ETM Experimental and Therapeutic Medicine 1792-0981 1792-1015 D.A. Spandidos 10.3892/etm.2014.1624 etm-07-06-1495 Articles Analysis of multiple factors involved in acute progressive cerebral infarction and extra- and intracranial arterial lesions CHENYUEFU1 LIUYAJIE2 LUOCHENGHONG1 LUWEIHENG1 SUBINRU1 Department of Neurology, Shilong People’s Hospital, Southern Medical University, Dongguan, Guangdong 523326, P.R. China Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China Correspondence to: Dr Binru Su, Department of Neurology, Shilong People’s Hospital, Southern Medical University, Dongguan, Guangdong 523326, P.R. China, E-mail: subinru@gmail.com 6 2014 14 03 2014 7 6 1495 1505 04 11 2013 03 03 2014 Copyright © 2014, Spandidos Publications 2014 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

In order to identify the potential factors involved in the development of acute progressive cerebral infarction (PCI), the association between potential risk factors and extra- and intracranial arterial lesions was investigated. A total of 608 patients underwent cerebral angiography to analyze the morphological characteristics between the PCI and NPCI groups. In addition, data from numerous cases of extra- and intracranial arterial lesions were collected and compared with the control groups, and the associations between the severity of arterial lesions and the potential influential factors were analyzed. In the blood vessels responsible for cerebral infarction, various degrees of atherosclerotic plaques and stenosis were observed. Age, high-density lipoprotein (HDL) levels, glycosylated hemoglobin and blood pressure affected the degrees of hardening, plaques and stenosis. Analysis of cerebral artery stenosis revealed that age, diabetes mellitus and plasma fibrinogen were risk factors for cerebral artery stenosis, while the HDL/low density lipoprotein ratio was a protective factor. Therefore, the results of the present study indicate that the lesions of blood vessels are a major pathological change in PCI and multiple factors are involved in the pathogenesis.

 progressive cerebral infarction carotid atherosclerosis cerebral artery stenosis stroke in progression Introduction

Progressive cerebral infarction (PCI) is a brain disorder caused by insufficient blood supply. Cerebral infarction may lead to cerebral ischemia, hypoxia, necrosis and finally neurological deficit (1). Recently, studies of cerebral infarction have focused on identifying risk factors. Multiple measures have also been taken, including health education, acute-stage patient care, vascular stenting and surgery, neuroradiology, early rehabilitation. However, the prevention and treatment of cerebral infarction remains largely unsuccessful and the prognosis is severe. Between 50 and 70% of surviving patients are left with paralysis, aphasia and dementia (2). Therefore, it is particularly important to identify risk factors for the development of PCI.

At present, there are no ideal strategies that effectively prevent the progression of cerebral infarction. With the rapid progress in the treatment of intravascular hydrocephalus and the continuous improvement of interventional equipment, stenting and angioplasty are feasible in the treatment of intracranial vascular stenosis (3). These treatments are recommended for patients with intracranial arterial stenosis who do not respond well to medical treatment or whose arterial stenosis is >50%, according to the guidelines from the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Interventional Radiology and the American Society of Neuroradiology (4). However, the clinical value of vascular balloon angioplasty and stent implantation in preventing the progression of cerebral infarction remains unknown.

The present study enrolled patients with PCI and those with non-progressive cerebral infarction (NPCI) in order to compare and analyze the cerebral angiographic characteristics. Differences in vascular stenosis and vascular morphology were revealed by cerebral angiography. The aim of the present study was to provide further theoretical basis for interventional therapy of cerebrovascular disease.

 Materials and methods Case selection criteria

Data from 608 PCI patients (male 419, female 189) admitted to the Department of Internal Medicine at Shilong People’s Hospital (Guangdong, China) were collected between May 2010 and May 2013. The inclusion criteria met the diagnostic criteria set in the first edition of the Chinese Guidelines for Cerebrovascular Disease Prevention (5) and were confirmed by head computed tomography or magnetic resonance imaging examinations. The patients were divided into two groups: PCI and NPCI groups. The PCI group included patients who had been admitted within 24 h after the onset of the disease, but had not been treated within 6 h of onset. The diseases were progressing and the patients scored ≥2 points according to the United States National Institute of Health Stroke Scale (NIHSS) (6). The NPCI group (control group) included patients who were admitted within 24 h after onset and whose diseases had reached the peak, thus progression had stopped 6 h after onset. These patients scored <2 points on the NIHSS. The study protocol was approved by the Institutional Ethical Committee for Research on Human Subjects (Guangzhou, China) and informed written consent was obtained from each patient.

 Carotid artery ultrasonography

To examine the extent of common carotid artery atherosclerosis, the intima media thickness (IMT) and the vessel diameters were measured by ultrasonography. The severity of the carotid artery lesions was classified into four groups: Normal (IMT ≤0.9 mm), hardening (0.9 mm<IMT≤1.5 mm), plaque formation (IMT>1.5 mm) and stenosis (narrowing, >30%).

 Cerebral angiography

A Seldinger puncture was created in the femoral arteries of patients from the two groups. Angiography was performed using catheters at the aortic arch, bilateral common carotid arteries and vertebral arteries. Based on the North America Symptomatic Carotid Endarterectomy Trial method (7), vascular stenosis was assessed by doctors experienced in neurointervention. The degree of cerebral artery stenosis was classified into two groups based on the reduction in vessel diameter: Mild stenosis (≤50%) and severe stenosis (>50%). The severity of arterial lesions was evaluated.

 Statistical analysis

Continuous data are presented as mean ± SD and were analyzed with a Student’s t-test or one-way analysis of variance (when the variance was irregular Welch correction was used). Categorical data were analyzed with a χ2 test. To identify the potential risk factors for the development of PCI, the linear regression method and multivariate logistic regression analyses were used. P<0.05 was considered to indicate a statistically significant difference.

 Results Single factor analysis

Associations between multiple potential risk factors and carotid artery atherosclerosis were firstly analyzed. As shown in Table I, the incidence rate of diabetes was significantly higher in patients with carotid artery atherosclerosis when compared with those with normal carotid arteries (χ2=18.988; P<0.01). As the severity of atherosclerosis increased, the diabetes incidence also increased, indicating the involvement of diabetes in the pathogenesis of carotid artery atherosclerosis. Similarly to diabetes, the incidence of hypertension was also significantly higher in patients with carotid artery atherosclerosis when compared with those with normal carotid arteries (χ2=82.107; P<0.01). The incidence of hypertension increased to 90% in patients with carotid artery stenosis, demonstrating the effect of hypertension on carotid artery stenosis. Hyperlipidemia was more common among patients with impaired carotid arteries, despite the less evident difference in the incidence (χ2=10.312; P=0.016). Notably, other factors, including smoking, alcohol consumption, cholesterol and lipoprotein, were not significantly different between the normal carotid artery and the dysfunctional carotid artery groups. The ages of the patients varied among the groups with different carotid artery lesions. Stenosis occurred more frequently in older patients.

In addition, whether the factors listed in Table I contributed to the development of cerebral artery stenosis was investigated. As shown in Table II, diabetes, hypertension, hyperlipidemia and age were associated with the severity of cerebral artery stenosis, exhibiting a similar pattern to carotid artery atherosclerosis. However, smoking and alcohol consumption was also demonstrated to affect the narrowing of cerebral arteries, contrary to carotid arteries.

Furthermore, whether these factors were involved in the development of neurological deficits, including stroke and progressive stroke, was investigated. The factors that contributed to the severity of cerebral stenosis (Table II) also affected the incidence of stroke (Table III) in a similar manner. This observation also enhances the correlation of stroke and cerebral artery stenosis. However, the data showed that only hyperlipidemia, alcohol consumption and age were significantly different between the patients with or without progressive stroke (Table IV; P<0.05).

 Multivariate logistic regression analysis

Multiple linear regression analysis revealed that multicollinearity existed between systolic and diastolic pressure, total cholesterol and LDL. Due to extensive variance, two factors (diastolic blood pressure and total cholesterol) were rejected in the model and the results are shown in Table V. The results demonstrated that these factors exhibited significant differences at various levels of carotid artery atherosclerosis (hardened, hardened plaque and stenosis groups), when compared with the normal group. The odds ratio was set at >1 for risk factors and otherwise protective factors. As shown in Table VI, the influencing factors of cerebral artery stenosis included age, diabetes, plasma fibrinogen and HLR (HDL/LDL ratio), among which age, diabetes mellitus and plasma fibrinogen were identified as risk factors, whereas HLR was a protective factor. As shown in Table VII, risk factors were also identified for stroke. These included fasting blood glucose and smoking. However, multivariate analysis of the bivariate correlation between progressive stroke and cerebral artery atherosclerosis exhibited no significant correlation (Table VIII). For effects of fasting blood glucose and plasma fibrinogen (FIB) classification, as shown in Table IX, age, diabetes and smoking were important factors for carotid atherosclerosis. Similarly, age and diabetes were also the important factors in FIB classification of cerebral artery stenosis (Table X).

 Discussion

PCI is a refractory cerebral vascular disease with an incidence rate of 20–30% in patients with cerebral infarction. PCI often leads to brain deterioration and thereby significantly increases the mortality rate (8–10). The occurrence and development of PCI are affected by a number of factors and mechanisms. Among the numerous risk factors, atherosclerosis, stenosis or occlusion of the trunk and main branches of cerebral arteries are major independent risk factors (11). Consistent with a previous study (12), the data of the present study demonstrated that the corresponding vessels in the infarction region had various degrees of vascular sclerosis and stenosis.

Multiple mechanisms of cerebral infarction caused by atherosclerosis have been proposed, including intravascular thrombosis, vascular stenosis and reduced perfusion pressure in terminal cerebral vessels (8). When intravascular plaques detach from the arterial thrombus or atherosclerosis directly involves the perforator vessels, cerebral infarction may occur. The atherosclerotic vessels are more prone to thrombosis, which aggravates the preexisting vascular stenosis or occlusion (13). Thrombosis may exacerbate cerebral ischemia unless collateral circulation is formed in time. When collateral circulation does not form, cerebral infarction becomes progressive. Stenosis of the cerebral vessels is an additional mechanism underlying the progression of infarction (14). The narrowed cerebral vessels are more likely to have local thrombosis. Thrombosis may extend to the distal vessels resulting in stenosis, and detachment of the thrombus from the wall may also cause an arterial embolism (15,16). When stenosis occurs in the internal carotid, vertebral basilar or other medium-sized arteries, blood flow to the distal branches decreases. With low perfusion, the distal narrowed vessels fail to form effective collateral circulation to bypass the blockage. The results of the present study revealed that atherosclerotic plaques and stenosis existed in the corresponding vessels of cerebral infarction. These observations indicate that cerebral vascular lesions play an important role in the pathogenesis of PCI. In addition, the current study identified that numerous factors, including age, HDL, glycosylated hemoglobin and blood parameters, correlated with the severity of atherosclerosis, plaque formation and stenosis in the carotid artery. Factors affecting cerebral artery stenosis were also identified, including age, diabetes, plasma fibrinogen and HLR, among which age, diabetes mellitus and plasma fibrinogen were risk factors, while HLR was a protective factor. Therefore, in patients with acute cerebral infarction, early treatment of vascular stenosis and cerebral artery recanalization may improve cerebral perfusion, thus, prevent the progression and recurrence of cerebral infarction. A previous study demonstrated that placing a stent in the narrowed vessels of patients with PCI, particularly in those with artery stenosis when performed within 16 h of disease onset and treated within 8 h, achieves favorable effects (17). In conclusion, the results of the present study indicate that the lesions of responsible blood vessels play an important role in PCI. The observations provide supporting evidence for interventional therapy for cerebrovascular disease.

 Acknowledgements

This study was supported by the Science and Technology Program for Dongguan Higher Education, Science, Research and Health Care (grant number 201010515000333). The authors would like to thank Forevergen Biosciences for assistance with the experiments and for valuable discussion and 91SCI Company for language editing assistance.

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Association of potential risk factors with severity of carotid atherosclerosis.

Risk factor Carotid atherosclerosis Total Test statistic P-value
Normal Hardening Plaque Stenosis
Gender, n (%)
 Male 60 (69.0) 67 (67.7) 197 (69.6) 62 (74.7) 386 (69.9) 1.189 0.756
 Female 27 (31.0) 32 (32.3) 86 (30.4) 21 (25.3) 166 (30.1)
Diabetes, n (%)
 No 75 (86.2) 75 (75.8) 185 (65.4) 50 (60.2) 385 (69.7) 18.988 <0.01
 Yes 12 (13.8) 24 (24.2) 98 (34.6) 33 (39.8) 167 (30.3)
Hypertension, n (%)
 No 49 (56.3) 24 (24.2) 37 (13.1) 8 (9.6) 118 (21.4) 82.107 <0.01
 Yes 38 (43.7) 75 (75.8) 246 (86.9) 75 (90.4) 434 (78.6)
Hyperlipidemia, n (%)
 No 56 (64.4) 51 (51.5) 127 (45.0) 39 (47.0) 273 (49.5) 10.312 0.016
 Yes 31 (35.6) 48 (48.5) 155 (55.0) 44 (53.0) 278 (50.5)
Smoking, n (%)
 No 60 (69.0) 58 (58.6) 172 (60.8) 43 (51.8) 333 (60.3) 5.379 0.146
 Yes 27 (31.0) 41 (41.4) 111 (39.2) 40 (48.2) 219 (39.7)
Wine consumption, n (%)
 No 78 (89.7) 87 (87.9) 241 (85.2) 71 (85.5) 477 (86.4) 1.393 0.707
 Yes 9 (10.3) 12 (12.1) 42 (14.8) 12 (14.5) 75 (13.6)
Age, yearsa 53.2±11.6 62.3±11.3 66.4±10.0 68.6±8.3 43.4 <0.01
Systolic blood pressure, mmHga 136.3±21.3 151.3±23.8 153.2±23.5 153.6±22.1 12.9 <0.01
Diastolic blood pressure, mmHga 81.2±12.8 85.3±13.3 85.2±12.3 83.7±9.1 2.6 0.049
Platelet count (109/l)a 235.788±67.761 253.153±95.158 237.735±76.974 236.602±70.103 1.135 0.334
International normalized ratioa 1.001±0.080 1.006±0.088 1.033±0.109 1.041±0.170 2.911 0.034
Plasma fibrinogen (g/l) a 3.301±0.789 3.564±0.796 3.805±0.990 3.862±1.011 7.297 <0.01
Total cholesterol (mmol/l)a 4.675±1.208 4.959±1.137 4.980±1.156 5.043±1.499 1.639 0.179
Triglyceride (mmol/l)a 1.661±1.165 1.741±1.112 1.738±1.069 1.643±0.937 0.254 0.859
HDL (mmol/l)a 1.087±0.334 1.226±0.508 1.135±0.549 1.114±0.340 1.451 0.227
LDL (mmol/l)a 2.596±0.992 2.905±0.993 2.773±1.002 2.936±1.123 2.039 0.107
HLRa 0.480±0.253 0.492±0.405 0.478±0.330 0.451±0.397 0.219 0.883
Fasting blood glucose (mmol/l)a 5.878±1.691 6.222±2.006 6.698±3.055 6.866±3.622 2.640 0.049
Glycated hemoglobin (%)a 6.233±1.948 6.197±1.415 6.942±2.016 6.970±1.881 4.122 0.007
Homocysteine (μmol/l)a 13.574±5.586 13.941±4.898 14.849±6.470 15.002±5.258 1.031 0.379

Mean ± SD.

HDL, high-density lipoprotein; LDL, low-density lipoprotein; HLR, HDL/LDL ratio.

Association between potential risk factors with the severity of cerebral artery stenosis.

Cerebral artery stenosis
Risk factor Narrowing ≤50% Narrowing >50% Total Test statistic P-value
Gender, n (%)
 Male 185 (68.0) 234 (69.6) 419 (68.9) 0.186 0.666
 Female 87 (32.0) 102 (30.4) 189 (31.1)
Diabetes, n (%)
 No 221 (81.3) 209 (62.2) 430 (70.7) 26.339 <0.001
 Yes 51 (18.8) 127 (37.8) 178 (29.3)
Hypertension, n (%)
 No 79 (29.0) 50 (14.9) 129 (21.2) 18.039 <0.001
 Yes 193 (71.0) 286 (85.1) 479 (78.8)
Hyperlipidemia, n (%)
 No 154 (56.6) 149 (44.5) 303 (49.9) 8.850 0.003
 Yes 118 (43.4) 186 (55.5) 304 (50.1)
Smoking, n (%)
 No 185 (68.0) 195 (58.0) 380 (62.5) 6.387 0.011
 Yes 87 (32.0) 141 (42.0) 228 (37.5)
Wine consumption, n (%)
 No 246 (90.4) 281 (83.6) 527 (86.7) 6.037 0.014
 Yes 26 (9.6) 55 (16.4) 81 (13.3)
Age, yearsa 60.7±12.1 65.8±10.4 −5.6 <0.01
Systolic blood pressure, mmHga 147.9±24.9 151.4±22.7 −1.8 0.065
Diastolic blood pressure, mmHga 84.0±12.7 84.0±12.0 0.026 0.979
Platelet count (109/l)a 237.345±78.032 245.263±78.838 −1.229 0.220
International normalized ratioa 1.029±0.101 1.020±0.118 0.884 0.377
Plasma fibrinogen (g/l)a 3.460±0.859 3.871±1.045 −5.124 <0.001
Total cholesterol (mmol/l)a 4.862±1.199 5.023±1.206 −1.632 0.103
Triglyceride (mmol/l)a 1.642±0.996 1.753±1.140 −1.27 0.204
HDL (mmol/l)a 1.191±0.447 1.116±0.491 1.942 0.053
LDL (mmol/l)a 2.715±1.011 2.846±0.990 −1.598 0.111
HLRa 0.520±0.408 0.444±0.252 2.686 0.008
Fasting blood glucose (mmol/l)a 6.000±2.149 6.846±3.188 −3.874 <0.001
Glycated hemoglobin (%)a 6.415±1.837 7.009±1.985 −3.115 0.002
Homocysteine (μmol/l)a 14.084±4.669 14.992±6.561 −1.615 0.107

Mean ± SD.

HDL, high-density lipoprotein; LDL, low-density lipoprotein; HLR, HDL/LDL ratio.

Association between potential risk factors and the severity of stroke.

Risk factor No stroke Stroke with large artery atherosclerosis Stroke with small artery atherosclerosis Total Test statistic P-value
Gender, n (%)
 Male 113 (64.6) 154 (70.0) 109 (73.6) 376 (69.2) 3.201 0.202
 Female 62 (35.4) 66 (30.0) 39 (26.4) 167 (30.8)
Diabetes, n (%)
 No 140 (80.0) 131 (59.5) 109 (73.6) 380 (70.0) 20.714 <0.001
 Yes 35 (20.0) 89 (40.5) 39 (26.4) 163 (30.0)
Hypertension, n (%)
 No 59 (33.7) 34 (15.5) 19 (12.8) 112 (20.6) 27.388 <0.001
 Yes 116 (66.3) 186 (84.5) 129 (87.2) 431 (79.4)
Hyperlipidemia, n (%)
 No 104 (59.4) 88 (40.2) 75 (50.7) 267 (49.3) 14.578 0.001
 Yes 71 (40.6) 131 (59.8) 73 (49.3) 275 (50.7)
Smoking, n (%)
 No 128 (73.1) 119 (54.1) 90 (60.8) 337 (62.1) 15.161 0.001
 Yes 47 (26.9) 101 (45.9) 58 (39.2) 206 (37.9)
Wine consumption, n (%)
 No 167 (95.4) 175 (79.5) 126 (85.1) 468 (86.2) 20.845 <0.01
 Yes 8 (4.6) 45 (20.5) 22 (14.9) 75 (13.6)
Age, yearsa 61.7±11.3 65.5±11.1 62.6±11.6 6.2 0.002
Systolic blood pressure, mmHga 140.7±21.4 152.54±22.9 157.3±23.0 24.1 <0.01
Diastolic blood pressure, mmHga 79.6±9.8 85.7±12.4 88.2±12.7 27.5 <0.01
Platelet count (109/l)a 233.751±72.418 244.735±76.258 247.944±83.259 1.559 0.211
International normalized ratioa 1.031±0.094 1.013±0.094 1.011±0.087 2.097 0.124
Plasma fibrinogen (g/l)a 3.368±0.879 3.984±1.103 3.659±0.835 17.363 <0.001
Total cholesterol (mmol/l)a 4.742±1.142 5.082±1.228 4.909±1.113 4.039 0.018
Triglyceride (mmol/l)a 1.677±1.236 1.762±1.071 1.719±0.972 0.291 0.748
HDL (mmol/l)a 1.192±0.407 1.114±0.566 1.142±0.463 1.189 0.305
LDL (mmol/l)a 2.542±0.907 2.936±0.997 2.796±0.984 7.966 <0.001
HLRa 0.542±0.357 0.418±0.212 0.498±0.454 8.833 <0.001
Fasting blood glucose (mmol/l)a 5.765±2.347 7.166±3.402 6.414±2.354 11.659 <0.001
Glycated hemoglobin (%)a 6.243±1.376 7.219±2.189 6.613±1.879 10.379 <0.001
Homocysteine (μmol/l)a 14.301±4.473 15.051±6.512 14.640±6.106 0.500 0.607

Mean ± SD.

HDL, high-density lipoprotein; LDL, low-density lipoprotein; HLR, HDL/LDL ratio.

Association between potential risk factors and progressive stroke.

Progressive stroke
Risk factor No (n=368) Yes (n=60) Total Test statistic P-value
Gender, n (%)
 Male 262 (71.2) 43 (71.7) 305 (71.3) 0.006 0.940
 Female 106 (28.8) 17 (28.3) 123 (28.7)
Diabetes, n (%)
 No 248 (67.4) 40 (66.7) 288 (67.3) 0.012 0.912
 Yes 120 (32.6) 20 (33.3) 140 (32.7)
Hypertension, n (%)
 No 58 (15.8) 13 (21.7) 71 (16.6) 1.300 0.254
 Yes 310 (84.2) 47 (78.3) 357 (83.4)
Hyperlipidemia, n (%)
 No 179 (48.8) 21 (35.0) 200 (46.8) 3.929 0.047
 Yes 188 (51.2) 39 (65.0) 227 (53.2)
Smoking, n (%)
 No 217 (59.0) 29 (48.3) 246 (57.5) 2.387 0.122
 Yes 151 (41.0) 31 (51.7) 182 (42.5)
Wine consumption, n (%)
 No 318 (86.4) 37 (61.7) 355 (82.9) 22.331 <0.01
 Yes 50 (13.6) 23 (38.3) 73 (17.1)
Age, yearsa 63.5±11.1 68.8±12.0 −3.4 <0.01
Systolic blood pressure, mmHga 153.6±24.1 152.8±19.0 0.3 0.766
Diastolic blood pressure, mmHga 85.7±12.9 87.1±11.7 −0.8 0.432
Platelet count (109/l)a 244.019±79.526 246.967±89.006 −0.261 0.794
International normalized ratioa 1.031±0.118 0.975±0.099 3.46 <0.01
Plasma fibrinogen (g/l)a 3.789±0.982 3.964±1.135 −1.234 0.218
Total cholesterol (mmol/l)a 4.980±1.229 5.278±1.148 −1.756 0.080
Triglyceride (mmol/l)a 1.706±1.022 1.686±0.923 0.14 0.889
HDL (mmol/l)a 1.121±0.355 1.204±0.998 −0.635 0.528
LDL (mmol/l)a 2.840±1.032 3.032±0.935 −1.349 0.178
HLRa 0.458±0.298 0.453±0.459 0.083 0.934
Fasting blood glucose (mmol/l)a 6.610±2.599 7.782±4.420 −1.997 0.050
Glycated hemoglobin (%)a 7.073±2.108 6.494±1.995 1.917 0.056
Homocysteine (μmol/l)a 14.847±6.432 13.731±5.049 1.429 0.156

Mean ± SD.

HDL, high-density lipoprotein; LDL, low-density lipoprotein; HLR, HDL/LDL ratio.

Logistic regression analysis of factors affecting carotid atherosclerosis.

95% CI of OR value
Risk factor B SE Wald P-value OR value Lower limit Upper limit
Hardening
 Intercept −10.138 6.565 2.385 0.123
 Age 0.063 0.030 4.445 0.035 1.066 1.004 1.130
 Systolic blood pressure 0.029 0.016 3.045 0.081 1.029 0.996 1.063
 Platelet count 0.003 0.004 0.338 0.561 1.003 0.994 1.011
 International normalized ratio 4.015 3.747 1.148 0.284 55.413 0.036 85,759.316
 Plasma fibrinogen 0.386 0.406 0.901 0.342 1.471 0.663 3.260
 Triglyceride 0.542 0.408 1.763 0.184 1.720 0.772 3.830
 HDL 1.878 0.947 3.932 0.047 6.540 1.022 41.851
 LDL 0.441 0.397 1.232 0.267 1.554 0.714 3.382
 HLR −0.269 1.235 0.048 0.827 0.764 0.068 8.601
 Fasting blood glucose 0.197 0.172 1.314 0.252 1.218 0.870 1.705
 Glycated hemoglobin −0.929 0.363 6.546 0.011 0.395 0.194 0.805
 Homocysteine 0.037 0.065 0.314 0.576 1.037 0.912 1.179
 Gender −0.319 0.781 0.167 0.683 0.727 0.157 3.356
 Diabetes 2.322 1.161 3.999 0.046 10.195 1.047 99.254
 Hypertension 0.887 0.742 1.428 0.232 2.427 0.567 10.390
 Hyperlipidemia 0.640 0.806 0.629 0.428 1.896 0.390 9.203
 Smoking 1.522 0.777 3.839 0.050 4.582 1.000 21.002
 Wine consumption −0.232 0.926 0.063 0.802 0.793 0.129 4.868
Plaque formation
 Intercept −13.361 6.013 4.938 0.026
 Age 0.092 0.028 10.952 0.001 1.096 1.038 1.157
 Systolic blood pressure 0.023 0.015 2.369 0.124 1.024 0.994 1.055
 Platelet count 0.004 0.004 0.785 0.376 1.004 0.996 1.012
 International normalized ratio 6.320 3.414 3.428 0.064 555.608 0.690 447,157.189
 Plasma fibrinogen 0.454 0.377 1.449 0.229 1.574 0.752 3.296
 Triglyceride 0.248 0.393 0.400 0.527 1.282 0.594 2.768
 HDL 1.874 0.929 4.070 0.044 6.512 1.055 40.209
 LDL −0.220 0.377 0.341 0.559 0.802 0.383 1.681
 HLR −1.205 1.166 1.068 0.301 0.300 0.030 2.946
 Fasting blood glucose 0.143 0.152 0.886 0.346 1.154 0.856 1.556
 Glycated hemoglobin −0.367 0.288 1.628 0.202 0.693 0.394 1.218
 Homocysteine 0.056 0.061 0.844 0.358 1.058 0.938 1.193
 Gender 0.092 0.702 0.017 0.896 1.096 0.277 4.341
 Diabetes 2.163 1.092 3.921 0.048 8.700 1.022 77.035
 Hypertension 1.147 0.635 3.269 0.071 3.150 0.908 10.927
 Hyperlipidemia 1.236 0.730 2.864 0.091 3.441 0.822 14.393
 Smoking 1.006 0.698 2.077 0.150 2.735 0.696 10.749
 Wine consumption 0.337 0.840 0.160 0.689 01.400 0.270 7.267
Stenosis
 Intercept −12.001 6.638 3.268 0.071
 Age 0.104 0.033 10.273 0.001 1.110 1.041 1.183
 Systolic blood pressure 0.016 0.016 0.898 0.343 1.016 0.983 1.049
 Platelet count 0.000 0.005 0.000 0.996 1.000 0.991 1.009
 International normalized ratio 5.469 3.692 2.194 0.139 237.189 0.171 329,261.826
 Plasma fibrinogen 0.539 0.403 1.787 0.181 1.713 0.778 3.773
 Triglyceride −0.067 0.461 0.021 0.884 0.935 0.379 2.307
 HDL 1.833 1.100 2.780 0.095 6.256 0.725 53.975
 LDL −0.072 0.460 0.025 0.875 0.930 0.378 2.291
 HLR −2.148 1.809 1.410 0.235 0.117 0.003 4.047
 Fasting blood glucose 0.133 0.165 0.647 0.421 1.142 0.827 1.577
 Glycated hemoglobin −0.406 0.317 1.637 0.201 0.666 0.358 1.241
 Homocysteine 0.059 0.066 0.800 0.371 1.061 0.932 1.209
 Gender 0.276 0.801 0.118 0.731 1.317 0.274 6.332
 Diabetes 2.237 1.151 3.778 0.052 9.362 0.982 89.303
 Hypertension 1.654 0.789 4.387 0.036 5.225 1.112 24.552
 Hyperlipidemia 0.947 0.804 1.387 0.239 2.577 0.533 12.450
 Smoking 1.449 0.767 3.570 0.059 4.259 0.947 19.142
 Wine consumption 0.161 0.929 0.030 0.862 1.175 0.190 7.251

CI, confidence interval; SE, standard error; OR, odds ratio; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HLR, HDL/LDL ratio.

Logistic regression analysis of factors affecting cerebral artery stenosis (significant factors).

95% CI of OR value
Risk factor B SE Wald P-value OR value Lower limit Upper limit
Age 0.030 0.012 6.174 0.013 1.031 1.006 1.056
Diabetes 1.054 0.295 12.772 0.000 2.869 1.609 5.133
Plasma fibrinogen 0.299 0.147 4.148 0.042 1.348 1.011 1.797
HLR −0.925 0.420 4.841 0.028 0.396 0.174 0.904

HLR, high-density lipoprotein/low-density lipoprotein ratio; CI, confidence interval; OR, odds ratio; SE, standard error.

Logistic regression analysis of factors affecting stroke.

95% CI of OR value
Risk factor B SE Wald P-value OR value Lower limit Upper limit
Large artery atherosclerosis
 Intercept −6.995 3.664 3.645 0.056
 Age 0.010 0.019 0.262 0.609 1.010 0.972 1.049
 Systolic blood pressure 0.013 0.009 1.763 0.184 1.013 0.994 1.031
 Platelet count −0.001 0.003 0.153 0.696 0.999 0.994 1.004
 International normalized ratio −1.453 2.100 0.479 0.489 0.234 0.004 14.348
 Plasma fibrinogen 0.356 0.235 2.294 0.130 1.427 0.901 2.261
 Triglyceride −0.048 0.208 0.053 0.817 0.953 0.635 1.432
 HDL 0.021 0.750 0.001 0.978 1.021 0.235 4.441
 LDL 0.381 0.411 0.858 0.354 1.464 0.654 3.279
 HLR −0.690 1.890 0.133 0.715 0.502 0.012 20.399
 Fasting blood glucose 0.400 0.174 5.302 0.021 1.492 1.061 2.097
 Glycated hemoglobin 0.308 0.259 1.419 0.234 1.361 0.819 2.261
 Homocysteine −0.020 0.038 0.271 0.602 0.981 0.910 1.056
 Gender 0.296 0.479 0.383 0.536 1.345 0.526 3.439
 Diabetes 0.111 0.552 0.040 0.841 1.117 0.379 3.294
 Hypertension 0.293 0.530 0.306 0.580 1.341 0.474 3.789
 Hyperlipidemia 0.505 0.454 1.239 0.266 1.657 0.681 4.034
 Smoking 0.183 0.464 0.155 0.694 1.200 0.483 2.983
 Wine consumption 1.635 0.728 5.041 0.025 5.127 1.231 21.358
Small artery occlusion
 Intercept −5.180 3.822 1.837 0.175
 Age −0.005 0.020 0.063 0.802 0.995 0.956 1.035
 Systolic blood pressure 0.019 0.010 3.312 0.069 1.019 0.999 1.039
 Platelet count 0.003 0.003 1.292 0.256 1.003 0.998 1.008
 International normalized ratio −3.342 2.372 1.985 0.159 0.035 0.000 3.697
 Plasma fibrinogen 0.061 0.250 0.060 0.806 1.063 0.652 1.735
 Triglyceride −0.018 0.212 0.007 0.932 0.982 0.648 1.489
 HDL −1.230 0.926 1.763 0.184 0.292 0.048 1.796
 LDL 0.803 0.422 3.626 0.057 2.232 0.977 5.100
 HLR 2.486 1.812 1.881 0.170 12.010 0.344 418.996
 Fasting blood glucose 0.361 0.180 4.022 0.045 1.434 1.008 2.041
 Glycated hemoglobin 0.196 0.271 0.523 0.469 1.217 0.715 2.069
 Homocysteine −0.054 0.042 1.671 0.196 0.947 0.873 1.028
 Gender 0.285 0.510 0.312 0.577 1.330 0.489 3.615
 Diabetes 0.005 0.607 0.000 0.994 1.005 0.306 3.302
 Hypertension 0.736 0.593 1.542 0.214 2.088 0.653 6.679
 Hyperlipidemia −0.128 0.495 0.067 0.796 0.880 0.333 2.322
 Hyperlipidemia 0.068 0.501 0.018 0.892 1.070 0.401 2.855
 Smoking 1.513 0.768 3.886 0.049 4.542 1.009 20.455

CI, confidence interval; OR, odds ratio; SE, standard error; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HLR, HDL/LDL ratio.

Logistic regression analysis of factors affecting progressive stroke.

95% CI of OR value
Risk factor B SE Wald P-value OR value Lower limit Upper limit
Age 0.067 0.018 14.401 <0.001 1.070 1.033 1.108
Wine consumption 1.724 0.400 18.570 0.001 5.608 2.560 12.286
International normalized ratio −6.955 2.292 9.203 0.002 0.001 0.000 0.085
Fasting blood glucose 0.314 0.079 15.916 <0.001 1.369 1.173 1.598
Glycated hemoglobin −0.553 0.158 12.290 <0.001 0.575 0.423 0.784

International normalized ratio and glycated hemoglobin were protective factors (P<0.05), fasting blood glucose, age and alcohol consumption were risk factors (P<0.05). In total factor model, only 57 cases occurred progressive stroke so the single factor was age, hyperlipidemia, drinking, international normalized ratio, fasting blood glucose, glycated hemoglobin (P=0.057). CI, confidence interval; OR, odds ratio; SE, standard error.

Effect of fasting blood glucose and FIB classification on carotid atherosclerosis.

95% CI of OR value
Risk factor B SE Wald P-value OR value Lower limit Upper limit
Hardening
 Intercept −13.523 6.101 4.912 0.027
 Age 0.066 0.031 4.533 0.033 1.069 1.005 1.136
 Systolic blood pressure 0.028 0.017 2.821 0.093 1.029 0.995 1.063
 Platelet count 0.002 0.004 0.236 0.627 1.002 0.993 1.011
 International normalized ratio 4.318 3.937 1.202 0.273 75.015 0.033 168,551.521
 Triglyceride 0.732 0.445 2.708 0.100 2.079 0.870 4.971
 HDL 1.812 1.011 3.215 0.073 6.124 0.845 44.394
 LDL 0.551 0.413 1.780 0.182 1.735 0.772 3.898
 HLR −0.175 1.264 0.019 0.890 0.839 0.070 10.005
 Glycated hemoglobin −0.872 0.345 6.381 0.012 0.418 0.212 0.822
 Homocysteine 0.025 0.065 0.150 0.698 1.026 0.902 1.166
 Diabetes 2.883 1.210 5.681 0.017 17.875 1.669 191.421
 Hypertension 0.906 0.801 1.280 0.258 2.474 0.515 11.888
 Hyperlipidemia 0.283 0.835 0.115 0.735 1.327 0.258 6.816
 Smoking 1.578 0.796 3.934 0.047 4.845 1.019 23.043
 Wine consumption −0.026 0.989 0.001 0.979 0.974 0.140 6.761
 Gender −0.274 0.816 0.113 0.737 0.760 0.154 3.760
 Fasting blood glucose 1 0.313 1.013 0.096 0.757 1.368 0.188 9.965
 Fasting blood glucose 2 0.133 1.014 0.017 0.896 1.142 0.157 8.328
 Fasting blood glucose 3 −0.260 0.992 0.069 0.793 0.771 0.110 5.388
 Plasma fibrinogen 1 −1.408 1.031 1.865 0.172 0.245 0.032 1.846
 Plasma fibrinogen 2 0.242 0.978 0.061 0.805 1.273 0.187 8.654
 Plasma fibrinogen 3 −0.125 0.936 0.018 0.893 0.882 0.141 5.523
Plaque formation
 Intercept −17.606 5.621 9.811 0.002
 Age 0.094 0.029 10.782 0.001 1.099 1.039 1.162
 Systolic blood pressure 0.023 0.016 2.254 0.133 1.024 0.993 1.055
 Platelet count 0.004 0.004 0.795 0.373 1.004 0.996 1.012
 International normalized ratio 6.246 3.601 3.009 0.083 516.125 0.444 599,451.170
 Triglyceride 0.358 0.423 0.717 0.397 1.431 0.624 3.280
 HDL 1.847 0.989 3.490 0.062 6.343 0.913 44.055
 LDL −0.133 0.394 0.113 0.736 0.876 0.405 1.896
 HLR −1.207 1.202 1.010 0.315 0.299 0.028 3.151
 Glycated hemoglobin −0.275 0.259 1.122 0.289 0.760 0.457 1.263
 Homocysteine 0.054 0.061 0.769 0.381 1.055 0.936 1.190
 Diabetes 2.713 1.146 5.609 0.018 15.076 1.596 142.377
 Hypertension 1.384 0.692 3.998 0.046 3.991 1.028 15.500
 Hyperlipidemia 0.877 0.753 1.355 0.244 2.403 0.549 10.518
 Smoking 1.105 0.719 2.364 0.124 3.019 0.738 12.350
 Wine consumption 0.727 0.892 0.664 0.415 2.069 0.360 11.890
 Gender 0.033 0.737 0.002 0.964 1.034 0.244 4.385
 Fasting blood glucose 1 0.582 0.915 0.404 0.525 1.790 0.298 10.766
 Fasting blood glucose 2 0.422 0.916 0.212 0.645 1.525 0.253 9.172
 Fasting blood glucose 3 −0.182 0.904 0.040 0.841 0.834 0.142 4.902
 Plasma fibrinogen 1 −1.163 0.929 1.568 0.211 0.313 0.051 1.930
 Plasma fibrinogen 2 0.262 0.893 0.086 0.769 1.300 0.226 7.476
 Plasma fibrinogen 3 −0.938 0.879 1.137 0.286 0.392 0.070 2.194
Stenosis
 Intercept −17.095 6.254 7.471 0.006
 Age 0.094 0.033 7.945 0.005 1.099 1.029 1.173
 Systolic blood pressure 0.013 0.017 0.603 0.437 1.013 0.980 1.048
 Platelet count −0.001 0.005 0.041 0.839 0.999 0.990 1.008
 International normalized ratio 6.102 3.870 2.487 0.115 446.693 0.227 878,531.134
 Triglyceride −0.010 0.480 0.000 0.984 0.990 0.387 2.535
 HDL 1.555 1.182 1.729 0.189 4.733 0.466 48.022
 LDL −0.034 0.492 0.005 0.945 0.966 0.368 2.536
 HLR −1.891 1.908 0.982 0.322 0.151 0.004 6.353
 Glycated hemoglobin −0.157 0.288 0.295 0.587 0.855 0.486 1.504
 Homocysteine 0.060 0.067 0.799 0.371 1.062 0.931 1.210
 Diabetes 2.665 1.215 4.808 0.028 14.367 1.327 155.573
 Hypertension 1.943 0.861 5.091 0.024 6.979 1.291 37.737
 Hyperlipidemia 0.685 0.827 0.686 0.407 1.985 0.392 10.048
 Smoking 1.584 0.787 4.055 0.044 4.874 1.043 22.773
 Wine consumption 0.555 0.974 0.326 0.568 1.743 0.259 11.746
 Gender 0.161 0.846 0.036 0.849 1.174 0.224 6.161
 Fasting blood glucose 1 1.193 1.063 1.260 0.262 3.298 0.411 26.501
 Fasting blood glucose 2 0.979 1.089 0.808 0.369 2.663 0.315 22.524
 Fasting blood glucose 3 1.366 1.009 1.835 0.176 3.921 0.543 28.311
 Plasma fibrinogen 1 −1.024 0.994 1.061 0.303 0.359 0.051 2.521
 Plasma fibrinogen 2 −1.151 1.053 1.194 0.275 0.316 0.040 2.492
 Plasma fibrinogen 3 −0.871 0.936 0.866 0.352 0.418 0.067 2.620

FIB, fibrinogen; CI, confidence interval; OR, odds ratio; SE, standard error; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HLR, HDL/LDL ratio.

Effect of fasting blood glucose and FIB classification on cerebral artery stenosis.

95% CI of OR value
Factors B SE Wald P-value OR value Lower limit Upper limit
Gender 0.033 0.361 0.009 0.926 1.034 0.509 2.100
Age 0.031 0.014 4.796 0.029 1.032 1.003 1.061
Diabetes 0.946 0.415 5.186 0.023 2.574 1.141 5.809
Hypertension 0.185 0.404 0.210 0.647 1.203 0.545 2.659
Hyperlipidemia 0.585 0.352 2.759 0.097 1.794 0.900 3.576
Smoking 0.265 0.346 0.586 0.444 1.303 0.662 2.565
Wine consumption 0.239 0.437 0.300 0.584 1.270 0.540 2.990
Systolic blood pressure 0.002 0.007 0.110 0.740 1.002 0.989 1.015
Platelet count 0.000 0.002 0.035 0.852 1.000 0.997 1.004
International normalized ratio −0.400 1.450 0.076 0.783 0.671 0.039 11.492
Triglyceride −0.142 0.162 0.772 0.380 0.868 0.632 1.191
HDL −0.006 0.345 0.000 0.985 0.994 0.505 1.953
LDL −0.055 0.203 0.074 0.785 0.946 0.636 1.408
HLR −0.788 0.666 1.403 0.236 0.455 0.123 1.676
Glycated hemoglobin 0.009 0.128 0.005 0.946 1.009 0.785 1.295
Homocysteine 0.033 0.029 1.255 0.263 1.033 0.976 1.094
Fasting blood glucose 1.497 0.683
Fasting blood glucose 1 −0.480 0.470 1.040 0.308 0.619 0.246 1.556
Fasting blood glucose 2 −0.276 0.477 0.335 0.563 0.759 0.298 1.932
Fasting blood glucose 3 −0.060 0.457 0.018 0.895 0.941 0.385 2.304
Plasma fibrinogen 1.967 0.579
Plasma fibrinogen 1 −0.269 0.415 0.421 0.516 0.764 0.339 1.723
Plasma fibrinogen 2 −0.427 0.402 1.129 0.288 0.653 0.297 1.434
Plasma fibrinogen 3 0.058 0.398 0.022 0.883 1.060 0.486 2.311

HDL, high-density lipoprotein; LDL, low-density lipoprotein; HLR, HDL/LDL ratio; CI, confidence interval; OR, odds ratio; SE, standard error.