Download Long-term survival in patients with coronary artery disease

IACC Vol. 23 . No. 5
Aptl 1994:1091-5
1091
Long-Term Survival in Patients With Coronary Artery Disease :
Importance of Peripheral Vascular Disease
KIM A . EAGLE. MD, FACC. CHARANJIT S . RIHAL . MI), FRIC D . FOSTER, MD. FACC,
MARY C . MICKEL. M S . BERNARD J . GERSH, MB, FACC- FOR THE CORONARY ARTERY SURGERY
STUDY (CASS) INVESTIGATORS
Boston. Massarhriserr.e and Seattle . Wanfliapron
Ubjrmioea. The propose of this study was 10 determine the
hnperlai m of peripheral arterial disease is predicting long.
ham survival in patients nfth clinically evident coronary artery
disease.
srlgmmN1. Patients in the Coronary Artery Surgery Study
(CAIA) Re utry were followed up for ?IG ycar .
MAhed. Survly.e In 2,2% patients with peripheral arterial
ditar was compared with that of 13.953 patients without peripheral arterial disease using Kaplan-hleler survival curves . All
patients had known stable corauary , artery dieewe. Clnicak
ejapho IECG) . ekest X-ray his and t, lerimtimt
variables or the two groups were compared mimg the chl square
ahlkde or the Iwoampie t cep . The Independent effect of
peripheral arterial disease (as well as other variables) an mortality
mar dehamhte ndltrJog a Cox proportional Intends model.
Rrrrl n. Patients with peripheral vascular &ease were more
likely M hove hypertension, diabera, family kidory of coronary
artery dlmeee, previous aoglonar myocardial adoration, previous
A number of studies (1-51 have suggested that patients with
peripheral arterial disease are at greatly increased risk for
mortality. predominantly because of the known association
with underlying coronary artery disease. Some report 1h .71
have suggested that aggressive treatment of suspected and
unsuspected corormry disease in such patients may lead m
imprisoned life expectancy. Nonetheless. the independent
effect of peripheral arterial disease an long-term survival in
patients with clinically evident coronary artery disease has
been less well studied . Studies of long-term survival id
patients with clinical coronary artery disease have focused
predominantly an such clinical factors as left ventricular
Finite die Caulk Unit and Depaaneet of Mcddne, Mavsaehuwels
Good Nwpital end Heaven) Medical School, Boom. 2.1a.wivocam : end
Cmrbrlig Cenlm, CAS& Uniwrshr of Waslinpon, 5eaale. Watlation.
Tie C M is uppated by Germ 5-eOI-HLO41 from the Netiund Heat,
ad slued IalL,w. Nmimot laaituees of Health, Eethod .. Mary had.
M.aertq cadre May 5.1993 : revised manawipt raetratSepteatar
211. 190 . saepted Novaoher 24.199L
tail Dr.
.
Kim A . Eenie, Aswciare Dirrcler of
akkar Cardklop. Cardiac
Me tahusells General Heepaol . Ambulatay Care Comer, Son, 469. 15 Palan a Street. Burton. Meene'l calls
L7
l31M,
01904 by
the A m nicen Cdteae ofCardtdeey
coroners brpesa sugary or to have masked. They also had a
higher incidence of congestive heart la ono, ECG abnormality
and modestly hrerered frequency of thrva-verse) disease . Independent correlates of lung-term mortality far the entire cohort
included age. smoking, dhhetes, number d discount coommary
vessels, left eertriedar function, h perrteanslon, pulmonary dis .
ease. angina) clam, previous myocardial admission and peripheral
vascular disease hill p < 0 .001). At any point in time. patients with
peripheral vascular disease bad a 25% greater likelihood or
annually than pattern without peripheral vascular disease (maid .
venture chFsquare 25 .03, homrd ratio 1 .23, 9316 confidence
interval L is to 1 .36, p < .0001).
0
Conrlasfoas. Peripheral vascular disease is a prong, Independent predictor of hug-term morality in patients with stable
coronary artery disease. Aggressive attempts at secondary disease
prevention are warranted in th is high risk group.
(1 Am Coil Carded 1994,23:10915)
function, number of diseased coronary arteries, involvement
of the left main coronary artery . advanced age. severity of
angina, hypertension and others. However, the European
prospective randomized study (6) of patients with coronary
artery disease suggested that peripheral arterial disease
might he an independent correlate of long-term mortality
after accounting for let) ventricular dysfunction, severity of
coronary stenoses and other factors . However. because the
European study was limited to 760 patients, it was difficult to
gain an exact estimation of the independent importance of
peripheral arterial disease on long-term prognosis .
We used the Coronary Artery Surgery Study (CASS)
Registry to further define the importance of peripheral
arterial disease in predicting long-term survival in patients
with clinically evident coronary artery disease. Our results
suggest that the presence of peripheral arterial disease
should he interpreted is an extremely strong prognostic
variable in patients being evaluated for coronary artery
disease and that because of poor survival across all subsets
of patients, a particularly aggressive strategy aimed at secondary prevention should be used in patients with both
coronary and peripheral arterial disease .
073 .ctootv.usr.m
~
o $
kip
rr
gg
. ~ B~RS
~
~4
r
[Hull
a
lift
~
lag
a
aan,
m
I
-
I
LT
um
ilk
m
~ ~
fill
law
rpa
!L 9,
Ell
13
I
3ACC Vol. 23, Na 5
Ap,a 1931:15914
EAGLE ET AL.
PERIPHERAL VASCULAR AND CORONARY ARTERY DISEASE
One of the covatiedes included in the Cnx mndel9 wag
type of therapy. For each site, the number of days after
angiogmphy within which 95% of patients received surgery
(amneg these undergoing surgery within I year) was calculated . The surgical group consisted of patients who had
surgery within the specified number of days . The actual date
of Purr., was the starting point for calculation of survival
time. The raedical group consisted of patients who did not
have surgery within the site-specific time period . Type of
therapy was "undetermined" in patients who did not have
surgery and died before reaching the average time to surM y . This adjusts for the discrepancy in exposure time
between the medical and surgical groups . Patients who died
before reaching the average time to surgery at that site were
exchded from analysis. Medically treated patients who
subsequently underwent coronary artery surgery remained
in the medical group .
1093
Table 1. Clinical Variables : Vascular Diseesse
AV lyrl
Femde geal., (W. 1
miehelm LN)
H9penne,on (%1
Family hhlory of aayloam
No
(n-13,953)
Yea
to-2,2%1
Value
53.7 z 9.0
35 .1 s 9.5
Is
c OAmI
e 0.0001
is
camel
44
50
< 0.0091
< 0 .0001
t9
a 0.0001
21
11
34
44
p
NJ (9,t
Smeint slams (31(
Neser
F.Crams
Previous NJ (41
23
45
32
More
50
5iupe
37
13
Stutbpk
Unmake angina (e1
Canadian Hun Foundation
41
40
48
34
< swat
19
36
39
0.02
8
35
39
17
9
67
5
29
42
25
15
<allot
class (T)
Results
Baseline ehaescteristia, Table 1 lists the baseline clinical
characteristics of 13,953 patients without peripheral vascular
disease compared with 2,296 wish this condition . Not uaexpectedfy, patients with peripheral vascular disease had a
higher frequency of traditional cardiovascular risk factors,
each as hypertension, diabetes, family history of coronary
artery disease . current soaking and previous myocardial
induction or eeousary bypass surgery. Also, the average age
was higher, and a greater proportion were women. Patients
with peripheral vascular disease also had more anginal
symptoms and a dig my higher incidence of congestive hears
fa0um
OsLovmdlRpva, ehd x .eey Iha and eathelefamim
variables. Table 2 compares patients with or without peripheral vascular disease with regard to baseline EM, cardiac
cutheterization . coronary anglography and veatriculography. Patients with vascular disease had a modest but signi4
icanlly higher prevalence of HCG abnmmalitiee or arrhythmia. systolic blood pressure and frequency or three-vessel
coroary artery disease .
IfiMlvatkts survival sods. Table 3 lists significant
independent correlates of survival as well as the multivariate
chiaquase values for each . After controlling for all independent predlclara, vascular disease retained a highly significant
correlation with mortality (chi-square 25.83, p < 0.0ODI) .
Vascular disease had a hazard ratio of 1 .25 (95% confidence
interval ICU 1 .15 to 1 .36). This suggests that at any time
during follow-up, the patient with vascular disease has a 25%
increased risk of dying after controlling for all other factors .
Table 4lisn the findings of multivariate analysis examining the importance of peripheral noncerebral vascular diseme elm and cerebrovascular disease alone . Cerebrovascolar disease correlated with an even worse prognosis
(head ratio 1 .43, 43% greater risk of death at any time) than
taoeeebral peripheral vascular disease (hazard ratio 1 .19,
19% greater risk of death during follow-up) . However, a
1
u
m
IV
CHF sm,c lIl
0
l
m
< OA00t
< D.m01
24
3
4
FLucuamlinpdnnent(tH
NaCHF
No inpoimem
sum
Mewls
Severe
&m-hlaelm 1451
Die alts 10)
Diuretic dregs 555
7
3
I
to
6
-
91
1
4
3
I
53
85
I
5
7
<stoat
53
21
31
NS
< 0Am1
< OAmI
u
22
Value, teesestd am,su veea 2 SO or percent of patirols. CHF heart Mum Mt - asacadid hdmctiua.
ra„ peer c
smaller number ofpatients with cerebsovasculardisease (351
patients) than mascerebrovascular disease (1,813 patients)
limits the precision of the estimated effect (hazard ratio 1.43,
95% CI 1,23 to 1 .66) am outcome, Figure I shows the
Kaplan-Meier survival curve for patients with or without
vascular disease.
DiscUaion
Importance of peripheral arterld dlseme . As in previous
studies (9,10), our Otdings support the observation that
severity of coronary artery disease and baseline left ventric
War function are very important determinants of survival in
patients with coronary artery disease . In this study of
>16,000 patients followed up for >10 years, 5 of the 14
independent predictors of outcome are measures of left
11
z
V
fl
V
#1 #1
AnaoR~Y
1
H 41
~~3_B~mSi
a r~~~ae
i
3
All
I
g
e
a
6
∎
T
•
•
7
R~&x.$~=.R$=$a$$
JACC Vol. 23, No . 5
EAGLE ET AL .
April 1997 :10915
PERIPHERAL
VASCULAR AND CORONARY ARTERY DISEASE
1095
arterial disease identifies the patient with more severe diffuse
vascular disease . This argument presupposes that our attempts to stratify risk by the severity of coronary artery
I . Smith GD. Shipley MI, Ruse O . Intermittent eloudicarion . heart disease
risk factors. sod nestlity:thewhilehattsWly.Cirtvlaton 1990$x:1923-31 .
disease on anelography were incomplete, limited perhaps by
2. Rannel Wis. Skinner Ji Jr, Sohwana M, Shuretof 0. Intermittent elaudi-
failure to use quantitative angiography or by the inability to
fully measure small arterial or microvascular disease . Another hypothesis is that peripheral arterial disease identifies
patients more prone to sudden thrombotic complications of
their vasculardisease. Finally, because smoking is so closely
associated with both poor long-teem outcome and the presence
of peripheral arterial disease, perhaps our analysis
References
casiun ; incidence in the Framinghan Unity . Ctrcuhdoo 1970;41:575-93.
3. Kamrel 19e. Won. DL . Options an same epidmdologc features of but,
musentdandimri se the Fb=0 t mstudy. J AMGesiarr Sae 1%5 :33:13.&
4 . Cnqui SIH . Franek A, Kiaubee MR. Eaneu.Connor E. Gahrid S. The
sensitrsity. spe :iReity and predictive sabre d tndhrnml clinical rvaam,
do . d peripheral aneial dilate; resalra rum ntndovasive anion in a
defined population . Circulation t985 ;71 :516.2:.
1. CrigrdMH.LamrRD,FrpnekA,etaLMonalitypvaapedalvflf Yin patents-ah periphery arterial disease . N EngtJ Mod 1992;mmt-y.
failed to identify risk factor interactions that together account for the observation .
Therapeutic importance . Given such striking mortality
risk over time, we believe that patients with mild coronary
symptoms and peripheral arterial disease warrant par-
6. Varnaaskac E. and the Eusapour Corpnmy Smaery Study Group .
Troelve-yeae fallonwp dsarvival in the rendmnired European coronary
nursery study. N Eno J Red 19n ;319;332-7.
7 . Hen- NR . aeveo EG. Young JR . n al. Cunaary every discos, in
periphery vascular patients: a classification of IOW coronary angioarans
This should include concerted
S. The Principal Investigators of CASS and Their Associates . The National
Heart, Long. and Blood Institute COrdnary Avery Surgery Study
1CASS). Circulation 1961 aoppt 1 :1-t-g1.
9. The Veremm .Administpstion Coronary Avery Bypass Surgery Cooper,
afire Study Group. Ekseo-ytor survival in the Veterans Adrnininnsion
mmli mired trial of coronary artery bypass ,
Wry for ersble angina.
N Engl l Std 1914 :311 :131.4
10 . CASS Prindpal Imvstigtors and Their Associates . Coronary Avery
ticularly careful treatment .
efforts to prevent disease progression with smoking cessation, control of lipid and glucose abnormalities and treatmem
of hypertension . Perhaps more aggressive coronary
revasculariaation in particular high risk subsets is also
warranted . Further studies of the relative benefits of coronary artery bypass surgery in this group
needed .
of patients are
and molts of rmgYal mapagernent . Ann snug 194V199:2_23-33.
Surgery Study (CtSS) : a randomirrd trial of eni,miary artery bypass
surgery . Survnal data. Circulation 1943:69:939-Sa.