Neurointervention.  2021 Mar;16(1):9-19. 10.5469/neuroint.2020.00108.

Obesity and Stroke: Does the Paradox Apply for Stroke?

Affiliations
  • 1Faculty of Medicine, University El Bosque, Bogota, Colombia
  • 2Consejo Latinoamericano de Neurointensivismo (CLaNi), Cartagena, Colombia
  • 3Centro de Investigaciones Biomedicas (CIB), Faculty of Medicine, University of Cartagena, Cartagena, Colombia
  • 4Department of Neurosurgery, All India Institute of Medical Sciences, Madhya Pradesh, India

Abstract

Historically, obesity has been identified as one of the most important risk factors for developing cardiovascular diseases including stroke; however, a theory called “The Obesity Paradox” has been recently considered. The paradoxical theory is that obese or overweight patients (according to body mass index score) can have better outcomes compared to leaner or malnourished patients. The paradox was initially discovered in patients with heart failure. The purpose of this manuscript was to investigate whether this paradox also applies to stroke patients, according to information available in the current literature.

Keyword

Obesity; Cerebrovascular disease; Stroke; Body mass index

Figure

  • Fig. 1. Increased activity of IkB/NFkB as the basis of the chronic inflammation and insulin resistance in type 2 diabetes. Intracellular fatty acyl-CoA levels found in insulin resistance and lipotoxicity, in correlation to the subsequent activation of the enzyme IkB kinase (via inflammatory factors such as fatty acyl-CoAs), will phosphorylate IkB, causing the release of NFkB (upon the polyubiquitination and degradation of IkB), which enters the nucleus where it is responsible for inflammation, cell proliferation and atherogenesis by the stimulation of inflammatory cytokines, growth factors, and iNOS, which in turn will stimulate TNFα, IL-6, and PKC, which will impede insulin signaling by serine phosphorylation of IRS-1 ultimately, causing insulin resistance. Therefore, the increased activity of IkB/NFkB will not only instigate inflammation but also further aid and boost atherogenesis. The MAP kinase pathway is responsible for the insulin-stimulated glucose impaired metabolism and for this reason, related to cardiovascular diseases. FACoA, Fatty acyl-CoA; IkB, Inhibitor kβ; IL1 and IL6, Interleukins 1 and 6; IRS, Insulin Receptor Substitute 1; MAP, Mitogen-Activated Protein; NFkB, Nuclear factor kβ; NO, Nitric Oxide; NOS, Nitric Oxide Synthase; PI3K, Phosphoinositide 3-kinase; PKC, Protein Kinase C; SCH, Src homology 2 domain; TNFα, Tumor Necrosis Factor alpha; Inflam, Inflammatory. Adapted and modified from the article of Yazici and Sezer (Adv Exp Med Biol 2017;960:277-304) [56].

  • Fig. 2. The adiposity and lipotoxicity in chronic disease. Adapted and modified from the article of Heymsfield and Wadden (N Engl J Med 2017;376:254-266) [57].


Reference

1. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham heart study. Circulation. 1983; 67:968–977.
Article
2. Yatsuya H, Yamagishi K, North KE, Brancati FL, Stevens J, Folsom AR; ARIC Study Investigators. Associations of obesity measures with subtypes of ischemic stroke in the ARIC study. J Epidemiol. 2010; 20:347–354.
Article
3. Wu S, Wu B, Liu M, Chen Z, Wang W, Anderson CS, et al. China Stroke Study Collaboration. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol. 2019; 18:394–405.
4. World Health Organization (WHO). Obesity and overweight [Internet]. Geneva: WHO;[cited 2020 Oct 28]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
5. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff (Millwood). 2009; 28:w822–w831.
Article
6. Cawley J, Meyerhoefer C. The medical care costs of obesity: an instrumental variables approach. J Health Econ. 2012; 31:219–230.
Article
7. Guzik A, Bushnell C. Stroke epidemiology and risk factor management. Continuum (Minneap Minn). 2017; 23:15–39.
Article
8. Hruby A, Hu FB. The epidemiology of obesity: a big picture. Pharmacoeconomics. 2015; 33:673–689.
Article
9. Kim Y, Kim CK, Jung S, Yoon BW, Lee SH. Obesity-stroke paradox and initial neurological severity. J Neurol Neurosurg Psychiatry. 2015; 86:743–747.
Article
10. Johnson W, Onuma O, Owolabi M, Sachdev S. Stroke: a global response is needed. Bull World Health Organ. 2016; 94:634–634. A.
Article
11. Lavie CJ, Arena R, Alpert MA, Milani RV, Ventura HO. Management of cardiovascular diseases in patients with obesity. Nat Rev Cardiol. 2018; 15:45–56.
Article
12. Guo Y, Yue XJ, Li HH, Song ZX, Yan HQ, Zhang P, et al. Overweight and obesity in young adulthood and the risk of stroke: a meta-analysis. J Stroke Cerebrovasc Dis. 2016; 25:2995–3004.
Article
13. Ovbiagele B, Nguyen-Huynh MN. Stroke epidemiology: advancing our understanding of disease mechanism and therapy. Neurotherapeutics. 2011; 8:319–329.
Article
14. Hankey GJ. Stroke. Lancet. 2017; 389:641–654.
Article
15. Díez-Tejedor E, del Brutto O, Alvarez Sabín J, Muñoz M, Abiusi G; Sociedad Iberoamericana de Enfermedades Cerebrovasculares. [Classification of the cerebrovascular diseases. Iberoamerican Cerebrovascular diseases Society]. Rev Neurol. 2001; 33:455–464. Spanish.
16. Cassella CR, Jagoda A. Ischemic stroke: advances in diagnosis and management. Emerg Med Clin North Am. 2017; 35:911–930.
17. Wang P, Wang Y, Zhao X, Du W, Wang A, Liu G, et al. In-hospital medical complications associated with stroke recurrence after initial ischemic stroke: a prospective cohort study from the China National Stroke Registry. Medicine (Baltimore). 2016; 95:e4929.
18. Jordán J, Ikuta I, García-García J, Calleja S, Segura T. Stroke pathophysiology: management challenges and new treatment advances. J Physiol Biochem. 2007; 63:261–277.
Article
19. Morales-Plaza CD, Aguirre-Castañeda C, Machado-Alba JE. [Predictors of stroke mortality in the Hospital Universitario San Jorge of Pereira (Colombia)]. Salud Uninorte. 2016; 32:56–64. Spanish.
Article
20. Haley MJ, Lawrence CB. Obesity and stroke: can we translate from rodents to patients? J Cereb Blood Flow Metab. 2016; 36:2007–2021.
Article
21. Letra L, Sena C. Cerebrovascular disease: consequences of obesity-induced endothelial dysfunction. In : Letra L, Seiça R, editors. Obesity and brain function. Cham: Springer;2017. p. 163–189.
22. Carbone S, Lavie CJ, Arena R. Obesity and heart failure: focus on the obesity paradox. Mayo Clin Proc. 2017; 92:266–279.
Article
23. Clark AL, Fonarow GC, Horwich TB. Obesity and the obesity paradox in heart failure. Prog Cardiovasc Dis. 2014; 56:409–414.
Article
24. Mitchell AB, Cole JW, McArdle PF, Cheng YC, Ryan KA, Sparks MJ, et al. Obesity increases risk of ischemic stroke in young adults. Stroke. 2015; 46:1690–1692.
Article
25. Brzecka A, Ejma M. Obesity paradox in the course of cerebrovascular diseases. Adv Clin Exp Med. 2015; 24:379–383.
Article
26. Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Woo MA, Tillisch JH. The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol. 2001; 38:789–795.
Article
27. Doehner W, Schenkel J, Anker SD, Springer J, Audebert HJ. Overweight and obesity are associated with improved survival, functional outcome, and stroke recurrence after acute stroke or transient ischaemic attack: observations from the TEMPiS trial. Eur Heart J. 2013; 34:268–277.
Article
28. Bhurosy T, Jeewon R. Overweight and obesity epidemic in developing countries: a problem with diet, physical activity, or socioeconomic status? ScientificWorldJournal. 2014; 2014:964236.
Article
29. Elagizi A, Kachur S, Lavie CJ, Carbone S, Pandey A, Ortega FB, et al. An overview and update on obesity and the obesity paradox in cardiovascular diseases. Prog Cardiovasc Dis. 2018; 61:142–150.
Article
30. Parto P, Lavie CJ, Arena R, Bond S, Popovic D, Ventura HO. Body habitus in heart failure: understanding the mechanisms and clinical significance of the obesity paradox. Future Cardiol. 2016; 12:639–653.
Article
31. Rodríguez-Castro E, Rodríguez-Yáñez M, Arias-Rivas S, Santamaría-Cadavid M, López-Dequidt I, Hervella P, et al. Obesity paradox in ischemic stroke: clinical and molecular insights. Transl Stroke Res. 2019; 10:639–649.
Article
32. Horwich TB, Fonarow GC, Clark AL. Obesity and the obesity paradox in heart failure. Prog Cardiovasc Dis. 2018; 61:151–156.
Article
33. GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017; 377:13–27.
Article
34. Dangayach NS, Grewal HS, De Marchis GM, Sefcik RK, Bruce R, Chhatlani A, et al. Does the obesity paradox predict functional outcome in intracerebral hemorrhage? J Neurosurg. 2018; 129:1125–1129.
Article
35. Forlivesi S, Cappellari M, Bonetti B. Obesity paradox and stroke: a narrative review. [published online ahead of print Mar 2, 2020]. Eat Weight Disord. 2020; [published online ahead of print Mar 2, 2020].
Article
36. Vilahur G, Ben-Aicha S, Badimon L. New insights into the role of adipose tissue in thrombosis. Cardiovasc Res. 2017; 113:1046–1054.
Article
37. Bosello O, Donataccio MP, Cuzzolaro M. Obesity or obesities? Controversies on the association between body mass index and premature mortality. Eat Weight Disord. 2016; 21:165–174.
Article
38. Ashwell M, Mayhew L, Richardson J, Rickayzen B. Waist-to-height ratio is more predictive of years of life lost than body mass index. PLoS One. 2014; 9:e103483.
Article
39. Wang S, Ren J. Obesity paradox in aging: from prevalence to pathophysiology. Prog Cardiovasc Dis. 2018; 61:182–189.
Article
40. Antonopoulos AS, Tousoulis D. The molecular mechanisms of obesity paradox. Cardiovasc Res. 2017; 113:1074–1086.
Article
41. Engin A. The definition and prevalence of obesity and metabolic syndrome. Adv Exp Med Biol. 2017; 960:1–17.
Article
42. Apovian CM. Obesity: definition, comorbidities, causes, and burden. Am J Manag Care. 2016; 22(7 Suppl):s176–s185.
43. Uribe AG, Gómez FR, Muñoz NJM, Bernal GB, Hoyos JLO, Tovar YG, et al. [Guía de práctica clínica: para la prevención, diagnóstico y tratamiento del sobrepeso y la obesidad en adultos. Sistema general de seguridad social en salud - Colombia. Guía completa. guía no. 52]. Bogotá: Ministerio de Salud y Protección Social;2016. Spanish.
44. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, INTERHEART Study Investigators, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004; 364:937–952.
Article
45. O’Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, INTERSTROKE investigators, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet. 2016; 388:761–775.
46. Kurth T, Gaziano JM, Berger K, Kase CS, Rexrode KM, Cook NR, et al. Body mass index and the risk of stroke in men. Arch Intern Med. 2002; 162:2557–2562.
Article
47. Oesch L, Tatlisumak T, Arnold M, Sarikaya H. Obesity paradox in stroke - myth or reality? A systematic review. PLoS One. 2017; 12:e0171334.
Article
48. Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, SMART Investigators and the Pragmatic Critical Care Research Group, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018; 378:829–839.
Article
49. Rautalin I, Kaprio J, Korja M. Obesity paradox in subarachnoid hemorrhage: a systematic review. [published online ahead of print Oct 29, 2019]. Neurosurg Rev. 2019.
Article
50. Lavie CJ, De Schutter A, Parto P, Jahangir E, Kokkinos P, Ortega FB, et al. Obesity and prevalence of cardiovascular diseases and prognosis-the obesity paradox updated. Prog Cardiovasc Dis. 2016; 58:537–547.
Article
51. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 384:766–781.
52. Triviño L, Ávila JC, Ramírez-Vélez R. [The paradox of obesity and its relationship to cardiorespiratory fitness in patients with heart failure]. Rev Colomb Cardiol. 2015; 22:218–223. Spanish.
53. Lavie CJ, Osman AF, Milani RV, Mehra MR. Body composition and prognosis in chronic systolic heart failure: the obesity paradox. Am J Cardiol. 2003; 91:891–894.
Article
54. Ortega FB, Ruiz JR, Labayen I, Lavie CJ, Blair SN. The fat but fit paradox: what we know and don’t know about it. Br J Sports Med. 2018; 52:151–153.
Article
55. Hughes JD, Samarage M, Burrows AM, Lanzino G, Rabinstein AA. Body mass index and aneurysmal subarachnoid hemorrhage: decreasing mortality with increasing body mass index. World Neurosurg. 2015; 84:1598–1604.
Article
56. Yazıcı D, Sezer H. Insulin resistance, obesity and lipotoxicity. Adv Exp Med Biol. 2017; 960:277–304.
Article
57. Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. N Engl J Med. 2017; 376:254–266.
Article
58. 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; 24:1443–1450.
Article
59. Kim BJ, Lee SH, Ryu WS, Kim CK, Lee J, Yoon BW. Paradoxical longevity in obese patients with intracerebral hemorrhage. Neurology. 2011; 76:567–573.
Article
60. Vemmos K, Ntaios G, Spengos K, Savvari P, Vemmou A, Pappa T, et al. Association between obesity and mortality after acute first-ever stroke: the obesity-stroke paradox. Stroke. 2011; 42:30–36.
Article
61. Hassan AE, Chaudhry SA, Jani V, Grigoryan M, Khan AA, Adil MM, et al. Is there a decreased risk of intracerebral hemorrhage and mortality in obese patients treated with intravenous thrombolysis in acute ischemic stroke? J Stroke Cerebrovasc Dis. 2013; 22:545–549.
Article
62. Skolarus LE, Sanchez BN, Levine DA, Baek J, Kerber KA, Morgenstern LB, et al. Association of body mass index and mortality after acute ischemic stroke. Circ Cardiovasc Qual Outcomes. 2014; 7:64–69.
Article
63. Andersen KK, Olsen TS. The obesity paradox in stroke: lower mortality and lower risk of readmission for recurrent stroke in obese stroke patients. Int J Stroke. 2015; 10:99–104.
Article
64. Hoffman H, Jalal MS, Furst T, Chin LS. The obesity paradox in spontaneous intracerebral hemorrhage: results from a retrospective analysis of the nationwide inpatient sample. Neurocrit Care. 2020; 32:765–774.
Article
65. Persaud SR, Lieber AC, Donath E, Stingone JA, Dangayach NS, Zhang X, et al. Obesity paradox in intracerebral hemorrhage. Stroke. 2019; 50:999–1002.
Article
66. Lavie CJ, De Schutter A, Milani RV. Body composition and the obesity paradox in coronary heart disease: can heavier really be healthier? Heart. 2015; 101:1610–1611.
Article
67. Kim BJ, Lee SH, Jung KH, Yu KH, Lee BC, Roh JK; For Korean Stroke Registry investigators. Dynamics of obesity paradox after stroke, related to time from onset, age, and causes of death. Neurology. 2012; 79:856–863.
Article
68. Rinaldo L, Hughes JD, Rabinstein AA, Lanzino G. Effect of body mass index on outcome after aneurysmal subarachnoid hemorrhage treated with clipping versus coiling. J Neurosurg. 2018; 129:658–669.
Article
69. Sharma A, Vallakati A, Einstein AJ, Lavie CJ, Arbab-Zadeh A, Lopez-Jimenez F, et al. Relationship of body mass index with total mortality, cardiovascular mortality, and myocardial infarction after coronary revascularization: evidence from a meta-analysis. Mayo Clin Proc. 2014; 89:1080–1100.
Article
70. Jackson RS, Black JH 3rd, Lum YW, Schneider EB, Freischlag JA, Perler BA, et al. Class I obesity is paradoxically associated with decreased risk of postoperative stroke after carotid endarterectomy. J Vasc Surg. 2012; 55:1306–1312.
Article
71. Pirson FAV, Hinsenveld WH, Staals J, de Greef BTA, van Zwam WH, Dippel DWJ, on behalf of MR CLEAN investigators, et al. The effect of body mass index on outcome after endovascular treatment in acute ischemic stroke patients: a post hoc analysis of the MR CLEAN trial. Cerebrovasc Dis. 2019; 48:200–206.
Article
72. Zhao L, Du W, Zhao X, Liu L, Wang C, Wang Y, et al. Favorable functional recovery in overweight ischemic stroke survivors: findings from the China National Stroke Registry. J Stroke Cerebrovasc Dis. 2014; 23:e201–e206.
Article
73. Bouslama M, Perez HJ, Barreira CM, Haussen DC, Grossberg JA, Belagaje SR, et al. Body mass index and clinical outcomes in large vessel occlusion acute ischemic stroke after endovascular therapy. Interv Neurol. 2020; 8:144–151.
Article
74. Chen Z, Su M, Li Z, Du H, Zhang S, Pu M, et al. Metabolic syndrome predicts poor outcome in acute ischemic stroke patients after endovascular thrombectomy. Neuropsychiatr Dis Treat. 2020; 16:2045–2052.
75. Branscheidt M, Schneider J, Michel P, Eskioglou E, Kaegi G, Stark R, et al. No impact of body mass index on outcome in stroke patients treated with IV thrombolysis BMI and IV thrombolysis outcome. PLoS One. 2016; 11:e0164413.
Article
76. Dasenbrock HH, Nguyen MO, Frerichs KU, Guttieres D, Gormley WB, Ali Aziz-Sultan M, et al. The impact of body habitus on outcomes after aneurysmal subarachnoid hemorrhage: a Nationwide Inpatient Sample analysis. J Neurosurg. 2017; 127:36–46.
Article
77. Platz J, Güresir E, Schuss P, Konczalla J, Seifert V, Vatter H. The impact of the body mass index on outcome after subarachnoid hemorrhage: is there an obesity paradox in SAH? A retrospective analysis. Neurosurgery. 2013; 73:201–208.
78. Schultheiss KE, Jang YG, Yanowitch RN, Tolentino J, Curry DJ, Lüders J, et al. Fat and neurosurgery: does obesity affect outcome after intracranial surgery? Neurosurgery. 2009; 64:316–326.
79. Tawk RG, Grewal SS, Heckman MG, Navarro R, Ferguson JL, Starke EL, et al. Influence of body mass index and age on functional outcomes in patients with subarachnoid hemorrhage. Neurosurgery. 2015; 76:136–141.
Article
80. Kagerbauer SM, Kemptner DM, Schepp CP, Bele S, Rothörl RD, Brawanski AT, et al. Elevated premorbid body mass index is not associated with poor neurological outcome in the subacute state after aneurysmal subarachnoid hemorrhage. Cent Eur Neurosurg. 2010; 71:163–166.
Article
81. Brinjikji W, Cloft H, Cekirge S, Fiorella D, Hanel RA, Jabbour P, et al. Lack of association between statin use and angiographic and clinical outcomes after pipeline embolization for intracranial aneurysms. AJNR Am J Neuroradiol. 2017; 38:753–758.
Article
82. Salem MM, Maragkos GA, Enriquez-Marulanda A, Ascanio L, Ravindran K, Alturki AY, et al. Statin therapy and diabetes do not affect aneurysm occlusion or clinical outcomes after pipeline embolization device treatment: a preliminary study. World Neurosurg. 2018; 120:e525–e532.
Article
83. Ekker MS, Boot EM, Singhal AB, Tan KS, Debette S, Tuladhar AM, et al. Epidemiology, aetiology, and management of ischaemic stroke in young adults. Lancet Neurol. 2018; 17:790–801.
Article
84. Lavie CJ, McAuley PA, Church TS, Milani RV, Blair SN. Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox. J Am Coll Cardiol. 2014; 63:1345–1354.
Full Text Links
  • NI
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr