Background: Cerebral small vessel diseases, including silent lacunar infarcts, white matter hyperintensities, and microbleeds, pose a risk for cerebrovascular disease, cognitive impairment, and the geriatric syndrome via effects on arterial stiffness. However, the vascular, physiological, and metabolic roles of arterial stiffness in cerebral small vessel diseases remain unclear. Summary: Arterial stiffness can be assessed using various indicators such as the ankle-brachial index, pulse wave velocity, cardio-ankle vascular index, and augmentation index. Arterial stiffness is independently associated with all components of cerebral small vessel disease including silent lacunar infarcts, white matter hyperintensities, and microbleeds, although there are some methodological differences between the various surrogate markers. Evidence of arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. Further, vascular narrowing due to atherosclerosis and vascular stiffness due to lipohyalinosis can accelerate the pulse waves. This hemodynamic stress, pulsatile pressure, or blood pressure variability can cause a ‘tsunami effect' towards the cerebral parenchyma and lead to cerebral small vessel disease. Previous studies have shown that silent lacunar infarcts and white matter hyperintensities are strongly associated with arterial stiffness. However, the association between microbleeds and arterial stiffness remains controversial, as there are two vessel mechanisms related to microbleeds: cerebral amyloid angiopathy and hypertensive small vessel disease. Key Messages: Cerebral small vessel disease with associated arterial stiffness is a risk factor for silent cerebral lesions, stroke, and cognitive impairment. Improvement of the living environment, management of risk factors, and innovation and development of novel drugs that improve arterial stiffness may suppress the progression of cerebral small vessel disease, and may reduce the risk for stroke and dementia.

1.
Wardlaw JM, Smith EE, Biessels GJ, et al; Standards for Reporting Vascular Changes on Neuroimaging (STRIVE v1): Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013;12:822-838.
2.
Pantoni L: Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010;9:689-701.
3.
Saji N, Kimura K, Kawarai T, Shimizu H, Kita Y: Arterial stiffness and progressive neurological deficit in patients with acute deep subcortical infarction. Stroke 2012;43:3088-3090.
4.
Lin CH, Chou CY, Liu CS, Huang CY, Li TC, Lin CC: Association between frailty and subclinical peripheral vascular disease in a community-dwelling geriatric population: Taichung Community Health Study for Elders. Geriatr Gerontol Int 2015;15:261-267.
5.
Kuroiwa Y, Miyano I, Nishinaga M, Takata J, Shimizu Y, Okumiya K, Matsubayashi K, Ozawa T, Kitaoka H, Doi Y, Yasuda N: Association between level of brachial-ankle pulse wave velocity and onset of activities of daily living impairment in community-dwelling older individuals. Geriatr Gerontol Int 2015;15:840-847.
6.
Saji N, Kimura K, Ohsaka G, Higashi Y, Teramoto Y, Usui M, Kita Y: Functional independence measure scores predict level of long-term care required by patients after stroke: a multicenter retrospective cohort study. Disabil Rehabil 2015;37:331-337.
7.
Takashima N, Turin TC, Matsui K, Rumana N, Nakamura Y, Kadota A, Saito Y, Sugihara H, Morita Y, Ichikawa M, Hirose K, Kawakani K, Hamajima N, Miura K, Ueshima H, Kita Y: The relationship of brachial-ankle pulse wave velocity to future cardiovascular disease events in the general Japanese population: the Takashima Study. J Hum Hypertens 2014;28:323-327.
8.
Kim J, Song TJ, Song D, Lee KJ, Kim EH, Lee HS, Nam CM, Nam HS, Kim YD, Heo JH: Brachial-ankle pulse wave velocity is a strong predictor for mortality in patients with acute stroke. Hypertension 2014;64:240-246.
9.
Gronewold J, Hermann DM, Lehmann N, Kröger K, Lauterbach K, Berger K, Weimar C, Kälsch HIM, Moebus S, Jöckel KH, Bauer M, Erbel R; Heinz Nixdorf Recall Study Investigative Group: Ankle-brachial index predicts stroke in the general population in addition to classical risk factors. Atherosclerosis 2014;233:545-550.
10.
Yukutake T, Yamada M, Fukutani N, Nishiguchi S, Kayama H, Tanigawa T, Adachi D, Hotta T, Morino S, Tashiro Y, Aoyama T, Arai H: Arterial stiffness predicts cognitive decline in Japanese community-dwelling elderly subjects: a one-year follow-up study. J Atheroscler Thromb 2015;22:637-644.
11.
Taniguchi Y, Fujiwara Y, Nofuji Y, Nishi M, Murayama H, Seino S, Tajima R, Matsuyama Y, Shinkai S: Prospective study of arterial stiffness and subsequent cognitive decline among community-dwelling older Japanese. J Epidemiol 2015;25:592-599.
12.
Scuteri A, Wang H: Pulse wave velocity as a marker of cognitive impairment in the elderly. J Alzheimers Dis 2014;42(suppl 4):S401-S410.
13.
Gutierrez J, Marshall RS, Lazar RM: Indirect measures of arterial stiffness and cognitive performance in individuals without traditional vascular risk factors or disease. JAMA Neurol 2015;72:309-315.
14.
Zhong W, Cruickshanks KJ, Schubert CR, Carlsson CM, Chappell RJ, Klein BE, Klein R, Acher CW: Pulse wave velocity and cognitive function in older adults. Alzheimer Dis Assoc Disord 2014;28:44-49.
15.
Hughes TM, Kuller LH, Barinas-Mitchell EJ, Mackey RH, McDade EM, Klunk WE, Aizenstein HJ, Cohen AD, Snitz BE, Mathis CA, Dekosky ST, Lopez OL: Pulse wave velocity is associated with β-amyloid deposition in the brains of very elderly adults. Neurology 2013;81:1711-1718.
16.
Yamashina A, Tomiyama H, Takeda K, Tsuda H, Arai T, Hirose K, Koji Y, Hori S, Yamamoto Y: Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertens Res 2002;25:359-364.
17.
Shirai K, Hiruta N, Song M, Kurosu T, Suzuki J, Tomaru T, Miyashita Y, Saiki A, Takahashi M, Suzuki K, Takata M: Cardia-ankle vascular index (CAVI) as a novel indicator of arterial stiffness: theory, evidence and perspectives. J Atheroscler Thromb 2011;18:924-938.
18.
Saji N, Kimura K, Yagita Y, Kawarai T, Shimizu H, Kita Y: Comparison of arteriosclerotic indicators in patients with ischemic stroke: ankle-brachial index, brachial-ankle pulse wave velocity, and cardio-ankle vascular index. Hypertens Res 2015;38:323-328.
19.
Saji N, Shimizu H, Kawarai T, Tadano M, Kita Y, Yokono K: Increased brachial-ankle pulse wave velocity is independently associated with white matter hyperintensities. Neuroepidemiology 2011;36:252-257.
20.
Saji N, Kimura K, Shimizu H, Kita Y: Silent brain infarct is independently associated with arterial stiffness indicated by cardio-ankle vascular index (CAVI). Hypertens Res 2012;35:756-760.
21.
Saji N, Kimura K, Yagita Y, Uemura J, Aoki J, Sato T, Sakurai T: Deep cerebral microbleeds and chronic kidney disease in patients with acute lacunar infarcts. J Stroke Cerebrovasc Dis 2015;11:2572-2579.
22.
Saji N, Shimizu H, Kawarai T, Tadano M, Kita Y, Yokono K: Clinical features of a first-ever lacunar infarction in Japanese patients: poor outcome in females. J Stroke Cerebrovasc Dis 2011;20:231-235.
23.
Lau KK, Wong YK, Chan YH, Teo KC, Chan KH, Wai Li LS, Cheung RT, Siu CW, Ho SL, Tse HF: Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases: relationships and comparisons with vascular markers of atherosclerosis. Atherosclerosis 2014;235:230-235.
24.
Tzourio C, Laurent S, Debette S: Is hypertension associated with an accelerated aging of the brain? Hypertension 2014;63:894-890.
25.
Saji N, Kimura K, Shimizu H, Kita Y: Association between silent brain infarct and arterial stiffness indicated by brachial-ankle pulse wave velocity. Intern Med 2012;51:1003-1008.
26.
Seo WK, Lee JM, Park MH, Park KW, Lee DH: Cerebral microbleeds are independently associated with arterial stiffness in stroke patients. Cerebrovasc Dis 2008;26:618-623.
27.
van Sloten TT, Protogerou AD, Henry RM, Schram MT, Launer LJ, Stehouwer CD: Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: a systematic review and meta-analysis. Neurosci Biobehav Rev 2015;53:121-130.
28.
Saji N, Sato T, Sakuta K, Aoki J, Kobayashi K, Matsumoto N, Uemura J, Shibazaki K, Kimura K: Chronic kidney disease is an independent predictor of adverse clinical outcomes in patients with recent small subcortical infarcts. Cerebrovasc Dis Extra 2014;4:174-181.
29.
Tomimoto H: Subcortical vascular dementia. Neurosci Res 2011;71:193-199.
30.
Arai H, Ouchi Y, Toba K, Endo T, Shimokado K, Tsubota K, Matsuo S, Mori H, Yumura W, Yokode M, Rakugi H, Ohshima S: Japan as the front-runner of super-aged societies: perspectives from medicine and medical care in Japan. Geriatr Gerontol Int 2015;15:673-687.
31.
Fazekas F, Kleinert R, Offenbacher H, Payer F, Schmidt R, Kleinert G, Radner H, Lechner H: The morphologic correlate of incidental punctate white matter hyperintensities on MR images. AJNR Am J Neuroradiol 1991;12:915-921.
32.
O'Rourke MF, Hashimoto J: Mechanical factors in arterial aging: a clinical perspective. J Am Coll Cardiol 2007;50:1-13.
33.
Saji N, Ogama N, Toba K, Sakurai T: White matter hyperintensities and the geriatric syndrome: an important role of arterial stiffness. Geriatr Gerontol lnt 2015;15(suppl 1):17-25.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.