Baseline characteristics of the 137 matched pairs that were used in this analysis are shown in Table 1. The proportion of males (75.9%) was much higher than that of females. Compared with controls, cases more likely to have head trauma, hypertensive. No significant difference was noted in diabetes, dementia, malignancy, kidney failure, smoking, anticoagulant use, alcohol use and marital status. As expected, among the controls, the lipid and lipoprotein parameters were highly intercorrelated (Table 2).
Table 1
Baseline characteristics of CSDH cases and matched control subjects
|
control(n = 411)
|
case(n = 137)
|
p
|
Male
|
75.9
|
75.9
|
|
Age(95%CI)
|
72(66, 82)
|
72(65, 82)
|
|
Head trauma
|
|
|
< 0.001
|
Yes
|
46.5
|
65.0
|
|
No
|
53.5
|
35.0
|
|
Hypertension
|
|
|
< 0.05
|
Yes
|
65.2
|
75.9
|
|
No
|
34.8
|
24.1
|
|
Diabetes mellitus
|
|
|
NS
|
Yes
|
86.4
|
85.4
|
|
No
|
13.6
|
14.6
|
|
Anticoagulant
|
|
|
NS
|
Yes
|
98.3
|
95.6
|
|
No
|
1.7
|
4.4
|
|
Malignancy
|
|
|
NS
|
Yes
|
94.4
|
93.4
|
|
No
|
5.6
|
6.6
|
|
Dementia
|
|
|
NS
|
Yes
|
99.0
|
97.0
|
|
No
|
1.0
|
3.0
|
|
Kidney failure
|
|
|
|
Yes
|
0.5
|
2.1
|
NS
|
No
|
99.5
|
97.8
|
|
Smoking
|
|
|
NS
|
Never
|
62.5
|
65.7
|
|
Former
|
12.2
|
5.8
|
|
Current
|
25.3
|
28.5
|
|
Drinking
|
|
|
NS
|
Never
|
76.9
|
73.0
|
|
Former
|
5.4
|
4.4
|
|
Occasion
|
5.4
|
6.6
|
|
Current
|
12.4
|
16.1
|
|
Marital status
|
|
|
NS
|
Marriage
|
18.0
|
23.4
|
|
Single
|
82.0
|
76.6
|
|
Values are given as median (interquartile range) or percentage |
CSDH: chronic subdural hematoma |
Table 2
Spearman correlation coefficients between measured variables among controls
|
Triglyceride
|
Total cholesterol
|
HDL-C
|
LDL-C
|
ApoA1
|
ApoB
|
Triglyceride
|
1
|
0.34*
|
-0.52*
|
0.29*
|
-0.23*
|
0.44*
|
Total cholesterol
|
0.34*
|
1
|
0.26*
|
0.84*
|
0.39*
|
0.82*
|
HDL-C
|
-0.52*
|
0.26*
|
1
|
0.03
|
0.84*
|
-0.06*
|
LDL-C
|
0.29*
|
0.84*
|
0.03
|
1
|
0.09
|
0.91*
|
ApoA1
|
-0.23*
|
0.39*
|
0.84*
|
0.09
|
1
|
0.08
|
ApoB
|
0.44*
|
0.82*
|
-0.06*
|
0.91*
|
0.08
|
1
|
Head trauma
|
0.11
|
0.04
|
-0.04
|
0.01
|
-0.03
|
0.01
|
Hypertension
|
0.03
|
-0.04
|
-0.06
|
-0.00
|
-0.09
|
-0.02
|
* P < 0.01 |
These p-values have been adjusted for multiple comparisons using Bonferroni correction |
HDL-C: High density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol, ApoA1: Apolipoprotein A1, ApoB: Apolipoprotein B |
In univariate analyses (Table 3), cases had significantly lower median levels of total cholesterol, HDL-C and ApoA1 than control. Additionally, ApoB were significantly higher among controls compared to cases. Baseline levels of triglycerides was higher and LDL-C was lower among the patients with CSDH than among control subjects, but these differences were not statistically significant. Similar results were demonstrated across quartiles and when comparing the fourth quartile of total cholesterol, HDL-C, ApoA1 to the first quartile in unadjusted analyses. Nevertheless, the fourth quartile of triglycerides were significantly higher among controls compared to cases in unadjusted analyses (Table 4). They were significant when comparing the highest quartile to the lowest quartile for total cholesterol (OR 0.35, 95%CI 0.19–0.63, P < 0,001), triglycerides (OR 1.94, 95%CI 1.04–3.60, p < 0,05), HDL (OR 0.25, 95%CI 0.12–0.49, P < 0,001), ApoA1 (OR 0.27,95%CI 0.14–0.52, P < 0,001) in unadjusted analyses.
Table 3
Baseline lipid biomarkers in the study population
|
Total
|
|
|
Control
|
Case
|
P value
|
Triglycerides (mmol/L)
|
1.57(0.93, 1.84)
|
1.62(1.11, 1.86)
|
0.8
|
Total cholesterol(mmol/L)
|
4.59(4.02, 5.22)
|
4.22(3.55, 4.77)
|
< 0.001
|
HDL-C (mmol/L)
|
1.31(1.04, 1.54)
|
1.13(0.95, 1.43)
|
< 0.001
|
LDL-C (mmol/L)
|
2.55(2.06, 3.03)
|
2.41(1.98, 2.86)
|
0.08
|
ApoA1 (g/L)
|
1.21(1.00, 1.36)
|
1.08(0.95, 1.23)
|
< 0.001
|
ApoB (g/L)
|
0.85(0.70, 0.99)
|
0.82(0.70, 0.94)
|
< 0.001
|
Values are given as median (interquartile range) |
CI: Confidence interval, HDL-C: High density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol, ApoA1: Apolipoprotein A1, ApoB: Apolipoprotein B |
Table 4
Unadjusted and adjusted odds of developing CSDH according to quartile of lipid biomarkers at baseline
Variable
|
|
Odds Ratio (95% Confidence interval)
|
|
|
|
1
|
2
|
3
|
4
|
P for trend
|
Triglycerides
|
|
|
Model1
|
1
|
1.87(1.00, 3.48)
|
2.57(1.40, 4.72)
|
1.94(1.04, 3.60)
|
0.04
|
|
Model2
|
1
|
1.92(1.01, 3.66)
|
2.64(1.42, 4.93)
|
1.98(1.05, 3.71)
|
0.03
|
|
Model3
|
1
|
2.13(1.10, 4.14)
|
3.06(1.58, 5.93)
|
2.06(1.07, 3.96)
|
0.03
|
Total cholesterol
|
|
|
Model1
|
1
|
0.64(0.38, 1.09)
|
0.54(0.32, 0.92)
|
0.35(0.19, 0.63)
|
< 0.001
|
|
Model2
|
1
|
0.75(0.43, 1.29)
|
0.60(0.35, 1.04)
|
0.34(0.19, 0.64)
|
< 0.001
|
|
Model3
|
1
|
0.71(0.40, 1.24)
|
0.55(0.32, 0.96)
|
0.29(0.15, 0.55)
|
< 0.001
|
HDL-C
|
|
|
Model1
|
1
|
0.87(0.53, 1.45)
|
0.61(0.37, 1.02)
|
0.25(0.12, 0.49)
|
< 0.001
|
|
Model2
|
1
|
0.81(0.48, 1.38)
|
0.59(0.35, 1.00)
|
0.26(0.13, 0.52)
|
< 0.001
|
|
Model3
|
1
|
0.77(0.45, 1.32)
|
0.57(0.33, 0.97)
|
0.25(0.12, 0.51)
|
< 0.001
|
LDL-C
|
|
|
Model1
|
1
|
0.82(0.49, 1.36)
|
0.76(0.45, 1.27)
|
0.57(0.33, 1.00)
|
0.05
|
|
Model2
|
1
|
0.85(0.50, 1.46)
|
0.79(0.46, 1.34)
|
0.61(0.35, 1.09)
|
0.09
|
|
Model3
|
1
|
0.75(0.43, 1.32)
|
0.77(0.44, 1.33)
|
0.54(0.30, 0.98)
|
0.06
|
ApoA1
|
|
|
Model1
|
1
|
0.8(0.48, 1.32)
|
0.6(0.36, 1.01)
|
0.27(0.14, 0.52)
|
< 0.001
|
|
Model2
|
1
|
0.80(0.48, 1.35)
|
0.64(0.38, 1.09)
|
0.27(0.14, 0.52)
|
< 0.001
|
|
Model3
|
1
|
0.84(0.50, 1.44)
|
0.62(0.36, 1.07)
|
0.25(0.12, 0.50)
|
< 0.001
|
ApoB
|
|
|
Model1
|
1
|
1.31(0.77, 2.22)
|
0.89(0.52, 1.52)
|
0.78(0.45, 1.37)
|
0.25
|
|
Model2
|
1
|
1.42(0.81, 2.49)
|
0.91(0.52, 1.58)
|
0.74(0.42, 1.33)
|
0.2
|
|
Model3
|
1
|
1.34(0.75, 2.37)
|
0.89(0.50, 1.57)
|
0.68(0.37, 1.23)
|
0.14
|
Model1 conditioned on age and gender |
Model2 conditioned on age and gender, and additionally adjusted for head trauma and hypertensive |
Model3 conditioned on model2, and additionally adjusted for diabetes mellitus, dementia, malignancy, kidney failure, anticoagulant use, smoking, alcohol use and marital status |
Each row is a separate model with CSDH as the outcome which included quartiles of that specific biomarker |
Biomarker quartile cut-points were based on all available controls |
HDL-C: High density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol, ApoA1: Apolipoprotein A1, ApoB: Apolipoprotein B |
In a multivariable model conditioned on age and gender, and additionally adjusted for head trauma and hypertensive, the ORs of CSDH associated with each biomarker quartile are shown in Table 4. Patients in the highest quartile of triglycerides had a 98% increase in the odds of CSDH versus those in the lowest quartile. Meanwhile, the odds of total cholesterol, HDL and ApoA1 decreased by 66%, 74% and 73%, respectively. Comparing the 4th quartile to the 1st quartile was significant for total cholesterol (OR 0.34, 05%CI 0.19–0.64, P < 0,001), triglycerides (OR 1.98, 95%CI 1.05–3.71, p < 0,05), HDL-C (OR 0.26, 95%CI 0.13–0.52, P < 0,001), ApoA1 (OR 0.27, 95%CI 0.14–0.52, P < 0,001). Another lipid biomarkers at baseline including LDL-C and ApoB were not significantly associated with CSDH. Additional adjustment for diabetes mellitus, dementia, malignancy, kidney failure, anticoagulant use, smoking, alcohol use and marital status did not substantially change the multivariable associations presented in Table 4.