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Obesity Increases Stroke Risk in Young Adults

2015; Lippincott Williams & Wilkins; Volume: 46; Issue: 6 Linguagem: Inglês

10.1161/strokeaha.115.009347

1524-4628

Walter N. Kernan, Jennifer L. Dearborn,

Acute Ischemic Stroke Management

HomeStrokeVol. 46, No. 6Obesity Increases Stroke Risk in Young Adults Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBObesity Increases Stroke Risk in Young AdultsOpportunity for Prevention Walter N. Kernan, MD and Jennifer L. Dearborn, MD, MPH Walter N. KernanWalter N. Kernan From the Departments of Internal Medicine (W.N.K.) and Neurology (J.L.D.), Yale School of Medicine, New Haven, CT. and Jennifer L. DearbornJennifer L. Dearborn From the Departments of Internal Medicine (W.N.K.) and Neurology (J.L.D.), Yale School of Medicine, New Haven, CT. Originally published5 May 2015https://doi.org/10.1161/STROKEAHA.115.009347Stroke. 2015;46:1435–1436Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2015: Previous Version 1 See related article, p 1690.A debate has been smoldering over the meaning of obesity in reducing the world burden of stroke. Like so many debates in medicine, it begins with disagreements about the interpretation of evidence, the meaning of statistical test results, and the role of bias. In one camp, are those who see that obesity is associated with increased risk for stroke and say that it as an important target for primary and secondary prevention. In the other, are those who agree that obesity increases stroke but say that it is more effective to treat the consequence of obesity that are responsible for stroke risk (ie, hypertension and dyslipidemia) than obesity itself.What everyone can agree on is that obesity is epidemic. In the United States, the prevalence of obesity (ie, body mass index [BMI] >30 kg/m2) increases with age from 17% for children aged 30 kg/m2 have about a 70% increased risk for ischemic stroke compared with patients with a BMI <25 kg/m2.4,5In this issue of Stroke, Mitchell et al6 raise further concern about obesity by showing an association with increased stroke risk in a study composed exclusively of young adults. Mitchell et al6 studied men and women aged 15 to 49 years who participated in 3 separate case–control studies. A total of 1201 case subjects with ischemic stroke were identified from 59 hospitals in the Maryland/Washington, DC, area. A total of 1154 control subjects were identified by random-digit dialing and frequency matched to case subjects for age (within 10 years), region of residence, and ethnicity.7,8 Despite the young age of the case subjects, 42% had hypertension, 17% had diabetes mellitus, and 40% were obese. In an analysis adjusted for age, sex, race, and smoking, obesity was associated with a 65% increased risk for ischemic stroke (odds ratio, 1.65; 95% confidence interval, 1.33–2.04), but the association was substantially attenuated by further adjustment for hypertension, and diabetes mellitus (odds ratio, 1.21; 95% confidence interval, 0.96–1.51).This finding of Mitchell et al6 on hypertension and diabetes mellitus is consistent with research among older populations. In fact, there is broad agreement that these factors partially mediate the observed association between obesity and risk for vascular disease. Other mediators include vascular inflammation, insulin resistance, and dyslipidemia. Herein lies the controversy on the interpretation of obesity research. In statistical terms, a mediator is something that is on the causal pathway between an independent variable and a dependent variable. For example, obesity causes the hypertension (the mediator) that causes the stroke. Adjustment for a mediator will always attenuate a measure of association, but whether it affects the importance of the unadjusted finding is a matter of interpretation.In the case of obesity among young adults, some will highlight the unadjusted findings of Mitchell et al6 to say we should treat the obesity to prevent the mediators which result in stroke. Others will say, treat the mediators and leave the obesity alone. If we had better therapy for obesity, there would probably be no controversy and we would all agree that treating obesity is the best first option. A justification for this approach is that the adjusted odds ratio of Mitchell et al6 was still 1.21 overall (95% confidence interval, 0.96–1.51) and 1.34 in men (95% confidence interval, 0.96–1.88). This elevated odds ratio suggests that residual risk may remain and that that even optimal prescription of risk-reducing therapy (eg, hypertension therapy) would still leave many young obese patients exposed to untreated risk. This is particularly true because the only practical risk-reducing therapy for mediators of vascular disease in obesity is hypertension therapy. Research has not firmly established that tight control of diabetes mellitus reduces risk for vascular disease; there are no specific therapies recommended for treating the inflammation of obesity, and many young patients are not currently considered candidates for lipid-lowering therapy.Another argument in favor of treating obesity in young adults (and not just the mediators) is that young adults carry the burden of obesity for more years than older patients and, therefore, may realize a larger lifetime benefit from weight reduction. Treatment of obesity, furthermore, would have benefits beyond stroke reduction, including a possible reduction in risk for vascular cognitive impairment and dementia through mechanisms that include modulation of inflammation, hypertension, hyperglycemia, dyslipidemia, and insulin resistance.9How reliable are the findings by Mitchell et al?6 Case–control studies achieve reliability by enrolling unbiased samples of cases and controls from the underlying population and accurately classifying clinical characteristics, including exposure status. Mitchell et al6 accepted case subject referrals7 and did not report their enrolled fraction, thus raising the possibility that their sample may not be fully representative of patients with ischemic stroke in their area. There is no obvious reason, however, why patients with obesity would be differentially enrolled. Control subjects were identified by random-digit dialing7 and, again, we are not told about the fraction of enrolled to eligible. Perhaps more concerning are the matching method and the method for classifying weight and height by self-report. Frequency matching did not result in case and control groups that were fully matched for age, sex, or race and this might have resulted in some residual confounding. Although self-report weight typically underestimates actual weight, there is no obvious reason that the error would be differential between case and control subjects. Ideally, the authors would have measured weight and obtained data on waist circumference, which may be more accurate than BMI in characterizing cardiovascular disease risk. Overall, however, the study is fairly well designed, and the results are likely to be reliable.The study by Mitchell et al6 was not designed to measure the effect of obesity on risk for recurrent stroke, but other research has stirred uncertainty by reporting that stroke patients with obesity may have a lower risk for major vascular events after ischemic stroke.10 This apparent protective effect of obesity in observational research, termed the obesity paradox, may be the result of a form of selection bias.11 In short, developing stroke as a consequence of obesity may be less harmful than developing a stroke as a result of other factors.11The findings by Mitchell et al6 have implications for clinical and public health approaches to stroke prevention. In the United States alone, the data from this study suggests that many strokes may be attributable to obesity annually among young adults. The worldwide burden would be much greater. To prevent obesity-associated stroke among young adults, clinical approaches include community and office-based screening to identify obese patients for weight loss and treatment of risk factors, such as hypertension. Obese young adults should be seen regularly by primary care providers who are trained to recognize stroke risk factors and prescribe appropriate preventive therapy. Weight loss is trickier because we do not have highly effective ways to treat obesity in the office. The American Heart Association and others recognize this and recommend referring obese patients to programs that can provide intensive counseling.12 Some young adults will be successful, but on a large scale, available research suggests that the modest average weight loss accomplished with intensive counseling may not substantially affect cardiovascular risk.13 More effective approaches to weight loss are likely to emerge from science examining the biochemistry of appetite and obesity, and from public policy initiatives that encourage healthier eating and more physical activity in communities. Until biochemical research fuels translational research and more effective obesity treatment, the study by Mitchell et al6 supports a clear message to young adult patients and the public that the harmful effects of obesity on the brain start early in life.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Guest Editor for this article was Tatjana Rundek, MD, PhD.Correspondence to Walter N. Kernan, MD, Suite 515, 2 Church St S, New Haven, CT 06519. E-mail [email protected]References1. Flegal KM, Carroll MD, Kit BK, Ogden CLPrevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010.JAMA. 2012; 307:491–497. doi: 10.1001/jama.2012.39.CrossrefMedlineGoogle Scholar2. Skinner AC, Skelton JAPrevalence and trends in obesity and severe obesity among children in the United States, 1999-2012.JAMA Pediatr. 2014; 168:561–566. doi: 10.1001/jamapediatrics.2014.21.CrossrefMedlineGoogle Scholar3. Kernan WN, Inzucchi SE, Sawan C, Macko RF, Furie KLObesity: a stubbornly obvious target for stroke prevention.Stroke. 2013; 44:278–286. doi: 10.1161/STROKEAHA.111.639922.LinkGoogle Scholar4. Hu G, Tuomilehto J, Silventoinen K, Sarti C, Männistö S, Jousilahti PBody mass index, waist circumference, and waist-hip ratio on the risk of total and type-specific stroke.Arch Intern Med. 2007; 167:1420–1427. doi: 10.1001/archinte.167.13.1420.CrossrefMedlineGoogle Scholar5. Kurth T, Gaziano JM, Rexrode KM, Kase CS, Cook NR, Manson JE, et al. Prospective study of body mass index and risk of stroke in apparently healthy women.Circulation. 2005; 111:1992–1998. doi: 10.1161/01.CIR.0000161822.83163.B6.LinkGoogle Scholar6. Mitchell AB, Cole JW, McArdle PF, Cheng Y-C, Ryan KA, Sparks MJ, et al. Obesity increases risk of ischemic stroke in young adults.Stroke. 2015; 46:1690–1692. doi: 10.1161/STROKEAHA.115.008940.LinkGoogle Scholar7. Bhat VM, Cole JW, Sorkin JD, Wozniak MA, Malarcher AM, Giles WH, et al. Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women.Stroke. 2008; 39:2439–2443. doi: 10.1161/STROKEAHA.107.510073.LinkGoogle Scholar8. MacClellan LR, Giles W, Cole J, Wozniak M, Stern B, Mitchell BD, et al. Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study.Stroke. 2007; 38:2438–2445. doi: 10.1161/STROKEAHA.107.488395.LinkGoogle Scholar9. De Felice FG, Ferreira STInflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease.Diabetes. 2014; 63:2262–2272. doi: 10.2337/db13-1954.CrossrefMedlineGoogle Scholar10. Ovbiagele B, Bath PM, Cotton D, Vinisko R, Diener HCObesity and recurrent vascular risk after a recent ischemic stroke.Stroke. 2011; 42:3397–3402. doi: 10.1161/STROKEAHA.111.624957.LinkGoogle Scholar11. Lajous M, Banack HR, Kaufman JS, Hernán MAShould patients with chronic disease be told to gain weight? The obesity paradox and selection bias.Am J Med. 2015; 128:334–336. doi: 10.1016/j.amjmed.2014.10.043.CrossrefMedlineGoogle Scholar12. Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society.Circulation. 2014; 129(25 suppl 2):S102–S138. doi: 10.1161/01.cir.0000437739.71477.ee.LinkGoogle Scholar13. The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.N Engl J Med. 2013; 369:145–154.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByWebb A and Werring D (2022) New Insights Into Cerebrovascular Pathophysiology and Hypertension, Stroke, 53:4, (1054-1064), Online publication date: 1-Apr-2022. Jacobs M and Ellis C (2021) Heterogeneity among women with stroke: health, demographic and healthcare utilization differentials, BMC Women's Health, 10.1186/s12905-021-01305-5, 21:1, Online publication date: 1-Dec-2021. Kumral E, Erdoğan C, Arı A, Bayam F and Saruhan G (2021) Association of obesity with recurrent stroke and cardiovascular events, Revue Neurologique, 10.1016/j.neurol.2020.06.019, 177:4, (414-421), Online publication date: 1-Apr-2021. Sharma G and Prossnitz E (2021) Targeting the G protein-coupled estrogen receptor (GPER) in obesity and diabetes, Endocrine and Metabolic Science, 10.1016/j.endmts.2021.100080, 2, (100080), Online publication date: 1-Mar-2021. Ramphul K, Ramphul Y, Sombans S, Lohana P, Verma R, Kumar N and Joynauth J (2021) Incidence and mortality rates of acute ischemic stroke in hospitalized patients in the United States, Archives of Medical Science – Atherosclerotic Diseases, 10.5114/amsad.2021.107820, 6:1, (132-134) Zambrano Espinoza M, Lail N, Vaughn C, Shirani P, Sawyer R and Mowla A (2021) Does Body Mass Index Impact the Outcome of Stroke Patients Who Received Intravenous Thrombolysis?, Cerebrovascular Diseases, 10.1159/000511489, 50:2, (141-146), . Prestgaard E, Mariampillai J, Engeseth K, Erikssen J, Bodegård J, Liestøl K, Kjeldsen S, Grundvold I and Berge E (2020) Change in Body Weight and Long-Term Risk of Stroke and Death in Healthy Men, Stroke, 51:5, (1435-1441), Online publication date: 1-May-2020.George M (2020) Risk Factors for Ischemic Stroke in Younger Adults, Stroke, 51:3, (729-735), Online publication date: 1-Mar-2020. Darke S, Duflou J, Kaye S, Farrell M and Lappin J (2019) Body mass index and fatal stroke in young adults: A national study, Journal of Forensic and Legal Medicine, 10.1016/j.jflm.2019.02.003, 63, (1-6), Online publication date: 1-Apr-2019. Clark D, Keith N, Weiner M and Xu H (2019) Outcomes of an RCT of videoconference vs. in‐person or in‐clinic nutrition and exercise in midlife adults with obesity, Obesity Science & Practice, 10.1002/osp4.318, 5:2, (111-119), Online publication date: 1-Apr-2019. Mendy V, Vargas R, Payton M, Sims J and Zhang L (2019) Trends in the Stroke Death Rate Among Mississippi Adults, 2000–2016, Preventing Chronic Disease, 10.5888/pcd16.180425, 16 Rovella V, Anemona L, Cardellini M, Scimeca M, Saggini A, Santeusanio G, Bonanno E, Montanaro M, Legramante I, Ippoliti A, Di Daniele N, Federici M and Mauriello A (2018) The role of obesity in carotid plaque instability: interaction with age, gender, and cardiovascular risk factors, Cardiovascular Diabetology, 10.1186/s12933-018-0685-0, 17:1, Online publication date: 1-Dec-2018. Vicente V, Cabral N, Nagel V, Guesser V and Safanelli J (2018) Prevalence of obesity among stroke patients in five Brazilian cities: a cross-sectional study, Arquivos de Neuro-Psiquiatria, 10.1590/0004-282x20180053, 76:6, (367-372) Johnson H, LaMantia J, Brown C, Warner R, Zeller L, Haggart R, Stonewall K and Lauver D (2017) My Hypertension Education and Reaching Target (MyHEART): Development and Dissemination of a Patient-Centered Website for Young Adults with Hypertension, JMIR Cardio, 10.2196/cardio.8025, 1:2, (e5) Aigner A, Grittner U, Rolfs A, Norrving B, Siegerink B and Busch M (2017) Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults, Stroke, 48:7, (1744-1751), Online publication date: 1-Jul-2017. Warren B and Odenheimer Brin E (2017) Advancing the physical activity curriculum at the collegiate level, Health Education, 10.1108/HE-07-2016-0026, 117:4, (372-381), Online publication date: 5-Jun-2017. Aycock D, Clark P and Hayat M (2016) Reducing Stroke Risk Among Young Adult African Americans: A Feasibility Study, Research in Nursing & Health, 10.1002/nur.21776, 40:2, (153-164), Online publication date: 1-Apr-2017. Yu P, Pan Y, Zheng H, Wang X, Yan H, Tong X, Jing J, Zhang X, Guo L and Wang Y (2017) Association of high waist-to-height ratio with functional outcomes in patients with acute ischemic stroke, Medicine, 10.1097/MD.0000000000006520, 96:13, (e6520), Online publication date: 1-Mar-2017. Sharma G and Prossnitz E (2017) G-Protein-Coupled Estrogen Receptor (GPER) and Sex-Specific Metabolic Homeostasis Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity, 10.1007/978-3-319-70178-3_20, (427-453), . Johnson H, Warner R, LaMantia J and Bowers B (2016) "I have to live like I'm old." Young adults' perspectives on managing hypertension: a multi-center qualitative study, BMC Family Practice, 10.1186/s12875-016-0428-9, 17:1, Online publication date: 1-Dec-2016. June 2015Vol 46, Issue 6 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.115.009347PMID: 25944321 Originally publishedMay 5, 2015 Keywordsstrokeprevention & controlobesityEditorialsPDF download Advertisement SubjectsIschemic Stroke