Clinical Investigative Study Central Aortic Pressure and Pulsatility Index in Acute Ischemic Stroke Jeong Yeon Kim, MD, PhD, Cheryl D. Bushnell, MD, MHS, Joong Hyun Park, MD, Seung Min Han, MD, Jin Hee Im, MD, Sang Won Han, MD, Jong Sam Baik, MD, PhD, Jae Hyeon Park, MD, PhD From the Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea (JYK, JHP, SMH, JHI, SWH, JSB, JHP); Department of Neurology, Wake Forest School of Medicine, Winston Salem, NC (CDB).
ABSTRACT BACKGROUND AND PURPOSE
We investigated the relationship between transcranial Doppler (TCD) pulsatility index (PI) and central aortic pressure by measurement of the aortic augmentation index (AIx). METHODS
We enrolled 148 consecutive patients with a diagnosis of acute ischemic stroke. Patients were eligible for the study if they experienced their first ischemic stroke within the preceding 7 days and were 45 years of age or older. At Day 7 (±2) after stroke onset, TCD studies were performed and AIx was measured by applanation tonometry on the same days. RESULTS
The mean age was 66.3 (47–90) years and 37.8% were women. The mean middle cerebral artery (MCA) PI was significantly related with age (r =.361), hypertension (r = .184), peripheral systolic blood pressure (SBP; r = .211), peripheral pulse pressure (PP; r = .396), aortic SBP (r = .184), aortic DBP (r = –.181), and aortic PP (r = .371). The basilar artery (BA) PI was significantly related with age (r = .311), peripheral DBP (r = –.267), peripheral PP (r = .358), aortic DBP (r = –.266), and aortic PP (r = .347). CONCLUSIONS
Keywords: Arterial stiffness, central aortic pressure, ischemic stroke, pulsatility index. Acceptance: Received October 15, 2013. Accepted for publication April 26, 2014. Correspondence: Address correspondence to Sang Won Han, Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine 761–1 Sanggye 7-dong, Nowongu, 139–707, Seoul, Korea. E-mail: [email protected]. Conflicts of Interest: All authors have no conflicts of interest. J Neuroimaging 2014;00:1-5. DOI: 10.1111/jon.12151
TCD PI was significantly related with central aortic pressure, especially PP. The PI in the MCA and BA is closely associated with the pulsatile component of BP in the systemic circulation.
Background and Purpose Aging is associated with the structural and functional changes of the arterial wall, leading to decreased elasticity and increased stiffness.1 Arterial stiffness is accelerated in the presence of diabetes mellitus (DM), hypercholesterolemia, hypertension, and metabolic syndrome. Previous studies show that arterial stiffness is associated with cognitive impairment, the presence of a lacunar infarction, white matter hyperintensities (WMH), and cerebral microbleeds (CMB).2,3 Arterial stiffness is increasingly recognized as an important determinant of cardiovascular (CV) risk and it may be directly involved in the process of atherosclerosis.4–6 Several findings suggest that increased arterial stiffness may be predictive of CV events through an increase in central pulse pressure (PP).1,7 The augmentation index (AIx) is a well-established index of aortic stiffness. Increased AIx and arterial stiffness are associated with several vascular risk factors, including age, smoking, hypertension, DM, and dyslipidemia.4,8 The pulsatility index (PI) is designed to measure vascular resistance and characterizes the shape of the spectral waveform.9
Low PI suggests low-resistance vascular beds with high-diastolic flow and rounded waveforms, whereas high PI suggests highresistance beds with low diastolic flow and peaked waveforms.10 This index becomes elevated with old age, DM, hypertension, intracranial hypertension, vascular dementia, and cerebral small vessel disease (SVD).11,12 The elevated PI in SVD has been postulated to reflect increased downstream vascular resistance in the cerebral circulation. We hypothesized that the transcranial Doppler (TCD) PI would reflect the pulsatile component of systemic blood pressure (BP) which in turn is related to arterial stiffness. In this context, we investigated the relationship between TCD PI and central aortic pressure by measurement of the aortic (AIx) in patients with acute ischemic stroke.
Methods Patient Selection For the study, we enrolled all consecutive patients with a diagnosis of acute ischemic stroke admitted to the Neurology
Copyright
◦ 2014 by the American Society of Neuroimaging C
1
Department at the Sanggye Paik hospital between November 2010 and October 2011. Patients were eligible for the study if they experienced their first ischemic stroke within the preceding 7 days and were 45 years of age or older. The diagnosis required brain CT and/or MRI to exclude hemorrhages and other causes of symptoms. A patient should have at least one vascular imaging, such as conventional angiography, MR angiography (MRA), or CT angiography. Standard systemic investigations performed in every patient included 12lead electrocardiography (ECG), chest x-ray, and blood tests. TCD, carotid duplex sonography, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and 24hour ECG (Holter) monitoring were performed in selected patients. AIx was a part of standard evaluation except in patients with poor systemic conditions such as decreased consciousness or an inability to accept the test. The patients’ demographics, vascular risk factors, and neurologic examination, including the National Institutes of Health stroke scale (NIHSS) score, were collected at baseline. The type of acute ischemic stroke was classified according the Trial of ORG 10172 in the Acute Stroke Treatment (TOAST) classification system, and the criteria were strictly applied.13
Transcranial Doppler At Day 7 (±2) after stroke onset, TCD studies were performed with Companion III (Nicolet Biomedical, Inc., Madison, Wisconsin, USA) according to the respective standardized manual of operations. Doppler signals from the main stem of the middle cerebral artery (MCA) were obtained transtemporally with a traditional 2-MHz transducer at depths of 56, 58, and 60 mm. If data were available for both arteries, the average value was used for analysis. Doppler signals from the basilar artery (BA) were obtained with a 2-MHz transducer below the occiput at depths of 78, 80, and 82 mm. For each artery, the mean, systolic, and diastolic flow velocities were measured. Gosling’s PI was determined as the difference between the peak systolic and end-diastolic velocities divided by the mean flow velocity (mFV) in each artery.14 The TCD PIs in patients with either significant (>50%) stenosis or occlusion of MCA or BA were excluded for the study.
Pulse Wave Analysis AIx was measured by applanation tonometry (SphygmoCor, Atcor, Australia) on the same days the TCD examinations were performed. Applanation tonometry was used to record radial artery pressure waveform continuously, and mean values of two screens of pulse waves were used for analysis. Only high-quality recordings, defined as an in-device quality index ࣙ80% (derived from an algorithm including average pulse height, pulse height variation, diastolic variation, and the maximum rate of rise of the peripheral waveform) and acceptable curves on visual inspection were included in the analysis. On the basis of the collected data, an averaged radial pressure waveform was generated and a corresponding aortic pressure waveform and BP calculated by the validated transfer function (SphygmoCor version 7.1). The aortic pressure waveform was used to calculate the AIx. In addition, since AIx is influenced by heart rate,
2
Journal of Neuroimaging Vol 00 No 0 xxxx 2014
an index normalized for heart rate of 75 bpm (AIx@75) was used.15
Statistical Analysis Data are expressed as the mean ± SD or numbers (%). The baseline characteristics were compared among the groups using a one-way ANOVA. Pearson’s correlation coefficients were calculated to evaluate the correlations of TCD PI with vascular risk factors, aortic pulsatility, and large artery stiffness. Simple and multivariate linear regression models were used to analyze the association of univariate significant variables. A two-sided P-value of .842 and P > .877). For the study, patients classified with cardioembolism (CE), stroke of other determined etiology (SOD), stroke of undetermined etiology incomplete evaluation (SUDi), or SUDm (more than two causes identified) were excluded. A total of 148 patients with largeartery atherosclerosis (LAA, 26), lacune (69), and SUDn (negative work up, 53) were finally enrolled in this study. Table 1 showed the baseline characteristics of the enrolled patients. The mean age was 66.3 (47–90) years and 37.8% were women. Of the 148 patients, 55.4% had a history of hypertension, 29.7% of diabetes, 13.5% of hypercholesterolemia, and 32.4% of current smoking. Brain CT was performed in 81.8% of patients. Brain MRI and diffusion-weighted imaging was performed in 96.6% of patients. All patients had at least one vascular imaging study (MRA in 97.3%, CTA in 2.7%, and cerebral angiography in 1.4%). Echocardiographic studies were performed in 98.2% of patients (TTE in 98.2% and TEE in 9.5%). The subtypes of ischemic stroke were classified and the most frequent stroke subtype was lacune (69, 46.6%), followed by SUDn (53, 35.8%), and LAA, (26, 17.6%). The baseline characteristics were well balanced among the groups. There were no significant differences in these characteristics except baseline NIHSS score (Table 1). Baseline NIHSS score was significantly higher in LAA subtype than lacunar and SUDn (P < .0001). Hemodynamic indices of the enrolled patients were shown in Table 2. There were no significant differences among the groups except AIx. The AIx was significantly higher in lacunar subtype than LAA (33.5% vs. 27.4%, P = .031). Of the 148 patients, 38 patients (25.7%) had poor temporal acoustic windows on one side. The mean MCA PI was significantly related with age (r = .361), hypertension (r =.184), peripheral systolic blood pressure (SBP; r = .211), peripheral PP (r = .396), aortic SBP (r = .184), aortic DBP (r = –.181), and aortic PP (r = .37). The BA PI was significantly related with age (r = .31), peripheral DBP (r = –.267), peripheral PP (r = .358), aortic DBP (r = –.266), and aortic PP (r = .347; Table 3). Multiple linear regression analysis revealed that age (P = .004, β coefficient = .254 in MCA, P = .002, β coefficient = .215 in BA) was significantly associated with increased PI.
Table 1. Baseline Characteristics of the Study Population
Age, years Female Hypertension Diabetes mellitus Hypercholesterolemia Smoking Random plasma glucose, mg/dL Total cholesterol, mg/dL LDL-cholesterol, mg/dL HDL-cholesterol, mg/dL Triglyceride, mg/dL Baseline NIHSS score
Total (n = 148)
LAA (n = 26)
Lacune (n = 69)
SUDn (n = 53)
P
66.3 (10) 56 (37.8) 82 (55.4) 44 (29.7) 20 (13.5) 48 (32.4) 117.9 (48.49) 176.7 (34.84) 114.2 (29.72) 43.7 (11.89) 123.2 (58.56) 2.9 (2.98)
68.3 (8.03) 7 (26.9) 14 (53.8) 5 (19.2) 1 (3.8) 9 (34.6) 131.7 (68.64) 178.2 (27.66) 113.2 (27.2) 46.4 (17.44) 112 (39.46) 5.2 (4.51)
66.7 (9.97) 30 (43.5) 42 (60.9) 22 (31.9) 9 (13) 20 (29) 118.1 (43.17) 173.8 (34.88) 112 (29.01) 42.3 (10.52) 131.84 (63.33) 2.3 (1.63)
64.7 (10.82) 19 (35.8) 26 (49.1) 17 (32.1) 10 (18.9) 19 (35.8) 111.1 (42.34) 179.8 (38.09) 117.6 (31.97) 43.9 (10.17) 117.4 (59.2) 2.5 (2.95)
.287 .31 .422 .435 .183 .7 .208 .624 .582 .367 .227
ABSTRACT BACKGROUND AND PURPOSE
We investigated the relationship between transcranial Doppler (TCD) pulsatility index (PI) and central aortic pressure by measurement of the aortic augmentation index (AIx). METHODS
We enrolled 148 consecutive patients with a diagnosis of acute ischemic stroke. Patients were eligible for the study if they experienced their first ischemic stroke within the preceding 7 days and were 45 years of age or older. At Day 7 (±2) after stroke onset, TCD studies were performed and AIx was measured by applanation tonometry on the same days. RESULTS
The mean age was 66.3 (47–90) years and 37.8% were women. The mean middle cerebral artery (MCA) PI was significantly related with age (r =.361), hypertension (r = .184), peripheral systolic blood pressure (SBP; r = .211), peripheral pulse pressure (PP; r = .396), aortic SBP (r = .184), aortic DBP (r = –.181), and aortic PP (r = .371). The basilar artery (BA) PI was significantly related with age (r = .311), peripheral DBP (r = –.267), peripheral PP (r = .358), aortic DBP (r = –.266), and aortic PP (r = .347). CONCLUSIONS
Keywords: Arterial stiffness, central aortic pressure, ischemic stroke, pulsatility index. Acceptance: Received October 15, 2013. Accepted for publication April 26, 2014. Correspondence: Address correspondence to Sang Won Han, Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine 761–1 Sanggye 7-dong, Nowongu, 139–707, Seoul, Korea. E-mail: [email protected]. Conflicts of Interest: All authors have no conflicts of interest. J Neuroimaging 2014;00:1-5. DOI: 10.1111/jon.12151
TCD PI was significantly related with central aortic pressure, especially PP. The PI in the MCA and BA is closely associated with the pulsatile component of BP in the systemic circulation.
Background and Purpose Aging is associated with the structural and functional changes of the arterial wall, leading to decreased elasticity and increased stiffness.1 Arterial stiffness is accelerated in the presence of diabetes mellitus (DM), hypercholesterolemia, hypertension, and metabolic syndrome. Previous studies show that arterial stiffness is associated with cognitive impairment, the presence of a lacunar infarction, white matter hyperintensities (WMH), and cerebral microbleeds (CMB).2,3 Arterial stiffness is increasingly recognized as an important determinant of cardiovascular (CV) risk and it may be directly involved in the process of atherosclerosis.4–6 Several findings suggest that increased arterial stiffness may be predictive of CV events through an increase in central pulse pressure (PP).1,7 The augmentation index (AIx) is a well-established index of aortic stiffness. Increased AIx and arterial stiffness are associated with several vascular risk factors, including age, smoking, hypertension, DM, and dyslipidemia.4,8 The pulsatility index (PI) is designed to measure vascular resistance and characterizes the shape of the spectral waveform.9
Low PI suggests low-resistance vascular beds with high-diastolic flow and rounded waveforms, whereas high PI suggests highresistance beds with low diastolic flow and peaked waveforms.10 This index becomes elevated with old age, DM, hypertension, intracranial hypertension, vascular dementia, and cerebral small vessel disease (SVD).11,12 The elevated PI in SVD has been postulated to reflect increased downstream vascular resistance in the cerebral circulation. We hypothesized that the transcranial Doppler (TCD) PI would reflect the pulsatile component of systemic blood pressure (BP) which in turn is related to arterial stiffness. In this context, we investigated the relationship between TCD PI and central aortic pressure by measurement of the aortic (AIx) in patients with acute ischemic stroke.
Methods Patient Selection For the study, we enrolled all consecutive patients with a diagnosis of acute ischemic stroke admitted to the Neurology
Copyright
◦ 2014 by the American Society of Neuroimaging C
1
Department at the Sanggye Paik hospital between November 2010 and October 2011. Patients were eligible for the study if they experienced their first ischemic stroke within the preceding 7 days and were 45 years of age or older. The diagnosis required brain CT and/or MRI to exclude hemorrhages and other causes of symptoms. A patient should have at least one vascular imaging, such as conventional angiography, MR angiography (MRA), or CT angiography. Standard systemic investigations performed in every patient included 12lead electrocardiography (ECG), chest x-ray, and blood tests. TCD, carotid duplex sonography, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and 24hour ECG (Holter) monitoring were performed in selected patients. AIx was a part of standard evaluation except in patients with poor systemic conditions such as decreased consciousness or an inability to accept the test. The patients’ demographics, vascular risk factors, and neurologic examination, including the National Institutes of Health stroke scale (NIHSS) score, were collected at baseline. The type of acute ischemic stroke was classified according the Trial of ORG 10172 in the Acute Stroke Treatment (TOAST) classification system, and the criteria were strictly applied.13
Transcranial Doppler At Day 7 (±2) after stroke onset, TCD studies were performed with Companion III (Nicolet Biomedical, Inc., Madison, Wisconsin, USA) according to the respective standardized manual of operations. Doppler signals from the main stem of the middle cerebral artery (MCA) were obtained transtemporally with a traditional 2-MHz transducer at depths of 56, 58, and 60 mm. If data were available for both arteries, the average value was used for analysis. Doppler signals from the basilar artery (BA) were obtained with a 2-MHz transducer below the occiput at depths of 78, 80, and 82 mm. For each artery, the mean, systolic, and diastolic flow velocities were measured. Gosling’s PI was determined as the difference between the peak systolic and end-diastolic velocities divided by the mean flow velocity (mFV) in each artery.14 The TCD PIs in patients with either significant (>50%) stenosis or occlusion of MCA or BA were excluded for the study.
Pulse Wave Analysis AIx was measured by applanation tonometry (SphygmoCor, Atcor, Australia) on the same days the TCD examinations were performed. Applanation tonometry was used to record radial artery pressure waveform continuously, and mean values of two screens of pulse waves were used for analysis. Only high-quality recordings, defined as an in-device quality index ࣙ80% (derived from an algorithm including average pulse height, pulse height variation, diastolic variation, and the maximum rate of rise of the peripheral waveform) and acceptable curves on visual inspection were included in the analysis. On the basis of the collected data, an averaged radial pressure waveform was generated and a corresponding aortic pressure waveform and BP calculated by the validated transfer function (SphygmoCor version 7.1). The aortic pressure waveform was used to calculate the AIx. In addition, since AIx is influenced by heart rate,
2
Journal of Neuroimaging Vol 00 No 0 xxxx 2014
an index normalized for heart rate of 75 bpm (AIx@75) was used.15
Statistical Analysis Data are expressed as the mean ± SD or numbers (%). The baseline characteristics were compared among the groups using a one-way ANOVA. Pearson’s correlation coefficients were calculated to evaluate the correlations of TCD PI with vascular risk factors, aortic pulsatility, and large artery stiffness. Simple and multivariate linear regression models were used to analyze the association of univariate significant variables. A two-sided P-value of .842 and P > .877). For the study, patients classified with cardioembolism (CE), stroke of other determined etiology (SOD), stroke of undetermined etiology incomplete evaluation (SUDi), or SUDm (more than two causes identified) were excluded. A total of 148 patients with largeartery atherosclerosis (LAA, 26), lacune (69), and SUDn (negative work up, 53) were finally enrolled in this study. Table 1 showed the baseline characteristics of the enrolled patients. The mean age was 66.3 (47–90) years and 37.8% were women. Of the 148 patients, 55.4% had a history of hypertension, 29.7% of diabetes, 13.5% of hypercholesterolemia, and 32.4% of current smoking. Brain CT was performed in 81.8% of patients. Brain MRI and diffusion-weighted imaging was performed in 96.6% of patients. All patients had at least one vascular imaging study (MRA in 97.3%, CTA in 2.7%, and cerebral angiography in 1.4%). Echocardiographic studies were performed in 98.2% of patients (TTE in 98.2% and TEE in 9.5%). The subtypes of ischemic stroke were classified and the most frequent stroke subtype was lacune (69, 46.6%), followed by SUDn (53, 35.8%), and LAA, (26, 17.6%). The baseline characteristics were well balanced among the groups. There were no significant differences in these characteristics except baseline NIHSS score (Table 1). Baseline NIHSS score was significantly higher in LAA subtype than lacunar and SUDn (P < .0001). Hemodynamic indices of the enrolled patients were shown in Table 2. There were no significant differences among the groups except AIx. The AIx was significantly higher in lacunar subtype than LAA (33.5% vs. 27.4%, P = .031). Of the 148 patients, 38 patients (25.7%) had poor temporal acoustic windows on one side. The mean MCA PI was significantly related with age (r = .361), hypertension (r =.184), peripheral systolic blood pressure (SBP; r = .211), peripheral PP (r = .396), aortic SBP (r = .184), aortic DBP (r = –.181), and aortic PP (r = .37). The BA PI was significantly related with age (r = .31), peripheral DBP (r = –.267), peripheral PP (r = .358), aortic DBP (r = –.266), and aortic PP (r = .347; Table 3). Multiple linear regression analysis revealed that age (P = .004, β coefficient = .254 in MCA, P = .002, β coefficient = .215 in BA) was significantly associated with increased PI.
Table 1. Baseline Characteristics of the Study Population
Age, years Female Hypertension Diabetes mellitus Hypercholesterolemia Smoking Random plasma glucose, mg/dL Total cholesterol, mg/dL LDL-cholesterol, mg/dL HDL-cholesterol, mg/dL Triglyceride, mg/dL Baseline NIHSS score
Total (n = 148)
LAA (n = 26)
Lacune (n = 69)
SUDn (n = 53)
P
66.3 (10) 56 (37.8) 82 (55.4) 44 (29.7) 20 (13.5) 48 (32.4) 117.9 (48.49) 176.7 (34.84) 114.2 (29.72) 43.7 (11.89) 123.2 (58.56) 2.9 (2.98)
68.3 (8.03) 7 (26.9) 14 (53.8) 5 (19.2) 1 (3.8) 9 (34.6) 131.7 (68.64) 178.2 (27.66) 113.2 (27.2) 46.4 (17.44) 112 (39.46) 5.2 (4.51)
66.7 (9.97) 30 (43.5) 42 (60.9) 22 (31.9) 9 (13) 20 (29) 118.1 (43.17) 173.8 (34.88) 112 (29.01) 42.3 (10.52) 131.84 (63.33) 2.3 (1.63)
64.7 (10.82) 19 (35.8) 26 (49.1) 17 (32.1) 10 (18.9) 19 (35.8) 111.1 (42.34) 179.8 (38.09) 117.6 (31.97) 43.9 (10.17) 117.4 (59.2) 2.5 (2.95)
.287 .31 .422 .435 .183 .7 .208 .624 .582 .367 .227
