Six hundred and fifty-eight patients (441 men and 217 women; mean age, 65.9 ± 11.2 years) with transient ischemic attack or acute ischemic stroke were included in the final analyses. Of the 658 patients analyzed, DSA was performed in 24 patients (3.6%) and the remaining 634 patients underwent CTA. The patients were divided into four subgroups as follows: No cerebral atherosclerotic stenosis (NCAS) (55.6%), Isolated ICAS (27.7%), Isolated ECAS (7.0%), and ICAS combined with ECAS (9.7%). The characteristics of the study participants in the groups of NCAS, Isolated ICAS, Isolated ECAS, and ICAS combined with ECAS groups are shown in Supplementary Table 1.
Sex-specific characteristics are shown in Table 1. Women were older and had lower diastolic blood pressure, and non-HDL-C/HDL-C, TC/HDL-C, RC/HDL-C, LDL-C/HDL-C, apo B/HDL-C, and apo B/apo A-I ratios than men. A significantly higher proportion of current smokers were men (P <0.001), and their TC, HDL-C, and apo A-I levels were lower than those in women. Multivariable analysis of ICAS and (or) ECAS according to gender was shown in Supplementary Table 2.
Table 1 Characteristics of the study participants according to gender
Variables
|
Men (n=441)
|
Women (n=217)
|
P Value
|
Age, year
|
64.6±11.2
|
68.5±10.7
|
<0.001
|
Systolic blood pressure, mmHg
|
152.8±23.8
|
154.1±26.0
|
0.522
|
Diastolic blood pressure, mmHg
|
88.7±16.0
|
84.7±14.6
|
0.002
|
Hypertension, n (%)
|
311 (70.5)
|
165 (76.0)
|
0.137
|
Diabetes mellitus, n (%)
|
144 (32.7)
|
74 (34.1)
|
0.711
|
Current smoking, n (%)
|
251 (56.9)
|
4 (1.8)
|
<0.001
|
Previous stroke, n (%)
|
131 (29.7)
|
56 (25.8)
|
0.297
|
Coronary heart disease, n (%)
|
51 (11.6)
|
29 (13.4)
|
0.507
|
Number of ICAS lesions
|
0(0-1)
|
0(0-1)
|
0.771
|
NCAS
|
238(54.0)
|
128(59.0)
|
0.223
|
Isolated ICAS
|
115(26.1)
|
67(30.9)
|
0.196
|
Isolated ECAS
|
38(8.6)
|
8(3.7)
|
0.020
|
ICAS and ECAS
|
50(11.3)
|
14(6.5)
|
0.047
|
TC, mmol/L
|
4.35±1.06
|
4.67±1.10
|
<0.001
|
TG, mmol/L
|
1.66±1.23
|
1.62±1.01
|
0.664
|
HDL-C, mmol/L
|
1.09 (0.94-1.24)
|
1.26(1.09-1.51)
|
<0.001
|
LDL-C, mmol/L
|
2.82±0.91
|
2.97±0.99
|
0.061
|
Non-HDL-C, mmol/L
|
3.16 (2.48-3.90)
|
3.21(2.53-3.96)
|
0.384
|
RC, mmol/L
|
0.42±0.40
|
0.37±0.35
|
0.121
|
Apo A-I, g/L
|
1.22±0.35
|
1.40±0.27
|
<0.001
|
Apo B, g/L
|
0.99±0.53
|
0.96±0.29
|
0.520
|
Lipid Ratio
|
|
|
|
TC/HDL-C
|
4.12±1.37
|
3.74±1.22
|
0.001
|
TG/HDL-C
|
1.71±1.77
|
1.45±1.67
|
0.069
|
LDL-C/HDL-C
|
2.68±1.06
|
2.39±0.94
|
0.001
|
RC/HDL-C
|
0.44±0.53
|
0.35±0.55
|
0.036
|
Non- HDL-C/HDL-C
|
3.12±1.37
|
2.73±1.22
|
0.001
|
Apo B/HDL-C
|
2.25 (1.65-2.91)
|
1.87 (1.44-2.48)
|
<0.001
|
Apo B/apo A-I
|
0.78 (0.60-0.98)
|
0.69 (0.53-0.86)
|
<0.001
|
ICAS intracranial atherosclerotic stenosis, ECAS extracranial atherosclerotic stenosis, NCAS no cerebral atherosclerotic stenosis, TC total cholesterol, TG triglycerides, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, RC remnant cholesterol, Non-HDL-C non-high-density lipoprotein cholesterol, Apo B apolipoprotein B, Apo A-I apolipoprotein A-I.
Results are expressed as mean±standard deviation, median with interquartile range or n (%).
Each lipid ratio was examined based on sex to assess its relationship with the risk of ICAS or ECAS. In this study, the lipid ratio in the fourth quartile was compared with that of the first quartile. The corresponding OR and 95% CI of lipid ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C, RC/HDL-C, non-HDL-C/HDL-C, apo B/apo A-I, and apo B/HDL-C) in the first quartile are listed in Figure 1. Compared with other lipid ratios, apo B/apo A-I showed the strongest relationship with ICAS after adjustment for potential confounding factors (first quartile vs. fourth quartile; OR, 2.32; 95% CI, 1.44–3.73). Moreover, after adjustment for age, sex, current smoking, hypertension, DM, previous stroke, and coronary heart disease, this significant relationship was also observed for other lipid ratios (TC/HDL-C, OR = 2.04, 95% CI = 1.26–3.31; RC/HDL-C, 1.64, 1.01–2.65; non-HDL-C/HDL-C, 2.04, 1.26–3.31; LDL-C/HDL-C, 1.92, 1.19–3.10; apo B/HDL-C, 2.28, 1.41–3.71; fourth quartile vs. first quartile; Figure 1A). These adjusted logistic regression analyses were repeated for ECAS, but no significant association was observed between lipid ratios and ECAS (Figure 1B).
Box-plots of the TC/HDL-C (Figure 2A), LDL-C/HDL-C (Figure 2B), RC/HDL-C (Figure 2C), Non-HDL-C/HDL-C (Figure 2D), Apo B/ HDL-C (Figure 2E), and Apo B/Apo A-I (Figure 2F) ratios are shown in Figure 2. Patients with ICAS had significantly higher LDL-C/HDL-C (Figure 2B), apo B/HDL-C (Figure 2E), and apo B/apo A-I ratios (Figure 2F) than those without ICAS in both sexes (P <0.05). However, this difference was not observed for the TG/HDL-C (Figure 2A) and RC/HDL-C (Figure 2C) ratios. A significant difference in the non-HDL-C/HDL-C ratio was observed only in men (Figure 2D). Because the result was similar to that of the non-HDL-C/HDL-C ratio, the TC/HDL-C ratio is not presented in Figure 2.
Analyses of ROC curves revealed that the apo B/apo A-I ratio exhibited the highest AUC value (0.588) for ICAS among all of the lipid levels alone and the lipid ratios (Table 2). However, the apo B/apo A-I ratio exhibited the highest AUC value only in men but not in women (men: 0.579; women: 0.613). In women, the apo B/HDL-C ratio demonstrated an optimal AUC value (0.617) for predicting ICAS risk. Overall, lipid ratios had higher AUC values than those for the lipid levels alone for the identification of ICAS. Additionally, the AUC in women was higher than that in men for all lipid ratios analyzed.
Table 2 Comparison of AUC for each evaluated variable in predicting ICAS
|
Total
|
Men
|
Women
|
AUC(95% CI)
|
AUC(95%CI)
|
AUC(95%CI)
|
Lipid measures
|
|
|
|
TC
|
0.543 (0.498-0.589)
|
0.537 (0.481-0.592)
|
0.562 (0.482-0.642)
|
TG
|
0.525 (0.480-0.570)
|
0.499 (0.444-0.554)
|
0.576 (0.500-0.652)
|
HDL-C
|
0.462 (0.417-0.507)
|
0.480 (0.426-0.535)
|
0.435 (0.356-0.514)
|
LDL-C
|
0.555 (0.510-0.601)
|
0.547 (0.491-0.603)
|
0.573 (0.493-0.653)
|
Non-HDL-C
|
0.559 (0.513-0.604)
|
0.543 (0.488-0.599)
|
0.590 (0.511-0.669)
|
RC
|
0.538 (0.493-0.583)
|
0.529 (0.475-0.584)
|
0.558 (0.481-0.635)
|
Apo A-I
|
0.456 (0.411-0.501)
|
0.465 (0.410-0.520)
|
0.424 (0.345-0.504)
|
Apo B
|
0.576 (0.531-0.622)
|
0.561 (0.505-0.617)
|
0.605 (0.527-0.683)
|
Lipid ratios
|
|
|
|
TC/HDL-C
|
0.566 (0.521-0.611)
|
0.546 (0.491-0.601) *
|
0.608 (0.531-0.684)
|
TG/HDL-C
|
0.535 (0.490-0.579) *
|
0.511 (0.456-0.566) *
|
0.580 (0.503-0.657)
|
LDL-C/HDL-C
|
0.570 (0.525-0.615)
|
0.555 (0.499-0.611)
|
0.603 (0.526-0.680)
|
RC/HDL-C
|
0.544 (0.500-0.589)
|
0.530 (0.475-0.584)
|
0.575 (0.498-0.652)
|
Non- HDL-C/HDL-C
|
0.566 (0.521-0.611)
|
0.546 (0.491-0.601) *
|
0.608 (0.531-0.684)
|
Apo B/ HDL-C
|
0.578 (0.533-0.623)
|
0.562 (0.506-0.617)
|
0.617 (0.541-0.693)
|
Apo B/apo A-I
|
0.588 (0.543-0.633)
|
0.579 (0.523-0.634)
|
0.613 (0.536-0.690)
|
TC total cholesterol, TG triglycerides, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, RC remnant cholesterol, Non-HDL-C non-high-density lipoprotein cholesterol, Apo B apolipoprotein B, Apo A-I apolipoprotein A-I, AUC area under the curve; 95%CI 95% confidence interval, ICAS intracranial atherosclerotic stenosis. * P <0.05, AUC were compared with apo B/apo A-I ratio in lipid ratios.