Brief
report
Glycated
hemoglobin
in
ST-elevation
myocardial
infarction
without
previously
known
diabetes:
Its
short
and
long
term
prognostic
role
Chiara
Lazzeri
*,
Serafina
Valente,
Marco
Chiostri,
Claudio
Picariello,
Paola
Attana`,
Gian
Franco
Gensini
IntensiveCardiacCoronaryUnit,HeartandVesselDepartment,AziendaOspedaliero-UniversitariaCareggi,Florence,Italy
1.
Introduction
Dataontheprognosticroleofglycatedhemoglobin(HbA1c)in patientswithacutemyocardialinfarctionarestill controver-sial[1–9].
WeassessedtheprognosticroleofHbA1cforshortandlong termmortalityin518consecutivepatientswithSTelevation myocardialinfarction(STEMI)andwithoutpreviouslyknown diabetes.Allweretreatedwithmechanicalrevascularization.
2.
Methods
From1st January 2008 to 30th June2010, 518 non-diabetic STEMI patients (within 12h from symptoms’ onset) were
admittedtoourIntensiveCardiacCareUnit(ICCU)[10–14].Renal replacement therapyandmechanicalventilation were used, whenneeded[10–13].AfterPCI,fastingglucose,insulin[12,13], C-peptide, HbA1c, troponin I, uric acid, C-reactive protein, alanineaminotransferase (ALT), aspartateaminotransferase (AST)[15],gammaglutamyltransferase(GGT)[16],NT-proBrain NatriureticPeptide(NT-proBNP)[13],totalcholesterol, trigly-cerides, HDL, fibrinogen and creatinine were measured. Glomerular filtration rate (1ml/min/1.73m2) was calculated
[17]aswellasLDL(nv60–190).Peakglucose,peakTnIandnadir glomerularfiltrationratewerealsomeasured.Insulinresistance wasdefinedbytheHomeostaticModelAssessment(HOMA). HOMA was calculated according to the following formula: {[fastinginsulin(microU/ml)][fastingglucose(mmol/l)]}/22.5 [27]. Subjects whose values exceeded the sex-specific 75th
diabetesresearch andclinical practice 95 (2012)e14–e16
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Articlehistory: Received12May2011 Receivedinrevisedform 22September2011
Accepted26September2011 Publishedonline5November2011 Keywords: STEMI Glycatedhemoglobin Nondiabetic Prognosis
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In 518 consecutive STEMI non-diabetic patients, glycated hemoglobin>6.5% was not associatedwithincreasedshortandlongtermmortality,butwasassociatedwithhigher admissionglucosevalues,worsein-hospitalglycemiccontrolandahigherincidenceof acuteinsulinresistance(HOMAindex).
#2011ElsevierIrelandLtd.Allrightsreserved.
*Correspondingauthor.Tel.:+39557947518. E-mailaddress:lazzeric@libero.it(C.Lazzeri).
ContentsavailableatSciverseScienceDirect
Diabetes
Research
and
Clinical
Practice
j o u r n a lh o m e p a g e :w w w . e l s e v i e r . c o m / l o c a t e / d i a b r e s
0168-8227/$–seefrontmatter#2011ElsevierIrelandLtd.Allrightsreserved. doi:10.1016/j.diabres.2011.09.028
percentile(i.e.1.80forwomenand 2.12formen) wereconsidered tohaveinsulinresistance(HOMA-IR)[11,12,18].
ThestudyprotocolwasinaccordancewiththeDeclarationof HelsinkiandapprovedbythelocalEthicsCommittee.Informed consentwasobtainedinallpatientsbeforeenrolment.
3.
Statistical
analysis
Dataarereportedasfrequencies(percentages)andmedians (95%ConfidenceInterval–CI)andanalyzedbymeansofx2(or Fisher’sexacttext,whenpredictedcountsinalmostonecell werelessthan5)forcategoricalvariablesandMann–Whitney U-test for continuous variables (which, at Kolmogorov– Smirnov normality test, were almost all non-normally distributed),respectively.In-ICCUmortalitywasassessedby logisticregression;aunivariantanalysisidentifiedparameters that weresignificantly associated with outcome and these wereused ascandidatevariables ina multivariantlogistic regressionmodel.Nagelkerkepseudo-R2and
Hosmer–Leme-showgoodness-of-fitanalysesarereported.Sincethe multi-variablemodelwasslightlyoverfitted,duetothelownumber ofevents,thedatawasfurtherassessedbyplottingareceiver operating characteristic (ROC) curve with each patient’s estimated probability of death, in order to determine the discriminationachievedbythearea underthecurve (AUC). LongtimesurvivalwasexploredbymeansofKaplan–Meier analysiswithrespecttoHbA1casadichotomousvariable (Log-ranktesthasbeenreported),aswellas,afterproportionalityof risk assessment with Cox regression analysis, in both a univariantandmultivariantmanner.Inthislatteranalysis, variables for inclusion were carefully chosen, given the numberofeventsavailable,toensureparsimonyofthefinal model;non-significantvariablesweredroppedbymeansof backwardselection.DichotomousHbA1cwasforcedintothe analyses. A p value <0.05 was considered statistically significant(SPSS13.0;SPSSInc.,Chicago,IL).
4.
Results
PatientswithHbA1c6.5%showedhighervaluesof admis-sion, peak and discharge glucose (p<0.001, <0.001 and <0.001, respectively) and a higher incidence of HOMA positivity (p=0.001) as well as higher values of ESR (p<0.001),fibrinogen(p<0.001)andtriglycerides(p=0.001) andlowervaluesofHDL(p=0.018).Therewerenodifferences inshortandlong-termmortalityratesorintheuseofdevices. Independentpredictorsforin-hospitalmortalitywere
(multi-variate backward logistic regression analysis): admission glycemia (OR:3.95,95%CI: 1.92–8.12, p<0.001),eGFR (1ml/ min/1.73m2 increase)(OR: 0.96,95%CI:0.93–0.98, p=0.002),
peak Tn I (10ng/ml increase) (OR: 1.03, 95%CI: 1.01–1.06, p=0.088). Hosmer and Lemeshow test x2=2.58, p=0. 589; NagelkerkeR2=0.46;areaundertheROCcurve93%(95%CI:88–
99%, p<0.001). HbA1c was not associated within-hospital death (OR: 7.21, 95%CI: 0.75–69.69, p=0.088). At follow-up (medianof39.7months(22.2–57.1)),theKaplan–Meiersurvival curveshowednosignificantdifferencesbetweenpatientswith HbA1c<6.5%andthosewith6.5%.Table1showstheCox regressionanalysisforlongtermmortality.
5.
Discussion
Inpatientswithoutahistoryofdiabetes,onlysmallstudieson theprognosticroleofHbA1cwithdifferentmethodsandresults exist[6–9].In150non-diabeticpatientswithMI,mortalityrate andtheriskofcardiogenicshockincreasedwithHbA1c[6].Ina high-riskMIpopulation[8]HbA1cwasariskmarkerofdeathat follow-upinpatientswithoutahistoryofdiabetesandnotin diabeticpatients.InasmallgroupofMIpatients(diabeticand non-diabetic)treatedwiththrombolysis[7],therewere signifi-cantrelationshipsbetweenadmissionglucose,HbA1cleveland mortalityatfollow-up.Conversely,in504unselected, consecu-tivenon-diabeticSTEMIpatientssubmittedtoPCI, hyperglyce-mia (not glycated hemoglobin) was a predictor of 30-day outcome [9]. The main finding of our investigation is that HbA1cvalueswerenotrelatedtomortality,shortandlongterm, in consecutive STEMI patients without previously known diabetes,whoweresubmittedtomechanicalrevascularization. Inourinvestigation,patientswithHbA1clevelshigherthan 6.5%didnotshowahigherinfarctsize(asindicatedbyTnIand leftventricularejectionfraction)oramorecriticallyillness(as inferred bytheuseofdevices).Discrepancies withprevious papersaremainlyrelatedtonumberconsistency[6],population selectioncriteria[7]andtypeofrevascularization[9].Different frompreviousstudies[6–9],weobservedforthefirsttimethat higherHbA1cvalueshelpsinidentifyingasubsetofpatients who,intheearlyphaseofSTEMI,showanabnormalglucose response tostressasindicatedbyhighervalues ofglucose, worseglycemiccontrolduringICCUstay(peakglycemia)anda higherincidenceofacuteinsulinresistance(HOMAindex).All thesefactorshavebeenassociatedwithincreasedriskofearly deathbyothers[19]andus[10–12,18,20].
Patients with HbA1c>6.5% also showed a increased inflammatory activation(increasedvaluesoffibrinogenand ESR),suggestingalinkbetweenacuteglucosedysmetabolism andinflammationintheearlyphaseofSTEMI[19,20].
Inconclusion,thoughincreasedvaluesofHbA1carenot associated with a worse prognosis, non-diabetic STEMI patients with HbA1c>6.5% may merit closer attention to in-hospital glucose management, since they exhibit an abnormalglucoseresponsetostress.
Conflict
of
interest
Theauthorsdeclarethattheyhavenoconflictofinterest.
Table1–AdjustedCoxregressionanalysis.
HR 95%CI p Wald
Age(1yearstep) 1.0541.018–1.0920.003 8.828 DischargeLVEF(1%step) 0.9510.914–0.9900.014 6.028 NadireGFR(1ml/min/1.73m2step)0.9810.963–0.9990.045 4.023
HbA1c>6.5% 0.7050.213–2.3380.568 0.326 LVEF:leftventricularejectionfraction;eGFR:estimatedglomerular filtrationrate.
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