1 Nutr Hosp. 2013;28(3): ISSN CODEN NUHOEQ S.V.R. 318 Originl / Obesidd Body mss index, bdominl obesity, body ft nd migrine fetures in women Vness Rossoni de Oliveir 1, Fernnd Cmboim Rockett 1,2, Kmil Cstro 1, Alexndre d Silveir Perl 3, Márci Loren Fgundes Chves 3,4 nd Ingrid D. Schweigert Perry 1,4 1 Food nd Nutrition Reserch Center. Hospitl de Clínics de Porto Alegre. Universidde Federl do Rio Grnde do Sul. Porto Alegre. Brzil. 2 Post-Grdution Progrm in Medicine: Medicl Sciences. Universidde Federl do Rio Grnde do Sul. Brzil. 3 Neurology Service. Hospitl de Clínics de Porto Alegre. Porto Alegre. Brzil. 4 Deprtment of Internl Medicine. School of Medicine. Universidde Federl do Rio Grnde do Sul. Porto Alegre. Brzil. Abstrct Bckground: Studies seeking to estblish n ssocition between migrine nd nthropometric prmeters hve thus fr been inconclusive. Furthermore, drugs used for migrine prophylxis my be ssocited with chnges in body weight. Objective: To investigte the potentil ssocition of nthropometric prmeters nd body ft percentge with ttck ptterns nd use of prophylctic mediction in migrineurs. Methods: Cross-sectionl study tht ssessed the body mss index, wist circumference, body ft percentge nd relted clinicl vribles (chrcteristics of ttcks nd the use of prophylctic mediction) in femle outptients with migrine. Results: 166 femle migrineurs ged 18 yers (men ge, 45 ± 14 yers) were included in the study. Migrine without ur ws most prevlent (71.7%). Men body mss index nd body ft percentge were 27.8±6.0 kg/m² nd 36.4 ± 8.3% respectively. Body mss index nd wist circumference were wekly correlted with frequency of ttcks over 6 months (rs = 0.162, p < 0.05 nd rs = 0.187, p < 0.05 respectively). These correltions remins wek considering only premenopusl women, but dispper in the older women. Strtifiction of nlysis by migrine type field shows moderte correltion between migrine with ur nd frequency of ttcks over 6 months nd body mss index (rs = 0.369, p < 0.05), s well s wist circumference (rs = 0.423, p < 0.01). Ptients who were on prophylctic mediction hd higher body mss index, wist circumference, nd body ft percentge vlues (p < 0.01, Student t-test). Conclusion: This study reveled potentil, though tenuous ssocition between migrine nd nthropometric prmeters nd frequency of ttcks, which does not reflect on the durtion, severity, nd disbility of ttcks, with ptterns differing by migrine type, reproductive ge nd prophylctic mediction. (Nutr Hosp. 2013;28: ) DOI: /nh Key words: Migrine. Obesity. Overweight. Abdominl obesity. Body ft. Correspondence: Ingrid Dlir Schweigert Perry. Hospitl de Clínics de Porto Alegre. Centro de Pesquis Clínic - room Ru Rmiro Brcelos, CEP Porto Alegre - RS. Brzil. E-mil: Recibido: 14-II ª Revisión: 21-II Aceptdo: 27-III ÍNDICE DE MASA CORPORAL, OBESIDAD ABDOMINAL, GRASA Y LAS CARACTERÍSTICAS DE LA MIGRAÑA EN MUJERES Resumen Introducción: Los estudios que trtn de estblecer un socición entre l migrñ y los prámetros ntropométricos hst hor hn sido poco concluyentes. Además, los fármcos utilizdos pr l profilxis de l migrñ pueden estr socidos con cmbios en el peso corporl. Objetivos: Investigr l posible socición de los prámetros ntropométricos y el porcentje de grs corporl con ptrones de tque y el uso de l profilxis en los pcientes con migrñ. Métodos: Estudio trnsversl que evluó el índice de ms corporl, circunferenci de cintur, porcentje de grs corporl y ls vribles clínics (crcterístics de los tques y uso de medicción) en mujeres con migrñ. Resultdos: 166 mujeres con migrñ 18 ños (edd medi, 45 ± 14 ños) fueron incluidos en el estudio. Migrñ sin ur er más frecuente (71,7%). L medi del índice de ms corporl y porcentje de grs corporl fueron 27,8 ± 6,0 kg/m² y 36,4 ± 8,3%, respectivmente. Índice de ms corporl y l circunferenci de cintur se correlcionron débilmente con l frecuenci de los tques durnte 6 meses (rs = 0,162, p < 0,05 y r = 0,187, p < 0,05, respectivmente). Ests correlciones se mntiene débil considerndo sólo ls mujeres premenopáusics, pero desprecen en ls mujeres myores. L estrtificción de los nálisis por tipo migrñ muestr un correlción moderd entre l migrñ con ur y l frecuenci de los tques de más de 6 meses y el índice de ms corporl (rs = 0,369, p < 0,05), sí como l circunferenci de cintur (rs = 0,423, p < 0,01). Los pcientes que estbn tomndo medicmentos profilácticos tuvieron un myor índice de ms corporl, circunferenci de l cintur, y los vlores de porcentje de grs corporl (p < 0,01, prueb t de Student). Conclusiones: Este estudio reveló un potencil, unque débil socición entre l migrñ y los prámetros ntropométricos y l frecuenci de tques, que no reflej l durción, l grvedd y l incpcidd de los tques, que tienen diferentes modelos según el tipo de migrñ, l edd reproductiv y l medicción profiláctic. (Nutr Hosp. 2013;28: ) DOI: /nh Plbrs clve: Migrñ. Obesidd. Sobrepeso. Obesidd bdominl. Grs corporl. 1115
2 Abbrevitions ABEP: Associção Brsileir de Empress de Pesquis /Brzilin Assocition of Reserch Compnies. BF%: Body Ft Percentge. BMI: Body Mss Index. HCPA: Hospitl de Clínics de Porto Alegre. MIDAS: Migrine Disbility Assessment Test. MwA: Migrine With Aur. MwoA: Migrine Without Aur. WC: Wist circumference. Introduction Migrine, one of the min primry hedche disorders, is benign, highly prevlent neurologicl condition tht is most common in the economiclly productive popultion, 1 Cucsins, 2 nd women. 3 Migrine is chrcterized by recurring moderte to severe hedches, with frontotemporl, unilterl or bilterl distribution, pulsting qulity, ccompnied by nuse, vomiting, photophobi, phonophobi, or osmophobi, occurs in ttcks lsting 4 to 72 hours, nd my be preceded by focl neurologicl phenomen known s ur. 4,5 Migrine is estimted to ffect 34.5% of dult women nd 20.1% of dult men in the generl popultion. 3 In Brzil, ntionwide study found migrine prevlence rte of 15.2%. 6 In the U.S., the estimted ntionl cost burden of migrine exceeds $11 billion per yer. 7 Obesity, chronic, multifctoril disese chrcterized by n excessive buildup of dipose tissue, 8 is globl public helth problem. 9 Approximtely 60% of the dult U.S. popultion cn be clssified s overweight or obese, 10 the prevlence of obesity nd overweight in Brzilin dults is 14.7% nd 49% respectively. 11 Studies estimte tht the nnul medicl expenditure ttributble to obesity in the U.S. is on the order of $147 billion. 12 Recent reserch hs suggested tht n ssocition exists between obesity nd migrine. 13 However, epidemiologicl studies conducted in Brzil 6 nd elsewhere 14,15 hve filed to find ny ssocition between body mss index (BMI) nd migrine prevlence. Nevertheless, Bigl et l. 14,16 found tht overweight is ssocited with greter frequency nd severity of migrine ttcks. Although clinicl nd epidemiologicl trils hve demonstrted reltionship between hedche nd BMI, there is little informtion on the reltionship between body ft distribution nmely, centrl obesity or body ft percentge nd migrine. 17 On the other hnd, migrine sufferers my be subject to chnges in body weight produced by the use of prophylctic medictions. 18 Most drugs used in migrine prophylxis promote weight gin, lthough some pper to hve no influence on body weight nd some my even promote weight loss. 18,19 This study sought to scertin whether nthropometric prmeters nd body ft percentge cn influence the pttern of migrine ttcks. Methods This cross-sectionl study used convenience smpling strtegy. We recruited consecutively 166 femle migrineurs ged 18 yers, treted t the outptient Hedche Clinic of the Deprtment of Neurology t Hospitl de Clínics de Porto Alegre (HCPA), tertiry referrl hospitl in Rio Grnde do Sul, Brzil, between Mrch 2010 nd August All hd dignosis of migrine mde by neurologist (ASP) ccording to Interntionl Hedche Society criteri. 5 Sociodemogrphic dt (ge, mritl sttus, eductionl level, self-reported skin color, nd socioeconomic sttus), clinicl informtion [(clssifiction of migrine, frequency nd durtion of ttcks, migrine fmily history, reproductive ge (pre nd postmenopusl) nd medictions used)], dt on disbility, nd nthropometric prmeters (weight, height, nd wist circumference) were collected, by mens of history nd physicl exmintion, during n investigtor-led ptient encounter ( specil visit to pply the study protocol). The severity nd disbility cused by ttcks ws ssessed with visul nlog pin nd Migrine Disbility Assessment Test MIDAS criteri. 20 Socioeconomic sttus ws defined on the bsis of the Brzilin Assocition of Reserch Compnies (Associção Brsileir de Empress de Pesquis, ABEP) Economic Clssifiction Criterion, which uses purchsing power to strtify the popultion into five socioeconomic clsses, A through E, with A representing the richest strtum of society nd E, the poorest 21. Weight nd height were used to clculte BMI, using the formul BMI = (weight [kg]/height [m] 2 ), nd nutritionl sttus clssifiction ws bsed on the World Helth Orgniztion cutoff points for dults 22 nd the Lipschitz cutoffs for the elderly. 23 Wist circumference (WC) ws mesured t the nrrowest point of the trunk nd clssified ccording to World Helth Orgniztion stndrds, 24 with WC 80 or 88 cm representing incresed or substntilly incresed risk of crdiovsculr disese nd metbolic complictions respectively. Body ft percentge (BF%) ws mesured by the bioelectricl impednce method with Mltron body composition nlyzer (BF-906, Mltron Interntionl Ltd, Essex, UK). This study ws pproved by the Hospitl de Clínics de Porto Alegre Reserch Ethics Committee with protocol # All prticipnts provided written informed consent. Ctegoricl vribles were expressed s bsolute nd reltive frequencies, nd continuous vribles, s men nd stndrd devition or medin nd interqurtile rnge s pproprite. The chi-squre test ws used 1116 Nutr Hosp. 2013;28(4): Vness Rossoni de Oliveir et l.
3 to test for ssocition between ctegoricl vribles; the Student t-test, for comprison of mens; nd Spermn s rnk correltion coefficient to test for correltions between nthropometric prmeters nd frequency, severity, nd durtion of migrine ttcks. Dt were nlyzed in the Sttisticl Pckge for the Socil Sciences 18.0 softwre, nd results were considered significnt when p Results Tble I Sociodemogrphic profile of the smple (n = 166) Chrcteristics N (%) or men ± SD Age (yers) 45.0 ± (18.7%) (19.9%) (24.1%) (27.1%) (10.2%) Eductionl level (n = 166) Illiterte 9 (5.5%) Some primry 46 (27.9%) Primry eduction 41 (24.8%) Secondry eduction 58 (35.2%) Higher eduction 1 (6.7%) Economic clss (ABEP clssifiction ) A 7 (4.2%) B 62 (37.3%) C 86 (51.8%) D 11 (6.6%) Self-reported skin color White 121 (72.9%) Blck 15 (9.0%) Brown 14 (8.4%) Other 16 (9.6%) Mritl sttus Single 53 (31.9%) Mrried/cohbiting 83 (50.0%) Divorced 17 (10.2%) Widowed 13 (7.8%) ABEP, Associção Brsileir de Empress de Pesquis (Brzilin Assocition of Reserch Compnies). 21 The sociodemogrphic profile of the smple is described in tble I. There were no ssocitions between socioeconomic nd eductionl level, mritl sttus, or ge nd migrine severity s mesured both by the MIDAS instrument nd visul nlog pin scle. Age did not correlte with ttck frequency or durtion either. Seventy-three (44.0%) were employed t the time of the study; of these, 41 (56.1%) reported bsenteeism due to migrine ttcks (tble II). Migrine without ur ws highly prevlent. Age t onset of first migrine ttck ws < 20 yers, nd the medin time elpsed since the first migrine ws 17.5 yers (interqurtile rnge, yers). Substntil Tble II Clinicl profile of the smple (n = 166) N (%) or men ± SD, Chrcteristics or medin (interqurtile rnge) Migrine type With ur 47 (28.3%) Without ur 119 (71.7%) Age t onset (yers) 22.0 ( ) (16.3%) (30.1%) (24.7%) (28.9%) Disese durtion (yers) 17.5 ( ) Positive fmily history of migrine 113 (68.1%) Migrine prophylxis Yes 119 (71.7%) Tricyclic ntidepressnts 75 (63.0%) Anticonvulsnts 33 (27.7%) Bet blockers 28 (23.5%) Clcium chnnel blockers 4 (3.3%) Antipsychotics 2 (1.6%) Severity (visul nlog scle) (5.4%) (25.9%) (68.7%) Disbility (MIDAS grde ) I 50 (30.1%) II 37 (22.3%) III 39 (23.5%) IV 40 (24.1%) Number of ttcks over 6-month period 24 ( ) Durtion of ttcks (hours) (1-312) 2 20 (12.0%) (53.6%) (12.0%) (13.3%) (9.0%) Work or school dys lost over 3-month period (n = 41) 2 (1-3) Comorbidities Dibetes 6 (3.6%) Hypertension 48 (28.9%) Neuropsychitric disorders 16 (9.6%) Thyroid disorders 11 (6.6%) MIDAS, Migrine Disbility Assessment Test. 20 number of ptients reported fmily history of migrine. Migrine-induced disbility, s mesured by the MIDAS instrument rnged from grde I to grde IV. On verge, ptients hd experienced 24 migrine ttcks over the 6 months preceding the study, with the predominnt durtion of ttcks being 24 hours. Most ptients reported men ttck severity of 8 to 10 on visul nlog pin scle, nd most were on prophylctic medictions. Hypertension ws the min comorbidity in this smple (tble II). BMI, bdominl obesity, body ft nd migrine in women Nutr Hosp. 2013;28(4):
4 Tble III Anthropometric profile of the smple (n = 166) Prmeter N (%) or men ± SD BMI (n =166) 27.8 ± 6.0 kg/m 2 Adults (n = 149) Obese, clss III 7 (4.2%) Obese, clss II 8 (4.8%) Obese, clss I 29 (17.5%) Overweight 47 (28.3%) Norml weight 57 (34.3%) Underweight 1 (0.6%) Older dults (n = 17) Overweight 9 (52.9%) Norml weight 5 (29.4%) Thin 3 (17.6%) MwA (n = 47) 27.8 ± 6.0 kg/m 2 MwoA (n = 119) 27.8 ± 6.1 kg/m 2 WC 84.3 ± 13.1 cm 80 < 88 cm 38 (22.9%) 88 cm 58 (34.9%) MwA (n = 47) 83.3 ± 12.4 cm MwoA (n = 119) 84.7 ± 13.4 cm BF% (n = 163) 36.4 ± 8.3% MwA (n = 44) 35.6 ± 7.1% MwoA (n = 119) 36.2 ± 8.7% BMI: Body mss index; WC: Wist circumference; MwA: Migrine with ur; MwoA: Migrine without ur; BF%: Body ft percentge. No sttisticlly significnt differences in BMI, WC, or BF% between the MwA nd MwoA groups (Student t-test). According to BMI nd WC vlues, substntil number of ptients were overweight nd thus t risk of crdiovsculr disese nd metbolic complictions (tble III). There were no sttisticlly significnt differences in BMI, WC, or BF% between the MwA nd MwoA groups. Although the ssocitions were wek, BMI nd WC correlted positively with the number of migrine ttcks over 6-month period (tble IV), wheres BF% did not. Considering only premenopusl women, there ws lso wek correltion between BMI nd WC nd the number of crises over 6-month period. However, in the postmenopusl women this correltion dispper (tble IV). Even if there ws no difference in nthropometric prmeters between types of migrine (tble III), in migrine with ur, there ws moderte, positive correltion between BMI nd WC nd ttck frequency over 6 months, wheres neither prmeter ws ssocited with ttck frequency in ptients who experienced migrine without ur (tble IV). Anlysis of ttck durtion nd severity (s mesured on visul nlog scle) in the pooled smple (migrine with nd without ur) reveled no correltion with nthropometric prmeters (tble IV). If considered women in pre nd post menopusl ge Tble IV Correltions between nthropometric prmeters nd frequency, severity, nd durtion of migrine ttcks BMI (r S ) WC (r S ) BF% (r S ) Frequency (number of ttcks over 6-month period) Overll (n = 166) MwA (n = 47) b MwoA (n = 119) Pre menopusl women (n = 136) b Post menopusl women (n = 30) Severity (visul nlog scle) Overll (n = 166) MwA (n = 47) MwoA (n = 119) Pre menopusl women (n = 136) Post menopusl women (n = 30) Durtion Overll (n = 166) MwA (n = 47) MwoA (n = 119) Pre menopusl women (n = 136) Post menopusl women (n = 30) p < 0.05; b p < 0.01 (Spermn s rnk correltion coefficient). BMI: Body mss index; WC: Wist circumference; MwA: Migrine with ur; MwoA: Migrine without ur; BF%: Body ft percentge. there ws lso no correltion. However, in the pooled smple there ws positive correltion between ttck severity nd durtion (r s = 0.229; p = 0.003). The degree of migrine-relted disbility, s mesured with the MIDAS instrument, ws not ssocited with BMI, WC, or BF%, even in the totl smple, even if considered the reproductive ge (chi-squred test). There ws no ssocition between the clss of prophylctic mediction used nd BMI, WC, or BF%, the exception of tricyclic ntidepressnts, which were ssocited with incresed WC (p = 0.044). As compred to ptients who were not on phrmcologicl prophylxis, ptients who were receiving ny prophylctic mediction hd greter BMI (28.6 ± 6.0 kg/m 2 vs ± 5.6 kg/m 2, p = 0.003), BF% (37.6 ± 7.6% vs ± 8.6%, p < 0.001), nd WC (86.4 ± 12.8 cm vs ± 12.4, p = 0.001) (Student t-test). Discussion As reported elsewhere in the literture, 6,25 migrine without ur ws predominnt in our smple. 5 The greter frequency of migrine mong ptients in socioeconomic clsses B nd C, s well s the high representtiveness of prticipnts self-reporting s white, s described previously, 26 my be due to the nture of the smple, which consisted of outptients treted t public helth cre in Southern Brzil. This restriction my limit the interprettion of the influence of these fctors on ttck severity nd migrine-relted disbility in the 1118 Nutr Hosp. 2013;28(4): Vness Rossoni de Oliveir et l.
5 study popultion. The reported pin severity nd high rte of bsenteeism mong employed prticipnts 27 lso reflect the relity of n outptient smple. Approximtely 60% of prticipnts in the study smple were overweight or obese. This is worrisome finding, which corrobortes the globl epidemic sttus of obesity. 9 Considering overweight lone, the findings of this study re similr to those of previous popultion surveys of migrineurs. 6,14,16 However, our dt suggest greter prevlence of overweight thn previous, ntionwide popultion study, which found tht less thn 50% of people with migrine were overweight or obese. 6 Wheres Queiroz et l. 6 reported n obesity rte similr to tht of the overll Brzilin popultion, 11 our smple hd higher prevlence of obesity (roughly 12% vs. 26.5% respectively). These spects should be considered in the context of the smple of the present study, which, gin, consisted of outptients whose chrcteristics my hve been distinct from those of popultion study smples, both in terms of the use of prophylctic mediction nd in terms of regionl differences in the prevlence of obesity. 11 Although Peterlin et l. 17 found tht migrine ws more prevlent in obese individuls, there is no cler reltionship between BMI nd migrine, s demonstrted by the fct tht other popultion studies filed to find similr results. 6,15,16 However, n ssocition between BMI nd frequency nd severity of migrine ttcks hs been reported by some uthors, 13,16 nd ppers to hve been corroborted in our smple, with potentil correltion, however wek, between greter frequency of ttcks nd higher BMI. After strtifiction of nlysis by migrine type, this correltion ws found to be stronger in the migrine with ur group, s ws the correltion between centrl distribution of body ft nd frequency of ttcks. These dt re consistent with those of previous study of severely obese femle migrineurs, in which most prticipnts hd dignosis of migrine with ur. 28 The uthors of tht study suggested tht the presence of ur my be ssocited with high estrogen levels, nd tht extrovrin production of estrogen in dipose tissue might ccount for this phenomenon, which does not occur in migrine without ur, where ttcks re ssocited with low levels of estrogen. A lrge popultion study found tht centrl distribution of body ft ws ssocited with incresed prevlence of migrine in women, lthough the correltion did not hold fter the ge of Contrdicting the forementioned findings of Horev et l., 28 who only exmined severely obese women (with potentilly greter extrovrin output of estrogen) of reproductive ge, Peterlin et l. 17 found tht the ssocition between WC nd migrine cesed to be significnt in less severely obese women over the ge of 55, with presumbly lower estrogen output. According to Bond et l., 29 there ppers to be reltionship between obesity nd migrine, prticulrly in reproductive-ged women. Although in our study, we found correltion between BMI nd WC nd higher frequency of crises, this ws wek correltion tht remined wek, even when the smple ws strtified into women in pre nd post menopusl. We must consider tht our smple consisted predominntly of pre menopusl women. Although with limited smple, the correltion is lost in the post menopusl women, which my be contributing to tht proposed by the literture tht points to ssocited endocrine effects. 17,29. Besides the fct tht in this study, pproximtely 37.3% of prticipnts were ged 50 yers, most were modertely obese (overweight or grde 1 obesity), nd 57.8% hd WC bove normlity cutoffs. All these spects my hve contributed to the wekness of the detected correltions. These spects could lso be ssocited with the lck of correltion between nthropometric prmeters nd migrine-relted disbility. Bigl et l. 16 found tht disbility vried ccording to BMI, with some disbility occurring in 32% of ptients with norml BMI, 37.2% of overweight ptients, 38.4% of obese ptients, nd 40.9% of severely obese ones. Bond et l. 30 reported tht severely obese migrineurs experienced improvement in symptoms fter weight loss due to britric surgery. Possible reltionships between migrine nd obesity hve lso been prtly explined by the presence of inflmmtory meditors common to both conditions. 30 Evidence shows tht n improved understnding of the role of dipose tissue in ctivtion of the inflmmtory cscde could led to suggestions of new tretment nd prevention strtegies for the reduction of obesity-ssocited morbidity nd mortlity. This, in turn, could be n importnt brekthrough for migrine, which is ssocited with neurovsculr inflmmtion Furthermore, migrine nd obesity like re comorbidities ssocited with vriety of crdiovsculr diseses nd re risk fctor for stroke, prticulrly in women who suffer from migrine with ur. 34 Of the vrious medictions vilble for migrine prophylxis, those most often used in the study popultion were tricyclic ntidepressnts (prticulrly mitriptyline), nticonvulsnts (vlproic cid nd topirmte), nd bet blockers (proprnolol). Amitriptyline nd vlproic cid re ssocited with the most severe weight gin, 35 wheres proprnolol ws ssocited with less weight gin in some studies. 36,37 Conversely, topirmte hs been reported to id weight loss. 37,38 In our smple, BMI, BF%, nd WC vlues were higher mong ptients on migrine prophylxis, which might indicte n ssocition between prophylctic mediction nd chnges in body weight. When nlysis ws strtified by drug clss, the only detectble ssocition ws between use of tricyclics nd WC; the reltionship between use of these medictions nd BMI, s previously reported in the literture, 36,39 ws not present in our smple. One limittion to the interprettion of these findings ws the unvilbility of nthropometric dt for the prticipnts s of the strt of prophylctic therpy. BMI, bdominl obesity, body ft nd migrine in women Nutr Hosp. 2013;28(4):
6 In conclusion, this study demonstrted potentil, though tenuous, connection between migrine nd certin nthropometric prmeters (BMI nd WC) with respect to the frequency of migrine ttcks, with no reflection, however, on their durtion or severity. Reproductive ge nd migrine type ppers to be determinnt of this correltion, which ws stronger in migrine with ur nd dispper in post-menopusl women. These results suggest tht migrine prophylxis strtegies should tke into ccount not only phrmcologicl spects, but lso mngement of nutritionl sttus. Acknowledgments Sources of finncil support: Fundo de Incentivo à Pesquis e Eventos (FIPE/HCPA), Pró-Reitori de Pesquis (PROPESQ-UFRGS), nd the Fundção de Ampro à Pesquis do Estdo do Rio Grnde do Sul (FAPERGS). References 1. Bigl ME, Lipton RB. The epidemiology, burden, nd comorbidities of migrine. Neurol Clin 2009; 27: Stewrt WF, Lipton RB, Libermn J. Vrition in migrine prevlence by rce. Neurology 1996; 47 (1): Bigl M, Libermn JN, Lipton RB. 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