Acta Neurol Scand 2014: 130: 394–399 DOI: 10.1111/ane.12286
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Arterial stiffness as a risk factor for cerebral aneurysm Matsukawa H, Shinoda M, Fujii M, Uemura A, Takahashi O, Niimi Y. Arterial stiffness as a risk factor for cerebral aneurysm. Acta Neurol Scand: 2014: 130: 394–399. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – A low ankle–brachial index (ABI) is associated with increased mortality and risk of myocardial infarction and stroke in the general population. Arterial stiffness can be assessed noninvasively by the measurement of brachial–ankle pulse wave velocity (PWV), a simple and reproducible method. Because the importance of ABI and baPWV in the pathogenesis of cerebral aneurysms remains uncertain, we aimed to measure ABI and baPWV in patients with intracranial saccular and dissecting aneurysms to clarify whether these aneurysms are associated with arterial stiffness and atherosclerosis. Materials and methods – We prospectively investigated 78 patients diagnosed with intracranial saccular (n = 66) and dissecting (n = 12) aneurysms. The control group consisted of an age- and gendermatched normal population. We compared the clinical characteristics in patients with intracranial saccular aneurysms and controls, those with intracranial dissecting aneurysms and controls, and those who had cerebral aneurysms with and without subarachnoid hemorrhage. We also compared ABI and baPWV among saccular aneurysm locations and evaluated the correlation between the number of saccular aneurysms and ABI and baPWV. Results – Multivariate logistic regression analysis shows that hypertension and higher baPWV (>1400 cm/s) are significantly associated with saccular aneurysms. Simple regression analysis revealed no correlation between the number of saccular aneurysms and ABI (r = 0.064, P = 0.611), and baPWV (r = 0.007, P = 0.956). Conclusions – The baPWV was associated with intracranial saccular aneurysms even after adjustment of hypertension and smoking. Assessment of the baPWV may aid the evaluation of the intracranial saccular aneurysm and the development of strategies for screening patients with intracranial saccular aneurysms.
Introduction
The ankle–brachial blood pressure index (ABI) is an established clinical test for the assessment of peripheral arterial disease and an indicator of generalized atherosclerosis (1, 2). A low ABI is associated with increased mortality and risk of myocardial infarction and stroke in the general population, independent of conventional vascular risk factors and prevalent cardiovascular disease (1, 2). Arterial stiffness can be assessed non-invasively by the measurement of pulse wave velocity (PWV), a simple and reproducible method (3). 394
H. Matsukawa1, M. Shinoda1, M. Fujii1, A. Uemura3, O. Takahashi2, Y. Niimi3 1
Department of Neurosurgery, St. Luke’s International Hospital, Chuo-ku, Tokyo, Japan; 2Division of General Internal Medicine, Department of Medicine, St. Luke’s International Hospital, Chuo-ku, Tokyo, Japan; 3 Department of Neuroendovascular Therapy, St. Luke’s International Hospital, Chuo-ku, Tokyo, Japan
Key words: ankle–brachial index; cerebral aneurysm; pulse wave velocity H. Matsukawa, Department of Neurosurgery, St. Luke’s International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan Tel.: +81-3-3541-5151 Fax:+81-3-3544-064 e-mail: [email protected] Accepted for publication July 10, 2014
PWV measures the speed of a blood pressure wave between two given sites of the artery. In addition to conventional carotid–femoral PWV measurements, brachial–ankle PWV (baPWV) measurements can provide useful information on arterial stiffness (4, 5), particularly in large populations (6) because the method is convenient. Some studies also showed that arterial stiffness was an independent predictor of the risk of symptomatic stroke (7). Cerebral aneurysms contain saccular and dissecting forms. Saccular aneurysms, abnormal focal outpouchings of cerebral arteries, cause substantial
baPWV and intracranial saccular aneurysms rates of morbidity and mortality (8). Intracranial artery dissections are defined by the presence of a mural hematoma located in the arterial wall. To date, the importance of ABI and baPWV in the pathogenesis of cerebral aneurysms remains uncertain. Our aim was to measure ABI and baPWV in patients with intracranial saccular and dissecting aneurysms, and controls, to clarify whether these aneurysms are in fact associated with arterial stiffness and atherosclerosis. Methods
The study is reported based on criteria from the Strengthening the Reporting of Observational Study in Epidemiology (STROBE) statement (9). The study protocol was approved by the St. Luke’s International Hospital Research Ethics Committee (Tokyo, Japan) (13-R096), and written informed consent was obtained from all competent patients, or from a relative of patients incapacitated by their intracranial saccular and dissecting aneurysms. Study participants
We prospectively investigated 78 consecutive adult patients diagnosed with intracranial saccular (n = 66) and dissecting (n = 12) aneurysms at the Department of Neurosurgery at St. Luke’s International Hospital between August 2013 and March 2014. The control group consisted of an age- and gender-matched normal population of patients who underwent brain check-up MRI as one of a series of health examinations and had no abnormal brain findings, whether they had other disorders or not. Clinical characteristics
We collected the following data: age, sex, smoking history (current vs former/never), alcohol consumption status (consuming or not consuming alcohol more than 5 days a week), body mass index, laboratory data (glomerular filtration rate, uric acid, total cholesterol level, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, glucose, hemoglobin A1c), past medical history (hypertension, hypercholesterolemia, diabetes mellitus, ischemic heart disease, stroke (transient ischemic attack, cerebral infarction, and/or intracerebral hemorrhage), and ischemic heart disease), family history of subarachnoid hemorrhage, aneurysmal location, ABI, and baPWV. Height and weight were
measured with participants wearing light clothing and no shoes. Body mass index was calculated as weight in kilograms divided by height in meters squared. Information regarding smoking history, past medical history, and familial history of stroke was obtained from the patients, their family members, and/or their physicians. Hypertension was defined as taking antihypertensive agents prescribed by a physician, a systolic blood pressure ≥140 mmHg, and/or a diastolic blood pressure ≥90 mmHg (a systolic blood pressure ≥130 mmHg and/or a diastolic blood pressure ≥80 mmHg for diabetic patients) before the onset if patients developed stroke. Diabetes mellitus was defined as taking oral antidiabetic agents, insulin treatment, a fasting plasma glucose level ≥7.0 mmol/l, a random plasma glucose level >11.1 mmol/l, or a hemoglobin A1c level ≥6.5%. Hypercholesterolemia was defined as taking antihyperlipidemic agents or having a total cholesterol level >5.2 mmol/l. Radiological characteristics
Three-dimensional time-of-flight magnetic resonance (MR) angiography was performed on a 1.5T Signa Excite, Intera, or 3T Verio (GE Medical Systems, Milwaukee, WI, Philips, New York, NY, or Siemens, Munich, Germany). MR angiography was obtained using a head coil, and acquisition was oriented in the coronal plane. The diagnosis of intracranial saccular and dissecting aneurysms was based on the findings of MR imaging/angiography, 3-D computed tomographic angiography, and/or digital subtraction angiography. Saccular aneurysms were classified into four locations: anterior cerebral artery, middle cerebral artery, internal carotid artery, and posterior circulation (posterior cerebral, superior cerebellar, anterior inferior cerebellar, posterior inferior cerebellar, basilar, and vertebral artery). Diagnosis of siVAD was made according to the Spontaneous Cervicocephalic Arterial Dissections Study criteria (10). Experienced neuroradiologist (A.U.), blinded to clinical characteristics, evaluated the radiological characteristics. ABI and baPWV – We measured ABI and baPWV at 14 days after the onset or stabilization of the neurological deficit in patients with subarachnoid hemorrhage, at the diagnosis in patients with unruptured cerebral aneurysms, and at the brain checkup in controls using an oscillometric device (Form PWV/ABI; Omron Colin, Tokyo, Japan) (11, 12). The ABI data were obtained after 5 min of rest in the supine position by specially trained
395
Matsukawa et al. laboratory technicians. An ABI of more than 1.4 was identified as non-compressible and excluded from this study because this may lead to false elevation of the ankle pressure. In some patients with diabetes, renal insufficiency, or other diseases causing vascular calcification or Moenckeberg’s medial calcinosis, the vessels at the ankle become non-compressible and the Doppler signal cannot be obliterated even with cuff pressures of more than 300 mm Hg (13, 14). Briefly, pressure waveforms of the brachial and tibial arteries were simultaneously recorded by placing occlusion cuffs connected to a plethysmographic sensor around both the arms and ankles. The time delay (T) of the two waveforms was measured between the feet. The path lengths from the suprasternal notch to the arm (Lb) and from the suprasternal notch to the ankle (La) were automatically calculated by individual height. baPWV was calculated using the following equation: baPWV = (La Lb)/T (m/s). baPWV was measured for an average of 10 s, and the right arm-to-right ankle baPWV was used. The rationale for using baPWV rather than the carotid–femoral PWV was based on the finding that baPWV closely correlates with aortic PWV determined by invasive and non-invasive methods (5, 6). After examinations had been performed on both the right and left sides, we chose the lower ABI and the higher baPWV for analyses (11). Statistical analysis
Statistical analysis was performed using SPSS for Mac (version 21.0; SPSS, Armonk, NY). Variables are expressed as mean standard deviation, median (interquartile range: 25th–75th percentile), or number of patients (%), as appropriate. The chi-square test or Fisher’s exact test was performed for categorical variables as appropriate. The normality of the data was evaluated using the Shapiro–Wilk’s test. Normally distributed continuous variables were compared using Student’s t-test and non-normally distributed variables using the Mann–Whitney U-test. First, we compared the clinical characteristics of patients with intracranial saccular aneurysms and controls, those with intracranial dissecting aneurysms and controls, and those who had cerebral aneurysms with and without subarachnoid hemorrhage. Second, multivariate logistic regression analysis was performed using variables that showed significant differences on univariate analysis. Third, we also compared ABI and baPWV among saccular aneurysm locations by 396
Tukey’s test. Finally, we evaluated the correlation between the number of saccular aneurysms and ABI and baPWV by simple regression analysis. Differences were considered significant at P < 0.05 for a 95% CI. Results
Clinical characteristics of 78 patients with saccular (n = 66) and dissecting (n = 12) aneurysms and controls are shown in Table 1. A significantly higher proportion of patients with saccular aneurysms showed a current smoking and hypertension, and their median baPWV showed a significantly higher level compared with controls’. Median hemoglobin A1c level was lower in patients with dissecting aneurysm than controls’. SAH patients were significantly younger and had a higher glomerular filtration rate and lower levels of total cholesterol and hemoglobin A1c than nonSAH patients’. Other characteristics showed no significant differences among the groups. We performed receiver operating characteristics curve analysis for baPWV, and We would like to ask you to revise as follows: “We performed receiver operating characteristics curve analysis for baPWV, and we selected the baPWV cutoff point (1400 cm/ s) that optimized sensitivity and specificity.”. We performed multivariate logistic regression analysis using variables that were significantly associated with intracranial saccular aneurysms. It shows that hypertension and higher baPWV (>1400 cm/s) are still significantly associated with saccular aneurysms (Table 2). Both ABI and baPWV showed no significant differences among aneurysm locations (Table 3). Simple regression analysis revealed no correlation between the number of saccular aneurysms and ABI (r = 0.064, P = 0.611), and baPWV (r = 0.007, P = 0.956). Discussion
While it is known that atherosclerosis causes various diseases and is especially important as a risk factor for stroke (15, 16), a quantitative comparison of the grade of atherosclerosis between patients with intracranial aneurysms and controls has not yet been reported. The results of the present study showed that baPWV was higher in patients with intracranial saccular aneurysms than controls’, but it showed no significant difference among saccular aneurysm locations. In addition, no significant difference in ABI and baPWV was found between patients with intracranial dissecting aneurysms and controls, and between those who had intracranial saccular or dissecting
baPWV and intracranial saccular aneurysms Table 1 Clinical characteristics of patients with unruptured and ruptured posterior communicating artery aneurysms Saccular aneurysm (+) n = 66
Variables Baseline characteristics Age, years Male Current smoking Alcohol consumption Median body mass index Laboratory data Median GFR Uric acid Total cholesterol LDL cholesterol Median HDL cholesterol Median triglyceride Median glucose Median hemoglobin A1c Past medical history Hypertension Hypercholesterolemia Diabetes mellitus Stroke Ischemic heart disease Familial SAH Median ABI Median baPWV
Dissecting aneurysm
Control n = 66
(+) n = 12
62 22 11 15 23
(14) (33) (17)* (23) (20–24)
62 22 3 7 23
(13) (33) (4.5) (11) (20–25)
55 10 0 3 22
82 5.2 207 121 62 74 97 5.6
(72–93) (1.2) (39) (34) (51–71) (57–116) (89–107) (5.3–5.8)
75 5.4 204 119 59 85 91 5.6
(67–91) (1.2) (32) (26) (51–72) (54–114) (86–102) (5.4–5.9)
79 6.1 195 114 53 117 107 5.5
37 14 5 4 4 6 1.1 1633
(56)** (21) (7.6) (6.1) (6.1) (9.1) (1.1–1.2) (1436–1914)**
18 16 12 0 0 3 1.1 1389
(27) (24) (18)
9 6 1 4 2 4 1.2 1488
(4.6) (1.1–1.2) (1226–1783)
SAH
Control n = 12
(15) (83) (25) (21–25) (59–124) (1.9) (38) (28) (19) (53–227) (94–125) (5.3–5.7)* (75) (50) (8.3) (33) (17) (33) (1.1–1.2) (1208–1787)
(+) n = 26
55 10 0 5 23
(42) (21–28)
56 12 3 8 22
80 6.3 193 111 55 114 101 5.9
(69–94) (1.3) (27) (33) (47–68) (84–152) (96–115) (5.4–6.1)
86 5.3 192 113 55 64 99 5.4
4 1 1 0 0 0 1.1 1534
(10) (83)
(33) (8.3) (8.3)
(1.1–1.2) (1183–1780)
15 3 0 1 2 3 1.1 1538
(18)* (46) (12) (31) (19–25) (82–107)* (1.6) (39)* (32) (48–69) (56–103) (86–114) (5.2–5.7)* (58) (12) (3.8) (7.7) (12) (1.1–1.2) (1346–1802)
( ) n = 52 64 20 8 10 22
(11) (39) (15) (19) (21–24)
79 5.3 212 124 62 88 97 5.6
(66–87) (1.3) (37) (33) (49–74) (57–132) (92–108) (5.4–5.9)
31 17 6 6 4 4 1.1 1630
(59) (33) (12) (12) (7.7) (7.7) (1.1–1.2) (1480–1829)
SD, standard deviation; SAH, subarachnoid hemorrhage. Variables showing significant difference by univariate analysis (*P < 0.05 and **P < 0.0001). Data are expressed as number of patients (%), unless otherwise indicated. Table 2 Multivariate logistic regression analysis for intracranial saccular artery aneurysm Univariate
Multivariate
Variable
OR (95% CI)
P value
OR (95% CI)
P value
Hypertension* baPWV > 1400* Smoking
3.3 (1.6–6.9) 3.6 (1.7–7.7) 4.2 (1.1–16)
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Arterial stiffness as a risk factor for cerebral aneurysm Matsukawa H, Shinoda M, Fujii M, Uemura A, Takahashi O, Niimi Y. Arterial stiffness as a risk factor for cerebral aneurysm. Acta Neurol Scand: 2014: 130: 394–399. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – A low ankle–brachial index (ABI) is associated with increased mortality and risk of myocardial infarction and stroke in the general population. Arterial stiffness can be assessed noninvasively by the measurement of brachial–ankle pulse wave velocity (PWV), a simple and reproducible method. Because the importance of ABI and baPWV in the pathogenesis of cerebral aneurysms remains uncertain, we aimed to measure ABI and baPWV in patients with intracranial saccular and dissecting aneurysms to clarify whether these aneurysms are associated with arterial stiffness and atherosclerosis. Materials and methods – We prospectively investigated 78 patients diagnosed with intracranial saccular (n = 66) and dissecting (n = 12) aneurysms. The control group consisted of an age- and gendermatched normal population. We compared the clinical characteristics in patients with intracranial saccular aneurysms and controls, those with intracranial dissecting aneurysms and controls, and those who had cerebral aneurysms with and without subarachnoid hemorrhage. We also compared ABI and baPWV among saccular aneurysm locations and evaluated the correlation between the number of saccular aneurysms and ABI and baPWV. Results – Multivariate logistic regression analysis shows that hypertension and higher baPWV (>1400 cm/s) are significantly associated with saccular aneurysms. Simple regression analysis revealed no correlation between the number of saccular aneurysms and ABI (r = 0.064, P = 0.611), and baPWV (r = 0.007, P = 0.956). Conclusions – The baPWV was associated with intracranial saccular aneurysms even after adjustment of hypertension and smoking. Assessment of the baPWV may aid the evaluation of the intracranial saccular aneurysm and the development of strategies for screening patients with intracranial saccular aneurysms.
Introduction
The ankle–brachial blood pressure index (ABI) is an established clinical test for the assessment of peripheral arterial disease and an indicator of generalized atherosclerosis (1, 2). A low ABI is associated with increased mortality and risk of myocardial infarction and stroke in the general population, independent of conventional vascular risk factors and prevalent cardiovascular disease (1, 2). Arterial stiffness can be assessed non-invasively by the measurement of pulse wave velocity (PWV), a simple and reproducible method (3). 394
H. Matsukawa1, M. Shinoda1, M. Fujii1, A. Uemura3, O. Takahashi2, Y. Niimi3 1
Department of Neurosurgery, St. Luke’s International Hospital, Chuo-ku, Tokyo, Japan; 2Division of General Internal Medicine, Department of Medicine, St. Luke’s International Hospital, Chuo-ku, Tokyo, Japan; 3 Department of Neuroendovascular Therapy, St. Luke’s International Hospital, Chuo-ku, Tokyo, Japan
Key words: ankle–brachial index; cerebral aneurysm; pulse wave velocity H. Matsukawa, Department of Neurosurgery, St. Luke’s International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan Tel.: +81-3-3541-5151 Fax:+81-3-3544-064 e-mail: [email protected] Accepted for publication July 10, 2014
PWV measures the speed of a blood pressure wave between two given sites of the artery. In addition to conventional carotid–femoral PWV measurements, brachial–ankle PWV (baPWV) measurements can provide useful information on arterial stiffness (4, 5), particularly in large populations (6) because the method is convenient. Some studies also showed that arterial stiffness was an independent predictor of the risk of symptomatic stroke (7). Cerebral aneurysms contain saccular and dissecting forms. Saccular aneurysms, abnormal focal outpouchings of cerebral arteries, cause substantial
baPWV and intracranial saccular aneurysms rates of morbidity and mortality (8). Intracranial artery dissections are defined by the presence of a mural hematoma located in the arterial wall. To date, the importance of ABI and baPWV in the pathogenesis of cerebral aneurysms remains uncertain. Our aim was to measure ABI and baPWV in patients with intracranial saccular and dissecting aneurysms, and controls, to clarify whether these aneurysms are in fact associated with arterial stiffness and atherosclerosis. Methods
The study is reported based on criteria from the Strengthening the Reporting of Observational Study in Epidemiology (STROBE) statement (9). The study protocol was approved by the St. Luke’s International Hospital Research Ethics Committee (Tokyo, Japan) (13-R096), and written informed consent was obtained from all competent patients, or from a relative of patients incapacitated by their intracranial saccular and dissecting aneurysms. Study participants
We prospectively investigated 78 consecutive adult patients diagnosed with intracranial saccular (n = 66) and dissecting (n = 12) aneurysms at the Department of Neurosurgery at St. Luke’s International Hospital between August 2013 and March 2014. The control group consisted of an age- and gender-matched normal population of patients who underwent brain check-up MRI as one of a series of health examinations and had no abnormal brain findings, whether they had other disorders or not. Clinical characteristics
We collected the following data: age, sex, smoking history (current vs former/never), alcohol consumption status (consuming or not consuming alcohol more than 5 days a week), body mass index, laboratory data (glomerular filtration rate, uric acid, total cholesterol level, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, glucose, hemoglobin A1c), past medical history (hypertension, hypercholesterolemia, diabetes mellitus, ischemic heart disease, stroke (transient ischemic attack, cerebral infarction, and/or intracerebral hemorrhage), and ischemic heart disease), family history of subarachnoid hemorrhage, aneurysmal location, ABI, and baPWV. Height and weight were
measured with participants wearing light clothing and no shoes. Body mass index was calculated as weight in kilograms divided by height in meters squared. Information regarding smoking history, past medical history, and familial history of stroke was obtained from the patients, their family members, and/or their physicians. Hypertension was defined as taking antihypertensive agents prescribed by a physician, a systolic blood pressure ≥140 mmHg, and/or a diastolic blood pressure ≥90 mmHg (a systolic blood pressure ≥130 mmHg and/or a diastolic blood pressure ≥80 mmHg for diabetic patients) before the onset if patients developed stroke. Diabetes mellitus was defined as taking oral antidiabetic agents, insulin treatment, a fasting plasma glucose level ≥7.0 mmol/l, a random plasma glucose level >11.1 mmol/l, or a hemoglobin A1c level ≥6.5%. Hypercholesterolemia was defined as taking antihyperlipidemic agents or having a total cholesterol level >5.2 mmol/l. Radiological characteristics
Three-dimensional time-of-flight magnetic resonance (MR) angiography was performed on a 1.5T Signa Excite, Intera, or 3T Verio (GE Medical Systems, Milwaukee, WI, Philips, New York, NY, or Siemens, Munich, Germany). MR angiography was obtained using a head coil, and acquisition was oriented in the coronal plane. The diagnosis of intracranial saccular and dissecting aneurysms was based on the findings of MR imaging/angiography, 3-D computed tomographic angiography, and/or digital subtraction angiography. Saccular aneurysms were classified into four locations: anterior cerebral artery, middle cerebral artery, internal carotid artery, and posterior circulation (posterior cerebral, superior cerebellar, anterior inferior cerebellar, posterior inferior cerebellar, basilar, and vertebral artery). Diagnosis of siVAD was made according to the Spontaneous Cervicocephalic Arterial Dissections Study criteria (10). Experienced neuroradiologist (A.U.), blinded to clinical characteristics, evaluated the radiological characteristics. ABI and baPWV – We measured ABI and baPWV at 14 days after the onset or stabilization of the neurological deficit in patients with subarachnoid hemorrhage, at the diagnosis in patients with unruptured cerebral aneurysms, and at the brain checkup in controls using an oscillometric device (Form PWV/ABI; Omron Colin, Tokyo, Japan) (11, 12). The ABI data were obtained after 5 min of rest in the supine position by specially trained
395
Matsukawa et al. laboratory technicians. An ABI of more than 1.4 was identified as non-compressible and excluded from this study because this may lead to false elevation of the ankle pressure. In some patients with diabetes, renal insufficiency, or other diseases causing vascular calcification or Moenckeberg’s medial calcinosis, the vessels at the ankle become non-compressible and the Doppler signal cannot be obliterated even with cuff pressures of more than 300 mm Hg (13, 14). Briefly, pressure waveforms of the brachial and tibial arteries were simultaneously recorded by placing occlusion cuffs connected to a plethysmographic sensor around both the arms and ankles. The time delay (T) of the two waveforms was measured between the feet. The path lengths from the suprasternal notch to the arm (Lb) and from the suprasternal notch to the ankle (La) were automatically calculated by individual height. baPWV was calculated using the following equation: baPWV = (La Lb)/T (m/s). baPWV was measured for an average of 10 s, and the right arm-to-right ankle baPWV was used. The rationale for using baPWV rather than the carotid–femoral PWV was based on the finding that baPWV closely correlates with aortic PWV determined by invasive and non-invasive methods (5, 6). After examinations had been performed on both the right and left sides, we chose the lower ABI and the higher baPWV for analyses (11). Statistical analysis
Statistical analysis was performed using SPSS for Mac (version 21.0; SPSS, Armonk, NY). Variables are expressed as mean standard deviation, median (interquartile range: 25th–75th percentile), or number of patients (%), as appropriate. The chi-square test or Fisher’s exact test was performed for categorical variables as appropriate. The normality of the data was evaluated using the Shapiro–Wilk’s test. Normally distributed continuous variables were compared using Student’s t-test and non-normally distributed variables using the Mann–Whitney U-test. First, we compared the clinical characteristics of patients with intracranial saccular aneurysms and controls, those with intracranial dissecting aneurysms and controls, and those who had cerebral aneurysms with and without subarachnoid hemorrhage. Second, multivariate logistic regression analysis was performed using variables that showed significant differences on univariate analysis. Third, we also compared ABI and baPWV among saccular aneurysm locations by 396
Tukey’s test. Finally, we evaluated the correlation between the number of saccular aneurysms and ABI and baPWV by simple regression analysis. Differences were considered significant at P < 0.05 for a 95% CI. Results
Clinical characteristics of 78 patients with saccular (n = 66) and dissecting (n = 12) aneurysms and controls are shown in Table 1. A significantly higher proportion of patients with saccular aneurysms showed a current smoking and hypertension, and their median baPWV showed a significantly higher level compared with controls’. Median hemoglobin A1c level was lower in patients with dissecting aneurysm than controls’. SAH patients were significantly younger and had a higher glomerular filtration rate and lower levels of total cholesterol and hemoglobin A1c than nonSAH patients’. Other characteristics showed no significant differences among the groups. We performed receiver operating characteristics curve analysis for baPWV, and We would like to ask you to revise as follows: “We performed receiver operating characteristics curve analysis for baPWV, and we selected the baPWV cutoff point (1400 cm/ s) that optimized sensitivity and specificity.”. We performed multivariate logistic regression analysis using variables that were significantly associated with intracranial saccular aneurysms. It shows that hypertension and higher baPWV (>1400 cm/s) are still significantly associated with saccular aneurysms (Table 2). Both ABI and baPWV showed no significant differences among aneurysm locations (Table 3). Simple regression analysis revealed no correlation between the number of saccular aneurysms and ABI (r = 0.064, P = 0.611), and baPWV (r = 0.007, P = 0.956). Discussion
While it is known that atherosclerosis causes various diseases and is especially important as a risk factor for stroke (15, 16), a quantitative comparison of the grade of atherosclerosis between patients with intracranial aneurysms and controls has not yet been reported. The results of the present study showed that baPWV was higher in patients with intracranial saccular aneurysms than controls’, but it showed no significant difference among saccular aneurysm locations. In addition, no significant difference in ABI and baPWV was found between patients with intracranial dissecting aneurysms and controls, and between those who had intracranial saccular or dissecting
baPWV and intracranial saccular aneurysms Table 1 Clinical characteristics of patients with unruptured and ruptured posterior communicating artery aneurysms Saccular aneurysm (+) n = 66
Variables Baseline characteristics Age, years Male Current smoking Alcohol consumption Median body mass index Laboratory data Median GFR Uric acid Total cholesterol LDL cholesterol Median HDL cholesterol Median triglyceride Median glucose Median hemoglobin A1c Past medical history Hypertension Hypercholesterolemia Diabetes mellitus Stroke Ischemic heart disease Familial SAH Median ABI Median baPWV
Dissecting aneurysm
Control n = 66
(+) n = 12
62 22 11 15 23
(14) (33) (17)* (23) (20–24)
62 22 3 7 23
(13) (33) (4.5) (11) (20–25)
55 10 0 3 22
82 5.2 207 121 62 74 97 5.6
(72–93) (1.2) (39) (34) (51–71) (57–116) (89–107) (5.3–5.8)
75 5.4 204 119 59 85 91 5.6
(67–91) (1.2) (32) (26) (51–72) (54–114) (86–102) (5.4–5.9)
79 6.1 195 114 53 117 107 5.5
37 14 5 4 4 6 1.1 1633
(56)** (21) (7.6) (6.1) (6.1) (9.1) (1.1–1.2) (1436–1914)**
18 16 12 0 0 3 1.1 1389
(27) (24) (18)
9 6 1 4 2 4 1.2 1488
(4.6) (1.1–1.2) (1226–1783)
SAH
Control n = 12
(15) (83) (25) (21–25) (59–124) (1.9) (38) (28) (19) (53–227) (94–125) (5.3–5.7)* (75) (50) (8.3) (33) (17) (33) (1.1–1.2) (1208–1787)
(+) n = 26
55 10 0 5 23
(42) (21–28)
56 12 3 8 22
80 6.3 193 111 55 114 101 5.9
(69–94) (1.3) (27) (33) (47–68) (84–152) (96–115) (5.4–6.1)
86 5.3 192 113 55 64 99 5.4
4 1 1 0 0 0 1.1 1534
(10) (83)
(33) (8.3) (8.3)
(1.1–1.2) (1183–1780)
15 3 0 1 2 3 1.1 1538
(18)* (46) (12) (31) (19–25) (82–107)* (1.6) (39)* (32) (48–69) (56–103) (86–114) (5.2–5.7)* (58) (12) (3.8) (7.7) (12) (1.1–1.2) (1346–1802)
( ) n = 52 64 20 8 10 22
(11) (39) (15) (19) (21–24)
79 5.3 212 124 62 88 97 5.6
(66–87) (1.3) (37) (33) (49–74) (57–132) (92–108) (5.4–5.9)
31 17 6 6 4 4 1.1 1630
(59) (33) (12) (12) (7.7) (7.7) (1.1–1.2) (1480–1829)
SD, standard deviation; SAH, subarachnoid hemorrhage. Variables showing significant difference by univariate analysis (*P < 0.05 and **P < 0.0001). Data are expressed as number of patients (%), unless otherwise indicated. Table 2 Multivariate logistic regression analysis for intracranial saccular artery aneurysm Univariate
Multivariate
Variable
OR (95% CI)
P value
OR (95% CI)
P value
Hypertension* baPWV > 1400* Smoking
3.3 (1.6–6.9) 3.6 (1.7–7.7) 4.2 (1.1–16)
