3.1 General information and antipsychotic drug use of the study participants
Eighty patients were included in this study, and the specific screening process is shown in Figure 2. All patients were treated with at least two atypical antipsychotics, with an average age of 43.16 ±10.92, including 51 male patients and 29 female patients. There was no statistical difference in age at admission or duration of schizophrenia in the two groups. Tobacco use was higher in male than female patients (P < 0.01). There was no significant difference in comorbid hypertension, type 2 diabetes, and hyperlipidemia during hospitalization. The name and proportion of the use of antipsychotics are shown in table 1.
Table 1 General information, comorbidities during hospitalization, and types of antipsychotics in patients with schizophrenia of different genders
|
Male
|
Female
|
t/χ2
|
P
|
Number
|
51
|
29
|
|
|
Age (years), mean ± SD
|
43.04±10.26
|
43.36±12.20
|
-0.12
|
0.91
|
Duration of schizophrenia
(years),mean ± SD
|
15.80±8.05
|
17.86±11.84
|
-0.82
|
0.42
|
Alcohol use, N(%)
|
10(19.6)
|
2(6.9)
|
2.34
|
0.13
|
Tobacco use(before hospitalization), N (%)
|
24(47.1)
|
0(0)
|
19.49
|
0.00
|
Comorbid condition,N(%)
|
Hypertension
|
6(11.8)
|
3(10.3)
|
0.04
|
0.85
|
Type 2 diabetes
|
8(15.7)
|
6(20.7)
|
0.32
|
0.57
|
Hyperlipidemia
|
12(23.5)
|
4(13.8)
|
1.09
|
0.30
|
Types of antipsychotic drugs(%)
|
Clozapine
|
40.39
|
55.86
|
|
|
Olanzapine
|
29.80
|
7.11
|
|
|
Aripiprazole
|
30.98
|
22.75
|
|
|
Ziprasidone
|
11.37
|
20.69
|
|
|
Risperidone
|
14.11
|
20.69
|
|
|
Amisulpride
|
20.0
|
12.41
|
|
|
Quetiapine fumarate
|
17.64
|
17.24
|
|
|
Paliperidone extended-release tablets
|
1.96
|
4.83
|
|
|
3.2 Comparisons of Electrocardiogram value and Chlorpromazine equivalent dose between different genders at different timepoint
There was no significant time effect and inter-group difference of chlorpromazine equivalent in patients of different genders(Table 2).QRS duration was longer in males than in females (Fgender=22.09, Pgender=0.00) but not significantly different, nor in RR intervals between genders. The QT, QTc, iCEB, and iCEBc all were significantly prolonged (P <0.05),and intergroup effects in iCEB and iCEBc(all P<0.01). There were significant time effects and significant time and sex interaction effects in TpTe, TpTe/QT, TpTe/QTc, and TpTe/QRS( P<0.01), and intergroup effects in TpTe, TpTe/QT, and TpTe/QTc(P<0.05) (Table 2).
Table 2.Comparisons of Electrocardiogram value and Chlorpromazine equivalent dose between different genders at different timepoint
|
|
Male
|
Female
|
Ftime
|
Ptime
|
Fgender
|
Pgender
|
Ftime×gender
|
Ptime×gender
|
Chlorpromazine equivalent dose(mg/d)
First year
Second year
Third year
Fourth year
Fifth year
|
770.41±321.77
713.27±344.87
694.90±317.58
660.20±334.63
633.67±319.41
|
716.03±342.93
789.29±412.62
800.00±394.88
830.36±381.84
714.29±412.73
|
1.21
|
0.32
|
1.32
|
0.26
|
1.63
|
0.18
|
QRS duration(ms)
First year
Second year
Third year
Fourth year
Fifth year
|
96.61±8.88
96.08±8.39
95.71±9.65
93.90±8.61
93.82±7.56
|
87.54 ±7.86
87.29±9.09
87.68±9.59
86.11±9.40
87.82±11.01
|
1.37
|
0.25
|
22.09
|
0.00
|
0.71
|
0.58
|
RR interval(s)
First year
Second year
Third year
Fourth year
Fifth year
|
0.72±0.14
0.77±0.14
0.79±0.14
0.78±0.16
0.74±0.17
|
0.79±0.20
0.76±0.16
0.78±0.14
0.80±0.17
0.77±0.17
|
1.48
|
0.22
|
0.42
|
0.52
|
1.21
|
0.31
|
QT interval(ms)
First year
Second year
Third year
Fourth year
Fifth year
|
360.80±36.39
375.41±35.84
379.98±32.92
380.51±34.37
379.82±29.56
|
375.04±49.42
384.96±33.42
393.71±50.12
392.86±38.69
383.50±33.86
|
4.64
|
0.00
|
3.24
|
0.08
|
0.37
|
0.82
|
QTc interval(ms)
First year
Second year
Third year
Fourth year
Fifth year
|
427.69±26.60
429.86±29.75
430.88±38.87
433.92±37.61
445.29±37.26
|
426.21±28.84
446.61±42.76
447.36±47.26
440.96±38.53
443.07±41.95
|
2.96
|
0.03
|
1.65
|
0.20
|
1.59
|
0.18
|
TpTe(ms)
First year
Second year
Third year
Fourth year
Fifth year
|
117.18±24.58
116.71±19.13
125.96±28.07
125.35±28.76
126.82±29.14
|
85.39±20.85
123.79±33.59
115.29±27.51
117.18±36.11
121.79±41.31
|
10.12
|
0.00
|
4.89
|
0.03
|
5.90
|
0.00
|
TpTe/QRS
First year
Second year
Third year
Fourth year
Fifth year
|
1.22±0.26
1.22±0.23
1.34±0.37
1.34±0.31
1.36±0.35
|
0.97±0.21
1.43±0.38
1.32±0.31
1.37±0.43
1.41±0.52
|
11.76
|
0.00
|
0.01
|
0.93
|
5.78
|
0.00
|
TpTe/QT
First year
Second year
Third year
Fourth year
Fifth year
|
0.33±0.07
0.31±0.05
0.33±0.06
0.33±0.06
0.33±0.07
|
0.23±0.06
0.32±0.08
0.29±0.07
0.30±0.09
0.32±0.09
|
6.70
|
0.00
|
9,87
|
0.00
|
10.42
|
0.00
|
TpTe/QTc
First year
Second year
Third year
Fourth year
Fifth year
|
0.27±0.05
0.27±0.04
0.29±0.05
0.29±0.06
0.29±0.06
|
0.20±0.05
0.28±0.06
0.26±0.06
0.27±0.08
0.27±0.09
|
8.70
|
0.00
|
7.84
|
0.01
|
6.11
|
0.00
|
iCEB
First year
Second year
Third year
Fourth year
Fifth year
|
3.75±0.52
3.93±0.58
4.02±0.58
4.09±0.56
4.07±0.45
|
4.30±0.58
4.44±0.49
4.52±0.69
4.61±0.59
4.42±0.59
|
6.27
|
0.00
|
23.72
|
0.00
|
0.67
|
0.60
|
iCEBc
First year
Second year
Third year
Fourth year
Fifth year
|
4.44±0.50
4.51±0.51
4.55±0.65
4.66±0.56
4.77±0.53
|
4.89±0.46
5.15±0.61
5.14±0.64
5.17±0.62
5.10±0.61
|
3.74
|
0.01
|
28.56
|
0.00
|
1.40
|
0.24
|
3.3 Effect of gender and time on ECG indicators
For the QRS duration, men are significantly longer than women (P <0.01), but time was not statistically significant for both significant effects of gender on the QTc interval. The fourth year of the male QT interval was significantly different from the first year, where was the female patients had no significant changes. Both iCEB and iCEBc changed significantly in 5 years, but they were different: male iCEB values in the third and fourth year were higher than those in the first year. It increased significantly in the fourth year (P <0.01), female iCEB in the fourth year (P <0.01), Male iCEBc was significantly larger in year 5 than in the first year (P <0.01), and female iCEBc in the second year over the first year (P <0.05). TpTe, TpTe / QT, and TpTe / QTc were significantly increased in the second year and the first year in women (P <0.01), but these measures did not significantly change in men. (Figure 3).
3.4 ROC curve of Ventricular Arrhythmia predicted by ECG Indexes of different genders
In schizophrenic patients, QTc ≥ 450ms in males and QTc ≥ 460ms in females were defined as malignant arrhythmias as the cut-off point for drawing the receiver working curve (ROC)(Figure 4). According to the Yoden index, the results show that when the area under the curve (AUC) of male iCEBc is 82.2%(P<0.001), the best critical value for identifying malignant arrhythmias is 4.528, the sensitivity is 84%, and the specificity is 67%. When the area under the curve (AUC) of female iCEBc is 72.4%(P<0.001), the best critical value, sensitivity, and specificity for identifying malignant arrhythmias are 5.315, the sensitivity is 74% and the specificity is 73%(Figure 4).