Skip to main content

Advertisement

SpringerLink
Log in

Inflammation markers and prediction of post-stroke vascular disease recurrence: The MITICO study

  • ORIGINAL COMMUNICATION
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Objective

Vascular disease recurrence following stroke is the main cause of morbidity and mortality. The MITICO study was designed to assess the prognostic value of markers of inflammation in relation to the risk of recurrence of vascular disease.

Patients and methods

Multi-centered prospective observational study, in patients with ischemic stroke not receiving anti-coagulation therapy and who were recruited within 1–3 months from stroke onset. Blood samples were obtained at baseline and follow- up for the determination of high-sensitive C reactive protein (CRP), IL-6, IL-10, ICAM-1, VCAM- 1, MMP-9 and cellular fibronectin. Four follow-up visits within the first year were to rule out recurrence.

Results

Of 965 patients from 65 hospitals, 780 (aged 67.5±11.2 years, 33.6 % female) were valid for main analysis. One-hundred and three patients (13.2 %) had a new adverse vascular event and 116 patients (14.9 %) a vascular event or vascular death (66.4 % stroke, 21.5 % coronary and 12.1 % peripheral). Levels of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL (ROC curve analyses) were associated with vascular disease recurrence risk (OR: 28.7; 95 % CI: 14.2–58.0 vs. OR: 4.1; 95 % CI: 2.4–7.1, respectively) following adjustment for confounding variables. Risk of adverse vascular event or death from vascular disease were associated with IL-6 (OR: 21.2; 95 % CI: 11.6–38.7) and VCAM-1 (OR: 3.8; 95 % CI: 2.3–6.4).

Conclusions

Baseline values of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL increase 21-fold and 4-fold, respectively, the risk of new vascular disease event or death from vascular disease in patients with ischemic stroke not receiving anti-coagulation treatment.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Arboix A, Garcia-Eroles L, Oliveres M, Massons JB, Targa C (1998) Clinical predictors of early embolic recurrence in presumed cardioembolic stroke. Cerebrovasc Dis 8:345–353

    Article  PubMed  CAS  Google Scholar 

  2. Amarenco P, Bogousslavsky J, Callahan A, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA; Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators (2006) High-dose atorvastatin after stroke or transient ischemic attack. N Eng J Med 355:549–559

    Article  CAS  Google Scholar 

  3. Appelros P, Nydevik I, Viitanen M (2003) Poor outcome after first-ever stroke. Predictors for death, dependency, and recurrent stroke within the first year. Stroke 34:122–126

    Article  PubMed  Google Scholar 

  4. Blanco M, Rodriguez-Yanez M, Sobrino T, Leira R, Castillo J (2005) Platelets, inflammation, and atherothrombotic neurovascular disease: the role of endothelial dysfunction. Cerebrovasc Dis 20(Suppl 2):32–39

    Article  PubMed  Google Scholar 

  5. Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction. A marker of atherosclorotic risk. Arterioscler Thromb Vasc Biol 23:168–175

    Article  PubMed  CAS  Google Scholar 

  6. Brown RD, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO (1996) Stroke incidence, prevalence, and survival: secular trends in Rochester, Minnesota through 1989. Stroke 27:373–380

    PubMed  CAS  Google Scholar 

  7. CAPRIE Steering Committee (1996) A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348:1329–1339

    Google Scholar 

  8. Castillo J, Leira R (2001) Predictors of deteriorating cerebral infarct: role of inflammatory mechanisms. Would its early treatment be useful? Cerebrovasc Dis 11(Suppl 1):40–48

    Article  PubMed  Google Scholar 

  9. Castillo J, Moro MA, Blanco M, Leira R, Serena J, Lizasoain I, Davalos A (2003) The release of tumor necrosis factor-α is associated with ischemic tolerance in human stroke. Ann Neurol 54:811–819

    Article  PubMed  CAS  Google Scholar 

  10. Chamorro A, Hallenbeck J (2006) The harms and benefits of inflammatory and immune response in vascular disease. Stroke 37:291–293

    Article  PubMed  Google Scholar 

  11. Chrysant SG, Chrysant GS (2006) The pleiotropic effects of angiotensin receptor blokers. J Clin Hypertens 8:261–268

    Article  CAS  Google Scholar 

  12. Comite ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Espanola de Neurologia (2004) Guia para el diagnostico y tratamiento del ictus. Prous Science, Barcelona

  13. Coull BM (2007) Inflammation and stroke. Stroke 38(part 2):631

    Article  Google Scholar 

  14. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H; LIFE Study Group (2002) Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 359:995–1003

    Article  PubMed  CAS  Google Scholar 

  15. Davi G, Santilli F (2006) Unveiling the inflammatory face of antiplatelet drugs. J Thromb Haemost 4:2137–2139

    Article  PubMed  CAS  Google Scholar 

  16. Deveraj S, Rogers J, Jialal I (2007) Statins and biomarkers of inflammation. Curr Atheroscler Rep 9:33–41

    Article  Google Scholar 

  17. Dhamoon MS, Sciacca RR, Rundek T, Sacco RL, Elkind MSV (2006) Recurrent stroke and cardiac risk after first ischemic stroke. The Northern Manhattan Study. Neurology 66:641–646

    Article  PubMed  CAS  Google Scholar 

  18. Dorrance AM, Rupp NC, Nogueira EF (2006) Mineralocorticoid receptor activation causes cerebral vessel remodeling and exacerbates the damage caused by cerebral ischemia. Hypertension 47(part 2):590–595

    Article  PubMed  CAS  Google Scholar 

  19. Elneihoum AM, Goransson M, Falke P, Janzal L (1998) Three-year survive and recurrence after stroke in Malmo, Sweden: an analysis of stroke registry data. Stroke 29:2114–2117

    PubMed  CAS  Google Scholar 

  20. Friday G, Alter M, Lai S-M (2002) Control of hypertension and risk of stroke recurrence. Stroke 33:2652–2657

    Article  PubMed  Google Scholar 

  21. Gilbert RE, Rumble JR, Cao Z, Cox AJ, van Eeeden P, Allen TJ, Kelly DJ, Cooper ME (2000) Endothelin receptor antagonism ameliorates mast cell infiltration, vascular hyperthrophy, and epidermal growth factor expression in experimental diabetes. Cir Res 86:158–165

    CAS  Google Scholar 

  22. Hankey GJ, Jamrozik K, Broadhurst RF, Forbes S, Burvill PW, Anderson CS, Stewart-Wynne EC (1998) Long-term risk of first recurrent stroke in the Perth Community Stroke Study. Stroke 29:2491–2500

    PubMed  CAS  Google Scholar 

  23. Harris AK, Hutchinson JR, Sachidanandam K, Johnson MH, Dorrance AM, Stepp DW, Fagan SC, Ergul A (2005) Type 2 diabetes causes remodeling of cerebrovasculature via differential regulation of matrix metalloproteinases and collagen synthesis. Role of endothelin-1. Diabetes 54:2638–2644

    Article  PubMed  CAS  Google Scholar 

  24. Hillen T, Coshall C, Tilling K, Rudd AG, McGovern R, Wolfe CDA (2003) Cause of stroke recurrence is multifactorial. Patterns, risk factors, and outcomes of stroke recurrence in the South London Stroke Register. Stroke 34:1457–1463

    Article  PubMed  Google Scholar 

  25. Jorgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS (1997) Stroke recurrence: Predictors, severity, and prognosis. The Copenhagen Stroke Study. Neurology 48:891–895

    PubMed  CAS  Google Scholar 

  26. Kang D-W, Lattimore SU, Latour LL, Warach S (2006) Silent ischemic lesion recurrence on magnetic resonance imaging predicts subsequent clinical vascular events. Arch Neurol 63:1730–1733

    Article  PubMed  Google Scholar 

  27. Lai SM, Alter M, Friday G, Sobel E (1994) A multifactorial analysis of risk factors for recurrence of ischemic stroke. Stroke 25:958–962 29. Libby P, Ridker PM, Maseri A (2002) Inflammation and aterosclerosis. Circulation 105:1135–1147

    Google Scholar 

  28. Leira EC, Chang K-C, Davis PH, Clarke WR, Woolson RF, Hansen MD, Adams HP Jr (2004) Can we predict early recurrence in acute stroke? Cerebrovasc Dis 18:139–144

    Article  PubMed  Google Scholar 

  29. Libby P, Ridker PM, Maseri A (2202) Inflammation and aterosclerosis. Circulation 105:1135–1147

    Article  Google Scholar 

  30. Lisabeth LD, Smith MA, Brown DL, Moye LA, Risser JMH, Morgenstern LB (2006) Ethnic differences in stroke recurrence. Ann Neurol 60:469–475

    Article  PubMed  Google Scholar 

  31. Liu L, Ikeda K, Yamori Y (2001) Changes in stroke mortality rates for 1950 to 1997: A great show-down of decline trend in Japan. Stroke 32:1745–1749

    PubMed  CAS  Google Scholar 

  32. Moroney JT, Bagiella E, Paik MC, Sacco RL, Desmond DW (1998) Risk factors for early recurrence after ischemic stroke. The role of stroke syndrome and subtype. Stroke 29:2118–2124

    PubMed  CAS  Google Scholar 

  33. Niessen LW, Barendregt JJ, Bonneux L, Kousstaal PJ (1993) Stroke trends in an aging population. Stroke 24:931–939

    PubMed  CAS  Google Scholar 

  34. PROGRESS Collaborative Group (2001) Randomized trial of a perindopril- based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischemic attack. Lancet 358:1033–1041

    Google Scholar 

  35. Ross GW, Petrovitch H, White LR, Masaki KH, Li CY, Curb JD, Yano K, Rodriguez BL, Foley DJ, Blanchette PL, Havlik R (1999) Characterization of risk factors for vascular dementia: the Honolulu-Asia Aging Study. Neurology 53:337–343

    PubMed  CAS  Google Scholar 

  36. Sacco RL, Foulkes MA, Mohr JP, Wolf PA, Hier DB, Price TR (1989) Determinants of early recurrence of cerebral infarction. The Stroke Data Bank. Stroke 20:983–989

    PubMed  CAS  Google Scholar 

  37. Shaya FT, El Khoury AC, Mullius CD, Du D, Skolasky R, Fatodu H, Garber H, Weir MR (2006) Drug therapy persistence and stroke recurrence. Am J Manag Care 12:313–319

    PubMed  Google Scholar 

  38. Stegmayr B, Asplund K (1996) Exploring the declining case fatality in acute stroke: population-based observations in the northern Sweden MONICA Project. J Intern Med 240:143–149

    Article  PubMed  CAS  Google Scholar 

  39. Sundstrom J, Vasan RS (2006) Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic events. Curr Opin Lipidol 17:45–53

    Article  PubMed  Google Scholar 

  40. Yokota C, Minematsu K, Hasegawa Y, Yamaguchi T (2004) Long-term prognosis, by stroke subtypes, alter a firstever stroke: A hospital-based study over a 20-year period. Cerebrovasc Dis 18:111–116

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Neurology, Clinical Neuroscience Research Laboratory, Hospital Clínico Universitario, 15706, Santiago de Compostela, A Coruña, Spain

    J. Castillo MD, PhD & T. Sobrino PhD

  2. Dept. of Neurology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    J. Álvarez-Sabín MD, PhD & J. Montaner MD, PhD

  3. Dept. of Neurosciences, Clínica Universitaria de Navarra, Pamplona, Spain

    E. Martínez-Vila MD, PhD

  4. Dept. of Neurology, Hospital Universitario La Princesa, Madrid, Spain

    J. Vivancos MD, PhD

Authors
  1. J. Castillo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Álvarez-Sabín MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Martínez-Vila MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Montaner MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Sobrino PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Vivancos MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the MÍTICO Study Investigators*

Corresponding author

Correspondence to J. Castillo MD, PhD.

Additional information

* see Appendix for full listing of participating centers and principal investigators.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Castillo, J., Álvarez-Sabín, J., Martínez-Vila, E. et al. Inflammation markers and prediction of post-stroke vascular disease recurrence: The MITICO study. J Neurol 256, 217–224 (2009). https://doi.org/10.1007/s00415-009-0058-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-009-0058-4

Key words

Search

Navigation