Ventricular20Hypertrophy.docx
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Ventricular20Hypertrophy
Hypertension.1997;29:
706-714.)
EffectofAfrican-AmericanRaceandHypertensiveLeftVentricularHypertrophyonCoronaryVascularReactivityandEndothelialFunction
JanL.Houghton;VivienneE.Smith;DavidS.Strogatz;NancyL.Henches;WarrenM.Breisblatt;AlbertA.Carr
theDivisionofCardiology,DepartmentofMedicine,Albany(NY)MedicalCollege(J.L.H.,V.E.S.,N.L.H.,W.M.B.);SchoolofPublicHealth,StateUniversityofNewYorkatAlbany(D.S.S.);andAugusta(Ga)PreventiveCardiology,PC(A.A.C.).
Abstract
ExcesscardiovascularmorbidityandmortalityamongAfrican(black)Americansremainsanimportantyetunexplainedpublichealthproblem.OnepossibleexplanationproposesthatintrinsicoracquiredabnormalitiesincoronaryvascularreactivityandendothelialfunctionresultinexcessischemiaamongblackAmericans.Toexaminethishypothesis,wesubjected80individualswithnormalcoronaryarteriestoinvasivetestingofcoronaryarteryandmicrovascularrelaxationusingintracoronaryinfusionsofacetylcholineandadenosine,aDopplertippedintracoronaryguidewire,andquantitativecoronaryangiography.Wemeasuredthepercentincreaseincoronarybloodflowandepicardialdiameteraftergradedinfusionofintracoronaryacetylcholineandincoronarybloodflowafterintracoronaryadenosinein31normotensivesubjects(10black,21white)and49hypertensivesubjectswithleftventricularhypertrophy(25black,24white).Categoricalandmultivariateanalysesrevealedthatinresponsetointracoronaryadenosineandacetylcholine,thedepressioninendothelium-independentand-dependentmicrovascularrelaxationduringpeakagonisteffectwaslargelyrelatedtothepresenceofchronichypertensionandleftventricularhypertrophy.Normotensivesubjectsdemonstratednointrinsicracialdifferencesinconduitandresistancevesselvasoreactivity.Inresponsetomaximalinfusionofacetylcholine,epicardialcoronaryarteriesconstrictedsimilarlyinblackandwhitesubjectswithhypertensiveleftventricularhypertrophyanddilatedsimilarlyinnormotensiveblackandwhitesubjects.Thus,ourstudyshowsthatinacohortofblackandwhitesubjectsreferredforcoronaryarteriographybecauseofchestpain,AfricanAmericanraceisnotassociatedwithexcessintrinsicoracquireddepressionincoronaryvascularrelaxationduringthepeakeffectoftheendothelium-dependentand-independentagonistsacetylcholineandadenosine,afteradjustmentforthepresenceofleftventricularhypertrophy.
KeyWords:
blacks•race•vasorelaxation•hypertrophy,leftventricular•vascularreactivity•endothelialfunction
Introduction
ExcesscardiovascularmorbidityandmortalityamongAfrican(black)Americansremainsanimportantyetunexplainedpublichealthproblem.12Furthermore,theparadoxicalfindingofalesserdegreeofcoronaryatherosclerosisbutworseprognosisafterdiagnosisofischemicheartdiseaseexistsamongblackAmericans.34Althoughmyocardialischemiaisgenerallysecondarytocoronaryarteryatherosclerosis,thedemonstrationofischemiawithnormalcoronaryarteries(syndromeX,aorticstenosis,leftventricularhypertrophy[LVH])hasclarifiedtheconceptsofmicrovascularanginaandnonatheroscleroticsupply/demandmismatch.56789Theseconcepts,togetherwithanevolvingunderstandingoftheendothelium,justifyinvestigationsthatemphasizethecentralimportanceofthecoronarymicrocirculationandendotheliumintheregulationofmyocardialperfusion.1011
Anumberofpossibleexplanationshavebeenadvancedtoaddresstheperceivedparadoxofgreatermyocardialischemiadespitelessatheroscleroticdiseaseamongblacks.Oneinvokessocietal-basedfactorsrelatedtosocioeconomicstatus,suchasaccesstomedicalcare,complianceissues,andthedurationofuntreatedorpoorlytreatedcardiovasculardisease.121314AsecondexplanationproposesthatcomorbiddiseasesorprocessesmoreprevalentinblackAmericans,suchashypertensionanddiabetesmellitus,mayaugmentischemiabyaffectingsupplyanddemandthroughmechanismsotherthanatherosclerosis.6151617Third,intrinsicabnormalitiesinthecoronaryendotheliumandmicrocirculationmaybepresentinblackAmericans,possiblyaspartofageneralizeddefectinvascularrelaxation,thusleadingtoabnormalperfusionofthemyocardiumintheabsenceofatherosclerosis.1819
OurpurposeinthisstudywastoexaminetheeffectsofhypertensiveLVHandraceoncoronaryarteryandarteriolarvasorelaxationinresponsetotheendothelium-dependentagentacetylcholineandthepredominantlyendothelium-independentagentadenosineinacohortofblackandwhiteAmericanswithangiographicallynormalcoronaryarteries.Comparisonsweremadeamongnormotensivesubjectsandsubjectswithcomplicatedhypertension,definedashypertensionplusLVH.Studysubjectswereidentifiedforpossibleparticipationafterclinicalreferralforcardiaccatheterizationbecauseofsuspectedischemicheartdisease.
Methods
Subjects
Subjectswereprospectivelyrecruitedfortheapprovedinvestigationalstudy(AlbanyMedicalCollegeInstitutionalReviewBoard)afterclinicalreferralforcardiaccatheterizationforevaluationofchestpain.Informedconsentwasobtained,whichdocumentedtheparticipants'understandingoftheinvestigationalnatureoftheprotocol.Thecurrentstudyispartofalargerstudywhosepurposeisexaminationoftheeffectsofhypertension,LVH,hemodynamicallyinsignificantatherosclerosis,sex,andethnicityoncoronaryarteryandarteriolarrelaxation.Enrolledsubjectshadnormalepicardialcoronaryarteriesdocumentedduringcoronaryangiography.Individualswereexcludedfromthestudyiftheyhadahistoryofmyocardialinfarction,balloonangioplasty,bypasssurgery,significantvalvularheartdisease,orotherseriousmedicaldisorder.Subjectsfastedforaminimumof8hoursbeforethestudy.Currentsmokerswereinstructedtorefrainfromsmokingforaminimumof8hours.
SubjectsweregroupedbyraceandpresenceofhypertensiveLVH.Hypertensionwasdefinedasreproduciblebloodpressuremeasurementsgreaterthanorequalto140/90mmHgorself-reportedtakingofantihypertensivemedication.Diabetesmellituswasdiagnosedbyself-reportedhistoryorfastingserumglucosegreaterthan7.8mmol/L(140mg/dL).
Allsubjectswerereferredforcardiaccatheterizationforevaluationofchestpainorananginaequivalent.Chestpainwasclassifiedasanginapectoris,atypicalangina,ornoncardiacchestpain.Anginapectoriswasdefinedintheclassicmannerassubsternalchestdiscomfort(heavinessorpressure)broughtonbyexertionandrelievedbyrestornitroglycerinoraprolongedepisodeofanginalpainatrestrequiringhospitalization.Atypicalanginawasdefinedaschestpainwithsomefeaturesofclassicanginabutothercharacteristicsnotgenerallyassociatedwithanginapectoris,suchasasharporpleuriticcharacterorintermittentrelationshiptoexercise.Noncardiacchestpainhadnofeaturesofanginaotherthanasubsternallocationofchestpain.Ananginaequivalentwasdefinedassymptomsorfindingscommonlyassociatedwithischemiaintheabsenceofchestpain,suchasdyspneaorheartfailure.Innormotensivesubjects,6black(60%)and13white(62%)werejudgedtohaveanginapectoris;2black(20%)and7white(33%),atypicalangina;2black(20%)and0white,ananginalequivalent;and0blackand1white(5%),noncardiacchestpain.InhypertensivesubjectswithLVH,13black(52%)and11white(46%)werejudgedtohaveanginapectoris;5black(20%)and9white(38%),atypicalangina;6black(24%)and2white(8%),ananginalequivalent;and1black(4%)and2white(8%),noncardiacchestpain.
Twenty-nineof45whitesubjects(64%)and24of35blacksubjects(69%)weretakingmedicationsforchestpainand/orhypertension.Seventeenofthese29whitesubjects(59%)and12ofthese24blacksubjects(50%)weretakingdrugsexpectedtohavecoronaryvasodilatingpropertiesalone(nitroglycerinand/orcalciumchannelblockers).Twowhite(7%)and1black(4%)subjectsweretakingaß-blockeralone.However,5white(17%)and6black(25%)subjectsweretakingbothaß-blockerandcoronaryvasodilator.Finally,theremaining5white(17%)and5black(21%)subjectsweretakinganangiotensin-convertingenzymeinhibitoror
-blockertogetherwithotherdrugs.Eightwhite(28%)and9black(38%)subjectsuseddiureticsinadditiontothemedicationsalreadydescribed.Wheneverpossible,vasoactiveandantihypertensivemedicationswerewithheldforaminimumof12hoursbeforethestudyalthoughthestudydesignpermittedsublingualnitroglycerinifdeemedclinicallynecessary;however,nosubjectrequiredsublingualnitroglycerinwithin4hours.In10of80studysubjects(5whiteand5black),medicationswithvasoactivepotentialwereusedwithin12hoursbecauseofclinicalindication.Medicationsusedwithin12hourswereasfollows:
calciumchannelblockersin2whitesubjects,nitroglycerinpreparationsin2whiteand2blacksubjects,ashort-actingangiotensin-convertingenzymeinhibitorin1whitesubject,and2ormoredrugsin3blacksubjects.Therewerenosignificantracialdifferencesindrugusage.Socioeconomicstatuswasassessedbythreeindicators:
yearsofformaleducation,possessionofprivatemedicalinsurance,andcurrentemploymentstatus.Bodymassindexwascalculatedasweight(inkilograms)dividedbyheight(inmeters)squared.Bloodwasobtainedwithsubjectsinthefastingstateformeasurementoftotalcholesterol,low-densityandhigh-densitylipoproteincholesterols,lipoprotein(a),andglucose.
LeftVentricularMassMeasurements
Leftventricular(LV)masswascalculatedwithM-