Large-vessel correlates of cerebral small-vessel disease
Abstract
Objective:
Our aim was to investigate the relationship of carotid structure and function with MRI markers of cerebral ischemic small-vessel disease.
Methods:
The study comprised 1,800 participants (aged 72.5 ± 4.1 years, 59.4% women) from the 3C-Dijon Study, a population-based, prospective cohort study, who had undergone quantitative brain MRI and carotid ultrasound. We used multivariable logistic and linear regression adjusted for age, sex, and vascular risk factors.
Results:
Presence of carotid plaque and increasing carotid lumen diameter (but not common carotid artery intima-media thickness) were associated with higher prevalence of lacunar infarcts: odds ratio (OR) = 1.60 (95% confidence interval [CI]: 1.09–2.35), p = 0.02 and OR = 1.24 (95% CI: 1.02–1.50), p = 0.03 (by SD increase). Carotid plaque was also associated with large white matter hyperintensity volume (WMHV) (age-specific top quartile of WMHV distribution): OR = 1.32 (95% CI: 1.04–1.67), p = 0.02, independently of vascular risk factors. Increasing Young elastic modulus and higher circumferential wall stress, reflecting augmented carotid stiffness, were associated with increasing WMHV (effect estimate [β] ± standard error: 0.0003 ± 0.0001, p = 0.024; β ± standard error: 0.005 ± 0.002, p = 0.008). Large WMHV was also associated with increasing Young elastic modulus (OR = 1.22 [95% CI: 1.04–1.42], p = 0.01) and with decreasing distensibility coefficient (OR = 0.83 [95% CI: 0.69–0.99], p = 0.04), independently of vascular risk factors. Associations of carotid lumen diameter with lacunar infarcts and of carotid stiffness markers with WMHV were independent of carotid plaque.
Conclusions:
In addition to and independently of carotid plaque, increasing carotid lumen diameter and markers of carotid stiffness were associated with increasing prevalence of lacunar infarcts and increasing WMHV, respectively.
Get full access to this article
View all available purchase options and get full access to this article.
Supplementary Material
File (tables_e-1_to_e-2-methods.doc)
- Download
- 123.00 KB
REFERENCES
1.
Longstreth WT. Brain vascular disease overt and covert. Stroke 2005;36:2062–2063.
2.
Vermeer SE, Longstreth WT, Koudstaal PJ. Silent brain infarcts: a systematic review. Lancet Neurol 2007;6:611–619.
3.
Debette S, Bis JC, Fornage M, et al. Genome-wide association studies of MRI-defined brain infarcts: meta-analysis from the CHARGE Consortium. Stroke 2010;41:210–217.
4.
Fornage M, Debette S, Bis JC, et al. Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium. Ann Neurol 2011;69:928–939.
5.
Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 2010;341:c3666.
6.
Pantoni L, Garcia JH, Gutierrez JA. Cerebral white matter is highly vulnerable to ischemia. Stroke 1996;27:1641–1646.
7.
Shrestha I, Takahashi T, Nomura E, et al. Association between central systolic blood pressure, white matter lesions in cerebral MRI and carotid atherosclerosis. Hypertens Res 2009;32:869–874.
8.
Romero JR, Beiser A, Seshadri S, et al. Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: the Framingham study. Stroke 2009;40:1590–1596.
9.
Manolio TA, Burke GL, O'Leary DH, et al. Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults: the Cardiovascular Health Study. CHS Collaborative Research Group. Arterioscler Thromb Vasc Biol 1999;19:356–365.
10.
3C Study Group. Vascular factors and risk of dementia: design of the Three-City Study and baseline characteristics of the study population. Neuroepidemiology 2003;22:316–325.
11.
Godin O, Dufouil C, Maillard P, et al. White matter lesions as a predictor of depression in the elderly: the 3C-Dijon Study. Biol Psychiatry 2008;63:663–669.
12.
Zhu YC, Tzourio C, Soumare A, Mazoyer B, Dufouil C, Chabriat H. Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study. Stroke 2010;41:2483–2490.
13.
Maillard P, Delcroix N, Crivello F, et al. An automated procedure for the assessment of white matter hyperintensities by multispectral (T1, T2, PD) MRI and an evaluation of its between-centre reproducibility based on two large community databases. Neuroradiology 2008;50:31–42.
14.
Debette S, Courbon D, Leone N, et al. Tea consumption is inversely associated with carotid plaques in women. Arterioscler Thromb Vasc Biol 2008;28:353–359.
15.
Laurent S, Cockcroft J, Van Bortel L, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006;27:2588–2605.
16.
Calvet D, Boutouyrie P, Touze E, Laloux B, Mas JL, Laurent S. Increased stiffness of the carotid wall material in patients with spontaneous cervical artery dissection. Stroke 2004;35:2078–2082.
17.
Van Bortel LM, Spek JJ. Influence of aging on arterial compliance. J Hum Hypertens 1998;12:583–586.
18.
Inoue K, Matsumoto M, Shono T, Toyokawa S, Moriki A. Increased intima media thickness and atherosclerotic plaques in the carotid artery as risk factors for silent brain infarcts. J Stroke Cerebrovasc Dis 2007;16:14–20.
19.
Matsumoto M, Inoue K, Moriki A. Associations of brachial-ankle pulse wave velocity and carotid atherosclerotic lesions with silent cerebral lesions. Hypertens Res 2007;30:767–773.
20.
de Leeuw FE, de Groot JC, Achten E, et al. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 2001;70:9–14.
21.
Fisher CM. Capsular infarcts: the underlying vascular lesions. Arch Neurol 1979;36:65–73.
22.
Benetos A, Laurent S, Hoeks AP, Boutouyrie PH, Safar ME. Arterial alterations with aging and high blood pressure: a noninvasive study of carotid and femoral arteries. Arterioscler Thromb 1993;13:90–97.
23.
Wikstrand J, Wiklund O. Frontiers in cardiovascular science: quantitative measurements of atherosclerotic manifestations in humans. Arterioscler Thromb 1992;12:114–119.
24.
Safar ME, Blacher J, Mourad JJ, London GM. Stiffness of carotid artery wall material and blood pressure in humans: application to antihypertensive therapy and stroke prevention. Stroke 2000;31:782–790.
25.
McEniery CM, Yasmin, Hall IR, Qasem A, Wilkinson IB, Cockcroft JR. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol 2005;46:1753–1760.
26.
Touboul PJ, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness consensus (2004-2006): an update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc Dis 2007;23:75–80.
27.
Bots ML, Hofman A, Grobbee DE. Increased common carotid intima-media thickness: adaptive response or a reflection of atherosclerosis? Findings from the Rotterdam Study. Stroke 1997;28:2442–2447.
28.
Ochi N, Kohara K, Tabara Y, et al. Association of central systolic blood pressure with intracerebral small vessel disease in Japanese. Am J Hypertens 2010;23:889–894.
29.
Kuo HK, Chen CY, Liu HM, et al. Metabolic risks, white matter hyperintensities, and arterial stiffness in high-functioning healthy adults. Int J Cardiol 2010;143:184–191.
30.
Mitchell GF, van Buchem MA, Sigurdsson S, et al. Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility—Reykjavik Study. Brain 2011;134:3398–3407.
31.
Henskens LH, Kroon AA, van Oostenbrugge RJ, et al. Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients. Hypertension 2008;52:1120–1126.
32.
van Elderen SG, Brandts A, Westenberg JJ, et al. Aortic stiffness is associated with cardiac function and cerebral small vessel disease in patients with type 1 diabetes mellitus: assessment by magnetic resonance imaging. Eur Radiol 2010;20:1132–1138.
33.
Schmidt R, Schmidt H, Haybaeck J, et al. Heterogeneity in age-related white matter changes. Acta Neuropathol 2011;122:171–185.
34.
Zieman SJ, Melenovsky V, Kass DA. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol 2005;25:932–943.
35.
Laurent S, Boutouyrie P. Recent advances in arterial stiffness and wave reflection in human hypertension. Hypertension 2007;49:1202–1206.
36.
Briet M, Collin C, Karras A, et al. Arterial remodeling associates with CKD progression. J Am Soc Nephrol 2011;22:967–974.
37.
Hanon O, Haulon S, Lenoir H, et al. Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke 2005;36:2193–2197.
38.
O'Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension 2005;46:200–204.
39.
Laurent S, Briet M, Boutouyrie P. Large and small artery cross-talk and recent morbidity-mortality trials in hypertension. Hypertension 2009;54:388–392.
40.
Safar ME, Blacher J, Jankowski P. Arterial stiffness, pulse pressure, and cardiovascular disease: is it possible to break the vicious circle? Atherosclerosis 2011;218:263–271.
Information & Authors
Information
Published In
Copyright
© 2013 American Academy of Neurology.
Publication History
Received: July 3, 2012
Accepted: October 10, 2012
Published online: January 23, 2013
Published in print: February 12, 2013
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
Study Funding
The 3C-Study is conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the Victor Segalen–Bordeaux II University, and the SanofiSynthélabo Company. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C-Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Fondation Plan Alzheimer, Conseils Régionaux of Bourgogne, Fondation de France, Ministry of Research-INSERM Program “Cohortes et collections de données biologiques,” Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseil Général de la Côte d’or. Dr. Brisset is a recipient of a grant from the Fondation pour la Recherche Médicale. Dr. Debette is a recipient of a “Chaire d’Excellence Junior” grant from the Agence Nationale de la Recherche (ANR). Dr. Tzourio has received fees from the Fondation Plan Alzheimer, the Fondation de Recherche sur l'Hypertension Artérielle, and the ABBOTT Company for participating in scientific committees. He has also received investigator-initiated research funding from the French National Research Agency (ANR) and the Fondation Plan Alzheimer for the 3C-Study.
Authors
Author Contributions
Dr. Marion Brisset: drafting the manuscript, statistical analysis, analysis and interpretation. Dr. Pierre Boutouyrie: critical revision of the manuscript for important intellectual content, study design, acquisition of data. Dr. Fernando Pico: critical revision of the manuscript for important intellectual content. Dr. Yicheng Zhu: critical revision of the manuscript for important intellectual content, acquisition of data. Dr. Mahmoud Zureik: critical revision of the manuscript for important intellectual content. Mrs. Sabrina Schilling: critical revision of the manuscript for important intellectual content, analysis and interpretation. Dr. Carole Dufouil and Dr. Bernard Mazoyer: critical revision of the manuscript for important intellectual content, acquisition of data. Dr. Stéphane Laurent: critical revision of the manuscript for important intellectual content, study design, acquisition of data. Dr. Christophe Tzourio: critical revision of the manuscript for important intellectual content, study design, acquisition of data, study supervision or coordination, obtaining funding. Dr. Stéphanie Debette: drafting/revising the manuscript for content, statistical analysis, study supervision or coordination.
Metrics & Citations
Metrics
Citation information is sourced from Crossref Cited-by service.
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
Cited By
- Intracranial Aneurysms and Cerebral Small Vessel Disease: Is There an Association between Large- and Small-Artery Diseases?, Journal of Clinical Medicine, 13, 19, (5864), (2024).https://doi.org/10.3390/jcm13195864
- Modern understanding of the pathogenetic mechanisms of small vessel disease, INTERNATIONAL NEUROLOGICAL JOURNAL, 19, 8, (266-272), (2024).https://doi.org/10.22141/2224-0713.19.8.2023.1032
- Sex differences in the correlation between white matter hyperintensity and 3-month outcome in acute stroke patients, Heliyon, 10, 9, (e30190), (2024).https://doi.org/10.1016/j.heliyon.2024.e30190
- Atherosclerotic plaque characteristics in extracranial carotid artery may indicate closer association with white matter hyperintensities than intracranial arteries: A CARE-II study, European Journal of Radiology, 170, (111208), (2024).https://doi.org/10.1016/j.ejrad.2023.111208
- Relation between severity of cerebral small vessel disease and pulsatility index of internal carotid artery in small vessel occlusion, Clinical Neurology and Neurosurgery, 237, (108127), (2024).https://doi.org/10.1016/j.clineuro.2024.108127
- Arterial Aging, Blood Pressure, and Brain Damage, Early Vascular Aging (EVA), (393-400), (2024).https://doi.org/10.1016/B978-0-443-15512-3.00030-1
- The Cross-Talk Between the Macro- and the Microcirculation, Early Vascular Aging (EVA), (187-199), (2024).https://doi.org/10.1016/B978-0-443-15512-3.00006-4
- The association of structural versus load-dependent large artery stiffness mechanisms with cerebrovascular damage and cortical atrophy in humans, GeroScience, 46, 6, (5587-5597), (2024).https://doi.org/10.1007/s11357-024-01254-5
- Pathophysiology of Subclinical Brain Damage in Hypertension: Large Artery Disease, Hypertension and Brain Damage, (95-107), (2024).https://doi.org/10.1007/978-3-031-64928-8_7
- Cerebral Small Vessels Disease in Hypertension, Hypertension and Brain Damage, (71-93), (2024).https://doi.org/10.1007/978-3-031-64928-8_6
- See more
Loading...
View Options
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.
If you need immediate support or to place an order, please call or email customer service:
- 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
- 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
- [email protected]
We appreciate your patience during this time and apologize for any inconvenience.