Skip to main content

Blood-Borne Biomarkers of Hypertension Predicting Hemorrhagic and Ischemic Stroke

  • Protocol
  • First Online:
Stroke Biomarkers

Abstract

Arterial hypertension is the most prevalent noncommunicable disease worldwide and has long been recognized as a major risk factor for stroke, cognitive decline, and dementia. The main goal for prevention is to identify high-risk patients, targeting the modifiable risk factors, and among these, hypertension is the most powerful one. Screening for subclinical brain deterioration is rarely performed because it requires very expensive and not widely available neuroimaging techniques. The main challenge is to detect asymptomatic brain lesions with noninvasive and cost-effective techniques that can be easily performed and interpreted for widespread screening in the community. In this chapter we present an update on the status of blood-based biomarkers explored as alternatives for early detection of brain damage in neurologically asymptomatic subjects (community studies, arterial hypertension, diabetes mellitus, and elderly individuals) and longitudinal studies to explore their value as long-term predictors of incident acute cerebrovascular events. This would undoubtedly have a very positive effect for primary stroke prevention. Numerous blood biomarkers have been investigated with very controversial results. Nevertheless, blood-based brain-specific biomarkers are beginning to stand out in this field and will probably be able to offer much more in the future for the detection of asymptomatic CSVD and in the long-term prediction of acute cerebrovascular events, due to the fact that they can more directly represent what is occurring in the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Feigin VL, Roth GA, Naghavi M et al (2016) Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Neurol 15(9):913–924

    PubMed  Google Scholar 

  2. Ministerio de Salud Pública (2018) Anuario Estadístico de Salud de la República de Cuba. Ministerio de Salud Pública, Habana. http://bvscuba.sld.cu/anuario-estadistico-de-cuba/

    Google Scholar 

  3. Spence JD (2018) Stroke prevention: editorial to accompany June issue of SVN. Stroke Vasc Neurol 3:e000171

    Google Scholar 

  4. Yu J-G, Zhou R-R, Cai G-J (2011) From hypertension to stroke: mechanisms and potential prevention strategies. CNS Neurosci Ther 17(5):577–584. https://doi.org/10.1111/j.1755-5949.2011.00264.x46

    Article  PubMed  PubMed Central  Google Scholar 

  5. Yoon SS, Fryar CD, Carroll MD (2015) Hypertension prevalence and control among adults: United States, 2011–2014. NCHS Data Brief no. 220. National Center for Health Statistics, Hyattsville, MD

    Google Scholar 

  6. Bonet Gorbea M, Varona Pérez P (2015) Encuesta Nacional de factores de riesgo y actividades preventivas de enfermedades no transmisibles. Cuba 2010–2011. Editorial Ciencias Médicas, Havana, pp 140–165. http://www.bvs.sld.cu/libros/encuesta_nacional_riesgo/hipertension.pdf

    Google Scholar 

  7. Whelton PK, Carey RM, Aronow WS et al (2018) 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. J Am Coll Cardiol 71(6):1269–1324. https://doi.org/10.1016/j.jacc.2017.11.006

    Article  CAS  Google Scholar 

  8. Scuteri A (2012) Brain injury as end-organ damage in hypertension. Lancet Neurol 11(12):1015–1017

    PubMed  Google Scholar 

  9. Sierra C, López-Soto A, Coca A (2011) Connecting cerebral white matter lesions and hypertensive target organ damage. J Aging Res 2011:438978. https://doi.org/10.4061/2011/438978

    Article  PubMed  PubMed Central  Google Scholar 

  10. González-García S, Hernández-Díaz Z, Quevedo-Sotolongo L, Peña-Sánchez M, Pino Peña Y, Fernández-Carriera R et al (2014) Resistive cerebral blood flow as a potential marker of subclinical brain damage in essential hypertension. World J Cardiovasc Dis 4(4):169–178

    Google Scholar 

  11. Henskens LH, van Oostenbrugge RJ, Kroon AA, Hofman PA, Lodder J, de Leeuw PW (2009) Detection of silent cerebrovascular disease refines risk stratification of hypertensive patients. J Hypertens 27(4):846–853

    CAS  PubMed  Google Scholar 

  12. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M et al (2013) 2013 ESH/ESC guidelines for the management of arterial HT: the task force for the management of arterial HT of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 31(7):1281–1357

    CAS  PubMed  Google Scholar 

  13. Longstreth WT Jr, Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR (1998) Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the cardiovascular Health Study. Arch Neurol 55(9):1217–1225

    PubMed  Google Scholar 

  14. Longstreth WT, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA et al (1996) Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke 27(8):1274–1282

    PubMed  Google Scholar 

  15. Sierra C (2014) Essential hypertension, cerebral white matter pathology and ischemic stroke. Curr Med Chem 21(19):2156–2164

    CAS  PubMed  Google Scholar 

  16. Liao D, Cooper L, Cai J, Toole JF, Bryan NR, Hutchinson RG et al (1996) Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control. The ARIC study. Stroke 27(12):2262–2270

    CAS  PubMed  Google Scholar 

  17. de Leeuw FE, De Groot JC, Oudkerk M, Witteman JC, Hofman A, van Gijn J, Breteler MM (2002) Hypertension and cerebral WML in a prospective cohort study. Brain 125:765–772

    PubMed  Google Scholar 

  18. van Boxtel M, Henskens LH, Kroon AA, Hofman PA, Gronenschild EH, Jolles J et al (2006) Ambulatory blood pressure, asymptomatic cerebrovascular damage and cognitive function in essential hypertension. J Hum Hypertens 20(1):5–13

    PubMed  Google Scholar 

  19. Gottesman RF, Coresh J, Catellier DJ, Sharrett AR, Rose KM, Coker LH et al (2010) Blood pressure and white-matter disease progression in a biethnic cohort: Atherosclerosis Risk in Communities (ARIC) study. Stroke 41(1):3–8

    PubMed  Google Scholar 

  20. Vermeer SE, Longstreth WT Jr, Koudstaal PJ (2007) Silent brain infarcts: a systematic review. Lancet Neurol 6(7):611–619

    PubMed  Google Scholar 

  21. Sanahuja J, Alonso A, Diez J, Ortega E, Rubinat E, Traveset A et al (2016) Increased burden of cerebral small vessel disease in patients with type 2 diabetes and retinopathy. Diabetes Care 39(9):1614–1620. https://doi.org/10.2337/dc15-2671

    Article  PubMed  Google Scholar 

  22. Rincon F, Wright CB (2014) Current pathophysiological concepts in cerebral small vessel disease. Front Aging Neurosci 6:24

    PubMed  PubMed Central  Google Scholar 

  23. Shi Y, Wardlaw JM (2016) Update on cerebral small vessel disease: a dynamic whole-brain disease. Stroke Vasc Neurol 1(3):83–92. https://doi.org/10.1136/svn-2016-000035

    Article  PubMed  PubMed Central  Google Scholar 

  24. Prabhakaran S, Wright CB, Yoshita M, Delapaz R, Brown T, De Carli C et al (2008) Prevalence and determinants of subclinical brain infarction: the Northern Manhattan Study. Neurology 70(6):425–430

    CAS  PubMed  Google Scholar 

  25. Sierra C (2011) Associations between ambulatory blood pressure parameters and cerebral white matter lesions. Int J Hypertens 2011:478710. https://doi.org/10.4061/2011/478710

    Article  PubMed  PubMed Central  Google Scholar 

  26. Cheung CY, Tay WT, Mitchell P, Wang JJ, Hsu W, Lee ML et al (2011) Quantitative and qualitative retinal microvascular characteristics and blood pressure. J Hypertens 29(7):1380–1391

    CAS  PubMed  Google Scholar 

  27. Grassi G, Schmieder RE (2011) The renaissance of the retinal microvascular network assessment in hypertension: new challenges. J Hypertens 29(7):1289–1291

    CAS  PubMed  Google Scholar 

  28. Brown Martínez M, Valdés-González Y, GonzálezOrtiz E, Hernández-González G, Valdés Sosa P, Galán García L et al (2014) Use of electroencephalography to identify asymptomatic cerebrovascular lesions among hypertensives. Rev Cubana Invest Bioméd 33:231–240

    Google Scholar 

  29. Hernández-González G, Bringas-Vega ML, Galán-García L et al (2011) Multimodal quantitative neuroimaging databases and methods: the Cuban Brain Mapping Project. Clin EEG Neurosci 42(3):149–159

    PubMed  Google Scholar 

  30. Heliopoulos I, Artemis D, Vadikolias K, Tripsianis G, Piperidou C, Tsivgoulis G (2012) Association of ultrasonographic parameters with subclinical white-matter hyperintensities in hypertensive patients. Cardiovasc Psychiatry Neurol 2012:616572

    PubMed  PubMed Central  Google Scholar 

  31. Kurata M, Okura T, Watanabe S, Higaki J (2005) Association between carotid hemodynamics and asymptomatic white and gray matter lesions in patients with essential hypertension. Hypertens Res 28(10):797–803

    PubMed  Google Scholar 

  32. Appel J, Potter E, Bhatia N, Shen Q, Zhao W, Greig MT (2009) Association of white matter hyperintensity measurements on brain MR imaging with cognitive status, medial temporal atrophy, and cardiovascular risk factors. Am J Neuroradiol 30:1870–1876

    CAS  PubMed  Google Scholar 

  33. Van Dijk EJ, Prins ND, Vrooman HA et al (2008) Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study. Stroke 39(10):2712–2719

    PubMed  Google Scholar 

  34. Pikula A, Beiser AS, DeCarli C et al (2012) Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the Framingham Offspring Study. Circulation 125(17):2100–2107

    CAS  PubMed  PubMed Central  Google Scholar 

  35. González-Quevedo A, González-García S, Hernández-Díaz Z et al (2016) Serum neuron specific enolase could predict subclinical brain damage and the subsequent occurrence of brain related vascular events during follow up in essential hypertension. J Neurol Sci 363:158–163

    PubMed  Google Scholar 

  36. Shoamanesh A, Preis SR, Beiser AS et al (2016) Circulating biomarkers and incident ischemic stroke in the Framingham Offspring Study. Neurology 87:1206–1211

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Shoamanesh A, Preis SR, Beiser AS et al (2015) Inflammatory biomarkers, cerebral microbleeds and small vessel disease. Framingham Heart Study. Neurology 84(8):825–832

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Moody DM, Brown WR, Challa VR, Anderson RL (1995) Periventricular venous collagenosis: association with leukoaraiosis. Radiology 194(2):469–476

    CAS  PubMed  Google Scholar 

  39. Wardlaw JM, Smith EE, Biessels GJ et al (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 12(8):822–838

    PubMed  PubMed Central  Google Scholar 

  40. Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9(7):689–701

    PubMed  Google Scholar 

  41. Rensma SP, van Sloten TT, Launer LJ, Stehouwer CDA (2018) Cerebral small vessel disease and risk of incident stroke, dementia and depression, and all-cause mortality: a systematic review and meta-analysis. Neurosci Biobehav Rev 90:164–173

    PubMed  PubMed Central  Google Scholar 

  42. Zhang CE, Wong SM, van de Haar FJ et al (2017) Blood–brain barrier leakage is more widespread in patients with cerebral small vessel disease. Neurology 88:1–7

    Google Scholar 

  43. Teng Z, Dong Y, Zhang D et al (2017) Cerebral small vessel disease and post-stroke cognitive impairment. Int J Neurosci 127(9):824–830

    PubMed  Google Scholar 

  44. Kern KC, Wright CB, Bergfield KL et al (2017) Blood pressure control in aging predicts cerebral atrophy related to small-vessel white matter lesions. Front Aging Neurosci 9:132

    PubMed  PubMed Central  Google Scholar 

  45. de Leeuw FE, de Groot JC, Achten E et al (2001) Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 70(1):9–14

    PubMed  PubMed Central  Google Scholar 

  46. Lin Q, Huang W-Q, Ma Q-L et al (2017) Incidence and risk factors of leukoaraiosis from 4683 hospitalized patients: a cross-sectional study. Med Baltim 96(39):e7682

    Google Scholar 

  47. Birns J, Jarosz J, Markus HS, Kalra L (2009) Cerebrovascular reactivity and dynamic autoregulation in ischaemic subcortical white matter disease. J Neurol Neurosurg Psychiatry 80(10):1093–1098

    CAS  PubMed  Google Scholar 

  48. de Groot JC, de Leeuw FE, Oudkerk M et al (2001) Cerebral white matter lesions and subjective cognitive dysfunction: the Rotterdam Scan Study. Neurology 56(11):1539–1545. http://www.ncbi.nlm.nih.gov/pubmed/11402112

    PubMed  Google Scholar 

  49. Jung S, Mono ML, Findling O et al (2012) White matter lesions and intra-arterial thrombolysis. J Neurol 259(7):1331–1336. https://doi.org/10.1007/s00415-011-6352-y

    Article  PubMed  Google Scholar 

  50. Vernooij MW, Ikram MA, Tanghe HL et al (2007) Incidental findings on brain MRI in the general population. N Engl J Med 357(18):1821–1828. https://doi.org/10.1056/NEJMoa070972

    Article  CAS  PubMed  Google Scholar 

  51. Pantoni L, Garcia JH (1995) The significance of cerebral white matter abnormalities 100 years after Binswanger’s report. A review. Stroke 26(7):1293–1301

    CAS  PubMed  Google Scholar 

  52. Mok V, Kim JS (2015) Prevention and management of cerebral small vessel disease. J Stroke 17(2):111–122. https://doi.org/10.5853/jos.2015.17.2.111

    Article  PubMed  PubMed Central  Google Scholar 

  53. Faraco G, Iadecola C (2013) Hypertension: a harbinger of stroke and dementia. Hypertens (Dallas, TX 1979) 62(5):810–817. https://doi.org/10.1161/HYPERTENSIONAHA.113.01063

    Article  CAS  Google Scholar 

  54. Manschot SM, Brands AMA, van der Grond J et al (2006) Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes. Diabetes 55(4):1106–1113

    CAS  PubMed  Google Scholar 

  55. van Harten B, Oosterman JM, Potter van Loon B-J, Scheltens P, Weinstein HC (2007) Brain lesions on MRI in elderly patients with type 2 diabetes mellitus. Eur Neurol 57(2):70–74. https://doi.org/10.1159/000098054

    Article  PubMed  Google Scholar 

  56. Taylor WD, MacFall JR, Provenzale JM et al (2003) Serial MR imaging of volumes of hyperintense white matter lesions in elderly patients: correlation with vascular risk factors. AJR Am J Roentgenol 181(2):571–576. https://doi.org/10.2214/ajr.181.2.1810571

    Article  PubMed  Google Scholar 

  57. Potter GM, Doubal FN, Jackson CA et al (2015) Enlarged perivascular spaces and cerebral small vessel disease. Int J Stroke 10(3):376–381. https://doi.org/10.1111/ijs.12054

    Article  PubMed  Google Scholar 

  58. Yang S, Qin W, Yang L et al (2017) The relationship between ambulatory blood pressure variability and enlarged perivascular spaces: a cross-sectional study. BMJ Open 7(8):e015719. https://doi.org/10.1136/bmjopen-2016-015719

    Article  PubMed  PubMed Central  Google Scholar 

  59. Iadecola C (2013) The pathobiology of vascular dementia. Neuron 80(4):844–866. https://doi.org/10.1016/j.neuron.2013.10.008

    Article  CAS  PubMed  Google Scholar 

  60. Wallin A, Ohrfelt A, Bjerke M (2012) Characteristic clinical presentation and CSF biomarker pattern in cerebral small vessel disease. J Neurol Sci 322(1–2):192–196. https://doi.org/10.1016/j.jns.2012.07.068

    Article  CAS  PubMed  Google Scholar 

  61. Wardlaw JM (2010) Blood-brain barrier and cerebral small vessel disease. J Neurol Sci 299(1–2):66–71. https://doi.org/10.1016/j.jns.2010.08.042

    Article  CAS  PubMed  Google Scholar 

  62. Doubal FN, MacLullich AMJ, Ferguson KJ et al (2010) Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke 41(3):450–454. https://doi.org/10.1161/STROKEAHA.109.564914

    Article  PubMed  Google Scholar 

  63. Li Y, Liu N, Huang Y et al (2016) Risk factors for silent lacunar infarction in patients with transient ischemic attack. Med Sci Monit 22:447–453. http://www.ncbi.nlm.nih.gov/pubmed/26864634

    PubMed  PubMed Central  Google Scholar 

  64. Launer LJ, Hughes TM, White LR (2011) Microinfarcts, brain atrophy, and cognitive function: the Honolulu Asia Aging Study Autopsy Study. Ann Neurol 70(5):774–780

    PubMed  PubMed Central  Google Scholar 

  65. Kloppenborg RP, Nederkoorn PJ, Grool AM et al (2017) Do lacunar infarcts have different aetiologies? Risk factor profiles of lacunar infarcts in deep white matter and basal ganglia: the second manifestations of arterial disease-magnetic resonance study. Cerebrovasc Dis 43(3–4):161–168

    PubMed  Google Scholar 

  66. Rutten-Jacobs LCA, Markus HS, Young UK (2017) Lacunar Stroke DNA Study. Vascular risk factor profiles differ between magnetic resonance imaging-defined subtypes of younger-onset lacunar stroke. Stroke 48(9):2405–2411

    PubMed  PubMed Central  Google Scholar 

  67. Debette S, Markus HS (2010) The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 341:c3666

    PubMed  PubMed Central  Google Scholar 

  68. Debette S, Beiser A, DeCarli C et al (2010) Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study. Stroke 41(4):600–606

    PubMed  PubMed Central  Google Scholar 

  69. Koga H, Takashima Y, Murakawa R et al (2009) Cognitive consequences of multiple lacunes and leukoaraiosis as vascular cognitive impairment in community-dwelling elderly individuals. J Stroke Cerebrovasc Dis 18(1):32–37

    PubMed  Google Scholar 

  70. Baezner H, Blahak C, Poggesi A et al (2008) Association of gait and balance disorders with age-related white matter changes: the LADIS Study. Neurology 70(12):935–942

    CAS  PubMed  Google Scholar 

  71. Kwon H-M, Lim J-S, Kim YS et al (2014) Cerebral microbleeds are associated with nocturnal reverse dipping in hypertensive patients with ischemic stroke. BMC Neurol 14(1):8. https://doi.org/10.1186/1471-2377-14-8

    Article  PubMed  PubMed Central  Google Scholar 

  72. Yates PA, Villemagne VL, Ellis KA, Desmond PM, Masters CL, Rowe CC (2014) Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations. Front Neurol 4:205. https://doi.org/10.3389/fneur.2013.00205

    Article  PubMed  PubMed Central  Google Scholar 

  73. Fladt J, Kronlage C, De Marchis GM (2018) Cerebral white matter disease and microbleeds in acute ischemic stroke: impact on recanalization therapies. A review of the literature. Neurosci Lett. https://doi.org/10.1016/j.neulet.2018.09.003

  74. Romero JR, Preis SR, Beiser A et al (2014) Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study. Stroke 45(5):1492–1494. https://doi.org/10.1161/STROKEAHA.114.004130

    Article  PubMed  PubMed Central  Google Scholar 

  75. Cordonnier C, Al-Shahi Salman R, Wardlaw J (2007) Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 130(Pt 8):1988–2003. https://doi.org/10.1093/brain/awl387

    Article  PubMed  Google Scholar 

  76. Granger JP (2006) An emerging role for inflammatory cytokines in hypertension. Am J Physiol Heart Circ Physiol 290(3):H923–H924. https://doi.org/10.1152/ajpheart.01278.2005

    Article  CAS  PubMed  Google Scholar 

  77. Shoamanesh A, Preis SR, Beiser AS, Vasan RS, Benjamin EJ, Kase CS et al (2015) Inflammatory biomarkers, cerebral microbleeds, and small vessel disease. Framingham Heart Study. Neurology 84(8):825–832

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Poels MMF, Vernooij MW, Ikram MA et al (2010) Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam Scan Study. Stroke 41(10, Supplement 1):S103–S106. https://doi.org/10.1161/STROKEAHA.110.595181

    Article  PubMed  Google Scholar 

  79. Writing Group Members D, Mozaffarian D, Benjamin EJ et al (2016) Heart disease and stroke statistics – 2016 update: a report from the American Heart Association. Circulation 133(4):e38–e360

    Google Scholar 

  80. Pandian JD, William AG, Kate MP et al (2017) Strategies to improve stroke care services in low- and middle-income countries: a systematic review. Neuroepidemiology 49(1–2):45–61. https://doi.org/10.1159/000479518

    Article  PubMed  Google Scholar 

  81. Marzona I, Avanzini F, Lucisano G et al (2017) Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study. Acta Diabetol 54(2):123–131. https://doi.org/10.1007/s00592-016-0899-0

    Article  PubMed  Google Scholar 

  82. Lawes CM, Vander HS, Rodgers A, International Society of Hypertension (2008) Global burden of blood-pressure-related disease, 2001. Lancet 371(9623):1513–1518. https://doi.org/10.1016/S0140-6736(08)60655-8

    Article  PubMed  Google Scholar 

  83. Gorelick PB (2002) New horizons for stroke prevention: PROGRESS and HOPE. Lancet Neurol 1(3):149–156

    PubMed  Google Scholar 

  84. Benjo A, Thompson RE, Fine D et al (2007) Pulse pressure is an age-independent predictor of stroke development after cardiac surgery. Hypertens (Dallas, TX 1979) 50(4):630–635. https://doi.org/10.1161/HYPERTENSIONAHA.107.095513

    Article  CAS  Google Scholar 

  85. O’Callaghan CJ, Williams B (2000) Mechanical strain-induced extracellular matrix production by human vascular smooth muscle cells: role of TGF-beta(1). Hypertens (Dallas, TX 1979) 36(3):319–324

    Google Scholar 

  86. Harrison DG, Widder J, Grumbach I et al (2006) Endothelial mechanotransduction, nitric oxide and vascular inflammation. J Intern Med 259(4):351–363. https://doi.org/10.1111/j.1365-2796.2006.01621.x

    Article  CAS  PubMed  Google Scholar 

  87. Cipolla MJ, Liebeskind DS, Chan S-L (2018) The importance of comorbidities in ischemic stroke: impact of hypertension on the cerebral circulation. J Cereb Blood Flow Metab. https://doi.org/10.1177/0271678X18800589

  88. Chrissobolis S, Sobey CG (2006) Recent evidence for an involvement of rho-kinase in cerebral vascular disease. Stroke 37(8):2174–2180. https://doi.org/10.1161/01.STR.0000231647.41578.df

    Article  CAS  PubMed  Google Scholar 

  89. Vaziri ND, Rodríguez-Iturbe B (2006) Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of hypertension. Nat Clin Pract Nephrol 2(10):582–593. https://doi.org/10.1038/ncpneph0283

    Article  CAS  PubMed  Google Scholar 

  90. Vaziri ND (2004) Roles of oxidative stress and antioxidant therapy in chronic kidney disease and hypertension. Curr Opin Nephrol Hypertens 13(1):93–99

    CAS  PubMed  Google Scholar 

  91. Sindhu RK, Roberts CK, Ehdaie A, Zhan C-D, Vaziri ND (2005) Effects of aortic coarctation on aortic antioxidant enzymes and NADPH oxidase protein expression. Life Sci 76(8):945–953. https://doi.org/10.1016/j.lfs.2004.10.014

    Article  CAS  PubMed  Google Scholar 

  92. Hirooka Y (2008) Role of reactive oxygen species in brainstem in neural mechanisms of hypertension. Auton Neurosci 142(1–2):20–24. https://doi.org/10.1016/j.autneu.2008.06.001

    Article  CAS  PubMed  Google Scholar 

  93. Kazama K, Anrather J, Zhou P et al (2004) Angiotensin II impairs neurovascular coupling in neocortex through NADPH oxidase-derived radicals. Circ Res 95(10):1019–1026. https://doi.org/10.1161/01.RES.0000148637.85595.c5

    Article  CAS  PubMed  Google Scholar 

  94. Girouard H, Park L, Anrather J, Zhou P, Iadecola C (2007) Cerebrovascular nitrosative stress mediates neurovascular and endothelial dysfunction induced by angiotensin II. Arterioscler Thromb Vasc Biol 27(2):303–309. https://doi.org/10.1161/01.ATV.0000253885.41509.25

    Article  CAS  PubMed  Google Scholar 

  95. Malone K, Amu S, Moore AC, Waeber C (2018) The immune system and stroke: from current targets to future therapy. Immunol Cell Biol. https://doi.org/10.1111/imcb.12191

  96. Nava M, Quiroz Y, Vaziri N, Rodriguez-Iturbe B (2003) Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats. Am J Physiol Renal Physiol 284(3):F447–F454. https://doi.org/10.1152/ajprenal.00264.2002

    Article  CAS  PubMed  Google Scholar 

  97. Pooja Naik LC, Sajja RK, Naik P, Cucullo L (2014) Diabetes mellitus and blood-brain barrier dysfunction: an overview. J Pharmacovigil 02(02):125. https://doi.org/10.4172/2329-6887.1000125

    Article  Google Scholar 

  98. Shere A, Eletta O, Goyal H (2017) Circulating blood biomarkers in essential hypertension: a literature review. J Lab Precis Med 2:99. https://doi.org/10.21037/jlpm.2017.12.06

    Article  Google Scholar 

  99. Wu O, Leng JH, Yang FF et al (2017) A comparative research on obesity hypertension by the comparisons and associations between waist circumference, body mass index with systolic and diastolic blood pressure, and the clinical laboratory data between four special Chinese adult groups. Clin Exp Hypertens 40(1):16–21. https://doi.org/10.1080/10641963.2017.1281940

    Article  PubMed  Google Scholar 

  100. Targher G (2014) Risk of ischemic stroke and decreased serum bilirubin levels. Is there a causal link? Arterioscler Thromb Vasc Biol 34:702–704

    CAS  PubMed  Google Scholar 

  101. Li R-Y, Cao Z-G, Zhang J-R et al (2014) Decreased serum bilirubin is associated with silent cerebral infarction. Arterioscler Thromb Vasc Biol 34:946–951

    CAS  PubMed  Google Scholar 

  102. Higuchi S, Kabeya Y, Uchida J et al (2018) Low Bilirubin levels indicate a high risk of cerebral deep white matter lesions in apparently healthy subjects. Sci Rep 8:6473. https://doi.org/10.1038/s41598-018-24917-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wang Y, Xu S, Pan S et al (2018) Association of serum neuron-specific enolase and bilirubin levels with cerebral dysfunction and prognosis in large-artery atherosclerotic strokes. J Cell Biochem. https://doi.org/10.1002/jcb.27281

  104. Cardon MW (2017) 50 years ago in the Journal of Pediatrics: an assessment of the creatine kinase test in the detection of carriers of Duchenne Muscular Dystrophy. J Pediatr 186:63

    PubMed  Google Scholar 

  105. Horjus DL, Oudman I, van Montfrans GA, Brewster LM (2011) Creatine and creatine analogues in hypertension and cardiovascular disease. Cochrane Database of Syst Rev 11:CD005184. https://doi.org/10.1002/14651858.CD005184.pub2

    Article  Google Scholar 

  106. Brewster LM, Mairuhu G, Bindraban NR, Koopmans RP, Clark JF, van Montfrans GA (2006) Creatine kinase activity is associated with blood pressure. Circulation 114:2034–2039

    CAS  PubMed  Google Scholar 

  107. Brewster LM, Coronel CMD, Sluiter W et al (2012) Ethnic differences in tissue creatine kinase activity: an observational study. PLoS One 7(3):e32471

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Brewster LM, Seedat YK (2013) Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review. BMC Med 11:141

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Horjus DL, Nieuwland R, Boateng KB et al (2014) Creatine kinase inhibits ADP-induced platelet aggregation. Sci Rep 9:6551

    Google Scholar 

  110. Karamat FA, Horjus DL, Haan YC et al (2015) The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC Trial): a randomized controlled first-in human trial. Br J Pharmacol 16:56

    Google Scholar 

  111. Watanabe M, Okamura T, Kokubo Y et al (2009) Elevated serum creatine kinase predicts first-ever myocardial infarction: a 12-year population-based cohort study in Japan, the Suita study. Int J Epidemiol 38(6):1571–1579. https://doi.org/10.1093/ije/dyp212

    Article  PubMed  Google Scholar 

  112. Kunutsor SK, Apekey TA, Cheung BMY (2015) Gamma-glutamyltransferase and risk of hypertension: a systematic review and dose-response meta-analysis of prospective evidence. J Hypertens 33:2373–2381

    CAS  PubMed  Google Scholar 

  113. Yang W, Kim CK, Kim DY et al (2018) Gamma-glutamyl transferase predicts future stroke: a Korean Nationwide Study. Ann Neurol 83(2):375–386. https://doi.org/10.1002/ana.25158

    Article  CAS  PubMed  Google Scholar 

  114. Vilar-Bergua A, Riba-Llena I, Nafría C et al (2015) Blood and CSF biomarkers in brain subcortical ischemic vascular disease: involved pathways and clinical applicability. J Cereb Blood Flow Metab 36(1):55–71. https://doi.org/10.1038/jcbfm.2015.68

    Article  CAS  Google Scholar 

  115. Abe A, Nishiyama Y, Harada-Abe M et al (2014) Relative risk values of age, acrolein, IL-6 and CRP as markers of periventricular hyperintensities: a cross-sectional study. BMJ Open 4(8):e005598

    PubMed  PubMed Central  Google Scholar 

  116. Mitaki S, Nagai A, Oguro H, Yamaguchi S (2016) C-reactive protein levels are associated with cerebral small vessel-related lesions. Acta Neurol Scand 133(1):68–74

    CAS  PubMed  Google Scholar 

  117. Jiménez MC, Rexrode KM, Glynn RJ et al (2015) Association between high-sensitivity C-reactive protein and total stroke by hypertensive status among men. J Am Heart Assoc 4:e002073

    PubMed  PubMed Central  Google Scholar 

  118. Satizabal CL, Zhu YC, Mazoyer B et al (2012) Circulating IL-6 and CRP are associated with MRI findings in the elderly: the 3C-Dijon Study. Neurology 78(10):720–727

    CAS  PubMed  Google Scholar 

  119. Kaptoge S, Di Angelantonio E, Lowe G et al (2010) C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375:132–140

    PubMed  Google Scholar 

  120. Tanaka F, Makita S, Onoda T et al (2010) Prehypertension subtype with elevated C-reactive protein: risk of ischemic stroke in a general Japanese population. Am J Hypertens 23:1108–1113

    CAS  PubMed  Google Scholar 

  121. Miwa K, Tanaka M, Okazaki S et al (2011) Relations of blood inflammatory marker levels with cerebral microbleeds. Stroke 42:3202–3206

    CAS  PubMed  Google Scholar 

  122. Hoshi T, Kitagawa K, Yamagami H et al (2005) Relations of serum high sensitivity C-reactive protein and interleukin-6 levels with silent brain infarction. Stroke 36:768–772

    PubMed  Google Scholar 

  123. Wright CB, Moon Y, Paik MC, Brown TR, Rabbani L, Yoshita M et al (2009) Inflammatory biomarkers of vascular risk as correlates of leukoariosis. Stroke 40(11):3466–3471

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Kim CK, Lee SH, Kim BJ et al (2011) Elevated leukocyte count in asymptomatic subjects is associated with a higher risk for cerebral white matter lesions. Clin Neurol Neurosurg 113(3):177–180

    PubMed  Google Scholar 

  125. Miralbell J, Soriano JJ, Spulber G et al (2012) Structural brain changes and cognition in relation to markers of vascular dysfunction. Neurobiol Aging 33:e9–e17

    Google Scholar 

  126. Han JH, Wong KS, Wang YY et al (2009) Plasma level of sICAM-1 is associated with the extent of white matter lesion among asymptomatic elderly subjects. Clin Neurol Neurosurg 111:847–851

    PubMed  Google Scholar 

  127. Hudson BI, Moon YP, Kalea AZ et al (2011) Association of serum soluble receptor for advanced glycation endproducts with subclinical cerebrovascular disease: the Northern Manhattan Study (NOMAS). Atherosclerosis 216(1):192–198

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Reinhard H, Garde E, Skimminge A et al (2012) Plasma NT-proBNP and white matter hyperintensities in type 2 diabetic patients. Cardiovasc Diabetol 11:119. https://doi.org/10.1186/1475-2840-11-119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Vilar-Bergua A, Riba-Llena I, Penalba A et al (2016) N-terminal pro-brain natriuretic peptide and subclinical brain small vessel disease. Neurology 87:1–7

    Google Scholar 

  130. Pikula A, Boger RH, Beiser AS, Maas R, De Carli C, Schwedhelm E et al (2009) Association of plasma ADMA levels with MRI markers of vascular brain injury: Framingham offspring study. Stroke 40:2959–2964

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Wright CB, Shah NH, Mendez AJ et al (2016) Fibroblast growth factor 23 is associated with subclinical cerebrovascular damage. The Northern Manhattan Study. Stroke 47:923–928

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Pavlovic AM, Pekmezovic T, Obrenovic R et al (2011) Increased total homocysteine level is associated with clinical status and severity of white matter changes in symptomatic patients with subcortical small vessel disease. Clin Neurol Neurosurg 113:711–715

    CAS  PubMed  Google Scholar 

  133. Seshadri S, Wolf PA, Beiser AS et al (2008) Association of plasma total homocysteine levels with subclinical brain injury: cerebral volumes, white matter hyperintensity, and silent brain infarcts at volumetric magnetic resonance imaging in the Framingham Offspring Study. Arch Neurol 65:642–649

    PubMed  PubMed Central  Google Scholar 

  134. Rosenberg GA, Bjerke M, Wallin A (2014) Multimodal markers of inflammation in the subcortical ischemic vascular disease type of vascular cognitive impairment. Stroke 45:1531–1538

    PubMed  PubMed Central  Google Scholar 

  135. Hassan A, Hunt BJ, O’Sullivan M et al (2004) Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain 127:212–219

    PubMed  Google Scholar 

  136. Lin HJ, Chen ST, Wu HY et al (2015) Urinary biomarkers of oxidative and nitrosative stress and the risk for incident stroke: a nested case-control study from a community-based cohort. Int J Cardiol 183:214–220. https://doi.org/10.1016/j.ijcard.2015.01.043

    Article  PubMed  Google Scholar 

  137. Aono Y, Ohkubo T, Kikuya M et al (2007) Plasma fibrinogen, ambulatory blood pressure, and silent cerebrovascular lesions: the Ohasama Study. Arterioscler Thromb Vasc Biol 27(4):963–968. https://doi.org/10.1161/01.ATV.0000258947.17570.38

    Article  CAS  PubMed  Google Scholar 

  138. Martí-Fàbregas J, Valencia C, Pujol J, García-Sánchez C, Martí-Vilalta J-L (2002) Fibrinogen and the amount of leukoaraiosis in patients with symptomatic small-vessel disease. Eur Neurol 48(4):185–190. https://doi.org/10.1159/000066161

    Article  PubMed  Google Scholar 

  139. Wei C-C, Zhang S-T, Liu J-F et al (2017) Association between fibrinogen and leukoaraiosis in patients with ischemic stroke and atrial fibrillation. J Stroke Cerebrovasc Dis 26(11):2630–2637. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.06.027

    Article  PubMed  Google Scholar 

  140. You C-J, Liu D, Liu L-L et al (2018) Correlation between fibrinogen and white matter hyperintensities among nondiabetic individuals with noncardiogenic ischemic stroke. J Stroke Cerebrovasc Dis 27(9):2360–2366. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.04.025

    Article  PubMed  Google Scholar 

  141. Breteler MM, van Swieten JC, Bots ML et al (1994) Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology 44(7):1246–1252

    CAS  PubMed  Google Scholar 

  142. van Overbeek EC, Staals J, Knottnerus ILH et al (2016) Plasma tPA-activity and progression of cerebral white matter hyperintensities in lacunar stroke patients. PLoS One 11(3):e0150740. https://doi.org/10.1371/journal.pone.0150740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Dohgu S, Takata F, Matsumoto J et al (2011) Autocrine and paracrine up-regulation of blood–brain barrier function by plasminogen activator inhibitor-1. Microvasc Res 81(1):103–107. https://doi.org/10.1016/j.mvr.2010.10.004

    Article  CAS  PubMed  Google Scholar 

  144. Markus HS, Hunt B, Palmer K, Enzinger C, Schmidt H, Schmidt R (2005) Markers of endothelial and hemostatic activation and progression of cerebral white matter hyperintensities: longitudinal results of the Austrian Stroke Prevention Study. Stroke 36(7):1410–1414. https://doi.org/10.1161/01.STR.0000169924.60783.d4

    Article  CAS  PubMed  Google Scholar 

  145. Yepes M (2015) Tissue-type plasminogen activator is a neuroprotectant in the central nervous system. Front Cell Neurosci 9:304. https://doi.org/10.3389/fncel.2015.00304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Knottnerus ILH, Winckers K, Ten Cate H et al (2012) Levels of heparin-releasable TFPI are increased in first-ever lacunar stroke patients. Neurology 78(7):493–498. https://doi.org/10.1212/WNL.0b013e318246d6b7

    Article  CAS  PubMed  Google Scholar 

  147. Wiseman S, Marlborough F, Doubal F et al (2014) Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis. Cerebrovasc Dis 37(1):64–75. https://doi.org/10.1159/000356789

    Article  CAS  PubMed  Google Scholar 

  148. Gottesman RF, Cummiskey C, Chambless L et al (2009) Hemostatic factors and subclinical brain infarction in a community-based sample: the ARIC study. Cerebrovasc Dis 28(6):589–594

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Kario K, Matsuo T, Kobayashi H et al (2001) Hyperinsulinemia and hemostatic abnormalities are associated with silent lacunar cerebral infarcts in elderly hypertensive subjects. J Am Coll Cardiol 37(3):871–877

    CAS  PubMed  Google Scholar 

  150. Tomimoto H, Akiguchi I, Ohtani R et al (2001) The coagulation-fibrinolysis system in patients with leukoaraiosis and Binswanger disease. Arch Neurol 58(10):1620–1625

    CAS  PubMed  Google Scholar 

  151. Hassan A, Hunt BJ, O’Sullivan M et al (2003) Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis. Brain 126(Pt 2):424–432

    PubMed  Google Scholar 

  152. Wada M, Nagasawa H, Kurita K et al (2007) Microalbuminuria is a risk factor for cerebral small vessel disease in community-based elderly subjects. J Neurol Sci 255(1–2):27–34. https://doi.org/10.1016/j.jns.2007.01.066

    Article  CAS  PubMed  Google Scholar 

  153. Nagai M, Hoshide S, Kario K (2012) Association of prothrombotic status with markers of cerebral small vessel disease in elderly hypertensive patients. Am J Hypertens 25(10):1088–1094

    CAS  PubMed  Google Scholar 

  154. Knottnerus ILH, Govers-Riemslag JWP, Hamulyak K et al (2010) Endothelial activation in lacunar stroke subtypes. Stroke 41(8):1617–1622. https://doi.org/10.1161/STROKEAHA.109.576223

    Article  PubMed  Google Scholar 

  155. Isenegger J, Meier N, Lämmle B et al (2010) D-dimers predict stroke subtype when assessed early. Cerebrovasc Dis 29(1):82–86. https://doi.org/10.1159/000256652

    Article  PubMed  Google Scholar 

  156. Poggesi A, Pasi M, Pescini F, Pantoni L, Inzitari D (2016) Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review. J Cereb Blood Flow Metab 36(1):72–94. https://doi.org/10.1038/jcbfm.2015.116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Strathmann FG, Schulte S, Goerl K, Petron DJ (2014) Blood-based biomarkers for traumatic brain injury: evaluation of research approaches, available methods and potential utility from the clinician and clinical laboratory perspectives. Clin Biochem 47(10–11):876–888

    CAS  PubMed  Google Scholar 

  158. Gazzolo D, Li Volti G, Gavilanes AW, Scapagnini G (2015) Biomarkers of brain function and injury: biological and clinical significance. Biomed Res Int 2015:389023. https://doi.org/10.1155/2015/389023

    Article  PubMed  PubMed Central  Google Scholar 

  159. Ehrenreich H, Hasselblatt M, Dembowski C et al (2002) Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 8(8):495–505

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Dambinova SA, Khounteev GA, Izykenova GA et al (2003) Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke. Clin Chem 49(10):1752–1762

    CAS  PubMed  Google Scholar 

  161. Weissman JD, Khunteev GA, Heath R, Dambinova SA (2011) NR2 antibodies: risk assessment of transient ischemic attack (TIA)/stroke in patients with history of isolated and multiple cerebrovascular events. J Neurol Sci 300:97–102

    CAS  PubMed  Google Scholar 

  162. Zerche M, Weissenborn K, Ott C et al (2015) Preexisting serum autoantibodies against the NMDAR subunit NR1 modulate evolution of lesion size in acute ischemic stroke. Stroke 46(5):1180–1186

    CAS  PubMed  Google Scholar 

  163. Dambinova SA, Maroon JC, Sufrinko AM et al (2016) Functional, structural, and neurotoxicity biomarkers in integrative assessment of concussions. Front Neurol 7:PMC5050199. https://doi.org/10.3389/fneur.2016.00172

    Article  Google Scholar 

  164. González-García S, González-Quevedo A, Hernandez-Diaz Z et al (2017) Circulating autoantibodies against the NR2 peptide of the NMDA receptor are associated with subclinical brain damage in hypertensive patients with other pre-existing conditions for vascular risk. J Neurol Sci 375:324–330. https://doi.org/10.1016/j.jns.2017.02.028

    Article  CAS  PubMed  Google Scholar 

  165. Dadu RT, Fornage M, Virani SS et al (2013) Cardiovascular biomarkers and subclinical brain disease in the atherosclerosis risk in communities study. Stroke 44(7):1803–1808. https://doi.org/10.1161/STROKEAHA.113.001128

    Article  PubMed  PubMed Central  Google Scholar 

  166. Duering M, Konieczny MJ, Tiedt S et al (2018) Serum neurofilament light chain levels are related to small vessel disease burden. J Stroke 20(2):228–238. https://doi.org/10.5853/jos.2017.02565

    Article  PubMed  PubMed Central  Google Scholar 

  167. Gattringer T, Pinter D, Enzinger C et al (2017) Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology 89(20):2108–2114. https://doi.org/10.1212/WNL.0000000000004645

    Article  PubMed  PubMed Central  Google Scholar 

  168. González-Quevedo A, García SG, OF C et al (2011) Increased serum S-100B and neuron specific enolase – potential markers of early nervous system involvement in essential hypertension. Clin Biochem 44(2–3):154–159. https://doi.org/10.1016/j.clinbiochem.2010.11.006

    Article  CAS  PubMed  Google Scholar 

  169. Gao Q, Fan Y, Mu L-Y et al (2015) S100B and ADMA in cerebral small vessel disease and cognitive dysfunction. J Neurol Sci 354(1–2):27–32. https://doi.org/10.1016/j.jns.2015.04.031

    Article  CAS  PubMed  Google Scholar 

  170. Xiao L, Sun W, Lan W et al (2014) Correlation between cerebral microbleeds and S100B/RAGE in acute lacunar stroke patients. J Neurol Sci 340(1–2):208–212. https://doi.org/10.1016/j.jns.2014.03.006

    Article  CAS  PubMed  Google Scholar 

  171. Prabhakar P, Chandra SR, Christopher R (2017) Circulating microRNAs as potential biomarkers for the identification of vascular dementia due to cerebral small vessel disease. Age Ageing 46(5):861–864. https://doi.org/10.1093/ageing/afx090

    Article  PubMed  Google Scholar 

  172. Karp X, Ambros V (2005) Developmental biology. Encountering microRNAs in cell fate signaling. Science 310(5752):1288–1289. https://doi.org/10.1126/science.1121566

    Article  CAS  PubMed  Google Scholar 

  173. Gurol ME, Irizarry MC, Smith EE et al (2006) Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy. Neurology 66(1):23–29. https://doi.org/10.1212/01.wnl.0000191403.95453.6a

    Article  CAS  PubMed  Google Scholar 

  174. Van Dijk EJ, Prins ND, Vermeer SE et al (2004) Plasma amyloid, apolipoprotein E, lacunar infarcts, and white matter lesions. Ann Neurol 55(4):570–575. https://doi.org/10.1002/ana.20050

    Article  CAS  PubMed  Google Scholar 

  175. Lee W-J, Jung K-H, Ryu YJ et al (2017) Cystatin C, a potential marker for cerebral microvascular compliance, is associated with white-matter hyperintensities progression. PLoS One 12(9):e0184999. https://doi.org/10.1371/journal.pone.0184999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Palsdottir A, Snorradottir AO, Thorsteinsson L (2006) Hereditary cystatin C amyloid angiopathy: genetic, clinical, and pathological aspects. Brain Pathol 16(1):55–59

    CAS  PubMed  Google Scholar 

  177. Levy E, Sastre M, Kumar A et al (2001) Codeposition of cystatin C with amyloid-beta protein in the brain of Alzheimer disease patients. J Neuropathol Exp Neurol 60(1):94–104

    CAS  PubMed  Google Scholar 

  178. Yang S, Cai J, Lu R et al (2017) Association between serum cystatin C level and total magnetic resonance imaging burden of cerebral small vessel disease in patients with acute lacunar stroke. J Stroke Cerebrovasc Dis 26(1):186–191. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.09.007

    Article  PubMed  Google Scholar 

  179. Weller RO, Djuanda E, Yow H-Y, Carare RO (2009) Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta Neuropathol 117(1):1–14. https://doi.org/10.1007/s00401-008-0457-0

    Article  CAS  PubMed  Google Scholar 

  180. Rost NS, Wolf PA, Kase CS et al (2001) Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke 32(11):2575–2579

    CAS  PubMed  Google Scholar 

  181. van Dijk EJ, Prins ND, Vermeer SE et al (2005) C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation 112(6):900–905

    PubMed  Google Scholar 

  182. Kaplan RC, McGinn AP, Baird AE et al (2008) Inflammation and hemostasis biomarkers for predicting stroke in postmenopausal women: the Women’s Health Initiative Observational Study. J Stroke Cerebrovasc Dis 17(6):344–355

    PubMed  PubMed Central  Google Scholar 

  183. Staszewski J, Piusińska-Macoch R, Brodacki B et al (2018) Il-6, PF-4, sCD40 l, and homocysteine are associated with the radiological progression of cerebral small-vessel disease: a 2-year follow-up study. Clin Interv Aging 13:1135–1141

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Walker KA, Power MC, Hoogeveen RC et al (2017) Midlife systemic inflammation, late-life white matter integrity, and cerebral small vessel disease. The Atherosclerosis Risk in Communities Study. Stroke 48:3196–3202

    PubMed  PubMed Central  Google Scholar 

  185. Wieberdink RG, van Schie MC, Koudstaal PJ et al (2010) High von Willebrand factor levels increase the risk of stroke: the Rotterdam study. Stroke 41:2151–2156

    CAS  PubMed  Google Scholar 

  186. Kaffashian S, Tzourio C, Soumare A et al (2014) Plasma ß-amyloid and MRI markers of cerebral small vessel disease: Three-City Dijon Study. Neurology 83(22):2038–2045. https://doi.org/10.1212/WNL.0000000000001038

    Article  CAS  PubMed  Google Scholar 

  187. Johnson NA, Jahng G-H, Weiner MW et al (2005) Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology 234(3):851–859. https://doi.org/10.1148/radiol.2343040197

    Article  PubMed  PubMed Central  Google Scholar 

  188. Maas MB, Furie KL (2009) Molecular biomarkers in stroke diagnosis and prognosis. Biomark Med 3(4):363–383

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alina González-Quevedo .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

González-Quevedo, A., Peña Sánchez, M., González García, S., Menéndez Saínz, M.C., Arteche Prior, M. (2020). Blood-Borne Biomarkers of Hypertension Predicting Hemorrhagic and Ischemic Stroke. In: Peplow, P.V., Martinez, B., Dambinova, S.A. (eds) Stroke Biomarkers. Neuromethods, vol 147. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9682-7_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9682-7_8

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9681-0

  • Online ISBN: 978-1-4939-9682-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics