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Side-effects of both antiretrovi-al drugs or drugs used in the treat-ent and/or prophylaxis of oppor-

unistic infections and neoplasmshould also be considered.4 Ganci-lovir, amphotericin B, cotrimox-zole, and pentamidine may causedP, especially if associated withucleoside reverse transcriptase in-ibitors (e.g., zidovudine). Thisan degenerate into ventricularbrillation and sudden cardiaceath. In the series described byil et al3 patients (75%) had echo-

ardiographic evidence of dilatedardiomyopathy. Moreover, 3 pa-ients (75%) used drugs that mayave caused QTc prolongation. Ofhese, 2 patients (50%) used cotri-oxazole, in association with fos-

arnet in 1 patient (25%). Uncor-ected electrolyte alterations,ossibly related to malnutritionnd/or to chronic diarrhea, wereresent in 2 patients (50%). Theselterations, which may be relatedo the individual clinical status ofhe patient and to the stage of HIVisease, should be evaluated andreated as early as possible, be-ause they further contribute torolonging the QTc interval. Fur-hermore, only 1 patient (25%)howed a normalization of the QTcnterval (0.38 second) after reduc-ion of the methadone dose.

The previously described clini-al variables may cause a signifi-ant bias of evaluation in definingethodone dose as the principal

ause of QTc prolongation in theeries described by Gil et al. Be-ides the small sample size (withelated high � error), the conclu-ions of the authors are not basedn a multivariate analysis (e.g.tepwise logistic regression analy-is) by which they could define theethadone dose as independent

ariable for prolongation of QTc.oreover, in this series, we do not

gree with authors that high-doseethadone could have unmasked a

re existing hidden genetic alter-tion (e.g., channelopathy); in con-rast, we believe that high-doseethadone may have enhanced the

ffect on the duration of the actionotential of the myocardium in theontext of either a preexisting car-iologic disease (e.g. dilated car-

iomyopathy) or a preexisting clin- m

48 THE AMERICAN JOURNAL OF CARDIO

cal condition (e.g. electrolytelterations in combination with orithout specific drug interactions).he dose of methadone should be

ndividualized in HIV-infected pa-ients according to their clinicaltatus as assessed by the Karnofskicore. Before administering meth-done, along with a baseline elec-rocardiogram, it is important toonduct a clinical evaluation of theatient and identify all the possibleauses responsible for a prolonga-ion of the QTc interval, especiallyreexisting cardiomyopathy, drugnteraction, and electrolyte alter-tions because these could enhancehe effect of methadone on ventric-lar potentials independently of itsosage.

Alfio Lucchini, MD

Melzo, Italy

Giuseppe Barbaro, MD

Roma, Italy

Giorgio Barbarini, MD

Pavia, Italy4 December 2003

. Gil M, Sala M, Anguera I, Chapinal O, Cervantes, Guma JR, Segura F. QT prolongation and tor-

ades des pointes in patients infected with humanmmunodeficiency virus and treated with metadone.m J Cardiol 2003;92:995–997.. Krantz MJ, Kutinsky IB, Robertson AD, MehlerS. Dose-related effects of methadone on QT pro-

ongation in a series of patients with torsade deointes. Pharmacotherapy 2003;23:802–805.. Barbaro G, Di Lorenzo C, Grisorio B, Barbarini, and the Gruppo Italiano per lo Studio Cardio-

ogico dei pazienti affetti da AIDS Investigators.ardiac involvement in the acquired immunodefi-iency syndrome: a multicenter clinical-pathologicaltudy. AIDS Res Hum Retroviruses 1998;14:1071–077.. Barbaro G. Cardiovascular manifestations of HIV

nfection. Circulation 2002;106:1420–1425.

doi:10.1016/j.amjcard.2003.12.071

he Metabolic Syndrome,ormerly Called MetabolicSyndrome X”

Roberts1 appeared surprised re-ently by the fact that none of theardiology fellows at his weeklyonference had made the diagnosisf “the metabolic syndrome” in theast year. But I am not, because inhe latest editions of 2 of theorld’s best known textbooks of

ardiology,2,3 I was unable to findthe metabolic syndrome” listed inhe index.

The term “the metabolic syn-rome” was the truncated form of

4

etabolic “syndrome X”. Reaven, n

LOGY� VOL. 94 JULY 1, 2004

n his notable Banting Lecture tohe American Diabetes Associationn 1988, described a syndromeharacterized by insulin resistance,yperglycemia, dyslipidemia, hy-ertension, and central obesity. Be-ng an endocrinologist and unfa-iliar with most of the cardiologic

iterature, he called it “syndrome”. But the term “syndrome X”ad already been used 15 years ear-ier by Kemp5 in an editorial pub-ished in 1973 to describe the an-inal syndrome with normaloronary arteriograms. To avoidonfusion between these 2 syn-rome X’s, an adjective “meta-olic” was used in case of the met-bolic syndrome X in distinctionrom the cardiac syndrome X.6–9

Over the ensuing years the met-bolic syndrome X became trun-ated to the metabolic syndromeor reasons not entirely clear to me.erhaps the mystery inherent in theesignation “X” in metabolic syn-rome X has been largely resolved.ut in cardiology the term syn-rome X is still being used despitehe fact that its mechanism hasargely been understood nowa-ays.10,11

Incidentally, if Roberts hadsked the same question about theetabolic syndrome to cardiology

ellows in China, he would haveotten a much better response, be-ause the metabolic syndrome isell known in China.12 The prev-

lence of metabolic syndrome inhina is 13.3% (12.7% in male and4.2% in female subjects).12 Inhina, obesity is the principal rea-

on for the increased prevalence ofhe metabolic syndrome.12

Finally, it is not the obesity, pere, that is an important risk factoror the metabolic syndrome: it ishere the obesity is that matters.y colleagues in China13 found

hat in postmenopausal women, itas the waist circumference rather

han the body mass index that cor-elated best with increased cardio-ascular and metabolic risk. A sim-le rule is that one’s waistircumference should not exceedalf of the stature.14 Just like com-aring apples and oranges, onehould not compare apples (ab-ominal obesity) and pears (ordi-

15

ary feminine body build).

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Tsung O. Cheng, MD

Washington, DC13 February 2004

. Roberts WC. The metabolic syndrome. Am Jardiol 2004;93:274.. Braunwald E. Heart Disease. 6th ed. Philadelphia:aunders, 2001.. Hurst JW. The Heart. 10th ed. New York:cGraw-Hill, 2001.

. Reaven GM. Role of insulin resistance in humanisease (Banting lecture 1988). Diabetes 1988;37:595–1607.. Kemp HG. Left ventricular function in patientsith anginal syndrome and normal coronary arterio-rams. Am J Cardiol 1973;32:375–376.. Koutis AD, Lionis CD, Isacsson A, Jakobsson A,ioretos M, Lindholm LH. Characteristics of themetabolic syndrome X” in a cardiovascular low riskopulation in Crete. Eur Heart J 1992;13:865–871.. Cheng TO. Characteristics of the metabolic syn-rome X. Eur Heart J 1993;14:143.. Cheng TO. Syndome X. N Z Med J 1994;107:139.. Cheng TO. Syndrome X confusion. Physportsmed 1994;22(10):49.0. Cannon RO III. The cardiovascular syndrome X:ow to recognize and how to manage. ACC Curr Jev 1999;8:(4)27–29.1. Cheng TO. Syndrome X. ACC Curr J Rev 2000;(3):102.2. Cheng TO. Metabolic syndrome in China. Cir-ulation 2004;109:e80.3. Hwu CM, Fuh JL, Hsiao CF, Wang SJ, Lu SR,ei MC, Kao WY, Hsiao LC, Ho LT. Waist cir-

umference predicts metabolic cardiovascular risk inostmenopausal Chinese women. Menopause 2003;0:73–80.4. Ho SY, Lam TH, Janus ED, and Hong Kongardiovascular Risk Factor Prevalence Study Steer-

ng Committee. Waist to stature ratio is moretrongly associated with cardiovascular risk factorshan other simple anthropometric indices. Ann Epi-emiol 2003;13:683–691.5. Cheng TO. Waist circumference vs body mass

ndex index in risk prediction of coronary heart dis-ase: comparing apples and oranges. J Intern Med;n press.

doi:10.1016/j.amjcard.2004.03.019

ngiotensin-Converting Enzymenhibitor Meta-Analysis Provides

isleading Conclusion

Angeli et al1 recently publishedmeta-analysis of the effects of

ngiotensin-converting enzymeACE) inhibitors versus all otherrugs for the prevention of conges-ive heart failure in patients withystemic hypertension. For eachrial, the authors combined thevents in all non-ACE controlroups regardless of the antihyper-ensive treatments patients in thoseroups received and compared thisvent rate with the event rate in theCE inhibitor arm. Then, they cal-

ulated a pooled estimate of theffects of ACE inhibitors versus allther antihypertensive agents. Thisrocedure assumes that all othergents are equal compared with

CE inhibitors. In other words, e

hat they are all uniformly better,orse, or no different than ACE

nhibitors.Figure 1 shows the meta-analy-

is of the same studies, but withouthis assumption. Figure 1 clearlyeveals that although diuretics ap-ear superior or no different fromCE inhibitors (odds ratio 1.07,5% confidence interval 0.80 to.43) in their ability to preventeart failure, ACE inhibitors areuperior to calcium channel block-rs in preventing heart failureodds ratio 0.84, 95% confidencenterval 0.76 to 0.93). This conclu-ion is consistent with the data, andseful to clinicians and patientseeking to make a clinical decisionased on this outcome. More im-ortantly, it shows superiority ofCE inhibitors over calcium chan-el blockers, suggesting a hierar-hy of agents with some better (di-retics and ACE inhibitors) thanthers (calcium channel blockers).his is contrast to the conclusion ofngeli et al,1 that all non-ACE in-ibitor agents are equal and that inurn they are equal to ACE inhibi-ors, a message that is not based onhe evidence they present, particu-arly with the results from the larg-

IGURE 1. Forest plot reanalysis of diuretichannel blockers on heart failure. ABCD �etes; ANBP2 � Second Australian Nationlockers; CAPPP � Captopril Prevention PrTOP-2 � Swedish Trial in Old Patients wipective Diabetes Study Group.

st trial, Antihypertensive and Lip- t

d-Lowering Treatment to Preventeart Attack Trial (ALLHAT).

Edward Mills, DPH, MSc

Victor M. Montori, MD, MSc

Lehana Thabane, PhD

Hamilton, Ontario, Canada

. Angeli F, Verdecchia P, Reboldi GP, Gattobigio, Bentivoglio M, Staessen JA, Porcellati C. Meta-nalysis of effectiveness or lack thereof of angioten-in-converting enzyme inhibitors for prevention ofeart failure in patients with systemic hypertension.m J Cardiol 2004;93:240–243.

doi:10.1016/j.amjcard.2004.02.075

imitations of Studies onasovagal Syncope

The report written by Ermis etl1 on the catecholamine responseuring tilt–table-induced vasova-al syncope illustrates 2 kinds ofifficulties of the vasovagal syn-ope studies. The first is the lack oftrue control group.2 The second is

he tilt-test limitations (the onlyne diagnostic tool available)2 thatnclude the timing of the bloodithdrawals during the test. The

ontrol group of the study of Ermist al1 is a group of patients with anterative syncope history but a neg-tive outcome to the tilt test. Med-cal history is the deciding factor of

-blockers plus diuretics, and calciumpropriate Blood Pressure Control in Dia-lood Pressure Study Group; BB � Beta-t; CCB � Calcium channel blockers;ypertension-2 study; UKPDS � UK Pro-

s, �Ap

al Bojecth H

he diagnosis of vasovagal syn-

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