alanine transaminase, AST aspartate transaminase, UN urea nitrogen, Cr creatinine
Correlations of triiodothyronine and free T3 levels with important biochemical indicators
Correlation analysis showed that triiodothyronine was positively correlated with the levels of TP (r = 0.15, P < 0.001), Alb (r = 0.40, P < 0.001), PA (r = 0.08, P = 0.01), and Hb (r = 0.37, P < 0.001). Triiodothyronine was negatively correlated with the levels of FBG (r = −0.28, P < 0.001), UN (r = −0.26, P < 0.001), and Cr (r = −0.12, P < 0.001).
Free T3 was positively correlated with the levels of TP (r = 0.14, P < 0.001), Alb (r = 0.50, P < 0.001), PA (r = 0.19, P < 0.001), Hb (r = 0.40, P < 0.001), and UA (r = 0.11, P = 0.001). Free T3 was negatively correlated with the levels of FBG (r = −0.26, P < 0.001), UN (r = −0.20, P < 0.001), and Cr (r = −0.05, P < 0.001; Table 3).
Table 3 Factors associated with triiodothyronine and free T3
|
Triiodothyronine
|
|
|
Free T3
|
|
r
|
P
|
|
|
r
|
P
|
TP
|
0.15
|
<0.001
|
|
|
0.14
|
<0.001
|
Alb
|
0.40
|
<0.001
|
|
|
0.50
|
<0.001
|
PA
|
0.08
|
0.01
|
|
|
0.19
|
<0.001
|
Hb
|
0.37
|
<0.001
|
|
|
0.40
|
<0.001
|
UA
|
0.06
|
0.07
|
|
|
0.11
|
0.001
|
FBG
|
−0.28
|
<0.001
|
|
|
−0.26
|
<0.001
|
TC
|
−0.07
|
0.05
|
|
|
0.01
|
0.70
|
TG
|
0.03
|
0.46
|
|
|
0.06
|
0.09
|
HDLC
|
0.06
|
0.08
|
|
|
0.07
|
0.06
|
LDLC
|
0.00
|
0.93
|
|
|
0.06
|
0.11
|
ALT
|
0.04
|
0.25
|
|
|
0.04
|
0.21
|
AST
|
−0.06
|
0.08
|
|
|
−0.06
|
0.07
|
UN
|
−0.26
|
<0.001
|
|
|
−0.20
|
<0.001
|
Cr
|
−0.12
|
<0.001
|
|
|
−0.05
|
<0.001
|
TP total protein, Alb albumin, PA prealbumin, Hb haemoglobin, UA uric acid, FBG fasting blood glucose, TC total cholesterol, TG triglyceride, HDLC high-density lipoprotein cholesterol, LDLC low-density lipoprotein cholesterol, ALT alanine transaminase, AST aspartate transaminase, UN urea nitrogen, Cr creatinine
Association of the free T3 level with mortality according to Cox proportional hazards models
Univariate Cox proportional hazards models showed that the free T3 level was associated with reduced patient mortality. Among the other biochemical indicators, Alb and Hb levels were negatively, whereas FBG, total cholesterol (TC), and ALT levels were positively, correlated with patient mortality. Multivariate models adjusted for other confounding factors showed that a lower free T3 level in elderly male patients is associated with all-cause mortality. Other indicators including Alb and Hb levels were negatively correlated and the ALT level positively correlated with patient mortality. Patients with respiratory diseases (RD), chronic kidney disease (CKD), and tumours had a higher mortality rate (Table 4). The free T3 level and 2-year mortality rate of all the patients were also determined. According to a receiver operating characteristic (ROC) analysis of the free T3 level and 2-year mortality rate, a cut-off free T3 level of 3.45 pmol/L yielded the highest Youden index (0.327), with a sensitivity of 0.675 and specificity of 0.642 (Figure 1).
Table 4. Cox proportional hazards models of the associations of thyroid hormone levels, biochemical indicators, and systemic disease with mortality
Parameters
|
Univariate adjusted
|
|
Multivariate adjusted
|
β
|
HR
|
95% CI
|
P
|
β
|
HR
|
95% CI
|
P
|
Free T3 (pmol/L)
|
−1.30
|
0.27
|
(0.19, 0.38)
|
<0.001
|
−0.66
|
0.52
|
(0.35, 0.77)
|
0.001
|
Alb
(g/L)
|
−1.55
|
0.21
|
(0.15, 0.29)
|
<0.001
|
−0.94
|
0.39
|
(0.27, 0.56)
|
<0.001
|
Hb
(g/L)
|
−1.54
|
0.21
|
(0.16, 0.29)
|
<0.001
|
−0.84
|
0.43
|
(0.30, 0.62)
|
<0.001
|
UA
(µmol/L)
|
−0.19
|
0.82
|
(0.53, 1.29)
|
0.40
|
−0.06
|
0.95
|
(0.58, 1.53)
|
0.82
|
FBG (mmol/L)
|
0.62
|
1.86
|
(1.30, 2.66)
|
0.001
|
−0.01
|
0.99
|
(0.67, 1.48)
|
0.96
|
TC
(mmol/L)
|
0.99
|
2.69
|
(1.63, 4.75)
|
0.001
|
0.23
|
1.26
|
(0.68, 2.36)
|
0.46
|
ALT
(U/L)
|
1.12
|
3.07
|
(1.99, 4.75)
|
<0.001
|
1.18
|
3.26
|
(2.03, 5.22)
|
<0.001
|
RD
|
1.16
|
3.20
|
(2.33, 4.39)
|
<0.001
|
0.42
|
1.52
|
(1.06, 2.17)
|
0.02
|
NSD
|
−0.02
|
0.99
|
(0.58, 1.68)
|
0.96
|
0.16
|
1.18
|
(0.68, 2.04)
|
0.56
|
CVD
|
0.42
|
1.52
|
(0.85, 2.75)
|
0.16
|
−0.04
|
0.96
|
(0.53, 1.75)
|
0.89
|
CKD
|
1.08
|
2.95
|
(2.07, 4.20)
|
<0.001
|
1.00
|
2.72
|
(1.91, 3.89)
|
<0.001
|
Tumour
|
1.04
|
2.82
|
(2.05, 3.88)
|
<0.001
|
0.97
|
2.63
|
(0.83, 3.77)
|
<0.001
|
T3 triiodothyronine, Alb albumin, Hb haemoglobin, UA uric acid, FBG fasting blood glucose, TC total cholesterol, ALT alanine transaminase, RD respiratory diseases, NSD nervous system disease, CVD cardiovascular disease, CKD chronic kidney disea
Figure 1 Receiver operating characteristic curve assessing the ability of the free triiodothyronine (T3) level to predict all-cause mortality (free T3 cut-off level, 3.445; sensitivity, 67.5%; specificity, 64.2%).
Comparison of 6-month, 1-year and 2-year survival rates between the NTIS and non-NTIS groups
During the 6-month follow-up period, 56 patients died: 41 in the NTIS group and 15 in the non-NTIS group. At 6 months, the survival rate was 78.65% in the NTIS group and 97.73% in the non-NTIS group (log-rank c2 = 95.23, P < 0.001, Figure 2a). During the 1-year follow-up period, 81 patients died: 61 in the NTIS group and 20 in the non-NTIS group. At 1 year, the survival rate was 68.23% in the NTIS group and 96.97% in the non-NTIS group (log-rank c2 = 158.37, P < 0.001, Figure 2b). A total of 157 patients died during the 2-year follow-up period; 68 in the NTIS group and 89 in the non-NTIS group. At 2 -years, the survival rate was 64.58% in the NTIS group and 86.52% in the non-NTIS group (log-rank c2 = 70.56, P < 0.001, Figure 2c).
Figure 2 Kaplan–Meier survival curves of the NTIS and non-NTIS groups for the period 6-months (a), 1-year (b) and 2-year (c) after study enrolment.