SERUM M  COMP LEMENT  MYOCA

 Research Arrticle Tahmin
na Monowar et a
al, Research Desk, 2013, Jan‐Ma
ar 2(1). 74‐89 ISSN 2319
9‐7315 SERUM
M COMPLEMENT (C3, C4)) LEVELS
S IN PAT
TIENTS WITH W
ACU
UTE MYOCA
ARDIAL INFARCT
TION Tahmina Monowara*, Md. Sayedurr Rahmanb, O
Osul Ahmed Chowdhuryc, Md. Shaha
abuddind, A. K
K. e Kundu
*
Assistantt Professor, D
Department off Microbiologyy, Faculty of M
Medicine, AIM
MST Universitty, Semeling, 08100 Bedong, K
Kedah Darul A
Aman, MALAY
YSIA, e‐mail: ttahmina_mon
nowar@yahoo
o.com. b
PhD Resseacrh Fellow
w, Departmentt of Biotechnology, AIMST
T University, S
Semeling, 081100 Bedong, K
Kedah Darul A
Aman, MALAY
YSIA. c
Principal and Head off the Microbio
ology Departm
ment, Sylhet M
M.A.G. Osmaani Medical College, Sylhett‐3100, desh. Banglad
d
Associatte Professor, e Assistant Professor, P
Department of Cardiology, Sylhet S
M.A.G
G. Osmani Medical College,, Sylhet‐3100, Bangladesh. ABSTRA
ACT The C3 an
nd C4 levels in
n the serum o
of 30 clinicallyy detected Acu
ute Myocardial Infarction (AMI) patientts was studied in
n the present sstudy followin
ng the guideliines of Banglaadesh Medicall Research Co
ouncil (BMRC). The ‐1
th
mean C3 a
and C4 level (
(mg.dl ) in the AMI patientts was increassed significantly at the 5 d
day (146.88 ± 58.77, 37.08 ± 177.71) in compaarison to the 1st day (134.551 ± 43.23, 35..09 ± 13.89) and a
that of th
he control subjects (101.55 ± 14.66, 1
24.77 ± ± 8.15). A positive correlatiion was found between th
he C3 and C4
4 levels in thee AMI patients at 1st day (r = 0
0.494) and 5th day (r = 0.195
5). The differeence between the mean of C3 and C4 levvels in patients and t
that of the con
ntrol subjectss was found siignificant at 1
1st day (C3: t588 = 3.956, P < 0.001; the AMI p
C4: t58 = 3
3.513, P < 0.00
01) and 5th dayy (C3: t58 = 4.099, P < 0.00
01; C4: t58 = 33.458, P < 0.00
01). The C3 an
nd C4 st
th
levels betw
ween the 1 d
day and 5 daay of AMI sho
owed an insign
nificant differrence (C3: F2,227 = 2.769, P >
> 0.05; C4: F2,27 = 2.129, P > 0.0
05). However, serum C3 an
nd C4 levels w
were significan
ntly increased in AMI patieents in compariso
on to the heaalthy control subjects. In the present study s
it was observed thaat the activatiion of complemeent system occurs after AM
MI and it is sug
ggestive of an acute phase a
and inflammaatory responsee. KEY WOR
RDS: Serum, C
Complementss, Acute Myoccardial Infarcttion. INTRODU
UCTION Cardiovasscular diseasess such as Corronary Heart D
Disease (CHD
D) and strokess are the largest causes of death in develop
ping countriess and are onee of the main contributors to disease bu
urden (Gaziano et al., 2006)). It is estimated
d that cardiovvascular diseasses caused 177.5 million (30
0%) of the 58
8 million deatths occurred world wide in 20
005 (WHO, 22005). By the year 2020, th
hese diseases are expected to increase b
by 120% for w
women and 137% for men in developing d
cou
untries as com
mpared with 30‐60% in deeveloped coun
ntries (Murraay and Lopez, 199
97). Exact data about the incidence and
d prevalence of Myocardiial Infarction (MI) in Bangladesh is laccking. a
pectorris, unstable angina, a
myoccardial Incidence of Ischemic Heart Diseasse (IHD ‐ thaat includes, angina www.rresearchdessk.net 74 Research Arrticle Tahmin
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9‐7315 infarction
n) was about t
hree per thou
usand until 1976. A study in
n 1985 revealeed that the inccidence of IHD
D was about 14 p
per thousand. Prevalence o
of IHD in urbaan population
n was reported to be as hig
gh as about 10
00 per thousand.. Myocardial I
Infarction is th
he leading cau
use of death in
n Bangladesh
h, mostly in th
he 4th decade of life (MoHFW,, 2005). IHD is caaused by an imbalance i
beetween the myocardial m
blo
ood flow and
d the metabo
olic demand of o the myocardiu
um. Reductio
on in coronarry blood flow
w is related to
o progressive atherosclerossis with increeasing occlusion of coronary arteries. Blo
ood flow can be further decreased d
byy superimposeed events su
uch as vasospasm
m, thrombosiss, or circulatorry changes leaading to hypoperfusion (An
nversa and Sonnenblick, 1990). The classiic WHO criteeria for an accute myocard
dial infarction
n require thatt two of the three elemen
nts be present: a) a a history suggestive of coronary isch
hemia for a prolonged p
perriod (>30mins), b) evolutiionary changes on o serial ECGs suggestive of o MI, and c)) a rise and faall in serum cardiac c
markeers consistentt with myonecro
osis. Only two
o out of these three criteriaa are needed b
because of th
he wide variab
bility in the paattern of patient presentation with AMI. (P
Pedoe‐Tunstalll et al., 1994). The comp
plement system
m, an essentiaal part of the i
immune systeem, can be acttivated by thee three pathwaays: a) classic patthway, b) alteernative pathw
way, and c) M
Mannose‐Binding Lectin (M
MBL) pathway (Arumugam et al., 2004; Stah
hl et al., 200
03). It plays an importantt role in the pathophysio
ology of ischeemic heart disease (Iltumur et e al., 2005). A single stud
dy showed that serum com
mplement leveels are predicctive of myoccardial infarction
n up to 4 yearss before the accute event (M
Muscari et al., 1
1995b). C3 is p
powerful pred
dictor of MI in
n men without previous ischem
mic events (M
Muscari et al., 1995a). Serum
m C3/C4 ratio
o is a novel m
marker for recu
urrent n acute coron
nary syndromee (Palikhe et a
al., 2007). cardiovasccular events in
The C3 is a useful risk f
factor in coro
onary (Seifert et al., 1991; M
Muscari et al., 1998; Széplak
ki et al., 2004; Ajjan et al., 200
05) artery diseease and atherrosclerosis un
niversally acco
ompanies AM
MI in vivo. It is
s initiated witthin 2 hours afteer coronary artery a
obstruction via dep
position of C3, C which maay be due to generation of o the alternativee pathway C33 convertase i
in the ischem
mic area (Väkeevä et al., 1994
4). High C3 l
evels might h
have a direct rolee in the hypeerproliferation
n of vascular smooth musscle cells (Lin
n et al., 2004
4) and indicatte the chronic complement dependent d
in
nflammation as a a special marker, m
and not as a com
mmon acute phase Széplaki et al.., 2006). reactant (
The mech
hanisms by wh
hich the com
mplement systeem is activateed during AM
MI are still uncclear, althoug
gh the releases of mitochondrrial constituen
nts, reperfusio
on, and throm
mbolytic agents have been proposed (Beennett et al., 19877; Hostetter aand Johnson, 1
1989; Kagiyam
ma et al., 1989
9). However, t
the experimen
nts in animalss have shown thaat complemen
nt activation c
can enhance in
nfarct size (M
Maroko et al., 11978; Buerke eet al., 1995). Cardiovasscular diseasess are the majjor causes of mortality and
d disease in the Indian sub
bcontinent caausing more than
n 25% of deaths (Gupta et al., 2008). In Bangladesh th
he incidence of MI is increeasing (Murraay and Lopez, 199
97) and mortaality due to A
AMI has been reported as 2
2.54% (MoHF
FW, 2005). Ho
owever, theree is no reported s
study on serum
m C3 and C4 l
levels in patieents with AMII in our counttry. Therefore, the present s
study, first of its kind in Bang
gladesh, was u
undertaken w
with a view to evaluate the levels of seru
um complemeent C3 and C4 in patients with
h AMI at 1st daay of onset and
d at 5th day aft
fter attack. www.rresearchdessk.net 75 Research Arrticle Tahmin
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9‐7315 Materialss and Method
ds Data Colllection Data weree collected fro
om enrolled p
patients who fulfill the incclusion criteriaa and collecteed by pre‐dessigned questionn
naire devised for the studyy. The questiionnaire was pre‐tested an
nd face validaated by consu
ulting experts an
nd the data weere processed, analyzed and
d interpreted using statistical method. Enrolmen
nt Criteria All the paatients admittted in the Coronary Caree Unit (CCU) of Sylhet MAG M
Osmani Medical Colleege & Hospital w
with typical isschemic type of chest pain (without havving previous h
history of myyocardial infarrction, unstable angina, coro
onary interveention, cardio
omyopathy, any a
other accute or chro
onic inflamm
matory conditionss, congenital heart diseasee or valvular heart diseasee) was consideered as the caases. On the other hand, heaalthy non smo
oker persons of 35‐80 yeaars age withou
ut any historyy of chest paain and allerg
gy was considered
d for control. Study Design umber of 30 diiagnosed patieents as cases a
and 30 as con
ntrols were sellected accordiing to the incllusion A total nu
and exclussion criteria. Sample C
Collection Samples w
were taken fro
om the selected persons affter having informed writteen consent fro
om each patieent or attending next to kin. R
Relevant perm
mission was taaken from thee concerned a
authority and
d ethical comm
mittee of Sylhet M
MAG Osmanii Medical Colllege and Hosspital. Under all aseptic preecautions, 5 m
ml of venous blood was colleccted from each patient durring the1st dayy of and 5th d
day after attacck by using a disposable syyringe, which was then transfferred to a properly labelleed test tube. The collected
d sample was allowed to clot c
at mperature. Thee clotted sam
mple was centrrifuged at 200
00 rpm for 10 minutes. Serrum thus prod
duced room tem
was taken
n into approprriately labelled
d micro‐centrrifuge tubes byy using micro
opipettes and kept in ‐200 C
C until further an
nalysis. Estimatio
on of Comple
ements Serum C3 and C4 level was assayed by using com
mmercially avaailable turbidiimetric monoreagent of Hu
uman, Germany (Cat. No. C3: TU‐C3, INF 1
1111001GB, 09‐‐2006‐01; C4: T
TU‐C4, INF 11111301GB, 09‐22006‐01). The C3/C4 antigens i
n sample or s
standard reactt with the antti‐C3/C4 antibo
odies in the reeagent. The absorbance inccrease g aggregates w
was measured
d by using thee ELISA mach
hine (Model: H
HumaLyser 30
000 of caused byy the resulting
Human, G
Germany) follo
owing the turbidimetric en
nd‐point meth
hod. Statistica
al Analysis Statistical analyses for correlation, t‐test t
and AN
NOVA were done by using SPSS program
mme for Win
ndows (version 155.0). Results a
and Discussio
ons In the preesent study, quantification
q
n by ELISA of o C3 and C4 was carried out among 30 3 AMI patien
nts as against 30
0 control subjects. Among them, 83.33%
% were male (n
n = 25) and th
he rest 16.67%
% were femalee (n = 5). The ag
ge range of thee patients wass 38‐80 years with a mean ± SD of 55.27 ± 10.31. Out o
of the total paatients www.rresearchdessk.net 76 Research Arrticle Tahmin
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9‐7315 13.33% (n = 4), 40% (n ( = 12) and 16.67% (n = 5) were fou
und to have positive p
family history of AMI, hypertenssion and diabeetes mellitus r
respectively. The C3 an
nd C4 levels i
n the AMI pa
atients at diff
fferent risk fa
actors The C3 an
nd C4 level (m
mg.dl‐1) was found higher in
n the age grou
up of <59 yearrs. The mean ± SD of the C
C3 and ‐1
st
C4 levels (
(mg.dl ) in th
he AMI patien
nts (<59 years)) at the 1 dayy was found ass 146.09 ± 39.223 and 38.87 ±
± 14.05 respectiveely; while at th
he 5th day it w
was found as 16
62.22 ± 64.16 a
and 39.96 ± 19
9.28 respectiveely. A lower C
C3 and C4 levels w
was found wiith the AMI p
patients belon
nging to the g
group of ≥59 y
years. The meean ± SD of C
C3 and C4 level (mg.dl‐1) in th
he age group of ≥59 years was w found ass 120.38 ± 37.225 and 32.10 ± ± 14.07 respecctively han the C4 leevel and the l
evels of the ccomplements increased witth the (Table 1). The C3 level was higher th
span of tim
me. th
The mean
n C3 and C4 leevel (mg.dl‐1) a
at both the 1st and 5
day w
was higher in f
female (C3: 14
49.96 ± 49.93, 152.91 ± 48.87; C
C4: 45.67 ± 12.336, 40.31 ± 9.0
01) than male (C3: 131.42 ± 42.23, 145.67 ±
± 61.37; C4: 322.99 ± 13.41, 36
6.43 ± 19.05). The complemen
nts levels increeased with tim
me span excep
pt the C4 in female (Table 1
). The comp
plement levelss in the AMI patients who
o have positivee family histo
ory of AMI, w
was higher at the 1st and 5th daay with an excception for thee C4 level at t
the 5th day (Taable 1). In thee present stud
dy, most of thee AMI patients were w
past smo
okers and theey had higherr level of C3 and a
C4 than the t present smokers. The mean level of C3 C was found higher in thee AMI patients with hyperrtension and vice versa for the C4 (Tab
ble 1). Similar ch
haracteristics w
were observed
d in the AMI p
patients havin
ng the historyy of diabetes (T
Table 1). In the preesent study, a total of nine p
patients weree treated with Streptokinasee. The mean C
C3 level (mg.d
dl‐1) at both the 1
1st day and 5th day in the AM
MI patients trreated with strreptokinase w
was higher (140.65 ± 42.86, 160.10 ± 64.30) than t
those wh
ho were not treated t
with streptokinase s
(120.19 ± 43.0
05, 116.02 ± 25.55). The C4
4 level t
exhibited downwards t
trend at the 5th
day in comparison to 1st day (Table 1)
C3 and C4 leveel was . The mean C
found to v
vary dependin
ng on social status (Table 1
1). The higherr frequency off AMI was fou
und to occur i
in the low‐incom
me group (46.6
67%) followin
ng the middle income (36.6
67%) and uppeer income gro
oup (16.66%). The C3 an
nd C4 levels i
n the AMI pa
atients at the
e 1st day and 5
5th day In the preesent study, the t level of C33 (mg.dl‐1) at the 1st day an
nd 5th day waas found to raange from 66.06 to 220.47 and
d 56.62 to 300
0.14 with a Meean ± SD of 1334.51 ± 43.23 a
and 146.88 ± 5
58.77 respectiively (Table 2). The level of C4
4 (mg.dl‐1) at the 1st day and 5th day was found to range from 12.73 to 64.07 and 9.10 to 87.11 w
with a Mean ± SD
D of 35.09 ± 133.89 and 37.08
8 ± 17.71 respectively (Tablee 2). There wass found a posiitive correlatio
on between th
he 1st day and 5th day for C33 (r = 0.539) an
nd C4 (r = 0.3337). A positive co
orrelation wass also found b
between the C
C3 and C4 leveels at 1st day (rr = 0.494) and
d 5th day (r = 0.195). The regreession line eq
quation betweeen the C3 an
nd C4 levels was w found ass Y = 13.760 + + 0.159 X at 1st day th
(Figure 1) and Y = 28.44
44 + 0.059X att 5 day (Figu
ure 2). The reg
gression line e
equation betw
ween the 1st daay and 5th day waas found as Y =
= 48.320 + 0.7733X for C3 (Fiigure 3) and Y
Y = 21.995 + 0.429X for C4 (
(Figure 4). A significaant differencee was found b
between the m
mean of each complement in the AMI p
patients and th
hat of st
th
the contro
ol subjects at 1 day (C3: t588 = 3.956, P < 0.001; C4: t58 = 3.513, P < 0.
.001) and 5 d
day (C3: t58 = 4
4.099, P < 0.001; C4: t58 = 3.458
8, P < 0.001). www.rresearchdessk.net 77 Research Arrticle Tahmin
na Monowar et a
al, Research Desk, 2013, Jan‐Ma
ar 2(1). 74‐89 ISSN 2319
9‐7315 However, an insignificcant difference was found
d between th
he 1st day an
nd 5th day fo
or the C3 an
nd C4 complemeent levels (C3: F2,27 = 2.769, P > 0.05; C4: F2,27 = 2.129, P
P > 0.05). In the preesent study, th
he incidence of AMI was fo
ound to be deependant on v
various risk faactors. Both t
the C3 and C4 leevels were fou
und higher in
n the age gro
oup of <59 yeears, which might m
be due to vulnerabillity to atheroscleerotic changess of the aging
g process. Mu
uscari et al. (2000) studied on serum C3 level on 1840
0 men aged 55–6
64 years in thee San Vitale d
district of Bolo
ogna, Italy an
nd found a low
wer level of C
C3 (<59 years: 1.10 ± 0.18 g.l‐1; ≥
≥59 years: 1.11 ± 0∙17 g.l‐1) than that of thee present stud
dy (Table 1). Th
hey found no relationship of the C3 level w
with age. Rash
hid et al. (20055) found high
her incidence of AMI in thee age group 50‐59 years. Jo
oshi et al. (2007) reported a hiigh rate of AM
MI in Bangladeshi people w
with the overaall age (mean ± SD) of 51.9 ± 11.0. Anand et al. (2008) obsserved that yo
ounger individuals comparred to older w
women and m
men have a strronger MI risk. Therefore, T
thee present find
dings correlatted with the findings of Rashid R
et al. (2005); Joshi et al. (2007) and
d Anand et al.. (2008). The level of C3 and C4
4 in the pressent study waas found to be a dependan
nt factor of sex. Higher leevel of complemeents was observed in the feemale than maale. With the exception of C
C4 in the fem
male group, thee level of the com
mplements was w found to increase with time span. Anand et all. (2008) observed that women w
experiencee their first acute a
MI on average a
9 yeaars later than men. Men were w
significan
ntly more lik
kely to suffer a M
MI prior to 60 years of age than were wo
omen. Rashid et al. (2005) observed a grreater risk of MI in man than woman. Oth
hers (Yusuf et al., 2001) also
o observed geender variation
n of MI. The present studyy does not correllate with theirr findings and
d smaller samp
ple size preclu
udes from draawing any valid conclusion. There wass found no clear relationsship of the co
omplements levels l
in the AMI patientss with the po
ositive family hisstory of AMI. Muscari et all. (2000) in th
heir study fou
und no relatio
onship of the C3 level (1.11 ± 0.18 g/l) with t
the positive faamily history of myocardiall infarction. S
Smoking was f
found to havee a positive relation with the h
higher level of complemen
nts. This findin
ng is in well a
agreement wiith the finding
gs of Muscarii et al. (2000) wh
ho found that past smokerss had significaantly higher C
C3 levels (1.14 ± 0.18 g/l) thaan current sm
mokers and those who had nevver smoked (1.09 ± 0.17 g/l).. Hypertenssion/Diabetess has a positivve relation witth the higher level of C3 co
omplement in
n the AMI pattients. A negativve relationship
p was observved for the C4
4 complemen
nt level. Musccari et al. (20
000) in their study found thee C3 levels in the AMI patieents with and
d without hyp
pertension as 1.16 ± 0.18 g/ll and 1.08 ± 0.17 g/l respectiveely. In the AM
MI patients wiith and witho
out diabetes, t
they found th
he C3 level as 1.20 ± 0.17 g//l and 1.10 ± 0.17 g/l respecttively. They also found that t
hyperten
nsion and diabetes, in deecreasing ord
der of significancce, are associaated with higher C3 level. T
The present s
study also sup
pports the find
dings of Musccari et al. (2000).. Complement componeents such as C3 C and C4 ch
hange very eaarly after the onset of coronary occlusiion in w
AMI, and
d concentratio
ons immediattely decline, but b rise on th
he following days. d
This im
mmune patients with response not only n
depeends on the treatment t
witth thrombolyttic therapy (sstreptokinase)) of patients in i the AMI grou
up but may also a
reflect im
mmune activaation due to myocardial m
in
njury (Leinoee et al., 2000)). The complemeent activation
n caused by sttreptokinase i
infusion involves the classsic pathway (F
Frangi et al., 1
1994). The in vivvo effects of streptokinase are not know
wn. Moreover,, the consequences of com
mplement activvation by fibrino
olytic agents have h
not been
n studied. Fraangi et al. (19
994) in their study observeed only mino
or and non‐signifficant changees in C4 and
d C3 levels (mg/dL). Theey observed C3 level (m
mean ± SD) before b
streptokin
nase treatmen
nt, 15 minutes after beginning of streptok
kinase infusio
on and the dayy after as 83 ±
± 4, 77 ± 6 and 72 7 ± 5 mg/dl respectively, while the C4
4 level was 36
6 ± 3, 35 ± 2 and 33 ± 2 mg/dl m
respecttively. www.rresearchdessk.net 78 Research Arrticle Tahmin
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ar 2(1). 74‐89 ISSN 2319
9‐7315 However, in the presen
nt study, Streeptokinase infusion depletted native com
mplement com
mponent, sin
nce C3 and C4 levvels were sign
nificantly mod
dified. The present study show
wed that the s
socio‐econom
mic condition a
also affects th
he complemen
nts level in thee AMI Low income a
and low level of education have been rep
ported to be a
associated witth premature acute patients. L
myocardiaal infarction in South Asiaans (Ismail et al., 2004). Some S
authorss showed a positive p
correlation between I
IHD and econ
nomic develop
pment (Buyam
mba‐Kabangu et al., 1987; M
McKeigue et a
al., 1989; Rosengren et al., 20011; Rashid et all., 2005). How
wever, the pressent finding is
s in well agreeement with th
he finding of I
Ismail et al. (200
04). C3 and C4
4 in the AMI Patients The mean
n level of C3 and C4 (mg
g.dl‐1) in the AMI A
patients increased ovver time. Thee high level of o the th
h
complemeents at the 5 day might bee due to the in
ncreased syntthesis of comp
plement comp
ponents, decrreased consumpttion, or adequ
uate regulation
n. Iltumur et al. (2005) fou
und a significaant higher peaak level (mg.d
dl‐1) of plasma C33 and C4 in paatients with A
AMI (141 ± 29 and 35 ± 11, respectively) t
han in patien
nts with the co
ontrol subjects (1114 ± 22 and 222 ± 7, respecttively) (P < 0.0
01). The C3 an
nd C4 concenttration (mg.d
dl‐1) in patientss with AMI starteed to increasee in from 1st daay (105.5 ± 21.5, 20.9 ± 6.3) to 2nd day (116
6.9 ± 25.3, 23.8
8 ± 6.8), reach
hing a peak on th
he 3rd day (140
0.8 ± 28.7, 33.5 ± 7.3) and th
hereafter decrreased on thee 7th day (129.22 ± 20.7, 35.2 ±
± 11.1). The plasm
ma levels of C33 and C4 weree significantlyy different bettween days in
n patients with
h AMI (P < 0.0001). Their find
dings support the present sttudy. Giasuddin
n et al. (2007) found mean serum C3 and
d C4 level (m
mg.dl‐1) in the A
AMI patients increasing frrom 1st th
day (154 ±
± 28.5 and 38 ± 13) to 7 daay (171 ± 28 aand 46 ± 15). T
Those values were higher t
than in the co
ontrol subjects (1132 ± 8 and 29
9 ± 6 respectiively). Similarr trends were also found w
with the presen
nt study. How
wever, the mean C3 and C4 values v
reporteed by Giasudd
din et al. (200
07) were high
her than the vvalues found in i the present sttudy, which m
might be due t
o ethnic or raacial difference or more afflluent socio‐ecconomic cond
ditions of Libyan people. In the present stud
dy, a positive correlation w
was found in t
the AMI patieents between 1
1st day and 5th daay for the C3 (
(r = 0.539) and
d C4 (r = 0.3337). Giasuddin
n et al. (2007) also found a significant po
ositive correlation
n of C3 and C4 C elevation in AMI patients (r = 0.5222 and r = 0.48
83, respectiveely). Thereforre, the present fin
ndings are in well agreement with the fin
ndings of Giassuddin et al. ((2007). plement C3 normally n
pressents in serum
m at relativelly high conceentrations (C
Charlesworth et al., The comp
1974). It is i also an insensitive marrker for com
mplement activvation (Whalley, 1987). On the other hand, complemeent C4 is an independent predictor of stroke (Cavu
usoglu et al., 2007). The co
omplement syystem plays an im
mportant rolee in the physiiopathology o
of AMI, taking
g part in myo
ocardial damaage and reperffusion injury. Lo
ocal activatio
on of the claassical, altern
native and lectin pathwayys of compleement in infaarcted myocardiu
um has been observed in a
animal modells for AMI (Am
msterdam et al., 1995; Colllard et al., 200
00). A parallel riises in C3 and
d C4 was obsserved in the present stud
dy. These resu
ults show thaat complemen
nt was activated, particularly v
via the classicaal pathway. www.rresearchdessk.net 79 Research Arrticle Tahmin
na Monowar et a
al, Research Desk, 2013, Jan‐Ma
ar 2(1). 74‐89 ISSN 2319
9‐7315 In the preesent study, the t lack of an
n increase of complement anaphylatoxiins in non‐strreptokinase‐trreated AMI patieents does not rule out thatt complementt activation m
may have occu
urred in the isschemic area.. Such activation
n might not caause detectablle levels of co
omplement catabolic peptid
des in the peripheral circullation. Previous o
observations m
may indicate t
that ischemia a by itself is ab
ble to cause en
nough compleement activation to be detecteed in the cirrculation (Yassuda et al., 19
990; Langloiss and Gawryl, 1988). How
wever, one of these publicatio
ons indicatess an activatiion that did
d not involvve the differrent complem
ment compo
onents proportion
nally (Langlo
ois and Gawryyl, 1988). Diffferences in the t
severity of o the clinicaal condition might m
explain th
he discrepanciies between ou
ur data and th
hose of the oth
her study (Yasuda et al., 1990). In this stu
udy, it was fou
und that seru
um C3 and C4
4 levels were s
significantly in
ncreased in A
AMI compared
d with the health
hy control sub
bjects. These results show
w that activatiion of compleement system
m occurs after AMI. The degreee of activateed complemeent system may m be associaated with thee myocardial necrotic sizee and cardiac dyysfunction in
n patients wiith AMI. Witth a better understanding
u
g of the infllammatory prrocess subsequen
nt to AMI, we w may be ablle to decreasee the ischemiic damage an
nd increase th
he survival raate for patients w
with AMI. There are some limitattions in the study; s
one is that it was a small cohortt study. The other o
is the laack of studying c
complement a
activation pro
oducts. Howevver, the latterr may be ignored, since it h
has previouslyy been shown thaat complemen
nt activation p
products increease in AMI p
patients in parrallel with inccrease in C3 an
nd C4 (Mollnes eet al., 1988 an
nd Yasuda et a
al., 1989). In a
addition, sincee it was an ob
bservational d
design, the fin
ndings are hypothesis‐generatting rather th
han conclusivee. However, the t possibilityy of involvem
ment of other novel pment and maintenance off AMI should continue. inflammattory markers in the develop
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9‐7315 C3 Risk Facctors 1st da
ay C4 5th day 1st d
day 5th day 09 ± 39.23  559 yrs 146.0
162.22 ± 64
4.16 38.8
87 ± 14.05 39.96 ± 19.228 ≥ 559 yrs 114.551 ± 44.21 120.38 ± 377.25 28.558 ± 11.43 32.10 ± 14.07 Ma
ale 131.4
42 ± 42.23 145.67 ± 61..37 32.9
99 ± 13.41 36.43 ± 19.05 Fem
male 149.9
96 ± 49.93 152.91 ± 48..87 45.6
67 ± 12.36 40.31 ± 9.01 Yess 140.118 ± 22.51 154.15 ± 31.0
00 39.8
89 ± 16.54 36.58 ± 12.022 No
o 132.9
91 ± 45.11 147.79 ± 61.99 34.0
02 ± 13.53 36.74 ± 18.38
8 Pre
esent 133.8
80 ± 41.39 145.61 ± 62..69 33.556 ± 13.39 36.39 ± 19.46 Past 137.337 ± 54.28 151.95 ± 433.78 41.27 ± 15.43 39.82 ± 8.15 Yess 141.336 ± 38.69 166.96 ± 71.95 34.779 ± 11.58 33.56 ± 18.46
6 No
o 129.9
95 ± 46.52 133.49 ± 455.47 35.330 ± 15.57 39.42 ± 17.333 Yess 143.9
99 ± 28.00 199.71 ± 92.11 33.8
89 ± 13.07 29.92 ± 15.711 No
o 133.0
06 ± 45.36 138.75 ± 49
9.73 35.228 ± 14.25 38.18 ± 18.022 Yess 140.6
65 ± 42.86 160.10 ± 64
4.30 33.225 ± 13.18 36.11 ± 14.822 No
o 120.119 ± 43.05 116.02 ± 25..55 39.4
42 ± 15.34 39.33 ± 24.0
08 Low
wer 140.9
94 ± 47.22 151.23 ± 59.44 36.0
09 ± 12.22 37.21 ± 20.60
0 Miiddle 131.72 ± 42.13 149.05 ± 555.78 34.4
46 ± 15.14 38.00 ± 12.89 Up
pper 122.6
67 ± 39.05 129.91 ± 73..05 33.773 ± 18.29 34.68 ± 21.68 Age Sex Positive
e Family H
History Smoking
g Hyperte
ension Diabetes Streptok
kinase Social Sttatus T
Table 1: The m
mean C3 and C4 levels (mg
g.dl‐1) in the A
AMI patients a
at different rissk factors. www.rresearchdessk.net 84 Research Arrticle Tahmin
na Monowar et a
al, Research Desk, 2013, Jan‐Ma
ar 2(1). 74‐89 ISSN 2319
9‐7315 Levelss of Complem
ments (mg.dll‐1)* Complement Level AMI P
Patients Co
ontrol Subjeccts C3 C4 1st day
y 5th day Low 66.06 56.62 777.03 High 220.477 300.14 130
0.35 Mean ± SD
D 134.51 ±
± 43.23 146.88 ± 58
8.77 1011.55 ± 14.66 Low 12.73 9.10 10..49 High 64.07 87.11 34
4.98 35.09 ±
± 13.89 37.08 ± 17.771 24
4.77 ± 8.15 *(C3: Normaal range: 75‐1355 mg/dl, Lineaar Range: 0‐3550 mg/dl; C4: Normaal range: 9‐36 m
mg/dl, Linearr Range: 6‐120
0 mg/dl) Tablle 2: The C3 a
and C4 levels i
in the AMI paatients at the 1
1st day and 5th day. www.rresearchdessk.net 85 Research Arrticle Tahmin
na Monowar et a
al, Research Desk, 2013, Jan‐Ma
ar 2(1). 74‐89 ISSN 2319
9‐7315 Figure
e 1: Correlation between
b
C3 & C4
4 complement le vel in AMI patien
nts at 1st day
70
60
Concentration of C4 (mg/dl)
50
40
30
20
10
0
0
50
100
1
150
200
250
Concentration of C3 (mg
g/dl)
www.rresearchdessk.net 86 Research Arrticle Tahmin
na Monowar et a
al, Research Desk, 2013, Jan‐Ma
ar 2(1). 74‐89 ISSN 2319
9‐7315 Figure
e 2: Correlation between
b
C3 & C4
4 complement lev
vel in AMI patien
nts at 5th day
100
90
80
70
Concentration of C4 (mg/dl)
60
50
40
30
20
10
0
0
50
0
100
150
0
200
0
250
0
300
350
Conce
entration of C3 (mg
g/dl)
www.rresearchdessk.net 87 Research Arrticle Tahmin
na Monowar et a
al, Research Desk, 2013, Jan‐Ma
ar 2(1). 74‐89 ISSN 2319
9‐7315 Figure
e 3: Correlation of
o C3 complemen
nt level in AMI pa
atients between 1st & 5th day
350
300
Concentration (mg/dl) of C3 in AMI patients at 5th day
250
200
150
100
50
0
0
50
100
150
ncentration (mg/dll) of C3 in AMI patients at 1st day
Con
200
250
www.rresearchdessk.net 88 Research Arrticle Tahmin
na Monowar et a
al, Research Desk, 2013, Jan‐Ma
ar 2(1). 74‐89 ISSN 2319
9‐7315 Figure
e 4: Correlation of
o C4 complemen
nt level in AMI pa
atients between 1st & 5th day
100
90
80
Concentration (mg/dl) of C4 in AMI patients at 5th day
70
60
50
40
30
20
10
0
0
10
0
20
0
30
0
40
0
50
0
60
70
C
Concentration
(mg//dl) of C4 in AMI pa
atients at 1st day
www.rresearchdessk.net 89