Published: 2018-10-03

Are risk factors of cerebral small vessel disease differ from those in patients with high atherothrombotic risk without cerebrovascular disease?

Clinic of Neurology, Military Institute of Medicine, Szaserow 128, 04-141 Warsaw, Poland
cerebral small vessel disease risk factors lacunar stroke vascular dementia vascular parkinsonism


Knowledge of risk factors for cerebral small vessel disease (CSVD) may generate hypothesis regarding possible targets for prevention. Our aim was to evaluate if atherothrombotic risk factors differ between patients with CSVD and with subjects without cerebrovascular disease but with high cardiovascular (CVD) risk. A single-center, cohort study was performed in consecutive patients with different CSVD manifestations.  The study group consisted of 205 patients: 52 with lacunar stroke (LS), 20 with subcortical hemorrhagic stroke (HS), 50 with vascular dementia (VaD), 28 with vascular parkinsonism (VaP) and 55 controls (CG) with high CVD risk (35 with atherosclerotic CVD, 20 with 10-year risk of CVD with SCORE?5). Logistic regression was used to analyze the influence of clinical and laboratory data on the occurrence of CSVD. Mean age, sex distribution, prevalence of smoking, hyperlipidemia, peripheral artery disease and obesity were similar in CSVD and CG. The factors significantly associated with CSVD compared to controls were diabetes mellitus, polymetabolic syndrome, elevated systolic blood pressure, low levels of eGFR, HDL, albumin and high uric acid, fibrinogen, fasting glucose, HbA1c and intima medic thickness (p<0.05). Hypertension, chronic kidney disease and elevated fasting blood glucose were related to LS and HS (p<0.1).  Diabetes was significantly associated with LS and VaD while smoking and low total cholesterol were related to HS (p<0.1). The study confirms that risk factors profile for CSVD differs from subjects with proatherogenic profile without history of cerebrovascular disease. Our results also support that unique risk factors profiles exist for different manifestations of the CSVD.


Download data is not yet available.


  1. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689-701.
  2. Wardlaw JM, Allerhand M, Doubal FN. Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities. Neurology 2014; 82:1331-1338.
  3. Mok V, Gorelick PB, Chen C. Risk factors as possible targets for prevention of small verssel disease. In Cerebral small vessel disease, Cambridge 2014, Edited by Pantoni L, Gorelic PB.
  4. Wardlaw JM, Smith C, Dichgans M. Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013, 12:5
  5. Norden AGW, Laat KF, Gons RAR et al. Causes and consequences of cerebral small vesseldisease. The RUN DMC study: a prospective cohortstudy. Study rationale and protocol. BMC Neurology 2011, 11:29
  6. Staszewski J, Piusińska-Macoch R, Skrobowska E, Brodacki B, Pawlik R, Dutkiewicz T et al. Significance of Haemodynamic and Haemostatic Factors in the Course of Different Manifestations of Cerebral Small Vessel Disease: The SHEF-CSVD Study—Study Rationale and Protocol. Neuroscience Journal 2013, 424695; doi: 10.1155/2013/424695
  7. Schulc E, Pallauf M, Mueller G, Wildbahner T, Themet C. Is the Barthel Index an Adequate Assessment Tool for Identifying a Risk Group in Elderly People Living at Home? Int J Nurs Clin Pract 2015; 2:140
  8. Hurtig HI (1993) Vascular parkinsonism. In: Stern MB, Koller WC (eds). Parkinsonian syndromes. New York: Marcel Dekker 81-83.
  9. Chui HC, Victoroff JI, Margolin D. Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers. Neurology 1992; 42: 473–480.
  10. Zijlmans JCM, Daniel SE, Hughes AJ. Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis. Mov. Disord 2004; 19:630-640.
  11. ESC/EAS Guidelines for the management of dyslipidaemias. The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; 32: 1769-818.
  12. Kessler CS, Joudeth Y. Evaluation and treatment of severe asymptomatic hypertension. Am Fam Physician 2010; 15: 470-6.
  13. Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12:822-38.
  14. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, at al. Force ASoECI-MTT. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr 2008;21:93–111.
  15. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation. 2009;120:1640–1645.
  16. Goblirsch G, Bershow S, Cummings K, Hayes R, Kokoszka M, Lu Y, et al. Stable coronary artery disease. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI) 2013; 5: 71
  17. Jackson C, Sudlow C. are lacunar strokes really different? A systematic review of differences in risk factor profiles between lacunar and nonlacunar infarcts. Stroke 2005;36:891-901.
  18. Khan U, Porteous L, Hassan A, Markus HS. Risk factor profile of cerebral small vessel disease and its subtypes. J Neurol Neurosurg Psychiatry 2007;78:702-706.
  19. Bezerra DC, Sharrett AR, Matsushita K, Gottesman RF, Shibata D, Mosley TH, Jr, et al. Risk factors for lacune subtypes in the atherosclerosis risk in communities (ARIC) study. Neurology. 2012;78:102–108.
  20. Khatri M, Wright CB, Nickolas TL, Yoshita M, Paik MC, Kranwinkel G, et al. Chronic kidney disease is associated with white matter hyperintensity volume: the Northern Manhattan Study (NOMAS). Stroke 2007;38:3121-3126.
  21. Ikram MA, Vernooij MW, Hofman A, Niessen WJ, van der Lugt A, Breteler MM. Kidney function is related to cerebral small vessel disease. Stroke 2008;39:55-61.
  22. Uao H, Takashima Y, Hashimoto M, Uchino A, Yuzuriha T. Subclinical cerebral abnormalities in chronic kidney disease. Contrib Nephrol. 2013;179;24-34.
  23. Vannorsdall TD, Jinnah HA, Gordon B, et al. Cerebral ischemia mediates the effect of serum uric acid on cognitive function. Stroke. 2008;39:3418–20.
  24. Schretlen DJ, Inscore AB, Jinnah HA, et al. Serum uric acid and cognitive function in community-dwelling older adults. Neuropsychology. 2007;21:136–40.
  25. Stinghen AE, Pecoits-Filho R. Vascular damage In Sidney disease – Beyond hypertension. Int J Hypertens 2011;2011:232-683.
  26. Schmidt R, Fazekas F, Hayn M, Schmidt H, Kapeller P, Roob G, et al. Risk factors for microangiopathy-related cerebral damage in the Austrian Stroke Prevention Study. J Neurol Sci. 1997; 152:15–21.
  27. Marti-Fabregas J, Valencia C, Pujol J, Garcia-Sanchez C, Marti-Vilalta JL. Fibrinogen and the amount of leukoaraiosis in patients with symptomatic small-vessel disease. Eur Neurol. 2002; 48:185–190.
  28. Xu WH, Dong C, Rundek T, Elkind MSV, Sacco RL. Serum Albumin Levels Are Associated With Cardioembolic and Cryptogenic Ischemic Strokes - Northern Manhattan Study. Stroke 2014;45:973-978
  29. Parkkinen J, Ojala P, Niiranen J, Jolkkonen J. Molecular mechanisms underlying neuroprotective effects of albumin after ischemic stroke. Stroke 2007;38:255.
  30. Longstreth WT Jr, Manolio TA, Arnold Al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke 1996;27:1274-1282.
  31. Ylikoski A, Erkinjuntti T, Raininko R. White matter hyperintensities on MRI in the neurologically nondiseased elderly. Analysis of cohorts of consecutive subjects aged 55 to 85 years living at home. Stroke 1995; 26:1171-1177.
  32. Vermeer SE, van Dijk EJ, Koudstaal PJ. Homocysteine, silent brain infarcts, and white matter lesions: the Rotterdam Scan Study. Ann Neurol 2002; 51:285-289.
  33. Rosenberg GA, Bjerke M, Wallin A. Multimodal markers of inflammation in the subcortical ischemic vascular disease type of vascular cognitive impairment. Stroke 2014; 45: 1531–1538.
  34. Jeerakathil T, Wolf PA, Beiser A. Stroke risk profile predicts white matter hyperintensity volume: the Framingham Study. Stroke 2004;35:1857-1861.
  35. Kase CS. Subcortical hemorrhages. In Donnan G, Norrving B, Bamford J, Bogusslavsky J, eds. Subcortical Stroke, 2nd edn. New York, NY:Oxford University Press; 2002:347-377.
  36. Gorrelick PB. Statin use and intracerebral hemorrhage: evidence for safety In recurrent stroke prevention? Arch Neurol 2012;69:13-16.
  37. Gouw AA, van der Flier WM, Fazekas F. Progression of white matter hyperintensities and incidence of new lacunes over a three-year period:the Leukoaraiosis and Disability study. Stroke 2008;39:1414-1420.
  38. Carmelli D, Swan GE, Reed T. Midlife cardiovascular risk factors and brain morphology in identical older male twins. Neurology 1999;52:1119-1124.
  39. Schmidt R, Hayn M, Fazekas F, Kapeller P, Esterbauer H. Magnetic resonance imaging white matter hyperintensities in clinically normal elderly individuals. Correlations with plasma concentrations of naturally occurring antioxidants. Stroke 1996;27:2043-2047.
  40. Schilling S, Tzourio C, Dufouil C, Zhu Y, Berr C, Alpérovitch A, et al. Plasma lipids and cerebral small vessel disease. Neurology 2014; 11:1844-52.

How to Cite

Staszewski J, Skrobowska E, Piusińska-Macoch R, Brodacki B, Stępień A. Are risk factors of cerebral small vessel disease differ from those in patients with high atherothrombotic risk without cerebrovascular disease?. JMS [Internet]. 2018Oct.3 [cited 2021Jan.27];87(3):145-53. Available from: