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OJHAS Vol. 10, Issue 1:
(Jan-Mar 2011) |
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| Determination and Correlation
of Anticardiolipin Antibody with High Sensitivity C- reactive Proteins
and its Role in Predicting Short Term Outcome in Patients with Acute
Coronary Syndrome |
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Anita S Malhotra, Associate
Professor, Department of Physiology, Government Medical College & Hospital,
Sector-32, Chandigarh, 160030,
Rajeev Sharma, Associate
Professor, Department of Physiology, GGS Medical College, Faridkot (Punjab)-151203,
Jyoti Mehta Demonstrator, Department
of Physiology, Indira Gandhi Medical College, Shimla,
Jeet Ram Kashyap, Assistant Professor, Department of Medicine, Government Medical College &
Hospital, Sector-32, Chandigarh, 160030,
Varsha Gupta, Professor, Department of Microbiology, Government
Medical College & Hospital, Sector-32, Chandigarh, 160030,
Nandini Kapoor, Associate
Professor, Department of Physiology, Government Medical College & Hospital,
Sector-32, Chandigarh, 160030,
Atul Sachdev, Professor, Department
of Medicine, Government Medical College & Hospital, Sector-32, Chandigarh, 160030
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Address for Correspondence |
Associate Professor,
Department of Physiology,
Guru Gobind Singh Medical College,
Faridkot (Punjab)- 151203, India.
E-mail:
rajeevsharma.md@gmail.com |
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Malhotra AS, Sharma R, Mehta J, Kashyap JR, Gupta V, Kapoor N,
Sachdev A. Determination and Correlation
of Anticardiolipin Antibody with High Sensitivity C- reactive Proteins
and its Role in Predicting Short Term Outcome in Patients with Acute
Coronary Syndrome. Online J Health Allied Scs.
2011;10(1):12 |
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Submitted: Mar 10,
2011 Accepted: Mar 31, 2011; Published: April 15, 2011 |
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| Abstract: |
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Anticardiolipin antibody (aCL)
is considered to be an independent risk factor while high sensitivity
C reactive protein (hsCRP) is an established marker for coronary artery
disease. This study was conducted to determine levels of aCL antibodies
and hsCRP, their correlation and role in predicting recurrence of events
in patients presenting with Acute Coronary Syndrome (ACS). Sixty patients
admitted with Acute Coronary Syndrome were followed up for 7 days or
until discharge. Patients were classified into two groups as those having
experienced an ischemic event needing intervention within 7 days (Group
I) and other having an event free recovery (Group II). aCL antibody
and hsCRP levels were estimated and compared in these two groups. Twenty
age and sex matched disease free persons served as controls. The levels
of aCL were significantly higher in patients with ACS as compared to
the controls (p=0.020). However the levels of aCL in Group I (13.39±9.46
GPL-U/ml) and Group II (13.51±9.93 GPL-U/ml) were not significantly
different (p =0.838). The mean hsCRP levels were higher in cases
with an event (23.30±10.68 mg/dl) than in cases without an
event (20.60±11.45mg/dl) though
it was not significant statistically (p=0.389). aCL and CRP were
not found to be significantly correlated in causing the recurrence of
events(p=0.178). Therefore anticardiolipin antibody is an independent
risk factor which could be implicated in the pathogenesis of ACS. However
it is not significantly associated with recurrence of short-term events
in patients with ACS. Also, aCL antibody does not have significant
correlation with hSCRP in causing recurrence of events in the patients
of acute coronary syndrome.
Key Words:
Acute coronary
syndrome; Anticardiolipin antibodies; High sensitivity C -reactive protein;
Myocardial infarction; Composite end point
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Coronary artery disease (CAD)
is one of the leading causes of morbidity and mortality worldwide. Acute
coronary syndrome (ACS) is a constellation of clinical symptoms that
encompasses acute myocardial infarction (ST-segment elevation &
non ST elevation AMI) and unstable angina (UA). In addition to the well
established risk factors like elevated low density lipoproteins (LDL),
decreased high density lipoprotein (HDL), sedentary lifestyle, obesity,
tobacco, hypertension and diabetes, newer risk factors like elevated
high-sensitivity C-reactive protein (hsCRP), antiphospholipid antibodies,
hyperhomocysteinemia, elevated fibrinogen, factor VII, plasminogen activator
inhibitor-1 (PAI-1) and platelet hyperreactivity are also being evaluated.(1)
Anticardiolipin
antibodies (aCL) belong to the group of anti-phospholipid antibodies.
They have been found to be associated with increased risk of development
of venous and arterial thrombosis and myocardial infarction.(2) An
association of anticardiolipin antibodies with coronary artery disease
(CAD) has been shown in some (3,4) but not all (5,6) studies. These antibodies
have also been shown to possess proinflammatory(7) and procoagulant (8) properties.
High levels of IgG aCL (GPL>40) have been strongly associated with
both arterial as well as venous thrombosis.(9) Independent correlation
of aCL with myocardial infarction and cerebral vascular accidents has
been reported.(10) However, there is a paucity of data regarding the
association of aCL with outcome in patients with ACS. C-reactive protein
(CRP), an inflammatory marker, is a novel and evolving biomarker for
the extent and severity of atherosclerotic lesion and provides a useful
predictive indicator for subsequent cardiovascular events.(11) CRP
is also considered an effective marker to track progress of cardiovascular
disease and response to treatment.(12) Blake and Ridker (13) have also
shown that elevated hsCRP can predict risk of cardiovascular events
in patients with ACS. Therefore, the present study was planned
to investigate the association of aCL and hs CRP levels with 7-day outcome
in patients with Acute Coronary Syndrome.
The study was conducted by
the Department of Physiology in collaboration with the Department of
Internal Medicine and Department of Microbiology, Government Medical
College and Hospital, Chandigarh, India. Prior approval from the institutional
ethics committee and an informed written consent was obtained from each patient
included in the study.
Sixty patients out of 72 patients
admitted in the Medical Emergency with a diagnosis of ACS based on
the guidelines of American Heart Association task force/ American College
of Cardiology (14) were enrolled in the study. Patients of either sex
with age more than 20 years and confirmed diagnosis of ACS (based on
clinical presentation, ECG findings and/or biochemical markers), presenting
within 72 hrs after onset of symptoms were included in study.
Patients
not included in study were those presenting with heart failure (overt
or ejection fraction <35% on echocardiogram), diastolic BP >110
mmHg or systolic BP <90 mmHg, patients with pacemakers, renal or
hepatic dysfunction, presence of infectious and/or autoimmune disease,
presence of active Treponema pallidum infection or history of intake
of drugs likely to alter aCL levels (phenothiazines, hydralazine, procainamide,
prednisone). Patients with past history of an episode of thromboembolic
event in the past 3 months or history of hemorrhagic stroke, MI in the
past 3 months or treatment with anticoagulant drugs like unfractionated
heparin (UFH) and low molecular weight heparin (LMWH) in the past 1
month were also excluded from study.
Patients were followed up for
7 days or until discharge and the endpoint were a composite of cardiac
death, recurrent angina and AMI needing intervention within 7 days.
Patients were classified into two groups as those who attained composite
endpoint during recovery (Group I) and other having an event free recovery
(Group II). Anticardiolipin antibody (aCL) and high sensitivity C-reactive
protein (hsCRP) levels were estimated and compared in these two groups.
Twenty healthy age and sex-matched persons served as controls in whom
aCL levels were measured.
aCL antibody levels were estimated
with standardized ELISA (Enzyme Linked Immunosorbent Assay) (Lab System
Company) by using Orgentee Diagnostika Gmbh for IgG antibodies. hsCRP
levels were estimated using ELISA kit (Calbiotech Inc.).
Statistical Analysis
All data were expressed as
Mean ± SD. Unpaired t-test was applied to compare the levels of aCL
antibody in patients with ACS and controls and Levels of aCL and hsCRP
between Groups I and II. Correlation between aCL and hs-CRP was determined
by Pearson's Correlation Coefficient. Logistic regression was applied
to correlate the levels of aCL and hs-CRP with short-term outcome in
patients with ACS. p- value < 0.05 was considered statistically significant.
Seventy two patients were evaluated
for enrollment in the study out of which 12 did not meet the inclusion/exclusion
criteria and were excluded. During the short-term follow-up period of
7 days, 19 patients (Group I) experienced an ischemic event and 41 patients
(Group II) remained event free. The levels of anticardiolipin antibody
were significantly higher in patients with ACS as compared to the controls
(p = 0.020) (Fig. 1). However the levels of aCL in Group I (13.39 ± 9.46
GPL-U/ml) and Group II (13.51± 9.93 GPL-U/ml) were not significantly
different (p = 0.838) (Fig. 2).
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Fig.1: Comparison of Anticardiolipin antibody (aCL) levels in patients and controls |
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Fig.2: Anticardiolipin
antibody levels among patients with and without an event |
The mean hsCRP levels were
higher in cases with an event (23.30± 10.68 mg/dl) than in cases without an
event (20.60±11.45mg/dl) but
this was not significant statistically (p = 0.389) (Fig. 3). No significant
correlation was found between the levels of aCL and CRP (p = 0.178).
Logistic regression analysis showed that there was no statistically
significant correlation between the level of anticardiolipin antibody
or hsCRP and the recurrence of ischemic events (p = 0.964 and p=0.380
respectively).
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Fig.3: Levels of high
sensitivity C- reactive proteins (hsCRP) among patients with and without
an event |
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Fig.4: Scatter plot showing
correlation between aCL and hsCRP |
In the present study, we have
demonstrated that levels of aCL in patients with Acute Coronary Syndrome
were significantly higher as compared to healthy controls. An association
of aCL antibodies with stable Coronary Artery Disease has been shown
in several studies. In one study, IgG and IgM aCL levels were found
to be higher in patients with ischemic heart disease than healthy controls.(15) Few other studies have also shown a positive association of the IgG aCL with coronary artery disease.(4,16)
Our previous study on patients of CAD with stent also supports this
view.(17)
It has been observed that the
presence of aCL antibodies precede the development of first MI and the
aCL titre remained stable for up to3 months after MI which indicate
that the aCL antibodies are not generated by tissue necrosis but rather
they participate in the pathogenesis of MI.(18) The proinflammatory
and procoagulant properties of aCL have earlier been well established
and now there appears to be sufficient clinical evidence to support
their role in pathogenesis of CAD. (3,4,16)
However, results of our
prospective evaluation failed to demonstrate a predictive role of aCL
antibodies in the development of subsequent coronary events in ACS patients.
In patients with ACS, plaque disruption and plaque erosion are considered
as the underlying cause for the development of ischemic cardiac event.(19) The role of aCL in the development of unstable plaque is not well
documented. In a study of 74 male patients with acute and chronic coronary
artery disease who underwent coronary angiography, 16 were diagnosed
with CAD, 34 had coronary stenosis with prior MI, 14 surviving acute
MI and 10 patients revealing no significant coronary narrowing. No significant
difference in the level of aCL was found in these four groups.(20) In
another study in 80 patients with ACS, no significant association was
found between reinfarction and aCL, however, a statistically significant
association was observed between aCL and restenosis.(21)
In our study the mean level
of aCL were comparatively lower than the reported studies showing association
of high titre of aCL with recurrence of coronary events.(21) This could
be due to somewhat different patient population. Moreover the recurrence
of coronary events can be attributed to many other procoagulant factors
like homocysteine, fibrinogen, factor VII, plasminogen activator Inhibitor-I,
and platelet hyperreactivity.(1) Some other factors like D-dimer, low
apoA-I and high apoB have also recently been advocated in
the recurrence of coronary events in the absence of identified
risk factors and with standard lipid parameters.(22)
The role of CRP in development
of atherothrombotic vascular events is well established.(23) There
are data that suggest a direct effect of CRP on endothelial cells, including
the upregulation of vascular adhesion molecule, stimulation of proinflammatory
mediators and the impairment of vascular NO dependent vasodilation.(24)
As per recommendation of American Heart Association, the hsCRP levels of 1 mg/L constitute low risk, 1-3 mg/L as average risk
and >3 mg/L as high risk group for assessment of cardiovascular risk.(25) On the same lines , Ridker has also shown association of increased
level of hsCRP (>3mg/L) with higher cardiovascular risk.(26) The
result of our study showed mean levels of 2.43mg/L
in patients with recurrence of event and 2.02 mg/ L in those without
events. Though the difference in the levels of hsCRP among two groups
was not statistically significant but higher levels in patients with
recurrence puts them in average risk group. This substantiates role
of hSCRP in acute coronary syndrome. However less values of hSCRP
obtained in our study could be attributed to small sample size.
In conclusion, anticardiolipin
antibodies could be implicated in the pathogenesis of Acute coronary
syndrome but are not significantly associated with recurrence of short-term
events in patients with ACS. In addition aCL does not seem to have significant
correlation with hsCRP in determining short term outcome in patients with acute
coronary syndrome.
- Feinbloom D,
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