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holipid Antibodies
CARLOS A. ROLDAN, MD, BRUCE K. SHIVELY. MD. FACC. CHI CHI LAU. MD,
FRANK T. GURt:LE, ERIKA A. SMITH, BS. MICHAEL H. CRAWFORD, MD, FACC
Albaquerqrre.New Mexico
Oaj&ves, The sins of this study were to belter characterize
valve diseasein systemic lupus erylhematosus and to determine itr
association with antiphospholipid antibodies.
Lltwkgromd. Estimates of &he pmslenc+ of valve disease in
group
IV p&&s
petientc &b
lupus e~#w-
The valve disease associated with syslemic lupus erythematows has been categorized as I) masses or vegetations
(Libman-Sacks endocarditis). 2) leaflet thickening. 3) valve
regurgitation and, infrequently, 4) valve stenosis (1.2). The
to
primary pat&e&c
&tor. Tbe rbamcteristic apv
of
leaflet thickening sod ttta%e~in pntietttswith ltip+t~et~?be!tta?o~~
may be oaiqae.
(J A, c0ll CmGd r992;20:1127_343
and
injury.These antibodiesare IgG, IgM or @Air.imunoglobulins directed against negatively charged phospholipids
present in the membrane of endothelial cells. They have
been found in patients with lupus erythemarosus. patients
with the antiphospholipid syndrome and infrequently in
normal subjects (14.15). Patients with antiphospholipid syndrome are those with positive antiphospholipid antibodies
and arterial or venous thrombotic events, thrombocytopenia
or frequent miscarriages who do nor meet criteria for nystemic lupus erythematosus. Valve abnormalities similar to
those associated with lupus erythematosos have been described in this syndrome (4.16,17).
The purpose of this study is twofold; I) to better characterize the valveabnormalities in parients with systemic lupus
erythematosus by using transesophageal echocardiogaphy.
and 2) to determine whether there is a specitic association
between anliphospholipid
antibodies and
valve disease.
Methods
Study patients. This research protocol was approved by
the Human Research Committee of the University of New
Mexico and all subjects signed informed consent. The study
group consisted of 54 patients with systemic lupus ervthematosus, Ill patlents with antiphospholipid syndrome and 35
age- and gender-matched normal subjects. The diagnoses of
sysiemis !upur erylhematosus was made according to the
criteria of Ihe American Rheumatologic Association (IS).
The patients with this diagnosis were unselected, representing about 80% of outpatients ~60 years ofas followed up al
the Rheumatology-Immunology
Division a1 two +Kted
hospitals. Twenty-one patients with lupus erylhematosus
>&I years of see were excluded on the basis of see because
degenerative v&e thickening, calcification and-regurgitation are frequent in this age group (1X20). We also excluded
three other patients with lupus erythematosus: 1wo patients
who had a history of rheumatic fever and one patient who
was an intravenous drug abuser.
in
multiple planes to define anatomy and the presence and
severity of valve regurgitation or stenosis. or both.
To assess mitral leaflet thickness, M-mode echocardiograms were recorded at the leaflet base, mid and tip in the
four chamber viea do,iug systole. Similar
M-mode word-
t mm
I to2 cm
I vs.
I orIIvs.group
IIIorIV.
tI
Andcardiolipln
w
IgM
Lupuranlicoagulan1
FalwpositiveVDRL
I vs.group
17
9
6
13
77
II
17
59
9
3
4
IgG WI
20
IeM IlLll
*Grwp
III. p < 0.03.VDRL = VenenlDisense
Research
L&oratotytest;der abbreviations
asin T;\bleI.
Gmp I
9(1
30
40
Iable
Graup ttt
ISLE t AB)
iApS)
59 t 61
34? 24
65+ 35
4oz 12
Abbwiations
were
BI in Table
- -
I and
2.
Abbreviations
as ia Tablc
Discussion
Major tindings. There are four major findings in this
Study. 1) Valve disease is present in the majority of patients
with systemic lupus erythematosus. 2) Patients with lupus
erythematosus have a similar frequency and severity of
valve disease regardless of the presence or absence of
antiphospholipid antibodies. 3) Antiphospholipid antibodies
in the absence of lupus erythematosus were not associated
with valve disease. 4) The leaflet thickening and associated
masses observed by tramesophageal echocardiography in
patients with lupus erythematosus have an appearance that
may be unique to this disease.
Comparison with previous studies. The results of this
Study differ from those of recent studies. We observed a
relative lack of
disease in patients with the primary or
secondary antiphospholipid syndrome (10%). Nihoyannop.
oulos et ai. (4) reported a much higher incidence (67%) of
valve disease in patients with either syndrome and Brenner
et al. (22) reported valve abnormalities in 32% of patients
with the primary antiphospholipid syndrome. These ditfcr
enccs may be related to the small size of the groups studied
in combination with other Selection factors. Our subjects
were neither suspected of having heart disease nor referred
for echocardiography. A differcncc in valve disease prevalence in the primary and secondary Syndromes may warrant
consideration. In our study, an equal number of patients
with antiphospholipid syndrome had a primary or a secondary syndrome. The duration of the disease also may influence the frequency of valve disease.
The reported prevalence of lupus erythematosusassociated valve disease varies widely depending on the
study methods used and patients studied. Bahl et al. (5)
recently reported the virtual absence of valve disease in
patients with a diagnosis of lupus erythematosus of <I
years duration. Galve et al. (I) reported an 18% prevalence
of abnormal valve morphology in patients with chronic lupus
erythematosus. Nihoyannopsulos et al. (4) found an overall
28% prevalence of valve disease (40% in those a;: anticardiolipin antibodies and 14% in those without antibodies) in
patients with lupus erythematosus. Enomoto et al. (3) reported a 79% prevalence of valve regurgitation in patients
with lupus erythematosus. Pathologic studies generally yield
an estimate of >5B% for the prevalence of valve involvement
valve
A~herrn RA. Lubbe WF. Cerebral and w&c lesions in SLE: aw&~io
withantiphosphobpld amihodlei (edirdrial). J Rheumaial 1988;15519-43.
Love PE. Sanlom SA. A!iphosQboliQ!d anl~balies: anlrcnrdrobpi and
Ihe lupus aticoag~lal in syilemiclupuserylhemat~w (SLEI and i
non-SLE disordsrr. Ann Intern Med 1990:112:682-98.
15. Fields HA. Toubbeh H. Sewler RP. Bankhurrt AD. Tbc prevalcce of
anticsrdiolipin anlibodu in a healthy cl& y populauon and 11sassociaLion with antinuclear adibadiss. J Rheumatal 1989316:6&5.
16. Ashen RA, Khamashls MA, Ordl-Km 1. Ed al. The primary aliQho;pholipid r)ndrome: major clinical and serulagical fealurr,. Mcditint 1909:68:366-74.
17. SammarilanoLR, GhamviAE, Lockshin MD. Anbphospholipld anljbcdy
syndrome: unmunoloaic and cbicamects. Semi Anhritir Rbeum 1990:
?(I:81-%.
IS.
13.
echocardiography that pa&ts with systemic lupuskry~hematosus have a similar prevalence and severity of valve
disease whether or not lhey have antipho$pholipid antibodits. These data do not support the hypothesis that antiphospholipid
antibodies
arc a primary paihogenetic factor in
hmus-associated valve disease. Finallv. the characteristic
appearance of leaflet thickening and a&ciated masses mav
be unique to lupus-associated valve disease.
WC gmlefully thank Domthy Patlack. PhD for her expert stillislirtl conbibulion.
Referenm
2. Klinkboff AV. Thompson CR. Reid GD. Tomlinroo CW. M-mode and
Iwo-dimcnsmnal e&cardiography
abnormalilier in systemic lupus
ciythematorur. JAMA 1985;253:327?-7.
3. Enomot K. Kaji Y. Mayumi T. ei ai. Frequcncyafvalvularregurgllatlo
by color Doppler echocardiogmphyin syslemic lupus crylhematosus. Am
1 Csrdiul 3991;67:28-13.
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CM. Cardiac abnormalilles I systemic lupus erjthemuorus. Circoiado
1990$1:369-75.
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crvtbemalosu~. Arch Path1 1941:32:569-6X
II. Shivel~
14.
19.
Klippel