Characteristics of study participants
The characteristics and serum indexes in the gallbladder stone and control groups are summarized in Table 1. There were 835 of 927 patients with GSD and 835 control subjects of 3471 healthy participants aged 30 to 82 years. Each group included 322 (38.6%) female participants. There was significantly higher weight, BMI, WC, WHtR, serum TC, TG, LDL-c levels and lower HDL-c levels in the GSD group than in the controls (P <0.05, respectively) (Table 1). There were 452 (54.1%) normal BMI, 319 (38.2%) overweight and 64 (7.7%) obese participants in the controls; in the GSD group, 331 (39.6%) had normal BMI, 386 (46.2 %) were overweight and 118 (14.1%) were obese. There were 40 (5.4%) and 81 (10%) participants with hypercholesterolemia in the GSD and the control group, respectively. Statistical analysis showed significantly higher hypercholesterolemia in the GSD versus the control group (P <0.001). In additional, there were 232 (27.5%) and 178 (21.1%) participants with NAFLD in the GSD and control groups, respectively. Statistical analysis showed significantly more NAFLD in the GSD group than in the control group (P =0.002).
Table. 1 Demographic and clinical data of the patients before and after matching
|
Before matching
|
After matching
|
|
Control Group
(N=3471)
|
GSD group
(N=927)
|
χ2/T value
|
P value
|
Control group
(N=835)
|
GSD group
(N=835)
|
χ2/T value
|
P value
|
Female (%)
|
1713 (49.4%)
|
331 (35.7%)
|
55.537
|
<0.001
|
38.6%, 322
|
38.6%,322
|
0.000*
|
1.000
|
Age (Year)
|
59.32±13.7
|
59.14±12.3
|
-6.041*
|
<0.001
|
58.68±11.4
|
58.65±11.4
|
-0.060
|
0.952
|
Han (%)
|
2982 (85.9)
|
790(85.2)
|
0.284*
|
0.594
|
760 (91.0)
|
765 (91.6)
|
0.189*
|
0.664
|
Occupation (%)
|
|
|
62.257*
|
<0.001
|
|
|
0.476*
|
0.976
|
Worker
|
218 (6.3)
|
62 (6.7)
|
0.202*
|
0.653
|
62 (7.5)
|
60 (7.2)
|
0.027*
|
0.869
|
Professional Technician
|
316 (9.1)
|
112 (12.1)
|
7.043*
|
0.008
|
112 (13.5)
|
109 (13.1)
|
0.051*
|
0.821
|
Manager
|
193 (5.6)
|
81 (8.7)
|
11.693*
|
0.001
|
81 (9.7)
|
79 (9.5)
|
0.028*
|
0.868
|
Retiree
|
2062 (59.4)
|
583 (62.9)
|
3.729*
|
0.053
|
515 (61.9)
|
518 (62.0)
|
0.023*
|
0.880
|
Others
|
682 (19.6)
|
89 (9.6)
|
57.144*
|
<0.001
|
62 (7.5)
|
69 (8.3)
|
0.406*
|
0.524
|
SBP(mmHg)
|
120.99±17.9
|
122.70±17.5
|
-2.586
|
0.01
|
122.05±17.2
|
122.22±16.2
|
0.209
|
0.834
|
DBP(mmHg)
|
76.76±10.6
|
77.49±10.77
|
-1.839
|
0.066
|
77.33±10.5
|
77.10±9.7
|
-0.465
|
0.642
|
FGB(mmol/L)
|
5.27±1.3
|
5.18±1.4
|
-0.677
|
0.499
|
5.38±1.5
|
5.34±1.2
|
-0.758
|
0.449
|
Height(cm)
|
165.27±8.6
|
166.95±8.2
|
-5.339
|
<0.001
|
166.38±7.2
|
166.71±8.1
|
0.870
|
0.384
|
Weight(Kg)
|
65.82±11.4
|
68.38±11.2
|
6.053
|
<0.001
|
66.77±10.7
|
68.44±10.9
|
3.170
|
0.002
|
BMI(Kg/m2)
|
24.00±3.1
|
24.44±2.9
|
0.905
|
<0.001
|
24.04±2.9
|
24.54±2.8
|
3.580
|
<0.001
|
Normal BMI(%)
|
1726 (49.7%)
|
431 (46.6%)
|
2.774*
|
0.096
|
452 (54.1%)
|
331 (39.6%)
|
35.332*
|
<0.001
|
Overweight(%)
|
1126 (32.4%)
|
392(42.4%)
|
31.477*
|
<0.001
|
319 (38.2 %)
|
386 (46.2%)
|
11.033*
|
0.001
|
Obesity(%)
|
619 (17.8%)
|
101 (10.9%)
|
27.441*
|
<0.001
|
64 (7.7 %)
|
118 (14.1 %)
|
18.226*
|
<0.001
|
WC(cm)
|
82.41±7.0
|
83.53±7.8
|
4.182
|
<0.001
|
82.83±6.7
|
87.75±7.9
|
13.759
|
<0.001
|
WHtR(%)
|
49.97±4.7
|
49.82±4.0
|
-6.768
|
<0.001
|
49.84±4.1
|
52.73±5.0
|
12.827
|
<0.001
|
TC(mmol/L)
|
4.88±0.9
|
4.90±1.0
|
0.610
|
0.542
|
4.65±0.8
|
4.87±0.9
|
5.329
|
<0.001
|
TG(mmol/L)
|
1.49±0.8
|
1.83±1.3
|
9.911
|
<0.001
|
1.51±0.8
|
1.83±1.2
|
6.120
|
<0.001
|
HDL-c(mmol/L)
|
2.53±1.0
|
1.28±0.3
|
-35.764
|
<0.001
|
2.25±0.9
|
1.28±0.3
|
-28.046
|
<0.001
|
LDL-c(mmol/L)
|
2.0±1.3
|
3.0±0.8
|
22.215
|
<0.001
|
2.00±1.0
|
2.99±0.8
|
21.502
|
<0.001
|
Drink (%)
|
506 (13.5)
|
124 (13.4)
|
0.009*
|
0.925
|
105 (12.6)
|
107 (12.8)
|
0.022*
|
0.883
|
Eating habits (%)
|
|
|
117.822*
|
<0.001
|
|
|
0.148*
|
0.986
|
Vegan
|
127 (3.7)
|
78 (8.4)
|
32.396*
|
<0.001
|
69 (8.3)
|
71 (8.5)
|
0.031*
|
0.860
|
vegetarian
|
508 (14.6)
|
115 (12.4)
|
3.074*
|
0.080
|
114 (13.7)
|
110 (13.2)
|
0.082*
|
0.774
|
Meat & vegetarians
|
2730 (78.7)
|
544 (58.7)
|
142.746*
|
<0.001
|
470 (56.3)
|
468 (56.0)
|
0.010*
|
0.921
|
Carnivorous diet
|
376 (10.8)
|
190 (20.5)
|
55.295*
|
<0.001
|
182 (21.8)
|
186 (22.3)
|
0.056*
|
0.813
|
NAFLD
|
744(21.4)
|
227(24.5)
|
4.083*
|
0.043
|
178(21.1)
|
232(27.5)
|
9.448*
|
0.002
|
HC
|
327 (9.4)
|
106 (11.5)
|
3.343*
|
0.068
|
40(4.8)
|
84(10.1)
|
17.211*
|
<0.001
|
GSD: gallbladder stone disease; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG: fasting blood glucose; BMI: body mass index; WC: waist circumference; WHtR: Waist height ratio; TC: total cholesterol; TG: triglyceride; HDL-c: high density lipoprotein cholesterol; LDL-c: low density lipoprotein cholesterol; NAFLD: nonalcoholic fatty liver disease; HC: hypercholesterolemia.
*means χ2 values for making a difference with t values.
The differences of hazard rate of gallbladder stone between patients with hypercholesterolemia and controls stratified by overweight and obesity or NAFLD
The differences in hazard rate of gallbladder stone in hypercholesterolemia and controls by obesity and overweight are summarized in Table 2. Among those with overweight and obesity, there were 39 and 15 participants with hypercholesterolemia in the GSD group, respectively, and 18 and 6 in the control group, respectively. There were significant differences in gallbladder stone morbidity between the hypercholesterolemia and control group in terms of overweight and normal BMI (χ2=4.813 and 10.424; P =0.028, and 0.001, respectively), while there was no significant difference in obesity (χ2=0.466, P =0.495).
Table 2. The difference of GSD between Hypercholesterolemia and non-hypercholesterolemia adjusted by overweight, obesity and normal BMI
|
Overweight
|
|
Obesity
|
|
Normal BMI
|
GSD
|
Control
|
|
GSD
|
Control
|
|
GSD
|
Control
|
Model 1
|
39*
|
18
|
|
15 &
|
6
|
|
30 §
|
16
|
Model 2
|
347**
|
301
|
|
103 & &
|
58
|
|
301 § §
|
436
|
Note:GSD: gallbladder stone disease;Model 1:Hypercholesterolemia;Model 2:Non-hypercholesterolemia
*vs ** : χ2=4.813, P=0.028, OR=1.879, 95%CI: 1.053~3.355
& vs && : χ 2=0.466, P=0.495, OR=1.408, 95%CI: 0.518~3.826
§vs§§: χ 2=10.424, P=0.001, OR=2.716, 95%CI: 1.455~5.070
As shown in Table 3, regarding NAFLD and non-NAFLD, there were 32 and 52 participants with hypercholesterolemia in the GSD group, respectively, and 9 and 31 in the control group, respectively. There was a significant difference regarding gallbladder stone morbidity between hypercholesterolemia and control groups in terms of NAFLD and non-NAFLD (χ2=9.157 and 7.839; P=0.002 and 0.005, respectively).
Table 3. The difference of GSD between hypercholesterolemia and non adjusted by NAFLD and non-NAFLD
|
NAFLD
|
|
non-NAFLD
|
GSD
|
Control
|
|
GSD
|
Control
|
Model 1
|
32*
|
9
|
|
52 &
|
31
|
Model 2
|
200**
|
169
|
|
551 & &
|
626
|
Note:GSD: gallbladder stone disease group;Model 1:Hypercholesterolemia;Model 2:Non-hypercholesterolemia
*vs ** : χ2=9.157, P=0.002, OR=3.004, 95%CI: 1.395~6.472
& vs && : χ 2=7.839, P=0.005, OR=1.906,95%CI: 1.204~3.017
Relationships between the indexes with BMI, WHtR, blood lipid, NAFLD, hyperlipidemia and hazard of cholesterol gallstone.
Table 4 shows the risk factors for developing GSD based on univariate and multivariate logistic regression. Univariate logistic regression showed significantly positive correlations for weight, BMI, WC, WHtR, NAFLD, hypercholesterolemia, serum TC, TG and LDL-c levels with hazard of GSD (P<0.05, all), while there were significantly negative correlations between serum HDL-c levels and risk of GSD (P<0.001). In addition, compared with patients with normal BMI, there was significantly more GSD in overweight and obese patients (P<0.001, both). Multivariate logistic regression including WC showed that there were significantly positive correlations between WC, NAFLD, hypercholesterolemia and risk of GSD (P<0.05, all), while there were significantly negative correlations between serum HDL-c, TG levels, BMI and risk of GSD (P<0.05, all). Multivariate logistic regression including WHtR showed that there was significantly positive correlations between WHtR, NAFLD, hypercholesterolemia, and risk of GSD (P<0.05, all), while there were significantly negative correlations between serum TG, HDL-c levels, BMI and risk of GSD (P<0.05, all).
Table 4. Univariate and multivariate analysis of gallbladder stone and BMI, WHtR, blood lipid, NAFLD and HTC
Factors
|
|
Univariate
|
|
Multivariate1
|
|
Multivariate2
|
β
|
OR
|
95%CI
|
P
|
β
|
OR
|
95%CI
|
P
|
β
|
OR
|
95%CI
|
P
|
Weight
|
0.013
|
1.013
|
1.004-1.022
|
0.004
|
*
|
*
|
*
|
*
|
*
|
*
|
*
|
*
|
BMI
|
0.044
|
1.045
|
1.010~1.081
|
0.011
|
-1.416
|
0.243
|
0.202~0.291
|
<0.001
|
-0.518
|
0.596
|
0.544~0.652
|
<0.001
|
Normal
|
|
1
|
|
|
|
|
|
|
|
|
|
|
Overweight
|
0.125
|
1.652
|
1.346~2.029
|
<0.001
|
|
/
|
/
|
/
|
|
/
|
/
|
/
|
Obesity
|
0.177
|
2.518
|
1.800~3.522
|
<0.001
|
|
/
|
/
|
/
|
|
/
|
/
|
/
|
WC
|
0.077
|
1.080
|
1.065~1.095
|
<0.001
|
0.517
|
1.677
|
1.571~1.790
|
<0.001
|
/
|
/
|
/
|
/
|
WHtR
|
0.11
|
1.116
|
1.092~1.141
|
<0.001
|
/
|
/
|
/
|
/
|
0.292
|
1.340
|
1.273~1.409
|
<0.001
|
TG
|
0.323
|
1.382
|
1.237~1.543
|
<0.001
|
-0.203
|
0.817
|
0.713~0.935
|
0.003
|
-0.205
|
0.814
|
0.721~0.919
|
0.001
|
HDL-c
|
-2.122
|
0.120
|
0.095~0.151
|
<0.001
|
-1.965
|
0.140
|
0.103~0.191
|
<0.001
|
-2.573
|
0.076
|
0.056~0.104
|
<0.001
|
LDL-c
|
0.965
|
2.625
|
2.330~2.957
|
<0.001
|
*
|
*
|
*
|
*
|
*
|
*
|
*
|
*
|
TC
|
0.251
|
1.286
|
1.150~1.437
|
<0.001
|
*
|
*
|
*
|
*
|
*
|
*
|
*
|
*
|
FBG
|
-0.026
|
0.974
|
0.906-1.047
|
0.481
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
NAFLD
|
0.389
|
1.475
|
1.180~1.845
|
0.001
|
0.557
|
1.746
|
1.202~2.537
|
0.003
|
0.371
|
1.449
|
1.042~2.018
|
0.028
|
HC
|
0.786
|
2.195
|
1.502~3.208
|
<0.001
|
0.874
|
2.397
|
1.398~4.112
|
0.001
|
0.872
|
2.392
|
1.456~3.929
|
0.001
|
SBP
|
0.001
|
1.001
|
0.996~1.007
|
0.67
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
DBP
|
0.000
|
1.000
|
0.991~1.010
|
0.919
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
Drink
|
0.082
|
1.085
|
0.813~1.448
|
0.579
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
BMI: body mass index; WC: waist circumference; WHtR: Waist height ratio; TG: triglyceride; HDL-c: high density lipoprotein cholesterol; LDL-c: low density lipoprotein cholesterol; NAFLD: nonalcoholic fatty liver disease; FBG: fasting blood glucose; HC: hypercholesterolemia; SBP: systolic blood pressure; DBP: diastolic blood pressure;.
*eliminated for the definition of BMI or hyperlipidemia in multivariate regression
- eliminated for no statistical significance in univariate regression
To investigate the possible reasons that caused this result, the data were further analyzed using univariate and multivariate logistic regression analysis (Table 5). The differences between GSD and control group were studied by stratifying with hypercholesterolemia. Univariate logistic regression showed significantly positive correlations between NAFLD, serum LDL-c levels, and risk of GSD (P<0.05 for all), high-level TC was a weak risk factor for GSD (P=0.082), while there were significantly negative correlations for male, weight, DBP, serum HDL-c, FBG levels and risk of GSD (P<0.001). Multivariate logistic regression showed that there were weak positive correlations between NAFLD and risk of GSD (P=0.054), and significantly negative correlations between serum HDL-c levels, weight, and hazard of GSD (P<0.01, both), with a weak negative correlation between serum LDL-c and hazard of GSD (P=0.071).
Table 5. Univariate and multivariate analysis of gallbladder stone and BMI, WHtR, blood lipid, NAFLD stratified by HC
Factors
|
|
Univariate
|
|
Multivariate
|
|
β
|
OR
|
95%CI
|
P
|
β
|
OR
|
95%CI
|
P
|
Gender (M)
|
-1.411
|
0.244
|
0.097-0.612
|
0.003
|
-0.887
|
0.412
|
0.112-1.518
|
0.183
|
Age
|
0.000
|
1.000
|
0.968-1.033
|
0.999
|
|
-
|
-
|
-
|
Weight
|
-0.04
|
0.961
|
0.929-0.994
|
0.022
|
-0.073
|
0.930
|
0.875-0.988
|
0.018
|
BMI
|
-0.087
|
0.917
|
0.811~1.036
|
0.164
|
|
-
|
-
|
-
|
WC
|
0.01
|
1.010
|
0.961~1.062
|
0.686
|
|
-
|
-
|
-
|
WHtR
|
0.065
|
1.067
|
0.987~1.154
|
0.105
|
|
-
|
-
|
-
|
SBP
|
-0.007
|
0.993
|
0.972-1.015
|
0.547
|
|
-
|
-
|
-
|
DBP
|
-0.044
|
0.957
|
0.919-0.995
|
0.029
|
-0.044
|
0.957
|
0.905-1.011
|
0.119
|
FBG
|
-0.376
|
0.687
|
0.485-0.973
|
0.034
|
-0.206
|
0.814
|
0.519-1.277
|
0.370
|
TC
|
0.423
|
1.526
|
0.948~2.457
|
0.082
|
0.544
|
1.722
|
0.818~3.627
|
0.153
|
TG
|
0.206
|
1.229
|
0.916~1.648
|
0.169
|
|
-
|
-
|
-
|
HDL-c
|
-1.188
|
0.305
|
0.169~0.548
|
<0.001
|
-1.939
|
0.144
|
0.055~0.376
|
<0.001
|
LDL-c
|
0.401
|
1.493
|
1.043~2.139
|
0.029
|
-0.641
|
0.527
|
0.263~1.056
|
0.071
|
NAFLD
|
1.002
|
2.723
|
1.155~6.420
|
0.022
|
1.189
|
3.284
|
0.979~11.013
|
0.054
|
Drink
|
0.189
|
1.208
|
0.544~2.680
|
0.643
|
|
-
|
-
|
-
|
BMI: body mass index; WHtR: Waist height ratio; TG: triglyceride; HDL-c: high density lipoprotein cholesterol; LDL-c: low density lipoprotein
cholesterol; NAFLD: nonalcoholic fatty liver disease; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG: fasting blood glucose; HC: hypercholesterolemia.
- eliminated for no statistical significance in univariate regression