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Indian Journal of Medicine 2011;1:24-30

Original article
Prevalence of β2 glycoprotein I dependent anticardiolipin antibodies in acute
myocardial infarction

Pazhanivel Mohan1* Ashok Kumar S1 Geetha S1 Raghavan K1 Subramaniyam V2 Shantha S3

Department of Medicine1, Department of Cardiology2, Department of Immunology3, Stanley Medical College, Chennai.
India

*corresponding author email: dr.pazhani@gmail.com

Published online on 17th Feb 2011

Copyright © 2011 Mohan P. This is an open-access article . The publisher and author permit unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Abstract
Background: Anticardiolipin antibodies (aCL) are autoantibodies that play an important role in
atherosclerosis. The purpose of our study was to determine the prevalence of beta2-glycoprotein I
dependent anticardiolipin antibodies (β2GPI) of isotypes IgG and IgM and their correlation with the
conventional cardiovascular risk factors in acute myocardial infarcts ≤55 years of age.

Methods and Results: The study population comprised of 63 patients with acute ST segment elevation
myocardial infarction. They were compared with an equal number of age and sex matched healthy controls.
The presence of aCL antibodies of classes IgG and IgM was determined. Those with IgG titer ≥10 (GPL U/ml)
and IgM titer ≥7 (MPL U/ml) were considered positive. The prevalence of β2GPI-dependent aCL antibodies
was 27% in the study group. This was significantly higher than the 4.8% observed in controls (P =0.001). The
isotype IgG was significantly increased (P =0.001) among the cases. However IgM isotype (P =0.47) did not
show a difference between the two groups. Of the conventional cardiovascular risk factors studied
(hypertension, diabetes, smoking, family history of a premature coronary artery disease), patients with
hypertension had a significant elevation of aCL antibodies (p=0.03).

Conclusion: The present study supports an association between anticardiolipin antibodies and myocardial
infarction. The prevalence of β2GPI-dependent aCL antibodies was 27%. IgG was the isotype associated with
acute myocardial infarction. Hypertension was the only risk factor associated with the presence of aCL
antibodies.
Key words: beta 2 glycoprotein I , anticardiolipin, myocardial infarction
Indian J Med 2011;1:24-30

Introduction

Coronary artery disease is the leading cause of death in the developed countries and is on an
increase in the developing world.1 The pathophysiological basis of acute coronary syndrome relies on
the existence of vulnerable atherothrombotic plaques within the coronary arteries. The initiation
and progression of atherosclerosis involves inflammatory and immunological mechanisms.
Anticardiolipin (aCL) antibodies are autoantibodies found to play an important role in
atherosclerosis. They are one of the most common acquired protein defects causing thrombosis. 2 An
aggressive lookout for the evaluation of coronary artery disease is required for some special risk
factors apart from the conventional factors.

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Indian Journal of Medicine 2011;1:24-30

Materials and Methods

It was an observational study conducted between January 2005 and January 2006. Patients aged 55
years or younger, of either sex, who fulfilled the World Health Organization criteria 3 for the diagnosis
of acute myocardial infarction admitted into the intensive coronary care unit of our hospital, were
included in the study. A cut off age of 55 was chosen, as the prevalence of positive ELISA
antiphospholipid test increases with age at a rate of 12-52%. 4 The study population was compared
with an equal number of age and sex matched healthy controls.

The history regarding the presence of conventional cardiovascular risk factors such as hypertension,
smoking, dyslipidemia, diabetes mellitus, and family history of premature coronary artery disease
was obtained. Blood samples were collected immediately after hospitalization to determine the
presence of beta2-glycoprotein I dependent anticardiolipin (β2GPI) antibodies. Laboratory
recommendations for the transport of samples were strictly followed.

The test is an indirect solid phase enzyme immunoassay (ELISA) for the quantitative measurement of
IgG and IgM class autoantibodies against cardiolipin in the presence of beta2-glycoprotein I ( β2GPI).
The result is depicted by a colour change which is measured photometrically at 450 nm. The amount
of color is directly proportional to the concentration of IgG and IgM antibodies present in the
original sample. In a normal range study with serum samples from healthy blood donors, the
following ranges have been established for the anti-cardiolipin test. Those with IgG titer ≥10 (GPL
U/ml) and IgM titer ≥7 (MPL U/ml) were considered positive. The study was approved by the
institutional ethical committee and all the participants gave a written informed consent.

Statistical analysis

Pearson Chi square test and Yates corrected Chi square test were used to compare the prevalence of
β2-GPI dependent aCL antibodies between the cases and controls. Chi square test was used to
correlate the conventional cardiovascular risk factors with aCL antibodies. A ‘p’ value <0.05 was
considered significant.

Results

The study population consisted of a total of 63 patients. The age group of the study population
ranged from 29-55 years, with a mean of 44+8 yrs. Acute myocardial infarction occurred
predominantly in males. Since age was a major risk factor for coronary artery disease (age>45 for
males and >55 for females), cases were divided into two subgroups. Patients aged < 45 years
marginally outnumbered those ≥45. (Table 1)

The distribution of the conventional cardiovascular risk factors (hypertension, diabetes mellitus,
smoking, and family history of premature coronary artery disease) in the study population is shown
in Table 1. Smoking was the most common risk factor noted in the study group.

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Indian Journal of Medicine 2011;1:24-30

Table I: Baseline characteristics of participants Table 2: Prevalence of β2 glycoprotein I dependent


anticardiolipin positivity
Baseline Characteristics no(%)
Antibody Study group Control group
Sex status
n=63 n=63
male 57 (90.5%)
Anticardiolipin
female 06 (9.5%) antibody
positive 17(27) 3(5)
Age
Anticardiolipin
<45yrs 29 (46%)
antibody
≥45 yrs 34 (54%) negative 46(73) 60(95)

IgG isotype 12 0
positive
Smoking 38 (60.3%)
IgM isotype 04 03
Hypertension 14 (22%) positive

IgG & IgM 01 0


Diabetes 13 (20.6%)
positive
Family history* 07 (11.1%)

*of premature coronary heart disease percentage mentioned in parentheses

The prevalence of β2GPI-dependent anticardiolipin antibodies in our study was 27%. This was
significantly higher than the 4.8%, observed in the control group (P =0.001), which is within the
anticipated normal range. (Table 2) IgG was the predominant isotype in 12 patients, IgM in 4, and
one had elevation of both the isotypes. The isotype IgG showed a statistically significantly elevation
(P =0.001) in the study group while IgM did not show such a difference between the two groups (P
=0.47). We also found a notable, although not a significant difference in the frequencies of β2GPI-
dependent aCL antibodies between the males and females (26.3% versus 33.3%, respectively).
Moreover, females constituted only 9.5% of the study population.

The hypertensive patients with myocardial infarction had a significantly elevated β2GPI dependent
aCL antibodies. However such an association was not observed with other conventional
cardiovascular risk factors like diabetes mellitus, smoking, age and family history of premature
coronary artery disease. (Table 3)

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Indian Journal of Medicine 2011;1:24-30

Table 3: Cardiovascular risk factors and cardiolipin antibody positivity

Risk factor Frequency Anticardiolipin Anticardiolipin p-value


positive negative

Diabetes

Yes 13 4 9 0.37

No 50 13 37

Hypertension

Yes 14 7 7 0.03

No 49 10 39

Smoking

Yes 38 12 26 0.3

No 25 5 20

Family history*

Yes 7 2 5 0.9

No 56 15 41

Age

>45yrs 29 10 19 0.21

≤45yrs 34 7 27

Sex

Male 57 15 42 0.7

Female 6 2 4

*of premature coronary heart disease

Discussion

The correlation between raised antiphospholipid antibodies and arterial thromboembolism has been
widely reported in the literature. 5-7 However, the association between increased levels of
antiphospholipid antibodies and myocardial infarction is less recognized.

There are a good number of studies that looked into the prevalence of conventional aCL antibodies
of isotype IgG and IgM in the absence of the β2GPI glycoprotein. (Table 4) The β2-GPI dependent aCL
antibodies were shown to be more specific for thrombosis than conventional anticardiolipin
antibodies. β2-GPI dependent binding to phospholipids differentiates autoimmune antiphospholipids
from those found in patients following infection. Antiphospholipid antibodies in autoimmune
diseases are thrombogenic and β2GPI dependent.18

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Table 4: Studies on the prevalence of conventional anticardiolipin antibodies

Study Prevalence of anticardiolipin antibodies


Eli Zuckerman et al 8 14% (either IgG or IgM)
Jerzy Dropinski et al 9 24% (either IgG or IgM)
Tsai RT et al 10 16% (either IgG or IgM)
Ferlazzo B et al 11 30% (either IgG or IgM)
Chandrashekhara S et al 12 13.8% (IgG)
Seijas M et al 13 12% (either IgG or IgM)
Singh K et al 14 4.2% (either IgG or IgM)
Hamsten A et al 15 21% (IgG)
Sletnes KE et al 16 6.2% (IgG)
Phadke K V et al 17 6.8% (IgG)

The frequency of antiphospholipid antibodies in various studies of the survivors of acute myocardial
infarction ranges from 6% to 47%. 15, 16, 19-26 Asherson27 reported 4% positivity of antiphospholipid
antibodies in patients with myocardial infarction. Eli Zuckerman et al 8 observed a high prevalence of
anticardiolipin antibodies (14%) in acute myocardial infarction. Patients with a high titer of
anticardiolipin antibodies had an increased risk of subsequent thromboembolic events or a
reinfarction after their acute episode.

There are also reports that fail to disclose an association between conventional aCL antibodies and
myocardial infarction or ischemic heart disease. 10, 14, 16, 17 Prospective controlled trials are necessary to
shed light on this controversial subject.

Outi Vaarala et al28 observed the presence of high IgG anticardiolipin antibody as an independent
risk factor for myocardial infarction or cardiac death. However this risk was not influenced by age,
smoking, systolic blood pressure, low-density lipoprotein, and high-density lipoprotein.

Ruihua Wu et al29 prospectively analyzed patients with raised levels of anticardiolipin antibodies (IgG
and IgA) and found that it predicted the occurrence of myocardial infarction after 10 to 20 years
independent of supine blood pressure, serum LDL/HDL ratio, body mass index and smoking.

Robin L.Brey et al 30 studied the role of anticardiolipin as a risk factor for ischemic stroke and
myocardial infarction. IgG β2GPI-dependent anticardiolipin antibodies were significantly associated
with the occurrence of ischemic stroke and myocardial infarction.

Conclusion
The present study supported an association between anticardiolipin antibodies and myocardial
infarction. The prevalence of β2-GPI dependent aCL antibodies was 27%. IgG antibody was the most
relevant isotype associated with acute myocardial infarction. Hypertensive patients had elevated β2-
GPI dependent aCL antibodies.

The association between anticardiolipin antibodies and myocardial infarction is relatively consistent
except for some difference observed in few studies. This could be attributed to the differences in the
study population and the test techniques involved. While majority of the studies have looked into
the survivors of myocardial infarction or patients with established ischemic heart disease, more
prospective studies are required to establish such an association.

Conflict of Interest: None declared


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Indian Journal of Medicine 2011;1:24-30

References:

1. World Health Organization. The World Health Report 2002. Available at: http://www.who.int/whr/en.
Accessed verified Feb 10th 2011

2. Bick RL. Antiphospholipid thrombosis syndromes.I 2001; 7:241-58.

3. Pedoe-Tunstall H, Kuulasmaa K, Amouyel P, et al: Myocardial infarction and coronary deaths in the World Health Organization
MONICA Project. Circulation 1994; 90: 583

4. Manoussakis MN, Tzioufas AG, Silis MP, Pange PJ, Goudevenos J, Moutsopoulos HM. High prevalence of anti-cardiolipin and other
autoantibodies in a healthy elderly population. Clin Exp Immunol 1987; 69: 557-565

5. Levine SR, Welch KMA. The spectrum of neurologic disease. Association with antiphospholipid antibodies. Arch Neurol. 1987; 44:
876-883

6. Asherson RA, Khamashta MA, Gil A. Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus,
“lupus like” disease and the “primary” antiphospholipid syndrome. Am J Med 1989; 86: 391-399

7. Harris EN, Gharavi AE, Asherson RA, et al. Cerebral infarction in systemic lupus erythematosus: association with anticardiolipin
antibodies. Clin Exp Rheumatol. 1984; 2: 47-51

8. Zuckerman E, Toubi E, Shiran A, Sabo E, Shmuel Z, Golan TD, Abinader E, Yeshurun D. Anticardiolipin antibodies and acute
myocardial infarction in non-systemic lupus erythematosus patients. Am J Med. 1996; 101: 381-386

9. Dropinski J, Szczeklik W, Rubis P, Sydor WJ. Anti-phospholipid antibodies and carotid-artery intima-media thickness in young
survivors of myocardial infarction. Med Sci Monit. 2003; 9: 145-149

10. Tsai RT, Wang CR, Lee GL, Chen MY, Lee YT, Chuang CY, Chen CY. Anticardiolipin antibodies in patients with acute myocardial
infarction. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi. 1991; 24: 213-220

11. Ferlazzo B, Bonanno D, Quattrocchi P, Paino AM, Arrigo F.Connections between ischemic heart disease and anti-cardiolipin
antibody positivity. Minerva Cardioangiol. 1993; 41:113-7

12. Chandrashekhara S, Kirthi R, Joyce varghese. Prevalence of anticardiolipin antibodies in various thrombotic conditions. JAPI. 2003;
51: 359-362

13. Seijas M, Martinez vazquez C, Rivera A, Rayo N, Ordi-Ros J, et al. Prevalence of antiphospholipid syndrome in patients under 65
years of age with acute myocardial infarction. Rev Clin Esp. 2001; 201: 118-21

14. Singh K, Gaiha M, Shome DK, Gupta VK, Anuradha S. The association of antiphospholipid antibodies with ischaemic stroke and
myocardial infarction in young and their correlation. JAPI 2001; 49: 527-529.

15. Hamsten A, Norberg R, Bjorkholm M, et al. Anitbodies to cardiolipin in young survivors of myocardial infarction: an association
with recurrent cardiovascular events. Lancet. 1986; 1: 113-116

16. Sletnes KE, Smith P, Abdelnoor N, et al. Aniphospholipid antibodies after myocardial infarction and their relation to mortality,
reinfarction and non- hemorrhagic stroke. Lancet. 1992; 339: 451-453

17. Phadke KV, Phillips RA, Clarke DTR, Jones M, Naish P, Carson P. Anticardiolipin antibodies in ischemic heart disease: marker or
myth? Br Heart J 1993; 69: 391-394

18. Hunt JE, McNeil HP, Morgan GJ, et al. A phospholipid-beta2-glycoprotein I complex is an antigen for anticardiolipin antibodies
occurring in autoimmune disease but not with infection. Lupus. 1992; 1: 75-81

19. Sletnes KE, Larsen EW, Stokland O, Wisloff F. Antiphospholipid antibodies detected as anticephalin and anticardiolipin antibodies
in patients with acute myocardial infarction: immunological response to myocardial necrosis? Thromb Res. 1990; 59: 675-680

20. Eber B, Kronberger-Schaffer E, Brussee H, et al. Anticardiolipin antibodies are no marker for survived myocardial infarction. Klin
Wochenschr.1990; 68: 594-596

21. Cortellaro M, Boschetti C, Cardilo M, Barbui T. Antiphospholipid antibodies in patients with previous myocardial infarction. Lancet
1992; 339: 929-930.

29
Indian Journal of Medicine 2011;1:24-30

22. Yilmaz E, Adalet K, Yilmaz G, et al. Importance of serum anticardiolipin antibody levels in coronary artery disease. Clin Cardiol.
1994; 17: 117-121

23. Adler Y, Finkelstein Y, Zandeman-Goddard G, et al. The presence of antiphospholipid antibodies in acute myocardial infarction.
Lupus 1995; 4: 309-313

24. Klemp P, Cooper RC, Strauss FJ, et al. Anticardiolipin antibodies in ischemic heart disease. Clin Exp Immunol. 1988; 74: 254-257

25. Raghavan C, Ditchfield J, Taylor RJ, et al. Influence of anticardiolipin antibodies on immediate patient outcome after myocardial
infarction. J Clin Pathol. 1993; 46: 1113-1115

26. Diaz MN, Becker RC. Anticardiolipin antibodies in patients with unstable angina. Cardiology. 1994; 84: 380-384

27. Asherson RA, Khamashta MA, Baguley E, et al. Myocardial infarction and antiphospholipid antibodies in SLE and related disorders.
Q J Med. 1989; 272: 1103-1115

28. Vaarala O, Manttari M, Manninen V, Tenkanen L, Puurunen M, Aho K, Palosuo T. Anti-cardiolipin antibodies and risk of myocardial
infarction in a prospective cohort of middle aged men. Circulation. 1995; 91: 23-27.

29. Wu R, Nityanand S, Berglund L, Lithell H, Holm G, Lefvert AK. Antibodies against cardiolipin and oxidatively modified LDL in 50-
year old men predict myocardial infarction. Arterioscler Thromb Vasc Biol 1997; 17:3159–63

30 Brey RL, Abbott RD, Curb JD, Sharp DS, Ross GW, Stallworth CL, Kittner SJ. Beta 2-Glycoprotein I- dependent anticardiolipin
antibodies and risk of ischemic stroke and myocardial infarction: the Honolulu Heart Program. Stroke. 2001; 32: 1701-1706

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