Background and Purpose. Cerebral white matter hyperintensities (WMHs) are regarded as typical MRI expressions of small-vessel disease (SVD) and are common in hypertensive patients. Hypertension induces pathologic changes in macrocirculation and in microcirculation. Changes in microcirculation may lead to SVD of brain and consequently to hypertensive end-organ damage. This damage is regarded the result of interactions between the macrovascular and microvascular levels. We sought to investigate the association of cerebral WMHs with ultrasonographic parameters of cerebral macrocirculation evaluated by carotid duplex ultrasound (CDU) and transcranial doppler (TCD). Subjects and Methods. The study was prospective, cross-sectional and consecutive and included hypertensive patients with brain MRI with WMHs. Patients underwent CDU and TCD. The clinical variables recorded were demographic characteristics (age, gender, race) and vascular risk factors (hypertension, diabetic mellitus, hypercholesterolemia, current smoking, and body mass index). Excluded from the study were patients with history of clinical stroke (including lacunar stroke and hemorrhagic) or transient ischemic attack (either hemispheric or ocular), hemodynamically significant (>50%) extra- or intracranial stenosis, potential sources of cardioembolism, and absent transtemporal windows. WMHs were quantified with the use of a semiquantitative visual rating method. Ultrasound parameters investigated were (1) common carotid artery (CCA) diameter and intima-media thickness, (2) blood flow velocity in the CCA and internal carotid artery (ICA), and (3) blood flow velocity and pulsatility index of middle cerebral artery (MCA). Results. A total of 52 patients fulfilled the study inclusion criteria (mean age years, 54% men, median WMH-score: 20). The only two ultrasound parameters that were independently associated with WMH score in multivariate linear regression models adjusting for demographic characteristics and vascular risk factors were increased mean common carotid artery (CCA) diameter ( , , , %) and increased middle cerebral artery pulsatility index (MCA-PI; , , , %). Among all ultrasound parameters the highest AUC (areas under the receiver operating characteristic curve) were documented for MCA-PI ( , 95% CI = 0.68？0.95, ) and mean CCA diameter ( , 95% CI = 0.67？0.92, ). Conclusions. Our study showed that in hypertensive individuals with brain SVD the extent of structural changes in cerebral microcirculation as reflected by WMHs burden is associated with the following ultrasound parameters of
References
[1]
B. Patel and H. S. Markus, “Magnetic resonance imaging in cerebral small vessel disease and its use as a surrogate disease marker,” International Journal of Stroke, vol. 6, no. 1, pp. 47–59, 2011.
[2]
A. A. Gouw, A. Seewann, W. M. van der Flier et al., “Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 82, no. 2, pp. 126–135, 2011.
[3]
S. E. Vermeer, W. T. Longstreth Jr., and P. J. Koudstaal, “Silent brain infarcts: a systematic review,” The Lancet Neurology, vol. 6, no. 7, pp. 611–619, 2007.
[4]
F. Feihl, L. Liaudet, and B. Waeber, “The macrocirculation and microcirculation of hypertension,” Current Hypertension Reports, vol. 11, no. 3, pp. 182–189, 2009.
[5]
D. E. Grobbee and M. L. Bots, “Carotid artery intima-media thickness as an indicator of generalized atherosclerosis,” Journal of Internal Medicine, vol. 236, no. 5, pp. 567–573, 1994.
[6]
A. E. Roher, Z. Garami, A. V. Alexandrov et al., “Interaction of cardiovascular disease and neurodegeneration: transcranial Doppler ultrasonography and Alzheimer's disease,” Neurological Research, vol. 28, no. 6, pp. 672–678, 2006.
[7]
A. Kearney-Schwartz, P. Rossignol, S. Bracard et al., “Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints,” Stroke, vol. 40, no. 4, pp. 1229–1236, 2009.
[8]
S. D. Shenkin, M. E. Bastin, T. J. MacGillivray et al., “Carotid intima-media thickness and cerebrovascular disease in community-dwelling older people without stroke,” Stroke, vol. 41, no. 9, pp. 2083–2086, 2010.
[9]
C. S. Kidwell, S. El-Saden, Z. Livshits, N. A. Martin, T. C. Glenn, and J. L. Saver, “Transcranial Doppler pulsatility indices as a measure of diffuse small-vessel disease,” Journal of Neuroimaging, vol. 11, no. 3, pp. 229–235, 2001.
[10]
M. Kurata, T. Okura, S. Watanabe, and J. Higaki, “Association between carotid hemodynamics and asymptomatic white and gray matter lesions in patients with essential hypertension,” Hypertension Research, vol. 28, no. 10, pp. 797–803, 2005.
[11]
G. Tsivgoulis, E. Stamboulis, V. K. Sharma et al., “Multicenter external validation of the ABCD2 score in triaging TIA patients,” Neurology, vol. 74, no. 17, pp. 1351–1357, 2010.
[12]
J. Heliopoulos, K. Vadikolias, P. Mitsias et al., “A three-dimensional ultrasonographic quantitative analysis of non-ulcerated carotid plaque morphology in symptomatic and asymptomatic carotid stenosis,” Atherosclerosis, vol. 198, no. 1, pp. 129–135, 2008.
[13]
D. Leys, H. Hénon, and F. Pasquier, “White matter changes and poststroke dementia,” Dementia and Geriatric Cognitive Disorders, vol. 9, supplement 1, pp. 25–29, 1998.
[14]
K. M. Vadikolias, N. D. Artemis, P. D. Mitsias et al., “Evaluation of the stability of blood flow over time in the dominant hemisphere: a functional transcranial Doppler study,” Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. 11, pp. 1870–1877, 2007.
[15]
I. Heliopoulos, M. Papaoiakim, G. Tsivgoulis et al., “Common carotid intima media thickness as a marker of clinical severity in patients with symptomatic extracranial carotid artery stenosis,” Clinical Neurology and Neurosurgery, vol. 111, no. 3, pp. 246–250, 2009.
[16]
E. G. Grant, C. B. Benson, G. L. Moneta et al., “Carotid artery stenosis: gray-scale and Doppler US diagnosis—Society of Radiologists in Ultrasound Consensus Conference,” Radiology, vol. 229, no. 2, pp. 340–346, 2003.
[17]
M. G. Veller, C. M. Fisher, A. N. Nicolaides et al., “Measurement of the ultrasonic intima-media complex thickness in normal subjects,” Journal of Vascular Surgery, vol. 17, no. 4, pp. 719–725, 1993.
[18]
Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) Trail Investigators, “Stroke outcomes and neuroimaging of intracranial atherosclerosis (SONIA): design of a prospective, multicenter trial of diagnostic tests,” Neuroepidemiology, vol. 23, no. 1-2, pp. 23–32, 2004.
[19]
B. C. Astor, A. R. Sharrett, J. Coresh, L. E. Chambless, and B. A. Wasserman, “Remodeling of carotid arteries detected with MR imaging: atherosclerosis risk in communities carotid MRI study,” Radiology, vol. 256, no. 3, pp. 879–886, 2010.
[20]
J. F. Polak, R. A. Kronmal, G. S. Tell et al., “Compensatory increase in common carotid artery diameter. Relation to blood pressure and artery intima-media thickness in older adults. Cardiovascular Health Study,” Stroke, vol. 27, no. 11, pp. 2012–2015, 1996.
[21]
H. Masuda, Y. J. Zhuang, T. M. Singh et al., “Adaptive remodeling of internal elastic lamina and endothelial lining during flow-induced arterial enlargement,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 10, pp. 2298–2307, 1999.
[22]
M. Czosnyka, H. K. Richards, H. E. Whitehouse, and J. D. Pickard, “Relationship between transcranial Doppler-determined pulsatility index and cerebrovascular resistance: an experimental study,” Journal of Neurosurgery, vol. 84, no. 1, pp. 79–84, 1996.
[23]
F. M. Faraci and D. D. Heistad, “Regulation of large cerebral arteries and cerebral microsvascular pressure,” Circulation Research, vol. 66, no. 1, pp. 8–17, 1990.
[24]
S. Fujishima, Y. Ohya, H. Sugimori et al., “Transcranial Doppler sonography and ambulatory blood pressure monitoring in patients with hypertension,” Hypertension Research, vol. 24, no. 4, pp. 345–351, 2001.
[25]
M. F. O'Rourke and M. E. Safar, “Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy,” Hypertension, vol. 46, no. 1, pp. 200–204, 2005.
[26]
T. Takahashi, T. Murata, K. Narita et al., “Multifractal analysis of deep white matter microstructural changes on MRI in relation to early-stage atherosclerosis,” NeuroImage, vol. 32, no. 3, pp. 1158–1166, 2006.
[27]
D. M. O. Pruissen, S. A. M. Gerritsen, T. J. Prinsen et al., “Carotid intima-media thickness is different in large- and small-vessel ischemic stroke: the SMART study,” Stroke, vol. 38, no. 4, pp. 1371–1373, 2007.
[28]
K. N. Vemmos, G. Tsivgoulis, K. Spengos et al., “Common carotid artery intima-media thickness in patients with brain infarction and intracerebral haemorrhage,” Cerebrovascular Diseases, vol. 17, no. 4, pp. 280–286, 2004.
