Document 7260

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The New England
0031"'^^^'
Journal of Medicine
'°1120
tCoftri'te IW*. b; ibeMMHiSiuKiu MeSal Snrittj
JUNE 6, 1974
Volume 290
PREDICTION OF CLINICAL CORONARY HEART DISEASE BY A TEST FOR THE
CORONARY-PRONE BEHAVIOR. PATTERN
C DAVID JESKIS*. PJIJX, RjtvH. Rosuaux, &&D., .«o STEPHEN J. ZYZANSKI, PH.D.
Abstract Prosp»ct.w<i stud/ of 2750 employed men
who competed a computer-scored last questionnaire
measuring tha coronary-prone TypoADctiavlor pattern
showed that high scorers had twice the incidence ol
new coronary hsart disease as tow scorers over a fouryear pBriod. sub]tcts with dirfarant Initial clinical manlfostalions Of coronary dlstas* did not differ from one
another In their Typ» A last scores. Th» double-blind
design ol there studies and Ihe orderly relation ol Typ»
A scores 10 coronary-disMso risk suggest thai th» coronary-prone benavior pattern is prospectively linked to
1(19 pathogenesis ot coronary heart disease. Tha find,
ings also indicate that the test questionnaire used Is a
valid means of measuring some of the ways in which
behavior contributes lo coronary risk. (N Engl J
Mad 280:1271-1275, 1974)
S there a pattern or stvUsof behavior that, lite other
Ipersons
risk factors, permits prospective identification of
at higherriskof development of clinical coro-
urgency, acceleration of common activities, restlessness, hostility, hypernlcrlnew, cxplojiveness of speech
amplitude, tenseness of facial musculature and feiilngs
nary heart disease? Ifsucli a pattern exists, can it be re- of struggle against the limitations of time and the inliably identified clinically or, even more valuably, for sensitivity of the environment. This, torrent of lire is
research and screening purposes, measured by some
usually, but not aluny?,channeled into a vocation or
automated means?
profession with Midi dedication that Type A persnns
Scientiticracarch. particularly in the past 15 years, often nedett oilier aipccia of their life, such as family
has produced evidence giving afiirmaiu-e answers to and recreation. Not all aspects of this behavior pattern
both these questions, Scientists in the Ctiited .State;, must be present simultaneously for a perron to be
the Netherlands, Australia and Israel have Indepen- classified as ]»ssessingii.Thc pattern is not a personaldently reported empirical studies of patients with coro- ity tmit or a stress reaction, but rather the observable
nary heart disease and control groups indicating that
behavior thai emerges when a person predisposed by
patients with coronary disease strive more diligently his character structure is confronted by a "triggering
toward achievement, arc more psrfcctianisuc, tense situation." The converse of this behavior pattern, Type
and unable 10 relax, put forth more effort and commit- H, is marked by an absence of Type A characteristics.
ment to job or profession and are more active and enerThere is considerable evidence that the association
getic than corresponding comparison groups.1
of this behavior pattern with coronary disease is genuThe Four eategonWof traits listed above ore compat- ine and noi due to artifact or sampling peculiarity.
ible with cm another and. considered as a single syn- Several independent retrospective studies and a major
prospective study now support tha association of the
drome, approximate the •'coronary-prone behavior
pattern" {Type A) as formulated by Friedman and Ro- ccronary-prrme Type A behavior pattern with dinic.il
curonary diwa«. The prospective findings are from the
ssnman. These investigators add the important intrreWestern Collaborative Group Study, which found
dienu of aggressiveness and timtr urgency as essential
2
Type A itirn to have HibMantinlly higher incidence
pins of ihe behavior pattern. Thus, the '"coronarypi one behavfor pattern" can br defined as an overt !:«• ratvs of romnary dfcenie inilependsnt of the contribuhavicr syndrome or styli- ol living characteriitd by ex. tion Irfmiitthrr rivVfc»-iw\from iii lint Tollcw-up re.
p»rt until ir> tiii.il ri-|t«n coverinij S'» years «f !oni;ivesso ol* ininpriitirttirvs. suivin'{ tor achievement.
av.sjrcMKrnc-; (somrtimo •stringently reprci^cd). lime luilm.ilIMJI. All ihrliRilimj-tfitiHlaredisciivnedmore
fully in j i-frnl rei-a**? jWijli-r.1
^•".iT.tl f.:>it»r» «i«-;r,!r(l ihs value ni drvrfopiiivra
mint- nubK'uictl |um.-(l:irrforttai-rciinin'i b«"ha\irjr
I*.|M- *1 |i.-i:itrr\:c.w ifcjutrrrl tr tiiti-il p«-r'.rifsrv:l, ccmtiii-jin.' vif itviuun ar.d alactl 1 » mim:t«<>f «-bri!u!^I
npr">inii::r-n linn- prr ir.tt-ninv. Tbi» ja-nirdnr.* -."V
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THENeWESOLASDJOfRXAl.CJrMEDlCISB
forts are decentralized to numerous locations. These
limitations stimulated the development of a sclfadminittend t pa|»r-and-pencilquutionn«iretha(can
JJMM>M«U»>'computer. Hrerious pnoKcaiionshave dc*
* ^ R r f e i ^ % t initial development of ihis test questionnaire (the Jenldris Activity Survey), 4 the relation of ike
Survey's scores to behavioMvpe"interview judgments
and the ability or the test ( o discriminate between
groups or patients with coronary heart disease and
healthy subjects. 1 *
T h e present report addresses itself to two fundamental issues regarding the adequacy of the self-administered, computer-scored test: whether the Survey is a reliable measure over lime, and whether it can identify
prospectively persons at higher riskoTincurringan initial episode of clinical coronary disease.
!iiisiti;(." lfciailrd dacriptru» «if tlte cTrveleptneiii cf tfte «.ulci
hx\t been uublUlKd.1-*
ScotitiR norms s«ie deris rd front all subjects in the Western CollitxitativrfSniipSipdyschacomptnedtlie l965Xunr\'.Euehcmn.
putcnt icalr V4> standudicci] iv haic mean oTatJand a suttdatd
dcsiaiiM of llLOin the aban population.Scores lit the potitise i\rcctiontgmnerihan 0>lndtcclcllieTvpeA dlrecUonjandKorcsIn
the nc;aiiie direction ific Ttpe B direction.
Otagnoa** al Carotusry Dluaaa
Dr. Herman X UhTcy, chief of the Dcpartaiuil of Elecsrscar.
diojwphy, Muunt Zion rftapital and Medical Center. Sjn r'ranch>
4.viM«ia^Kd«ltclcuUvU4ldiuyraru>riuiitca(iiiiJUtH]ofcaaQiiitatioin
of (he Western Coltahoraure Group Study. AB the tracin» thai IK
considered dennitelv or probably Indiutisvofrnyocardiiilinfarction
vere referred ID Dr. Harold Ktrtenb'.um. then chief of HKdidne at
Mount 2ion Hojpitil and Medical Center, whu served as indepen.
drot nieiUcal rclcrce. The medical refexee judged die ptetence vt
rnyocacdial hfatccion on the baits cf classic Q u a « pattern v
Abnwmafitic* cT the ST scgwerri or T waics (or both} vere nut
cuuidcred
adequate RK diagnosb of dcSnile infarction. Mm with
METHODS
deftnitc anomalies ofehese types uere conddcrcd to be isaspect
Study Population
casoi*' iicrwever! and nxic excluded both front the group of new
Tlsedata-oteprt^nledare derived trcmiVeWestrMCMIaocra* cases and from the control group free of coronary dixt-e. Attjina
p>ctivitwasdarnr><edb>-nT-jnsofihfcriitriaofHebcr<te,l.Al<ach
tlre Croup audi, which In I9604I Initialed nbmvailHi cf 313»
tVcstera CcUa&craiK'c Group Study re^\»mlnailfln. subfeeu »<«e
employ*!* faua 11 rfirpnrarinnl in California Subjem M « ytl
ma tea between 3d and Si/years of age at the time of ihcirmdls-idual ad:ed abosit interim iHnrssct. pain, or diicnrnfrms in llic chest and
utcof nieslicJl «cr%ices. Rcplkssugeesimspos*ibtcc*rducpfoblerns
tfltry into the study. At'(ho IStt annual it-esamimuni r.l the
croup, 3946. completed and ntltraed ill* IS© form of she Jenbbu mre referred 10 Dr. RMenbium.uf.neitli-r dirccdyor ihroucji the
Activity Survey. aicspumcRte of 02 per cent. Of time, N»Jiad * ttudy Half obtainecj fiinhcr cttoical intbnraiion on each easr. This
chnical intbrmation iaclucled dcuiltd contacts with the subject')
record of clinical coronary divjase btfoic ratty into the ColLabora.
penonal physician, hotpilal records, electronrdioeramt feoni phvsi.
live Croup Study, and SI additional men Mi'tailied their First cpitode of corcrutr disease after inuVe bm brfxs campleiiiif lite Jen- etuis* cHiccs arid [rvspilals. the tile ul previous electrr^aidiosraois
i3keniniheStudy.ajid.parrtcuIaiiyincat<soranF^rapcaoris;acU.
am* Activity Sunay. (An additional tevtn IMA incvrrcdaeitte myocardial infarction in 1965 but after the datcol the annual examina- r«l interview ivith the patient u-hen rtecMsaryforclan!ieatuin.Xej.
tion and die compietfanof the Survey.! a a prrvidui napfci hpic men Ihcr the phyticiatt lmoilcaion at the Siodj-r.o.- the independent ttl*
were included stius all cthcrcases of coronary tttart disrate occurring ajnosticiatu at iheMou.it ZionHrxpiul and Medial Center Ine"
the Jenkins Activity butvey xnrc> uf anr subjects dutina; the years
after imaVebal before Dectmlxrjl. l9to."7he seven ax lurejivea
thtsr mom prrctie>dciienit»ii a*ir.eidence eases sinre the 1965 Sur. that die diagnoses were made.
ny).AiMalGf2f^subJeniricvorcornnarydneaseaithriimeo(taS;r'inal diagnosis of coronary disease u»s done In-dcpendtntly of
th2thel9K3Suc\«yrnRncdtnKe70uprolInwrdtHrfiMtriean.ihrot>gli
both the stiff of the Harold Brunn Institute (R.1I.K-) sod the t.'nithe end of 196). A more coraptru drxnptb.lorihc characteristics oT veni^' of l^uorth Carolina-Eostcn Univenlsy leans (Ci>J. and
the stvdr papulation is $hw la an earlier itparlr
SJ.Z.). Data ss'ere izat rvchanr^sd until nne or more' sears had
cbr>scd. afterdLifriMes seere raade. ThK u-asa ''doabte.rjujid*' study
in the full 3enie.
Mvasurttmnl c! VarlAblti
TheJenldntAciMiySuivtytiaiJediimn) it a Gl-jtemmultiple,
choice quest isnaaire. preceded Tor cue and accuracy id keypunch.
inf. The forms Here fitted out by lb* studs- vjbjects at ssurl; or at
tome and rruitM directV so sWrern Ccllibocarive tlreup Kiudy
wafT. Forms utre bet punched, serilfed and then pnxened directly
cnan IBX( 3d) computer. Both die decks ulcaidi rmMinuig item
responses and tr.nc containing scores tv shefo'jrSurscs states »»ere
stored at the Schot] id Public Hejtih at IhrL'nuenin 0l>r.;th Carolina. Z\*o results u«rc ccmnwrucatfd to stiidt -ubpvis
Respmsse* to the Survey HerefirststciQhKi] and lliea -cored acmrrlinrjinshefinir-rparalr trrstes. llp-TspeA \rutr ssas«!esii;iird
r>slcldknottr.d! mcvureof llico-rwsors.jirunr bshaipv {Altera
It was denied IV nirjiw «]fa di\trinsinArtt.fii.Vii!o vqMi'Jtti tuo-d
on the items ib.-.l be»l <li*cnnrinai<.i men jm'^ed tn !:•* *l» pe \ Imr.i
these fjiiffd aiTspr II b; nica'is.iif tlKC&xrat i»irnim It luv,
brcnshtMMT.id'ipheati' tlirj3>rne*. |wl~ue:sloJ'h'''s.lsi«' tvjiei«i
t'*e\Sri:emOiEw:t»*fr,m"rl''liMiJ»*.'.;3!* m7Sz«-iCci:l*«t'p'*Mt-l> III
?f!dlt:i::i to the l'ii:f.\ hij!.*. ll.i/r Ji.i.ir-^:uKti.«!^ t>mi*1di
ir*e iM.ii.<i^M(,ri.t lb.*! furt- fj^rii t...iiult»fji.frl^it«^!k w i V f - m
^ n t rsirajtMn^nlfc'* the 'i'l-Ii. A |Mi»i>».i'ilk 1'Ii^ a ; « i.i3!iii..L^nt
i!rrfl«i.ii'itl>r ti^.1* in £*"-.% .r:*l C r - . 1 ^ t.l t.^ I'liL^aTits lr\i*.« ( Ml* t
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A measure designed to predict a future outenms cnit
achiev/j vs-orthwhile predictiv* itrength only if its reliability is Irish. I'trr ottr purpose, a test l o predict future
coronary disease must fjive stabb readings o\er lime
and results thai are ecjuintient hetsyeen different raters
ordilfercnt formiof tlieitat.'J'ite 1965, ISM and l?G9
ctiiiiontcftlifjentiitis Activity Sunev-cojitaitiedacoie"
nficlrntical ileitis', but caih uihsequeni edctiun alvo
ei;ntnined i'ex'isitniHorc^rlierspicstioiis and itvstly prejsarrrj itcrrrs. t'ttrllicrmnr*:. the *.ci!r< for r;y-li lot sscri*
itidepeiKlemly cteris'ed. This prccedstre re&ulted irr
su]i:eu}i;u difKrenl itcmc and sits'ally (lilhTctit siaiisii{.sl nri!;hn tnr thr saint* itrrtft m5:ti» inrn cavlt »rj!e I'JI
c.:i h \r;sr.
Tin- tfNt-«-!r<i .-i.rribti in r»—!!if5r*rr. li.r O.tiv- i,{
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TIE0312193
w
BEHAVIORAL WtEDICTtONOy HEART DISEASE-JENKINS F.T AI»
Vol. EM »n2J
from 0-3ti tr>0.6Q. The test-retest coefficients between
the 1955 and 1969 form* administered a t a four-year
Interval are not appreciably-lower than those between
the 13(55 and 1966 farms, g i v e n one year apart. The
scores associated with the coronary-prone T y p e A paltern arc thus shown to be stable over lime, with 90 per
centofpcrsonstiavinglesithan 10 prjintsdifference between (heir 1963 Surrey and t h e separately standard*
ized form that ihey took in 1969.
Prediction c! IMUal MinVtsUIen ol Clkdcal Coronary Hurt
Oliiaaa
T h e predictive validity of the Jenkins Activity Survey for identifying persuns in whom clinical coronary
disease subsequently developed is shown in Table I.
Among the 2750 men free of clinical coronary disease
w h o rook the Survey in 1965, 120 subjects had coronary disease before the end of 1 9 6 9 . T h « e subjects are
compared with a control sample selected by the following procedure. A 20 percent random satnpleof the
remaining men was drawn, and those Sited as having a
history of coronary disease or suspect coronary disease
(by electrocardiogram) were removed. Thus, the 524
Tabla t- Meaftiof S e c t s Inft»W»»tMnCo9*bOMHv»Group
Study lor F/osp»cti™ C a w OT Coconuy H»art P i u a u and
lh« Control Group.
S,«t
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control subjects shown In Table 1 v.«re known to be
still free of coronary disease at the end of the 1369
follotv-up interval.
Men in whom coronary disease developed after testing scored on average or +• 1.70 on ihe Type A Scab,
whereas, the control group's average score was slightly
less than the population mean ofO.Ofp «• 0.01. by onetailed probability test). It should be noted, however,
that the absolute magnitude of the deference was not
lar;;r. Xwteof the scoreson the scales derived by factcr
tmalisU >ha\«d -significant differences between cases
and t'/uiroli.
'Hi- viiiir rl.ua are analyzed in iircspeciFve desisjn in
l'it;-U"* 1.in which Mibjrcisarc i«nnsped by thairTjpt:
A MI.--, ,:1i;.nned in 1SI>> The- average annual iVifid-.-iuo-.l iphial cancan-duraw rpmxles \»34 plotted
hir ruh ji'-rmip *|"w Lite ul ivw mronaiy di.rjw
».»-.!n I I - J L I E I I luvi:i{T>pi- \ vn.n*>-tn-.iii-r i!..«:i
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%*lt' •• .••»«-.i.~"iihiMfi.ilii!*vhjiliB"intrilfjn«iiir».• .'v ' 1 . ; •* .1:1 lilfTitl-- 'It:*" -..uisr- r-JH«-m nri-vai!rtl
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- .:• -• • . - ii •'.!*• n n i r . i i 1 «Vm< thr :'..•»» J-"nki;i, Ar<rM*j»t^.- ^--*.-'
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JAS TYPE A SCORE
Figure 1. tr.cicenceol Coronary Heart Diseasa among Wtsiwn
CoHaborali»»t3rou» Study Msn According to Ass and Jenkins
Activity Survey <JAS) Typ» A Sccrn.
tlvity Survey. T h e approximate: parallelism o f the two
lines indicates that the uvoage decadesstudied showed
similar degrees or association between T y p e A.scorea
and the risk of new coronary disease. T h e two age
decades hxd similar distribution of Survey scores, in
addition to apparently similar regression Df rates of
coronary kearl disease on the Type A score. T h e regression for die entire age range o r + t to 64 years (at the
time of testing) is appreciably different from lero (p «•
0.0'J). Thedrparturefromalinear relation is negligible
(Table i). This findin? was determined by the chisquatc tot as modified by Cochran and Armitage to
test for linear trends.*"
T h e questiDii was then asked whether men with different presenting sympiunis of coronary disease, such
as acme myocardial infarction, "silent" and clinically
unrecognized infarction or classic angina pectoris
(without electrocardiographic or other evidence of infarction), would differ in their distributions of Jenkins
Activity Survey scores. Table 3 shows that men with
any one of thess three initiil presentations of coronary
disease showed elevated scares o n the T y p e A scale.
T h e three group means are not significantly different.
There is more variability between the group means on
the three factor scores, but in n o case did this reach statistical significance. The "Hard-Driving" score seemed
to be higher in m e n with o n l y angina pectoris and
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Tabla 2. lncM*nc« cf Corenity Hi art Dlsiasa among Uta In
lh9 Stuoy Group by Typ» A Score.
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T1S0312194
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THE S W ENGLAND JOVKXAUOF MKDKS.NE
ISM
June 6,197*
Tc*l« 3. u*anJ«itfein> Activity Survty Scores. c4 129 C a m o! lnows only the independent variables «ftd the other
CoKMisiyOistaM According (a Typ*.
only the dependent variables protects against, conM%oCAiattL Mieoxtru
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quite low in those with unrecognized myocardial infarction. This difference may deserve further attention
in larger samples, la summary, then, men with these
three subtype* of coronary disease did not differ systematically on the Jenkins Activity Survey.
DISCUSSION
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In this study, a self-administered psychologic test
based on clinical concepts and interpreted by a computer has predicted future emergence or coronary disease. The lest, thejenJdtil Activity Survey, Is based on
the conceptual formulation of Ihc coronary-prone behavjorpaltem,Type A, as developed by Friedman and
Rosenman since 1959. Psychologic and epidemiologic
methods were used to develop the test questionnaire
and to study its properties in populations.
Tin.- methods «f thi» Atudy were designed to overcome many of the common weaknesses found in clinicalresearch.The study reportedsharcs many of the following mcthudolDgic feature! with the Wntern Collaborative Group Study, of which it is a pare
FirstofalLthsprescntstudy Is prospective. The data
reported are based on the study population of men
found to bo free of coronary disease at the time or the
1955 Collaborative Group Study annual reexamination. Completing the Jenkins Activity Surrey was part
of this examination. Surveillance for the development
of new coronary disease was continued OVM the tiRXt
four years. Ths prospective design protects the study
against false inference* caused by selective survival or
study subjects and reiroipcctlve bUucs known to be
presentforsomekindsof variables when patients try to
recall their premorbid experiences and attitudes.
Secondly, this was a double-blind nudy. Ths investlryitort wh.n developer! and scored the Junkins Activity
Surveyfcnr'.vonly the study subject's hlemificaiiw
number and at;e, and did not participate in tlw IOIIJWUJ» imrstijatiuti «f ths? >idijscts nr in the dia^rtu^is of
oiroflary d:-*Q>e. Tile in\esti>.ja!cr5 tvh»» man.ii»cd the
follow-up itiitly, interpreted ths t'VmcKudiii^rnin*
r.nil >ti.«!rlii!a!<!i,iJri'j.i-»l>adt:i)lvrimil«l^aLlih2S;ir
\rj •• »f-% In its!i!:T'i,n.ihc3»lb;crt<li:ul mi mWra.-iliiHt
ir".e.-l.n!»,hrir?>«is,T:«.-v«lt»..Mlc!nrfiii>nirni#>l -<<»r
ir; »"- -:-ni» :tr»! .mrr/:m;; wl tridivltiiutl -*.JJ—» !*«•i-#:r: *V.»*»£ ifl-fur
-iliv i!i:t:i:d d l U tvi-rr I'M h-i;« *<.»i
IIJ- " si:.3difj" «t l!:c <n.n!c;jun «» tlia« «ri- t.uni
scious or unconscious biasing or the results for or
against the hypotheses being tested. The "bUndlnjf" of
ihcsubjcct* protects against '•self-fulfilling prophecies"
and theriskof differential reporting of symptoms by
persons who may have believed that they were at
higher or tower risk.
Thirdly, the system for scoring the Jenkins Activity
Survey uasderived a priori on the basisof the theory of
the coronary-prone Type A behavior pattern and cli nicnl judgment) of the presence or absence of this puttern. The scoring system was not derived a posteriori.
by finding which items empirically discriminated between cases tircotonary disease and nancases and then
reapplying the scale of combined iienvt to the same series or subjects. The latter, commonly used "predictive" approach must be considered no more than tentative until cross-validated on a completely new sample. The development of measures from a conceptual
framework reduces the possibilities of capitalizing on
chance vagaries of the cose and control groups. It also
increases the likelihood that the findings cart be generalized.
Previously published studies from the Western Collaborative Group have reported that the Type A scale
and the "Hard-Driving Scale" from the Activity Survey significantly discriminate between a randomly selected group of healthy men and a group in whom coronary heart disease had recently developed? A recent
replication of thi» work among hospitali7«l patients in
Bridgeport,Connecticut,shows that patientxivith coronary disease score appreciably higher on both these
Survey scales than patients hospitalized for acute conditions not of a cardiovascular nature-." Analyses of
Survey scores among men in the Western Collaborative Croup Study who suffered recurrent myocardial
infarction have shown, thai these persons score even higher on the Type A Scale than men having only one
episode of coronary disease.
All these retrospective findings are subject to question regarding the possible influence of selectivesurvivat and retrospective bias in answering the questionnaire. The prospective association of the Type A score
reported here lend* support to the earlier findings •':*
based on retrospective designs and to the conclusion
that the coronary-prone behavior pattern as measured
by ths Jenkins Activity Survey is a genuine precursor
of cornriary heart dlscate. The continuous stepwise
relation bsrmesa the level or the Type A score and the
rU': of tJevriopmcnt cf new coronary disease {Kiif- 1)
sii.-ggeMsihat theType A scalereffccts the dimensionality of ssjtn?factor,nltoM* lilulu'jie prtiprrrietarertoi as
jf t ttell ilrtin«l, that is ijrmiimly related to risk ofcer-enmy di.ra*f.
It wa> tlssjppoiiitirfcf. to M*I!MI r.<m-.cl ilzrsrnlsideim-tl lis f.uttir .m.dvvKiiI \hv j.-n!ctni Artnity Stmcy
iu-m jHiul provi! pr»-ili>.lk«- <.l lomajn diiKhe. St:>ce
thr""Itinl-Ilrmr.itSc.ile"it»»»<I as iheT>|v Alcaic
<I».lilr'm->!:«l rcrctutiy «ajr-i l;nx\ cmivAin tts t^o
a-
tJtt^,
TIEQ3121S5
&•••
•v.'-'
•M^
-••
A
I
<
Vid. :Sl> Xi>.S
IXUKOCVTES AND MYOCARDIAL l*K\RCriO>i-FKIEI»i.\.\ffiT
retrospective sludies mentioned, it was interred that
ihv h:ird-drivin:j component of the behavior pattern
WIMIHISI relevant to risk ofcoroniry disease in Typr A
men. The present prospective data Tail to support this
inference on the basis cf Survey scales completed by
persons who had recently incurred coronary disease.
'Hie present data on incidence or coronary disease
imply that no single conceptual component or the coronary-prone pattern measured by the Survey is as important in predicting coronary disease as the combination of elements that makes up the global assessment or
the Type A behavior pattern os originally defined. We
harc preliminary indications, houever, that a more
molecular level of analysis, prospective study or
individual Jenkins Activity Survey items, may prove
to be a more fruitful approach than the use of factor
scores.
Ax was true for many other technical developments
in their early stages, the present findings are probably
more important for their scientific implications than
for their practical application. The Jenkins Anility
Survey In Its present form still misclassifies too many
subjects to allow its use in the usual clinical setting for
evaluating coronary risk among individuals or small
groups. T he Type A scale of the survey Tails to identify
many persons in whom coronary disease subsequently
develops and label? many others as being at high risk
vho continue for years without development of dis-
eaie. in this respect it issimil.ir to all other commonly
used coronary risk factors. More research is needed
Twin to improve the present instrument and to nnjment it with other Circes of information to reduce its
rates of icisclaisilication.
lUtXULNCCS
I. J#l\\n* CD. P>>vtiu1^I? a*t s*cial prccdfws «T oonmuy disttM. N
Eaji j MM :s»:>44.23}. JW-MZ; vm
1 rstJiaxi M: CnhiiMii&ts of Ctnxucy Ansiy DiieucXak Yorft.
McOll'A-ll.tl fed! C.imiMO*. I»». rp SJ4»
X Ro^niMin M l Jctikiil\Ct>. iff anil It/.« at; CoKKtiir* tKJtt dl»j.uc in
15: MV-*<r.iCVlti!ioriiiveGftfipS>!uilt; taA TutU^upctpcrienci #T
> ! i.-.ri J IM\ tia pw«»
J 7*i*lin*Cft.RdMnm.irtItll.l"r«JttJi)M: Cl<irtap:asa4<>rnol»^Mi««
fV.Oii<j\i££i]tt>Lfrr lb; dcfcjidiaitiOaoriblcoraftai^'ptttttfcetutief
fJtftm M cnpk»v'il IHiM. J CKjnk Dh 3tt}TI-3i*.' 1907
? Jr.*Vn>C0./«f.mAtSl.lttMEiin3ARtl' P»jfn»u»»jr<lialhlaUMof
..t6ifiniec(.t<oreJ fell ft* the IHpfAcomuct.prOMbchawrp^iUN.
r-^.un>raMtJ MMW-MO.1971
6. J;'nUn>CD.ZtuntklM.RostomaRH.etJkA»o:£utMercooxunrtnr.t tduwor KOKI nib /connote at coenvuv lean dtsuai'j
7 Rc.i>:mjnRH.Fri^nujiM.StawR.«ta1:.\pr«i2kth«*luJyo?.XfOej:% *rfjn Jitttte: the WAlftn OrftaUnjutr Oiuvp SlvOv. MMA
•:3s!
X. ZlljnAt St. Stirtin* CO: EuieduOuiiaM »ilhiA 11M eanuuiy.proM
ttS-iMjr fjiuta. J ChMiic K) 72:731-795, IWO
9. Cutbran V>0. S?HK ntcllMxU ptilrca^lliHMg ihw w n m n x * ie»u. BlCnteimv IK4I7-4SI, J9J-I
[A Arn'itj« J": TM>fiifliaeir acsdsl* prapotftjiu a i 4 rrc^iMiuki. t&icuina |]j:s-)S», IJ3J
It. Kcaljitx H i>. Zj/amla ST. Ja&iu CD. et Mi Tfce coa;iuiy.prai« br|i i\vil piiittn in htnpilJl!/A] pitman W4b anil uilh«vt <OHHUJ>« brut
ihujcc IHjciolaEn M#(t [b| ^rat)
THE LEUKOCYTE COUNT AS A PREDICTOR OK MYOCARDIAL INFARCTION
G.tKV D . FR1ED1U.V. M.D.. M.S., ARTItUK U KL.U3KV. M.D.. A.NB A. B. SlECELAUB, XLS.
Abstract Trio rnulttprtasIc-eitarnlnaKon findings ol 464
persons In whom a first myocardial InfarcBon lator dtvelopsd w»re compared Willi those of two Control
groups, one matshad for age, sex and race {ordinary
controls), and lh« other malchad In addition lor
standard coronary risk (adore (risk controls). The total leukocyte count, measured, on the average, 15.a
months before the myocardial infaicion, was strikingly
related to envelopment ol infarclloa The mean leuio.
cyte count In cases wa*signllloantly higher (p<O.Q0l)
than in ailhgr control group. Ascending from lowest to
highest qua/tile in tho enses and ordinary controls lh»
increase in risk of myocardial Inlarctiem associated with
tho iBukoayls oount was similar to thai found for cholesterol and blood pressure. Cigarette smoking, whish
was strongly related ta the feukocyte count, may account lor about two thirds o(the> relation of the count lo
infarction. The faultocyto count may provo valuable in
the routine assessment of risk of myocardial infarction.
(N Engl J Med 230:1275-1276.1974)
OXSIDERABLE progress has been made tou-ard
G
identifying personal and environmental characteristics that predijpose to or predict the occurreiwc cf
ahly.obesily, and family history oi"coronary heart disease O'her, less well established rislc factors include
physical inactivity and certain psychologic traits. Assessment of combinations of these risk factors permits
theidemiltcalianofpnpulatiansiibsrcups that differ by
s-veral timtsin tlirtr rislt of a niyorardtai infarction.'
Houevrr, there instill much to be letsmed about the
prediction nr myorartlial infaretmn. <inr# al!i\";»cl!y
lotv.ri.'c vibitruiips. as. drterminsd by the abf>v« fapmr,.<i!f>tjia jjcrsonsin ivhom inftuctsoni develop, and
myocardial infarction. The '"risk factors" that have
beencnnfinr.«im a variety of studies include increased
age, male ssx, elevated serum cholesterol and other
l!j)id>, cigarette smo^ins. elevated blood pressure, diAIKICS in«Ui;iu or carbohydrate intolerance and. prr,hIbi>"-fi!<piiuif«>>rfMniiutVrJwJiS««!;!iinJ V t h i w KJI.
-«t IV,r- ..iir^-t v ! « ^ « €"lie Vnytin tli'.tinj < jl I ij&n. f.^tm «-••
(J*-.*,!-. !l. t|.cC"J-40 .1 5**+ i'^oirt^t) A*e t>Atinl.*j! ,;^ll.
v v . -i:». *ef »»^n.ari!iiiKU.»ei»e*t^i.%^ NJI.WI. i t . . u ,-u
I,
'-" v . n r •»:.!!— , 1 - •_" \=lrrKJ*i
-..->•.'>»•
- •••:
tuatsv pi*noEX i n Mippci-M-dly hit»h-r<«li »uhqrfti[ps n»•i: j u t !:«•!• nl i%v ilivntsr. T o tih-ntity m l d i r : n n j l ;ire«Krt't-.i. '.*• !i.»v.' li*vfi <i!it*l;irlh\'» a n i*\pliiratiJiy «nuU
i>*::;'-\:e*ri.iiriL5«.i !• i n j n u l i i p l i a ^ t l u i i l i h v l : ? ! ! , ! ! ^ *
•!ns'tiI>ii:i'i>i<n'uiii<iiitil»:ni!if.irrnitn«ih>rr|ni'niK
•! • • ' • • , n i l . ! i J i.i i tn4>ill< iti.itrhrtt i . t m r n l Mibjrrt.
TIEQ3121S3
SiZaViir*'"'-'*'
4sa
•
THE KEW ENOUND JOURNAL OF MEDICINE
^
RsnnNcxi
O K . IB, 1974
K«tnl«tu-Mtoftwi1»i«»rCiHmi<w.AmkcilU)ff Dli)l:m.m.
I.SBor X. rtan JM: DKrertncti In Ttaihiory cspaculet or Irish
9. F.OHlrwiil OY, Arkins IA. SchMck LO: VentHaiSiin watt i on a
aid ItiUu f « nAun. A* SUv Rts£r Hi i c t w e i .
ftorml BOat&liofi allte a utn-yor btuval. Aa> IK* Rttjir Cis
WD
9*:74-7D.19M
1. /*W PntaUM ram of rtwnit Mn-s>Kif?ertipfritorydittu* ia
10. Rntbar CM: h t r . i cKnleat JI») (tHtsifekiiGal stades otcarwac
rfrflafcten.AMRtvlttiiicOisIWSM-2U, 1974
tfMKh;iIi.Sa-K3JRnpif!Xi«.a}-»Xm7
J. tiiK fin fittliu ami wdrretanf (WWUM: M twhmSoiMie sariy.
11. Htufai tTT.CS<on ic,F<rrii SO J r . * di IV-Chro/ik nwirattry
Am R*V Rnrit Bis IM.-JtMM. »H
<Xttu4teMMutlrbl»wanfec-rcvfoll«w-vpHtfy:fccininNy
><> Atmor D), Cowk AS: tV Dua-T«u Mm n An hiradueilcin IgcsmKp«I.A3iifbbfcHciUiJtlS67.|iM,l5«»
jnterlted 10M UMa laatystl tulaf list <lU»-teM >P»m- Nc* York, 13. Morris JF. Koski A, Johmort LCi Spirwnf uic itaitdanls tar h t i i l y
Fi—frc\i.\Vll
S.Kit NH. But DH. Hull Cfl: SPSS: mnstial paciujtforthe
Meid
seine**.
New York. McGrur-HUl look
CMipiiy,
1570
a. SMdfcor «V. Octna WO: Sniulkal Ms lata*. si»n *J*«.
Ann. Iow.I«*aSult Vnlwrsiiy Press. IM7
7. K«T * C CiMtan R. Ben* HO, el at: Tin Vtttfins A<!mI»tiriiioi».
AcMycoeixrilivt study of palagovy fuaclkM. I.CttMcaSitlnMnstry
En normal mtllAinlMci'J&MJ-ist.iMI
t. Ferris BO St, Antersoa DO. Zkisaantd ft: Frificiw vahcs for
nOHUlaiii > U l i . AaiRirRtspIr Mi IW:J7-*7.1971
IJ. MeJinl XtMafch COUKS: Vatiit of thtnofMftyU'ui and clnow
tlerapy ;• esufy chronic twnchuls: a upon u 1M aMicil R n t u A
COJPXU by Iter WBrfcLn jarty on trials of cktiMUKnvy in early
«hnmiebro!KnWs. lrMrlJI:I3l3.ni2.19«
U. Ho-AlrJfcEvoJuiJonofilatiMjmwyMiJKilyUtifMktromhWi.
Br MtdJ MK-BJ. IS67
15. Sunowi B. Eade ftH: Count and prognosis s i ctironlc cfcstrwSw
luni A l t a i c a prosoactrve study of TOO ratieatt. N Enal J M«4 MO:
»7-tM,19*9
RELATION OF CORNEAL ARCUS TO CARDIOVASCULAR RISK FACTORS AND THE
" INCU1ENCE OF CORONARY DISEASE
liD., RtguRBjl/BRAND, PH.D., ROBERT I. SHOLTZ, M.S.
AKDrd.DAVhfErfKINS.PHj)^
Ab»tr«ct Tin relation of corntal arcus lo tba incldance or cBnical coronary (Mirt diuas* was pro
spedivaly jludi»d In 3152 man, 39-59 yaars old «t
intak*. During' <n>m 8 Ht^war foilow«vp p«rigd, coronary disease dsvaiopod In 25S InRUIly wall man. At
entry Into th* aludy, arcus cr«valtnc« was found to be
slgnlftoantly cerialaxt to agt, **rum cholesterol and
smsUng habits, but w i s not rotated lo hematocrit,
blood prauure, vrelaht or obesity, habitual physi-
cal activity or dist, parental history of coronary heart
diswasa. aarum trlglyc«f Wit or lipoprotein* or to alcohol usa. Subjects under SO years of aga with cornaal arcus had a signllioantly higher Incidence of
coronary heart disease evan after adjustment for age,
serum cholesterol and smoking habits. Corneal arcus at younger agaa is an Independent risk factor for
coronary hear! dfeeatt. (N Engl J Med 29t;1322-J324,
1974)
C
was not confirmed.' lis correlation with xanthomatosis
appears established." but an association with serum lip.
idsremainsdi»pu(ed. , * u
Thcc4dr>dieftli?t3r<u*i> correlated with coronary discase"-* is not universally accepted.** It is not correlated
with generalized arteriosclerosis studied at autopsy.' The
present studies were designed toclarify the clinical mean<
ing of cornea] arcus.
ORNEAL arcui has long intrigued clinfcunl. Atthough occurring at alrooM all agej, the term wan
(eniiii indicate! iw common auoealion with aging.1 It
initially aprieanas a iranilucent segment in ihe lower and
upper peripheral cornea and progreoej until the tegmenu lute circumrercritiaUy tobecorwasemitrandiKcni
annu'm and finally aiay become an opaqur, grayith or
yellow-whin: ring, usoally separated from the Umbiutiya
clear lone. HutoehemicaUyi it consitti ol cholcMcxoJ, triglyceride* and phospholipid], thut uggetting a dcrK-ation from drcutating blood by inlili ration at the limbus
from scleral vrwcl*." it is 3lmow untyerally obKned
in higher prevjJcr.ee in mjIej, , A * bui noteworthy difference* in raciiJ. color and geographic prevalence5 lid to
(he hypothesis of a g«nei5c basis, supported by reported
similar development in twins and a piltem of dominant
inheritance.*
Prevalence of arcus was nnl found to be related in
diabetes/ viuirfn deDcienrics/t.'Ocsity/lrypertenHan**
cr eccrcise.* A reported association with alcohol intake*
Bca lie Haiti Hnm-i taiHJ*. Manas Zan 1!MJ:ILII ir.i Mttkil
Cvntcr. S u i praMfiica, t>M S^Sodl of P V U M H O ! : K . t t m v t r » t y o l Cz^-
f»Vrt3.Ilcrk«!<7.a."'iiMO<?*.-t^c:loflk'!avk>raiEpHcrtirli?iy.Eo»:an
Vr^tiKiySchocicIMrO;s»«l^:'/rjirefla!lK(i«H\t>Uf
K««^-io
JI l i i tfiis-j} CttM lw.~£t. Vr!.---.l Zi:a lfejisitaal Mrdn.il CtHtt.
VO
ft.>t1«!l.3afi3n«Ki«.C\WIKi
Stt;^»r:cJ by at&nrsh jssaiiliL-'it-U^ilr:™ iScNrfaua*! Itnnai^l
1 «.-i*I.r^«v«. Sjr;."."^! ti-irrjtSifl l t « : ^
MATUUAI. ANO METHOD*
1 Tie Western CottatxxaUirGroupSmdy witin'niatedin 1960*
ai a fro«p«cu^v itutly tit the UKI Jcnceof clinical coronary IKM t
diiease in men 3919 59 >nrs old employed in 10 companies.
Cornprchentive tlala were cbtairtcd at entry inxa th« study and
umualtydurtitga mean 8 H-Jwr rultoH-upperxxl. Apopuladon
of 3102 healthy stibjects renjined at risic tor coronary Man discose, of »diora Tiii w«re 39 (o -19 and 9<H w«c S3 to 59 yttti of
>$: at entry iniott..- study, fniiialdaia indudeilctinlcal.hixlKni.
kiL dietary and behavta-st nrbhles wr^ise detailed raetbodct*
<isr/haidtre^il)facenrerjfXtcd.*Comr^arcuswasde[erfclrxdby
rnetIcu!ausKrt>siir.ij)«t!BnKithIlash!ii5htiIItirn!natSon.Ajiaa!l.
fainl. inmlunrj
^•eK-rti-jii.!*-
trginciH was noi esnudeteii
an arcus tor the
present pai isowi The rliei ami akakn! niakes were ofcta!::*! h)
a^esendayui^ry^thaiwaiaiiiliiKtindets^farallrxirientccn:(yiri^ms isi a rej^ewn iaihr«#rijj!e <*r C^*J subjects. Uiabctn was
itr:rn:JK!f d *itila M ru^crr.
Vjrimt%iii!?i«**:rpiUu(j<^!itl>rV/r%zcTnt^i!t.-.V<c3fnc^eOoi!p
V/jcl»luiebcci»pieieit!rtl,,t!riK«trd f:=i!:rs»Erera*e^Kpc:i
«ls^itoCrtt?d^le:i!>v tnlM!ieMi:i'i Kt-itlsTsrst %igr.j!i«ai»te was
jHlt.Jcitljs tl:e»t:i-\.;u.»ri'lrtt .'-;tl lir V^itcKlN |.rr»l Aj^esv
i"rt;iclJii.nv<tT.::t«ii»ei^erii.tnn\a^dirMii:j.sisd]\ejir.w!!li
CY-.^.i-r
„,
hjL*
f
f?
Z\-\Zl.
TIEQ312197
V«4. Ml No. 2 5
CORNEAL AXCUS IM COKONARV HEART DISEASE — ROSKNWAN ET AL.
oriniMmeni (or amnflarnd bciora, used the Mantd—ituntul
method."
Rswns
Aran was observed in 569 (25.3 per cent) ot 2248
younger men ausdin372(41.2p«rcent)of 904 older meii.
Subject* with and without arcus shone J no dif fcrciicesin
parental history of coronary heart diieue, in schooling or
in job or arocaiional physical activity. Reported diabetes
was associated vilh significantly higher arcus prevalence
in oldtrrr.cn. CurrentcgarcUe smokers exhibited significantly higher arcus prevalence i n bothdecades. although
there were no differences for light and heavy smokers.
There were n o significant differences between numbers
With and without arms for mean height, weight, overweight, reported weight gain since the age of 25. blood
pressure, scrum triglycerides, serum lipoproteins, diet,
alcohol intake or behavior pattern. Subjects with urciucxhibited significantly higher mean serum cholesterol in
both age groups that was not due to differences of age or
diet.
In screening ot the large number of variable* studied
fura possible relation with incidence of coronary heart disease o r with prevalence of arcus, chance alone might account lor significant associations. If a probability level of
p <0.0I wasujed WaHcUsirniiicancecf oburved associations, the arcus prevalence in younger subjects was significantly associated only with age, serial cholesterol and
current cigarette smoking. Rdatio n between arcus prcvileiice and age. serum cholesterol and smoking showed
thai when subjects were divided into fiveagegroups, those
variables were Independently related to prevalence of
arcus.
During $ K years of follow-up observation, 255 ol 3152
initially healthy subjects suffered an initial clinical coronary event. A significantly higher incidence of the disease in subjects with arcus was observed only in subjects
of the younger decade and only in men whose initial
manifcsUuoii was myocardial infarction. Thus, the aver*
age annual incidence ol all coronary heart disease during
follow-up observation was 11.4 p e r I0M subjects with as
compared to6.2 per IOOOwiihoutarcuj(p>0.0001).Tne
average annual Incidence o( symptomatic myocardial infauction was 6.8 per iOCO with arcus as compared (a 3.2
per 1000w'«hout(p <0.0Ol).
Table 1 explore) inter-relations between arcus 2nd
incidence ot the disease for subjects 3$ to 49 years Of
age when adjustment was made for age. serum cholesterol and cigarette smoking. T h e odds-ratio column is
equivalent to the relative risk of coronary heart disease in
Subjects with and without corneal arcus. When no adjustment was made for pouiiV confounding effects- of other
^ariabies, there wasa 1,9 timsshigherrisi in younger subjects mh areas ( p < 0.001). Dilfercnccswcrc rail significant in older subjects.
IiirideiKewtsth.cr.rei!Mtiedin younger subjects when
iirijiisirnentwas made si.T.;h-and ui YrrintrsrreiifeinaifoKS
fur the three factors. When ailjiiii ment was i:iade sc-pai.itrh :>j:d in pairs. aswrUassimttluinniKly fcr the three
|jntir>.s!ibieaswijl]Kiit!vMiI]\Iitiwcil.ti!.i:ti!i!rfIysi;4ii'-'itAiuh hr4»:errelnme»ivk.
132)
A review of earlier studies leaves the impression that
in white subjects, corneal arcus at younger ages way be
significantly associated both with higher serum lipidsand
with increased prevalence of clinical coronary heart disease1-1 but that such associations are lost in older age
groups. Rifkind1 found asignificanl association of corneal
arcus with coronary heart disease, especially in younger
Scottish men. and made the astute observation that corneal arcus and alherosdemiic lesions show striking similarities. Thus, both feaiureanaccumufaiioii of limilarlipids in relatively or totally avascular tissue, both increase
with age, both are more frequent in males, the prevalence
or corneal arcus is greater in younger subjects with coronary heart disease and in such younger subjects, bothare
associated with higher Krum lipids. However, it might be
pointed out that coronary atherosclerosis appears to result mure from the infiltration or deposition of circulatinglipid in to areas of iniimal damage, whereas corneal arcus appears to result from the infiltration ot circulating
lipid intuanarea independent of primary degenerative
processes.*
Tibia t. Association b*tw«mCo<n«at Arcus and mcldwica ol
CoronsryHtirtOlstaM Adjusted for Indicated FKtORlln SubI»cU3»to«YMrsOm,atEntrylnlolhi Study.
Oa«» &tr»Ub~H4l»llL SMNMKAMCC
tUrui* Cta-SqiMiiVAwr
A»ji«tHi*r FACTUM
ttC6e
Factors n f r n t e l upaniety:
ScnjmcfcoUUMot
A*
$m>*<IniM!u
F M I K I a&uttd is (airs:
A n A strum chotestcnt
AjcJtiracfcins
Smrittii X u t w n cboKiKn*
Factors afiinltJ lost then
Aye le s*nan cftoWtUrot
&Mto&»e
IX
I3.JI
»<acvl
1.7-1
1.13
I.K!
9M
10.4)
11.21
P-0.CO2
p-0.001
p<0.OM
t.<l
I.»
7.IS
B.5J
!.«
7.»
T-0.OC4
p»O.0M
p-0.035
I.»
fJH
p=» 0.015
->KWnil*JKt>MOlttllKHI>M»MC«M<tirQB.
•WIJiiawMWIiMaM—MtanKUlbfcMlIaill?'.
The present findings were obtained from aprospecuVe
study. The prevalence of arcus was significantly related
t o age. serum cimlesterol level and smoking habits. A
significantly higher incidence of myocardial infarction
was observed in subjects under 50 years of age who exhibited a corneal arcus. The data show that the observed
association of arcus In men under age 59 with the incidence of coronary heart disease is partly explained by its
inirr-retalion with three factors, of which serum cheksterot and age are most important. Younger subjects with
corneal arcus exhibited an almost twofoM higher risk of
coronary heart disease. However, when adjustment was
made for the three factors that significantly correlated
with arcus prevKrcnrv, the relative risk in men with arcus
wasdiminished. but the ys>iBcxh!h:ts:d a 1.6 times rclatirc
risk t p < 0.015).
RrnatNcn
t JtirfcnslB'4 1Sci.r.i^KH"ec72rcrs^c^ti\,Bt»ch.i<r!KS*iriHSn«i«'
k^ir!^!^nin^n.n«-:^r«I!«Yc-t Li:*.ei t 111 SILICM
J W i c t t J ^ lt!*I*^rf»ntj«-^>tie-iv Art^ifJ;S;^aw-l6S*1M-Zlft.
1VC
iZSXXC&5ZZ2aHttZSmZj£Z&A^^
TIE03121S3
THE SEW ENGLAND JOURNAL OF MEDICINE
1324
J. FooiJi H: Areas stsili* «XM«: in tibial tlevilepntMi tnl trie.
tbiiil|> to sena lipBs. yauiu aid IfeoarouUs. Ada OcWelewJ
[S^tHKHH 411-73,1954
4. McAmknr OM. 0|HM l> Amu MHlS> (• •tut**!**' mw. Br WW
JI;4U-tI7.iW
5. N*ara*| *VJ Ir,Uia*uL.S»yd<r B: Areas aols«*(*ili>. AulascmM*»«4:MHJUKI
*. HlUny V. M m B, Hutaijr R: tow HWUK In nhllM u <KUtn
unibuM andriik(icitti [K H a « a v M n m w y hull 4UOM. Br
HoriJJ2;«WS!.lW0
T. TfMmu J V, E*ias IA. Deirositn MA: Alcohol consiimjiiMi ax)
utui senilis: • i w A r»f a slinilicul ISJUMJM/. »i I AI'JKI
»VdJ747S),l»7J
Dec 19.1974
«. Walt CE: The KIII'IM of aressveailii toarUttaiclOTiU aiul wiief.
NEneHMedJIUHJ.KM
«.tov««aianRH.FrittoaaX.Sinus R.tlal: ApccikiiveUjcVofeorenur l i u l Unease: she %Mn9 CoibSsxaSu Group Seal;. MMA
10, FiMBWi M. Rosciuion XH: CkHiEariso* of (a! liulis ol Amman
n « and v.omtn: fostible rcbtwaihip (a lactdeaca of atrial cor«M« m « y 41«jM.Cuc«l»dootfcMII-ti7.IM7
It. RoKMunRH.FnafounM.SInBi R.eisl: Century Ijeineliwi* In
the Wetter* CdUiwvJvcGt«i>S!»Jy:» Igltm^ nptticMttHM
ytia. J ChrorB Ks 13:I71-ISP. 1970
ILKaMiJN.HmiMlWiSlaliifialtorccnaftttfaailysiiorilaUlftm
rcMSOielivtiluCileldiveaw.l KsdOnctr!ulUi7IM4l,Hn
UDOCAINE IN T H E PREVENTION OF PRIMARY VENTRICULAR FIBRILLATION
A. OotibltvBllsd, RindowlTfd Study of 212 Consecutive Pailcau
K.I.LIE,M.D, HEIKJ. Wruxss, M.D.,FHAMSJ. VMt CAWLLE. PH.D., AND DIKK DURKW,M.D.
Abiiraot To assess th* efficacy ol lidocalna In pr«venllng primary vantrfcufarf Ibr illation in aouta myocardial Infarction a double-blind, randomized study was
perform*) In 212 consecutive piU*nlJ under the. acj« of
70 year* admittedtothe hotpltal within six houw of Infarction.
Group A [107 patient*) received an IntravaiMtis
bolua Injection ol 100 mg ol Bdocatne followed by an
Infusion of lldosalna (3 mg par mlnula} lor 4a hours.
Qrcup B (106 patients) received 9 per cant glucose
and watar. The group* war* comparable In age, sax.
site and siza ol infarction, admission time and mor-
lalityrate.
Ventricular fibrillation did not occur In Group Abut
dldlnntna patients ol Group B(p < 0.002).
Side etlacls, Including drowsiness, numbusa,
spee^dlsturbancasanildizzinoss,d«va!op«dln16pa,ti»nts(15p»rcanl).
These findings indicate that lidocaine in tha dosage
given was highly effective In preventing primary vantrlcularlirjriiutlon.buirioldotisarvatlonofpatlenlsard
control of Infusion rates are required lo decrease tha
likelihood ofsldeeHeet$.(MEnalJM6d291:1324>1326.
1374)
A
symptoms. Excluded from the study were patients Hitheilher
congestive hean failure, cardiogenic ihock. complete atrioventricular block. penUtrnt bradycardia (rale ol less than 50 beau
per tntnule), p«nutent reniricular tachycardia or vetttncular
hbiilhdon an adnwlon. Paiienu y,eie iniiiiitjr admitted la the
sudyon<b<ibuUDlarrpkathuiorvo(eh<slpalnv^utuup1clous
eleoiixardio*jiphk<hange>.PaiieiiUircrerttiin«duitMtludy
if the diagnosis of acute myocardial infarction was eiuMUbcd
[.THOUGH lidocaine has been shown to be an eftec• live a n d safe drug In suppressing ventricular ectopic
activity and venirkular tachycardia.1-* recent investigation* hare suggested thai iu prophylactic administration
did not prevent primary ventricular fibrillation in acute
myocardial infarction.*' Since other studies have indicated that the antiarrhythmic effect of lidocaine might be
dose related*'' we devised a double-blind, randomized
study of intravenous lidccaine wilha higher dotage than
thai used previously.*-' In view of the high incidence of
primary ventricular fibrillation during the very first hours
of acute myocardial infarction,* the present study was
performed in patients admitted to the hoipital wiihinsix
hours of the onset of infarction. In the light of the present
controversy concerning the predictability of primary ventricular Iibrillauoa'*-11 patients withso-called warning arrhythmias were also Included in thtrswdy.Tbeseweredefined as ventricular cxtrasysioles fulfilling one of ihc fcltuvnngcrUeria: occurring with a frequency of more than 5
bents per minute: falling in the vulnerable phase of the
cardiac cycle; being multifocal in origin: or being coupled
or occurring in runs.
MaTeajAt. ANn METHODS
Tlit Mciy >«33caiticd nci hi pat kntsund^r the age *:f TO yea"
;; 'rajcrd to the hotpbsl v>!thia sh taurs of the oejei cl
by ih« appearance otdtaarioufc Q waves with svnlulSsjujy S T .
segaicitl or T-vave chanitn and serial rise of scrum enzymes
(creatine phosphotuase, glutamic uxahcetic INnwrriniie and
lacdcdehrdri^cnase}. ImmecKucly altar admiuiatt ta the coronary-care unit,anin!ravencui Intuibn vas started, andabohu
irjectionof IWrngc^tictncaineorSperceniglucoieaiidYfater
vas (iKi. The cbok: ol injection HU bucd on compiele randmnirailiin. Depaviingui the type of bolus injectionjiven, paiienu then received an infusion ol either lidocaine at a rate ol i
ntgpcrmlnuteorSpcrceni glucotcand KM.CT.TIK intiukm tras
continscd lor ASi hours at a ccmaan! raleftpute of an infusion
ptunp. The patienU vere not informed whether ihej mgit or
might ant receive (idocabe on the basil of rindomualion. The
natureol the infusedsclution was imlLnown (oboth tt>e medical
aiiathenursingstalX.Sobtequenide«eIcpnxnio(any<i(ih((Ofnplleaikiu lined above led todiscnniinuaticnof the tnfuswnfcut
(etenttunin die Mudv,Oiberccnditio»for termination ot the infinkn con listed oiseerrr retplraton depression, development
tJcoafiaia:iuroccurieiKecife?ittp:kseizurei.Can<iriuousetecUDcardksraphictnoaiKrinvvnis prilor media all patients during iheirswy in the tn«. wiih cainsuiMis tape recordffljtdurfojt
the first IS !sfrjrsnltnfU»M]I].B!IUM1 levels oltl^ocaine treredelerratctdbyfiasclKfiniaayjjraphi."
RESULTS
Pi on IV D*patis*z\ c f C*zix2czj vai Cf^ucal Pt]/A:c!cvyAS]! V !.-v
icnr:>aii> Can.'»Vp«l Liiii;^:e. tSmtav'r I!ii*?U»I c l Aar.'j«ii-».
Vr.Uc>S'n4 HHV.'JII^ ARiiKiias. N"erh*rT=oJt ijiilrsti rcpraii ri^ie^zv
b> T.r I u Ll ihc tk.MK.-s-t t l Cais'.:tY « J Ck-.:-ii W.jaiiiy.
Wititlfsin* Cav^un. tcrile Kr!ni«i»-^i3l 1^1. Ar.tfer&n. Ptfjs-
D-jrirsj; til? ^ittiH |seritHl InunJune. 3973. iiiSrpir>nib«-r. 1D7-I. 71t3 |U!.*n;:% hert- .sdniUti'd c«n^cci:tivclr to
llsc «i:n:s).tn-tarif tir.rt uiilj ilw visjwiied isKvp-"'^ «>t
.ut:irirAin.iriIv.li=L:riti-.:i. Ati<:rttii:);tailst:prrn!i*.ts1v
TIE03121S3
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