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Obesity Paradox in Ischemic Stroke: Clinical and Molecular Insights

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Abstract

It has recently emerged the concept of “obesity paradox,” a term used to describe the unexpected improved prognosis and lower mortality rates found in several diseases in patients with higher body weight. Concerning stroke, few clinical studies have assessed this obesity paradox showing contradictory results. Therefore, our aim was to compare clinical evolution and inflammatory balance of obese and non-obese patients after ischemic stroke. We designed a prospective case-control study in patients with acute ischemic stroke categorized into obese (body mass index, BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2). We compared clinical, anthropometric, radiological, and laboratory variables. The main outcome variable was the functional outcome at 3 months. We included 98 patients (48 non-obese and 50 obese). No differences in functional outcome at 3 months were found (p = 0.882) although a tendency of a greater recovery on neurological impairments was seen in obese subjects. Importantly, obese patients (p = 0.007) and patients who experienced poor outcome (p = 0.006) exhibited a higher reduction in body weight at 3 months after stroke. Moreover, pro-inflammatory IL-6 levels (p = 0.002) were higher in the obese group. However, IL-6 levels decreased over the first week in obese while increased in non-obese. On the contrary, levels of the anti-inflammatory IL-10 rose over the first week in obese patients, whereas remained stable in non-obese. In summary, despite exhibiting several factors associated with poor outcome, obese patients do not evolve worse than non-obese after ischemic stroke. Obesity may counterbalance the inflammatory reaction through an anti-inflammatory stream enhanced in the first moments of stroke.

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References

  1. Roth J, Qiang X, Marbán SL, Redelt H, Lowell BC. The obesity pandemic: where have we been and where are we going? Obes Res. 2004;12(Suppl 2):88S–101S.

    PubMed  Google Scholar 

  2. Gruberg L, Weissman NJ, Waksman R, Fuchs S, Deible R, Pinnow EE, et al. The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox? J Am Coll Cardiol. 2002;39:578–84.

    PubMed  Google Scholar 

  3. Fleischmann E, Teal N, Dudley J, May W, Bower JD, Salahudeen AK. Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients. Kidney Int. 1999;55:1560–7.

    CAS  PubMed  Google Scholar 

  4. Curtis JP, Selter JG, Wang Y, Rathore SS, Jovin IS, Jadbabaie F, et al. The obesity paradox: body mass index and outcomes in patients with heart failure. Arch Intern Med. 2005;165:55–61.

    PubMed  Google Scholar 

  5. Senoo K, Lip GYH. Body mass index and adverse outcomes in elderly patients with atrial fibrillation: the AMADEUS trial. Stroke. 2016;47:523–6.

    PubMed  Google Scholar 

  6. Landbo C, Prescott E, Lange P, Vestbo J, Almdal TP. Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1856–61.

    CAS  PubMed  Google Scholar 

  7. Escalante A, Haas RW, del Rincón I. Paradoxical effect of body mass index on survival in rheumatoid arthritis. Arch Intern Med. 2005;165:1624–9.

    PubMed  Google Scholar 

  8. Olsen TS, Dehlendorff C, Petersen HG, Andersen KK. Body mass index and poststroke mortality. Neuroepidemiology. 2008;30:93–100.

    PubMed  Google Scholar 

  9. Kim BJ, Lee SH, Jung KH, Yu KH, Lee BC, Roh JK. Dynamics of obesity paradox after stroke, related to time from onset, age, and causes of death. Neurology. 2012;79:856–63.

    PubMed  Google Scholar 

  10. Kazemi-Bajestani SMR, Ghayour-Mobarhan M, Thrift AG, Ferns GA, Frazadfard MT, Mokhber N, et al. Obesity paradox versus frailty syndrome in first-ever ischemic stroke survivors. Int J Stroke. 2015;10:E75.

    PubMed  Google Scholar 

  11. Jang SY, Shin Y, Kim DY, Sohn MK, Lee J, Lee S, et al. Effect of obesity on functional outcomes at 6 months post-stroke among elderly Koreans: a prospective multicentre study. BMJ Open. 2015;5:e008712.

    PubMed  PubMed Central  Google Scholar 

  12. Ryu W-S, Lee S-H, Kim CK, Kim BJ, Yoon B-W. Body mass index, initial neurological severity and long-term mortality in ischemic stroke. Cerebrovasc Dis. 2011;32:170–6.

    PubMed  Google Scholar 

  13. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011;121:2111–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Iadecola C, Anrathner J. The immunology of stroke: from mechanism to translation. Nat Med. 2012;17:796–808.

    Google Scholar 

  15. European Stroke Organisation (ESO) Executive Committee, ESO Writing Committee. Guidelines for Management of Ischaemic Stroke and Transient Ischaemic Attack 2008. Cerebrovasc Dis. 2008;25:457–507.

    Google Scholar 

  16. Alonso de Leciñana M, Egido JA, Casado I, Ribó M, Dávalos A, Masjuan J, et al. Guía para el tratamiento del infarto cerebral agudo. Neurología. 2014;29:102–22.

    PubMed  Google Scholar 

  17. Chumlea WC, Guo SS, Wholihan K, Cockram D, Kuczmarski RJ, Johnson CL. Stature prediction equations for elderly non-Hispanic white, non-Hispanic black, and Mexican-American persons developed from NHANES III data. J Am Diet Assoc. 1998;98:137–42.

    CAS  PubMed  Google Scholar 

  18. Chumlea WC, Guo S, Roche AF, Steinbaugh ML. Prediction of body weight for the nonambulatory elderly from anthropometry. J Am Diet Assoc. 1988;88:564–8.

    CAS  PubMed  Google Scholar 

  19. WHO. Obesity. Preventing and managing the global epidemic. Report of a WHO consultation. WHO technical report series 894. Geneva: World Health Organization; 2000.

    Google Scholar 

  20. Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35–41.

    Google Scholar 

  21. Sims JR, Gharai LR, Schaefer PW, Vangel M, Rosenthal ES, Lev MH, et al. ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology. 2009;72:2104–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Castillo J, Rodríguez I. Biochemical changes and inflammatory response as markers for brain ischaemia: molecular markers of diagnostic utility and prognosis in human clinical practice. Cerebrovasc Dis. 2004;17(Suppl 1):7–18.

    CAS  PubMed  Google Scholar 

  23. Smith CJ, Emsley HCA, Gavin CM, Georgiou RF, Vail A, Barberan EM, et al. Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol. 2004;4:2.

    PubMed  PubMed Central  Google Scholar 

  24. Spera PA, Ellison JA, Feuerstein GZ, Barone FC. IL-10 reduces rat brain injury following focal stroke. Neurosci Lett. 1998;251:189–92.

    CAS  PubMed  Google Scholar 

  25. Strle K, Zhou JH, Shen WH, Broussard SR, Johnson RW, Freund GG, et al. Interleukin-10 in the brain. Crit Rev Immunol. 2001;21:427–49.

    CAS  PubMed  Google Scholar 

  26. Blanco M, Castellanos M, Rodríguez-Yáñez M, Sobrino T, Leira R, Vivancos J, et al. High blood pressure and inflammation are associated with poor prognosis in lacunar infarctions. Cerebrovasc Dis. 2006;22:123–9.

    PubMed  Google Scholar 

  27. Leira R, Rodríguez-Yáñez M, Castellanos M, Blanco M, Nombela F, Sobrino T, et al. Hyperthermia is a surrogate marker of inflammation-mediated cause of brain damage in acute ischaemic stroke. J Intern Med. 2006;260:343–9.

    CAS  PubMed  Google Scholar 

  28. Castellanos M, Sobrino T, Pedraza S. High plasma glutamate concentrations are associated with growth in acute ischemic stroke. Neurology. 2008;71:1862–8.

    CAS  PubMed  Google Scholar 

  29. Castillo J, Alvarez-Sabín J, Martínez-Vila E, Montaner J, Sobrino T, Vivancos J. Inflammation markers and prediction of post-stroke vascular disease recurrence: the MITICO study. J Neurol. 2009;256:217–24.

    CAS  PubMed  Google Scholar 

  30. Rodríguez-Yáñez M, Sobrino T, Arias S, Vázquez-Herrero F, Brea D, Blanco M, et al. Early biomarkers of clinical-diffusion mismatch in acute ischemic stroke. Stroke. 2011;42:2813–8.

    PubMed  Google Scholar 

  31. Rodríguez-Yáñez M, Castellanos M, Sobrino T, Brea D, Ramos-Cabrer P, Pedraza S, et al. Interleukin-10 facilitates the selection of patients for systemic thrombolysis. BMC Neurol. 2013;13:62.

    PubMed  PubMed Central  Google Scholar 

  32. Campos F, Blanco M, Barral D, Agulla J, Ramos-Cabrer P, Castillo J. Influence of temperature on ischemic brain: basic and clinical principles. Neurochem Int. 2012;60:495–505.

    CAS  PubMed  Google Scholar 

  33. Towfighi A, Ovbiagele B. The impact of body mass index on mortality after stroke. Stroke. 2009;40:2704–8.

    PubMed  Google Scholar 

  34. Kim Y, Kim CK, Jung S, Yoon B, Lee S. Obesity-stroke paradox and initial neurological severity. J Neurol Neurosurg Psychiatry. 2015;86:743–7.

    PubMed  Google Scholar 

  35. Nalliah CJ, Sanders P, Kottkamp H, Kalman JM. The role of obesity in atrial fibrillation. Eur Heart J. 2016;37:1565–72.

    PubMed  Google Scholar 

  36. Kim CK, Ryu W-S, Kim BJ, Lee S-H. Paradoxical effect of obesity on hemorrhagic transformation after acute ischemic stroke. BMC Neurol. 2013;13:123.

    PubMed  PubMed Central  Google Scholar 

  37. Haley MJ, Lawrence CB. Obesity and stroke: can we translate from rodents to patients? J Cereb Blood Flow Metab. 2016;36:2007–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Maachi M, Piéroni L, Bruckert E, Jardel C, Fellahi S, Hainque B, et al. Systemic low-grade inflammation is related to both circulating and adipose tissue TNFα, leptin and IL-6 levels in obese women. Int J Obes. 2004;28:993–7.

    CAS  Google Scholar 

  39. Khaodhiar L, Ling P-R, Blackburn GL, Bistrian BR. Serum levels of interleukin-6 and c-reactive protein correlate with body mass index across the broad range of obesity. J Parenter Enter Nutr. 2004;28:410–5.

    CAS  Google Scholar 

  40. Terao S, Yilmaz G, Stokes KY, Ishikawa M, Kawase T, Granger DN. Inflammatory and injury responses to ischemic stroke in obese mice. Stroke. 2008;39:943–50.

    PubMed  Google Scholar 

  41. Bowes MP, Rothlein R, Fagan SC, Zivin JA. Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy. Neurology. 1995;45:815–9.

    CAS  PubMed  Google Scholar 

  42. Härtl R, Schürer L, Schmid-Schönbein GW, del Zoppo GJ. Experimental antileukocyte interventions in cerebral ischemia. J Cereb Blood Flow Metab. 1996;16:1108–19.

    PubMed  Google Scholar 

  43. Vila N, Castillo J, Dávalos A, Chamorro A. Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke. 2000;31:2325–9.

    CAS  PubMed  Google Scholar 

  44. Castellanos M, Castillo J, García MM, Leira R, Serena J, Chamorro A, et al. Inflammation-mediated damage in progressing lacunar infarctions. Stroke. 2002;33:982–7.

    PubMed  Google Scholar 

  45. Scherbakov N, Dirnagl U, Doehner W. Body weight after stroke: lessons from the obesity paradox. Stroke. 2011;42:3646–50.

    PubMed  Google Scholar 

  46. Wohlfahrt P, Lopez-jimenez F, Krajcoviechova A, Jozifova M, Mayer O, Vanek J, et al. The obesity paradox and survivors of ischemic stroke. J Stroke Cerebrovasc Dis. 2015;24:1443–50.

    PubMed  Google Scholar 

  47. Kim Y, Kim CK, Jung S, Ko S-B, Lee S-H, Yoon B-W. Prognostic importance of weight change on short-term functional outcome in acute ischemic stroke. Int J Stroke. 2015;10:62–8.

    PubMed  Google Scholar 

  48. Jonsson A-C, Lindgren I, Norrving B, Lindgren A. Weight loss after stroke: a population-based study from the Lund Stroke Register. Stroke. 2008;39:918–23.

    PubMed  Google Scholar 

  49. Myers J, Lata K, Chowdhury S, McAuley P, Jain N, Froelicher V. The obesity paradox and weight loss. Am J Med. 2011;124:924–30.

    PubMed  Google Scholar 

  50. Dinarello CA, Cannon JG, Mancilla J, Bishai I, Lees J, Coceani F. Interleukin-6 as an endogenous pyrogen: induction of prostaglandin E2 in brain but not in peripheral blood mononuclear cells. Brain Res. 1991;562:199–206.

    CAS  PubMed  Google Scholar 

  51. Kinoshita K, Chatzipanteli i K, Vitarbo E, Truettner JS, Alonso OF, Dietrich WD. Interleukin-1beta messenger ribonucleic acid and protein levels after fluid-percussion brain injury in rats: importance of injury severity and brain temperature. Neurosurgery. 2002;51:195–203.

    PubMed  Google Scholar 

  52. Dietrich WD, Chatzipanteli K, Vitarbo E, Wada K, Kinoshita K. The role of inflammatory processes in the pathophysiology and treatment of brain and spinal cord trauma. Acta Neurochir Suppl. 2004;89:69–74.

    CAS  PubMed  Google Scholar 

  53. Badjatia N. Hyperthermia and fever control in brain injury. Crit Care Med. 2009;37:S250–7.

    PubMed  Google Scholar 

  54. Contreras C, González F, Fernø J, Diéguez C, Rahmouni K, Nogueiras R, et al. The brain and brown fat. Ann Med. 2005;47:150–68.

    Google Scholar 

  55. Gallagher D, Visser M, Sepúlveda D, Pierson RN, Harris T, Heymsfield SB. How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups? Am J Epidemiol. 1996;143:228–39.

    CAS  PubMed  Google Scholar 

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Funding

This project was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2014-56336-R, SAF2015-71026-R and SAF2017-84267-R), Xunta de Galicia (Consellería Educación: GRC2014/027, 2016-PG068 and IN607A2018/3), Instituto de Salud Carlos III (Proyecto de Excelencia dentro de los Institutos de Investigación Sanitaria (PIE13/00024) and PI17/01103), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019), and by the European Union FEDER program. Furthermore, T. Sobrino (CPII17/00027) and F. Campos (CP14/00154) are recipients of research contracts from the Miguel Servet Program of Instituto de Salud Carlos III. The sponsors did not participate in study design, collection, analysis, or interpretation of the data, in writing the report, or in the decision to submit the paper for publication.

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Correspondence to Tomás Sobrino or José Castillo.

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This research was carried out in accordance with the Declaration of Helsinki of the World Medical Association (2008) and approved by the Ethics Committee of the Servizo Galego de Saúde. Informed consent was obtained from all individual participants included in the study. If patients were not able to sign, relatives gave signed informed consent.

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Rodríguez-Castro, E., Rodríguez-Yáñez, M., Arias-Rivas, S. et al. Obesity Paradox in Ischemic Stroke: Clinical and Molecular Insights. Transl. Stroke Res. 10, 639–649 (2019). https://doi.org/10.1007/s12975-019-00695-x

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