Sex-Specific Analysis of Cardiovascular Function

734 Pages·2018·27.522 MB·English

by  Peter L. M. Kerkhof, Virginia M. Miller

Advances in Experimental Medicine and Biology 1065
Peter L. M. Kerkhof · Virginia M. Miller E ditors
Sex-Specifi c
Analysis of
Cardiovascular
Function
Advances in Experimental Medicine
and Biology
Volume 1065
SeriesEditors:
IRUNR.COHEN,TheWeizmannInstituteofScience,Rehovot,Israel
ABELLAJTHA,N.S.KlineInstituteforPsychiatricResearch,Orangeburg,NY,USA
JOHND.LAMBRIS,UniversityofPennsylvania,Philadelphia,PA,USA
RODOLFOPAOLETTI,UniversityofMilan,Milan,Italy
NIMAREZAEI,TehranUniversityofMedicalSciences,Tehran,Iran
Moreinformationaboutthisseriesathttp://www.springer.com/series/5584
(cid:129)
Peter L. M. Kerkhof Virginia M. Miller
Editors
Sex-Specific Analysis
of Cardiovascular
Function
Editors
PeterL.M.Kerkhof VirginiaM.Miller
DepartmentofRadiology MayoClinic
andNuclearMedicine Rochester,MN,USA
AmsterdamCardiovascularSciences
VUUniversityMedicalCenter
Amsterdam,TheNetherlands
ISSN0065-2598 ISSN2214-8019 (eBook)
AdvancesinExperimentalMedicineandBiology
ISBN978-3-319-77931-7 ISBN978-3-319-77932-4(eBook)
https://doi.org/10.1007/978-3-319-77932-4
LibraryofCongressControlNumber:2018947190
#SpringerInternationalPublishingAG,partofSpringerNature2018
Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeor
part of the material is concerned, specifically the rights of translation, reprinting, reuse of
illustrations,recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,
andtransmissionorinformationstorageandretrieval,electronicadaptation,computersoftware,or
bysimilarordissimilarmethodologynowknownorhereafterdeveloped.
Theuseofgeneraldescriptivenames,registerednames,trademarks,servicemarks,etc.inthis
publication does not imply, even in the absence of a specific statement, that such names are
exemptfromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse.
Thepublisher,theauthorsandtheeditorsaresafetoassumethattheadviceandinformationinthis
bookarebelievedtobetrueandaccurateatthedateofpublication.Neitherthepublishernorthe
authorsortheeditorsgiveawarranty,expressorimplied,withrespecttothematerialcontained
hereinorforanyerrorsoromissionsthatmayhavebeenmade.Thepublisherremainsneutralwith
regardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.
Printedonacid-freepaper
ThisSpringerimprintispublishedbytheregisteredcompanySpringerInternationalPublishing
AGpartofSpringerNature.
Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland
Foreword
Sex-Specific Anaysis of Cardiovascular Function
Cardiovascular disease is the leading cause of morbidity and mortality for
womenintheWesternworld,andamajorcontributortotheirillnessspectrum
in developing countries. Despite these facts, until recent decades, cardiovas-
culardiseasewasconsideredaman’sproblem.Theconsequencewasthatthe
major evidencebase,randomized controlledtrialsofcardiovasculardiseases
andtheirtherapies, wereconductedpredominantly orexclusivelyinmiddle-
aged Caucasian men, with results extrapolated (albeit inappropriately) to
multiple other populations. Clinical research related to women’s health
involved largely what I have termed “bikini medicine,” addressing the body
systemscoveredbythebikinibathingsuit,i.e.,thebreastandthereproductive
system. Only in recent decades have we seen attention to broader aspects
of sex-specific medicine, alternately termed gender medicine, and its
consequences have been far reaching. Sex/gender differences entail both
those characteristics specific to one sex and those that differ in prevalence,
manifestations,and/oroutcomesbetweenthesexes.
Intheirinnovativeandcomprehensivetextbook,“Sex-SpecificAnalysisof
CardiovascularFunction,”ProfessorsPeterKerkhofandVirginiaMillerpro-
vide an amazing resource for the research and clinical adult and pediatric
cardiovascular communities. In chapters ranging from basic cardiovascular
physiology,genetics,hormonalstatus,genomics,proteomics,metabolomics,
biomarkers,biomedicalengineering,biostatistics,andthelike;toepidemiol-
ogy, translational issues, and clinical aspects of a broad spectrum of cardio-
vascular illnesses, the recently identified sex/gender differences (as well as
similarities) are explored. The widespread sex differences in cardiovascular
structure and function highlight the importance of consideration of sex as a
biologic variable and of sex influences on cardiovascular disease both in
preclinicalresearchandintheplanningandanalysisofcardiovascularclinical
trials.Althoughthecoronarycirculationandcoronaryheartdiseasehavebeen
themostintensivelystudiedinthearenaofcardiovascularsex-specificmedi-
cine, the editors and their authors appropriately explore the domains of the
cerebralcirculation,pulmonaryarterialhypertension,etc.
As recently as 2015, the Heart Research for All Act of the US Congress
mandatedthattherebeadequaterepresentationbysex,race/ethnicity,andage
forfederallyfundedclinicalresearchstudies,withtheresultsdisaggregatedby
these parameters. The same mandate applies to the basic science arena.
v
vi
Scientistsarerequiredtoprovidetheprovenanceoftheircellsandtissues,i.e.,
whether they derived from male or female animals, as well as the sex of the
animalsstudied,againdisaggregatingtheresultsbysex.Thislegislationthus
furtherhighlightstheimportanceofsexasabiologicalvariableinpreclinical
research.Thesamemandatesareineffectforclinicalresearchstudiessubmit-
tedtotheUSFoodandDrugAdministrationfordruganddeviceapproval.
Given the major sex-specific aspects of cardiovascular function both in
health and in major cardiovascular diseases; and the substantial sex-based
variation in the prevalence, expression, and costs of multiple cardiovascular
problems, several chapter authors suggest to their readers the use of gender
innovations and the mandate for development of new technologies, new
pharmacotherapies, and new diagnostic modalities. The knowledge gaps
highlightedinmultiplechaptersdefineasex-basedagendaforbasic,epidemi-
ologic,translational,andclinicalresearch,withtheoutcomeslikelytobenefit
both women and men. The terms “personalized medicine” and “precision
medicine” are recurrently cited as advances in patient care; sex/gender
considerationsareobviouspivotalcomponentsandcontributors.
A woman’s health relates to the health of her family, the health of her
community,andtherebytothehealthofthenation.Thus,effortstoimprove
women’shearthealth,evidence-basedapplicationofsex-specificpreventive,
diagnostic, and therapeutic interventions, have the potential to improve
national health status. Advances in the USA offer support to this thesis. In
theearlyyearsofsex-specificcardiovascularmedicine,andpriortointensive
educationalandadvocacycampaignsregardingheartdiseaseinwomen,1of
2USwomendiedofcardiovascularillness.In2018,thishasdecreasedto1in
4USwomen,astunningaccomplishment.
NanetteK.Wenger,MD,MACC,MACP,FAHA
ProfessorofMedicine(Cardiology)
EmoryUniversitySchoolofMedicine
Consultant,EmoryHeartandVascularCenter
FoundingConsultant,EmoryWomen’sHeartCenter
Atlanta,Georgia
Preface
One of the most fascinating aspects to explore in living systems concerns a
comparisonbetweenfemalesandmales.Inhumans,variousfindingsregard-
inganatomyandphysiologydifferconsiderablyforbothsexes,whilecultural
and social factors may also have distinct impact on the course of life,
including aspects of health and disease. Every parallel description of health
anddiseaseinwomenandmenisbestinterpreted againstthebackgroundof
theageconsidered.Thepresentbookaddressesalltheseelementsasfarasthe
cardiovascularsystemisconcerned.
Decipheringunderlyingpropertiesandmechanismsofcardiacandvascular
functioning will contribute to the formulation of effective guidelines to
promotehealth,totimely takepreventivemeasures, tomorepreciselyestab-
lish a diagnosis in case of disease, and to undertake curative action on a
personalized basis. In fact, application of precision medicine begins with
consideringsexandage.
Thebookpresentsanupdatedsurveyofsex-specificcharacteristicsofthe
cardiovascularsystem,basedon(epi)genetic,molecular,cellular,anatomical,
(electro)physiologic,andepidemiologicstudieswrittenbyeminentexpertsin
those fields. The contents cover important clinical data, spanning from the
fetustonewborn,child,adult,anduptotheelderly.Thisrangealsoincludes
pregnancy and associated cardiovascular adaptations, as well as related
disorders.Infact, fourchaptersaredevotedtocardiovasculardisorders typi-
callyorpredominantlyencounteredinwomen.
The biomedical engineering spectrum of sex-specific items starts with
basic disciplines such as a refreshing presentation of elementary
cardiophysiology,tocontinue withinsightfuloutlinesofmodernapproaches
includingwaveintensityanalysis,robot-assistedrehabilitation,bigdataanal-
ysis,andheartratevariability.Furthermore,dueattentionisgiventocircula-
torysystem–relatedeffectsofexerciseandaginginbothwomenandmen.
Startingwithashorthistoricalintroduction,thebookendswithannotated
referencevalues,alongwithguidelinesfortheirprudentinterpretation.
This carefully selected anthology is intended both as an eye-opener for
studentsandasasolidresourceforcliniciansdealingwithsex-specificaspects
of cardiovascular disease, either at the first encounter level of general
practitioners or for the medical specialist dealing with comorbidities
associated with cardiovascular disease. The editors expect that the present
comprehensive collection will stimulate sex-specific cardiovascular research
vii
viii Preface
and will be of distinctive importance in diagnosis and patient management.
Theextraordinarycontributionsbyallcliniciansandbasicscientistsinvolved,
often delivered during evening and weekend hours, are very much
appreciated.Theyoriginatefrom17countriesaroundtheworld,oftenforming
multinational teams, which fact provides evidence that diversity in thinking
leads to innovation in science and medicine with a global impact. We are
proudtomentionthat60%ofallauthorsarewomen.
Amsterdam,TheNetherlands PeterL.M.Kerkhof
Rochester,MN,USA VirginiaM.Miller
March7,2018
Contents
1 WomenandMenintheHistoryofWestern
Cardiology:SomeNotesonTheirPositionasPatients,
RoleasInvestigationalStudySubjects,andImpact
asProfessionals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PeterL.M.KerkhofandElenaOsto
2 AnIntroductiontoEpigeneticsinCardiovascular
Development,Disease,andSexualization. . . . . . . . . . . . . . 31
ChristineM.CunninghamandMansourehEghbali
3 EpidemiologyofCongenitalHeartDisease
withEmphasisonSex-RelatedAspects. . . . . . . . . . . . . . . . 49
ByungWonYoo
4 SexDifferencesinEpidemiologyofCardiac
andVascularDisease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
TatianaKuznetsova
5 BiostatisticsinCardiovascularResearch
withEmphasisonSex-RelatedAspects. . . . . . . . . . . . . . . . 71
MariekeM.terWeeandBirgitI.Lissenberg-Witte
6 TheInfluenceofAgeandSexontheElectrocardiogram. . 93
PeterW.Macfarlane
7 SafetyandEffectivenessofMedicalDeviceTherapy. . . . .. 107
RobbertZusterzeel
8 CardiophysiologyIllustratedbyComparingVentricular
VolumesinHealthyAdultMalesandFemales. . . . . . . . . . 123
PeterL.M.Kerkhof,TatianaKuznetsova,J.YashaKresh,
andNealHandly
9 SexDifferencesinRegulationofBloodPressure. . . . . . . . . 139
JaneF.Reckelhoff
10 ArterialFlow,PulsePressureandPulseWave
VelocityinMenandWomenatVariousAges. . . . . . . . . . . 153
AlbertoP.Avolio,TatianaKuznetsova,GuyR.Heyndrickx,
PeterL.M.Kerkhof,andJohnK.-J.Li
ix
x Contents
11 Wave-IntensityAnalysis:Sex-SpecificDifferences
inHemodynamicandVentilatoryResponsestoGraded
Exercise—EchocardiographicMeasurements. . . . . . . . . . . 169
MidoriTanaka,MotoakiSugawara,YasuoOgasawara,
andKiyomiNiki
12 SexDifferencesinAutonomicResponsetoExercise
TestinginPatientswithBrugadaSyndrome. . . . . . . . . . . . 181
MireiaCalvo,VirginieLeRolle,DanielRomero,
NathalieBéhar,PedroGomis,PhilippeMabo,
andAlfredoHernández
13 BenchmarkingHeartRateVariabilitytoOvercome
Sex-RelatedBias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
MassimoPagani,RobertoSala,MaraMalacarne,
andDanielaLucini
14 CardiovascularAllometry:Analysis,Methodology,
andClinicalApplications. . . . . . . . . . . . . . . . . . . . . . . . . . 207
JohnK.-J.Li
15 TheHeartasaPsychoneuroendocrine
andImmunoregulatoryOrgan. . . . . . . . . . . . . . . . . . . . . . 225
CarloDalLin,FrancescoTona,andElenaOsto
16 MitochondriaandSex-SpecificCardiacFunction. . . . . . . . 241
RosaVona,BarbaraAscione,WalterMalorni,
andElisabettaStraface
17 SexDifferencesintheCoronarySystem. . . . . . . . . . . . . . . 257
VivianyR.Taqueti
18 CerebralCirculationinMenandWomen. . . . . . . . . . . . . 279
AurangzebMemonandLouiseD.McCullough
19 ArterialWallPropertiesinMenandWomen:
HemodynamicAnalysisandClinicalImplications. . . . . . . 291
JohnK.-J.Li
20 Sex-SpecificCharacteristicsoftheMicrocirculation. . . . . . 307
VirginiaH.HuxleyandScottS.Kemp
21 Sex-SpecificVentricularandVascularAdaptations
toExercise. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
JillN.BarnesandQiFu
22 GrowthofCardiovascularStructuresfromtheFetus
totheYoungAdult. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
FredericDallaireandTaistoSarkola
23 HeartFunctionAnalysisinCardiacPatients
withFocusonSex-SpecificAspects. . . . . . . . . . . . . . . . . . . 361
PeterL.M.Kerkhof,RichardA.Peace,GuyR.Heyndrickx,
LilianJ.Meijboom,RalfW.Sprengers,andNealHandly