Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis

ABSTRACT: Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established car diovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD...

Full description

Autores:
Colorado Yohar, Sandra Milena
Dam, Veerle
van der Schouw, Yvonne T
Onland Moret, N Charlotte
Groenwold, Rolf HH
Peters, Sanne AE
Burgess, Stephen
Wood, Angela M
Moons, Karel GM
Oliver Williams, Clare
Schuit, Ewoud
Tikk, Kaja
Weiderpass, Elisabete
Holm, Marianne
Tjønneland, Anne
Kühn, Tilman
Fortner, Renée T
Trichopoulou, Antonia
Karakatsani, Anna
La Vecchia, Carlo
Ferrari, Pietro
Gunter, Marc
Masala, Giovanna
Sieri, Sabina
Tumino, Rosario
Panico, Salvatore
Boer, Jolanda MA
Verschuren, WM Monique
Salamanca Fernández, Elena
Arriola, Larraitz
Moreno Iribas, Conchi
Engström, Gunnar
Melander, Olle
Nordendahl, Maria
Wennberg, Patrik
Key, Timothy J
Matullo, Giuseppe
Overvad, Kim
Clavel Chapelon, Francoise
Boeing, Heiner
Quiros, J Ramon
di Angelantonio, Emanuele
Langenberg, Claudia
Sweeting, Michael J
Riboli, Elio
Nicholas J, Nicholas J
Danesh, John
Butterworth, Adam
Tipo de recurso:
Article of investigation
Fecha de publicación:
2019
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/36484
Acceso en línea:
https://hdl.handle.net/10495/36484
Palabra clave:
Menopausia
Menopause
Enfermedad Coronaria
Coronary Disease
Envejecimiento
Aging
Epidemiología
Epidemiology
Mujeres
Women
Factores de Riesgo
Risk Factors
Estudios de Casos y Controles
Case-Control Studies
Factores de Edad
Age Factors
Modelos de Riesgos Proporcionales
Proportional Hazards Models
Rights
openAccess
License
https://creativecommons.org/licenses/by-nc-nd/4.0/
id UDEA2_1da65ab6f9875695deb8c6968163cb37
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/36484
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis
title Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis
spellingShingle Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis
Menopausia
Menopause
Enfermedad Coronaria
Coronary Disease
Envejecimiento
Aging
Epidemiología
Epidemiology
Mujeres
Women
Factores de Riesgo
Risk Factors
Estudios de Casos y Controles
Case-Control Studies
Factores de Edad
Age Factors
Modelos de Riesgos Proporcionales
Proportional Hazards Models
title_short Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis
title_full Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis
title_fullStr Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis
title_full_unstemmed Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis
title_sort Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis
dc.creator.fl_str_mv Colorado Yohar, Sandra Milena
Dam, Veerle
van der Schouw, Yvonne T
Onland Moret, N Charlotte
Groenwold, Rolf HH
Peters, Sanne AE
Burgess, Stephen
Wood, Angela M
Moons, Karel GM
Oliver Williams, Clare
Schuit, Ewoud
Tikk, Kaja
Weiderpass, Elisabete
Holm, Marianne
Tjønneland, Anne
Kühn, Tilman
Fortner, Renée T
Trichopoulou, Antonia
Karakatsani, Anna
La Vecchia, Carlo
Ferrari, Pietro
Gunter, Marc
Masala, Giovanna
Sieri, Sabina
Tumino, Rosario
Panico, Salvatore
Boer, Jolanda MA
Verschuren, WM Monique
Salamanca Fernández, Elena
Arriola, Larraitz
Moreno Iribas, Conchi
Engström, Gunnar
Melander, Olle
Nordendahl, Maria
Wennberg, Patrik
Key, Timothy J
Matullo, Giuseppe
Overvad, Kim
Clavel Chapelon, Francoise
Boeing, Heiner
Quiros, J Ramon
di Angelantonio, Emanuele
Langenberg, Claudia
Sweeting, Michael J
Riboli, Elio
Nicholas J, Nicholas J
Danesh, John
Butterworth, Adam
dc.contributor.author.none.fl_str_mv Colorado Yohar, Sandra Milena
Dam, Veerle
van der Schouw, Yvonne T
Onland Moret, N Charlotte
Groenwold, Rolf HH
Peters, Sanne AE
Burgess, Stephen
Wood, Angela M
Moons, Karel GM
Oliver Williams, Clare
Schuit, Ewoud
Tikk, Kaja
Weiderpass, Elisabete
Holm, Marianne
Tjønneland, Anne
Kühn, Tilman
Fortner, Renée T
Trichopoulou, Antonia
Karakatsani, Anna
La Vecchia, Carlo
Ferrari, Pietro
Gunter, Marc
Masala, Giovanna
Sieri, Sabina
Tumino, Rosario
Panico, Salvatore
Boer, Jolanda MA
Verschuren, WM Monique
Salamanca Fernández, Elena
Arriola, Larraitz
Moreno Iribas, Conchi
Engström, Gunnar
Melander, Olle
Nordendahl, Maria
Wennberg, Patrik
Key, Timothy J
Matullo, Giuseppe
Overvad, Kim
Clavel Chapelon, Francoise
Boeing, Heiner
Quiros, J Ramon
di Angelantonio, Emanuele
Langenberg, Claudia
Sweeting, Michael J
Riboli, Elio
Nicholas J, Nicholas J
Danesh, John
Butterworth, Adam
dc.contributor.researchgroup.spa.fl_str_mv Demografía y Salud
dc.subject.decs.none.fl_str_mv Menopausia
Menopause
Enfermedad Coronaria
Coronary Disease
Envejecimiento
Aging
Epidemiología
Epidemiology
Mujeres
Women
Factores de Riesgo
Risk Factors
Estudios de Casos y Controles
Case-Control Studies
Factores de Edad
Age Factors
Modelos de Riesgos Proporcionales
Proportional Hazards Models
topic Menopausia
Menopause
Enfermedad Coronaria
Coronary Disease
Envejecimiento
Aging
Epidemiología
Epidemiology
Mujeres
Women
Factores de Riesgo
Risk Factors
Estudios de Casos y Controles
Case-Control Studies
Factores de Edad
Age Factors
Modelos de Riesgos Proporcionales
Proportional Hazards Models
description ABSTRACT: Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established car diovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors. Methods: We used data from EPIC-CVD, a case–cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 com prise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders. Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease ¼ 1.02, 95% confidence interval (CI) ¼ 1.01–1.03, p ¼ 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted ¼ 1.25, 95% CI ¼ 1.10–1.42, p < 0.001), but this attenuated after additional adjustment for age at meno pause and intermediates (HR ¼ 1.12, 95% CI ¼ 0.96–1.29, p ¼ 0.15). A proportion of the as sociation was explained by cardiovascular risk factors. Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovas cular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019
dc.date.accessioned.none.fl_str_mv 2023-08-31T20:00:31Z
dc.date.available.none.fl_str_mv 2023-08-31T20:00:31Z
dc.type.spa.fl_str_mv Artículo de investigación
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.coarversion.spa.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.citation.spa.fl_str_mv Dam V, van der Schouw YT, Onland Moret NC, Groenwold RHH, Peters SAE, et al. Association of menopausal characteristics and risk of coronary heart disease: a pan-European case-cohort analysis. Int J Epidemiol. [Internet]. 2019[citado día mes año]; 48(4), 1275–1285. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30796459/
dc.identifier.issn.none.fl_str_mv 0300-5771
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/36484
dc.identifier.doi.none.fl_str_mv 10.1093/ije/dyz016
dc.identifier.eissn.none.fl_str_mv 1464-3685
identifier_str_mv Dam V, van der Schouw YT, Onland Moret NC, Groenwold RHH, Peters SAE, et al. Association of menopausal characteristics and risk of coronary heart disease: a pan-European case-cohort analysis. Int J Epidemiol. [Internet]. 2019[citado día mes año]; 48(4), 1275–1285. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30796459/
0300-5771
10.1093/ije/dyz016
1464-3685
url https://hdl.handle.net/10495/36484
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Int. J. Epidemiol.
dc.relation.citationendpage.spa.fl_str_mv 1285
dc.relation.citationissue.spa.fl_str_mv 4
dc.relation.citationstartpage.spa.fl_str_mv 1275
dc.relation.citationvolume.spa.fl_str_mv 48
dc.relation.ispartofjournal.spa.fl_str_mv International Journal of Epidemiology
dc.rights.uri.spa.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-sa/2.5/co/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.spa.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
http://creativecommons.org/licenses/by-nc-sa/2.5/co/
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 11
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Oxford University Press
dc.publisher.place.spa.fl_str_mv Londres, Inglaterra
institution Universidad de Antioquia
bitstream.url.fl_str_mv https://bibliotecadigital.udea.edu.co/bitstreams/9e5e060a-dec8-4a84-aa28-239177bc7f34/download
https://bibliotecadigital.udea.edu.co/bitstreams/327da145-c158-40d5-95fa-49804e4637bf/download
https://bibliotecadigital.udea.edu.co/bitstreams/11c35c41-6a0a-4cbf-b83e-769fa52b69b3/download
https://bibliotecadigital.udea.edu.co/bitstreams/622d846d-7eab-455b-930c-4132306dbdd5/download
https://bibliotecadigital.udea.edu.co/bitstreams/5e30f526-4522-4172-80a7-85a21ae16735/download
bitstream.checksum.fl_str_mv 36959b3eb5c112eac6daea0d282ee267
e2060682c9c70d4d30c83c51448f4eed
8a4605be74aa9ea9d79846c1fba20a33
68cc894b990e8dd5074630b34d1bb3a4
258a53d28c7fae27052199539b7aff5a
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional de la Universidad de Antioquia
repository.mail.fl_str_mv aplicacionbibliotecadigitalbiblioteca@udea.edu.co
_version_ 1851052113344331776
spelling Colorado Yohar, Sandra MilenaDam, Veerlevan der Schouw, Yvonne TOnland Moret, N CharlotteGroenwold, Rolf HHPeters, Sanne AEBurgess, StephenWood, Angela MMoons, Karel GMOliver Williams, ClareSchuit, EwoudTikk, KajaWeiderpass, ElisabeteHolm, MarianneTjønneland, AnneKühn, TilmanFortner, Renée TTrichopoulou, AntoniaKarakatsani, AnnaLa Vecchia, CarloFerrari, PietroGunter, MarcMasala, GiovannaSieri, SabinaTumino, RosarioPanico, SalvatoreBoer, Jolanda MAVerschuren, WM MoniqueSalamanca Fernández, ElenaArriola, LarraitzMoreno Iribas, ConchiEngström, GunnarMelander, OlleNordendahl, MariaWennberg, PatrikKey, Timothy JMatullo, GiuseppeOvervad, KimClavel Chapelon, FrancoiseBoeing, HeinerQuiros, J Ramondi Angelantonio, EmanueleLangenberg, ClaudiaSweeting, Michael JRiboli, ElioNicholas J, Nicholas JDanesh, JohnButterworth, AdamDemografía y Salud2023-08-31T20:00:31Z2023-08-31T20:00:31Z2019Dam V, van der Schouw YT, Onland Moret NC, Groenwold RHH, Peters SAE, et al. Association of menopausal characteristics and risk of coronary heart disease: a pan-European case-cohort analysis. Int J Epidemiol. [Internet]. 2019[citado día mes año]; 48(4), 1275–1285. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30796459/0300-5771https://hdl.handle.net/10495/3648410.1093/ije/dyz0161464-3685ABSTRACT: Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established car diovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors. Methods: We used data from EPIC-CVD, a case–cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 com prise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders. Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease ¼ 1.02, 95% confidence interval (CI) ¼ 1.01–1.03, p ¼ 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted ¼ 1.25, 95% CI ¼ 1.10–1.42, p < 0.001), but this attenuated after additional adjustment for age at meno pause and intermediates (HR ¼ 1.12, 95% CI ¼ 0.96–1.29, p ¼ 0.15). A proportion of the as sociation was explained by cardiovascular risk factors. Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovas cular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.COL000324911application/pdfengOxford University PressLondres, Inglaterrahttps://creativecommons.org/licenses/by-nc-nd/4.0/http://creativecommons.org/licenses/by-nc-sa/2.5/co/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysisArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionMenopausiaMenopauseEnfermedad CoronariaCoronary DiseaseEnvejecimientoAgingEpidemiologíaEpidemiologyMujeresWomenFactores de RiesgoRisk FactorsEstudios de Casos y ControlesCase-Control StudiesFactores de EdadAge FactorsModelos de Riesgos ProporcionalesProportional Hazards ModelsInt. J. Epidemiol.12854127548International Journal of EpidemiologyPublicationORIGINALColoradoSandra_2019_AssociationMenopausalCharacteristics.pdfColoradoSandra_2019_AssociationMenopausalCharacteristics.pdfArtículo de investigaciónapplication/pdf704069https://bibliotecadigital.udea.edu.co/bitstreams/9e5e060a-dec8-4a84-aa28-239177bc7f34/download36959b3eb5c112eac6daea0d282ee267MD51trueAnonymousREADCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-81051https://bibliotecadigital.udea.edu.co/bitstreams/327da145-c158-40d5-95fa-49804e4637bf/downloade2060682c9c70d4d30c83c51448f4eedMD52falseAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/11c35c41-6a0a-4cbf-b83e-769fa52b69b3/download8a4605be74aa9ea9d79846c1fba20a33MD53falseAnonymousREADTEXTColoradoSandra_2019_AssociationMenopausalCharacteristics.pdf.txtColoradoSandra_2019_AssociationMenopausalCharacteristics.pdf.txtExtracted texttext/plain51086https://bibliotecadigital.udea.edu.co/bitstreams/622d846d-7eab-455b-930c-4132306dbdd5/download68cc894b990e8dd5074630b34d1bb3a4MD58falseAnonymousREADTHUMBNAILColoradoSandra_2019_AssociationMenopausalCharacteristics.pdf.jpgColoradoSandra_2019_AssociationMenopausalCharacteristics.pdf.jpgGenerated Thumbnailimage/jpeg17830https://bibliotecadigital.udea.edu.co/bitstreams/5e30f526-4522-4172-80a7-85a21ae16735/download258a53d28c7fae27052199539b7aff5aMD59falseAnonymousREAD10495/36484oai:bibliotecadigital.udea.edu.co:10495/364842025-03-26 17:09:59.195https://creativecommons.org/licenses/by-nc-nd/4.0/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.coTk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=