Pakistan Journal of Medical Sciences

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ISSN 1681-715X

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ORIGINAL ARTICLE

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Volume 21

October December 2005

Number 4


 

Abstract
PDF of this Article

C-Reactive protein in paroxysmal
lone atrial fibrillation

Dowod TAHM1, Amin AA2, Al-Sulaiman A3, Ali JI4 & Reda M5

Abstract

Objective: The objective of the study was to investigate a possible role of the acute phase protein C-Reactive Protein "CRP" in the patho-physiology of paroxysmal lone atrial fibrillation.

Setting: Department of Medicine and Cardiology, Al-Adan Hospital, Kuwait.

Methods and Results: CRP in 20 patients with paroxysmal lone atrial fibrillation (AF group) was compared with CRP in 20 healthy volunteers (Healthy group). CRP was higher in atrial fibrillation group than in healthy group (mean 0.50 versus 0.21 mg/dl; p = 0.0037).

Conclusion: Elevated CRP levels may reflect an inflammatory state that promotes the development of atrial fibrillation.

Key words: Atrial fibrillation, C-reactive protein, inflammation

Pak J Med Sci October-December 2005 Vol. 21 No. 4 437-440


1. Dr. Tarek Abdel Hamed Mostafa Dowod
Senior Registrar,
Department of Medicine

2. Dr. Amin Al-Sayed Amin
Senior Registrar,
Department of Cardiology

3. Dr. Arafat Al-Sulaiman
Clinical Chemistry Laboratory

4. Dr. Jaffer Ismail Ali
Registrar,
Department of Medicine

5. Dr. Mostafa Reda
Consultant Cardiologist &
Head of Cardiology Department

1-5: Al-Adan Hospital, Kuwait

Correspondence:
Dr. Tarek Abdel Hamed Mostafa Dowod
P. O. Box 47854,
Fahaheel, Kuwait
E-mail: doriya70@hotmail.com

Received: April 6, 2005
Accepted: August 30, 2005


Introduction

Atrial fibrillation (AF) the most common sustained atrial arrhythmia seen in clinical practice is associated with a two-fold increase in total cardiovascular mortality1 as well as potential for substantial morbidity including stroke, congestive cardiac failure and cardioomyopathy.

AF occurs with increasing frequency as people grow older 2. It is present in 0.5% of 50 to 59-year-old subjects whereas the lifetime prevalence of AF is nearly 9% among 80-89 year old subjects.3

AF is generally classified as either paroxysmal, where the episode terminates spontaneously, persistent, where cardio version is required for termination, or chronic, where cardio version is unsuccessful 4,5. Lone AF is defined as AF occurring in the absence of structural heart disease with normal metabolic, thyroid, pulmonary function and oxygen saturation.

Although a number of risk factors have been associated with AF, acute or chronic hemodynamics, metabolic or inflammatory stressors may lead to structural remodeling of the atria that promote progression and persistence of AF7. Evidence for an inflammatory contribution to at least some form of AF was initially suggested by high incidence of AF (25-40%) after cardiac surgery6.

Inflammatory response triggers the production and release of a multitude of inflammatory mediators. Acute phase response is characterized biochemically by changes in the levels of various acute phase proteins. CRP is the prototypical acute phase protein in humans8,9.

We focused in our study on a possible role of acute phase protein CRP in the patho-physiology of paroxysmal lone atrial fibrillation.

Patients and Methods

CRP in a group of patients with paroxysmal lone atrial fibrillation was compared with CRP in a healthy group of patients in sinus rhythm who were undergoing routine physical examination.

Healthy group: The healthy group consisted of twenty healthy volunteers undergoing routine screening physical examination that included high sensitive CRP determination.

Paroxysmal lone atrial fibrillation group: The AF group included twenty patients seen in CCU and medical department in Adan hospital where high sensitive CRP was routinely measured.

Exclusion criteria: Patients who had surgery within 60 days, a history of infection or an acute coronary syndrome within the month before CRP collection were excluded from the study.

Data Collection: Baseline clinical data was available from all patients, ECG, echocardiogram and additional clinical data was available from the AF group including the presence or absence of AF at the time of CRP sampling.

All the patients in AF group have normal echocardiogram, normal thyroid, metabolic and pulmonary functions including oxygen saturation. Patients who were in sinus rhythm at the time of blood sampling of CRP have been considered to have paroxysmal atrial fibrillation.

CRP Assay: Blood samples were drawn into plain tubes and sent to the laboratory. Samples were allowed to clot and serum separated and analyzed for high sensitive CRP. CRP was determined by immuno-nephelometry method on BN Prospec Analyzer (Dade Behring-Germany). According to the manufacturer’s manual, minimum measuring value is 0.017 mg/dl and patient reference value is < 0.3 mg/dl.

Statistical Analysis: The statistical analysis was performed using Excel 2000 software. Quantitative data were reported as mean ± standard deviation and compared using the paired two–tailed student’s T test. A probability level of < 0.05 was considered statistically significant.

Results

We studied a possible role of C Reactive Protein in the patho-physiology of paroxysmal lone atrial fibrillation. CRP in 20 patients, 8 Female (40%) and 12 Male (60%) their mean age 45.85+6.5 was compared with CRP in 20 healthy volunteers 10 Male (50%) and 10 Female (50%) their mean age was 33.6+ 5.82. Men were 1.5 times more likely to develop AF than women. As the study showed a statistically significant difference in age between the two groups (p= 0.0003). CRP was significantly higher in patients with paroxysmal atrial fibrillation (AF group) than in healthy group (p = 0.0037). The results of the study have been summarized in Table-I

Discussion

It has become clear in the recent years that important triggers initiating atrial fibrillation arise from focally discharging cells located most commonly at the pulmonary vein ostia 10. These foci may lead to frequent atrial ectopy and paroxysms of atrial fibrillation. Whether initiation of atrial fibrillation activates direct inflammatory effects or the presence of a pre-existing systemic inflammatory state promotes further persistence of atrial fibrillation remains unclear6.

The high rate activity of atrial fibrillation may lead to myocyte calcium overload and in some cases to the initiation of apoptotic loss of atrial myocytes11. CRP has been shown to act as an opsonin and may participate in the clearance of apoptotic myocytes12.

Myocyte loss is typically accompanied by replacement fibrosis. This low level inflammatory response may thus be part of structural remodeling process associated with increased persistence of atrial fibrillation13-14. Alternatively, the presence of a baseline elevated level of systemic inflammation may predispose patients with triggering atrial foci to development or persistence of atrial fibrillation.

This worsened progression of arrhythmia in the presence of systemic inflammation may be analogous to that observed in other states in which elevated CRP is associated with increased mortality and left ventricular dysfunction15.

In our study, men where 1.5 times more likely to develop AF than women. This was in lines with the most prior publications, which have also noted that men are at greater risk to have AF than women16-18. The statistically significant difference in age between the two groups (p=0.0003) reflects the increasing frequency of AF with increasing age. This is also in line with Framingham study2.

We report the association of paroxysmal lone atrial fibrillation, with elevated CRP, a marker of systemic inflammation. These results suggest that the elevated CRP may be related to the burden of atrial fibrillation. CRP was statistically significantly elevated in patients with lone atrial fibrillation in the absence of structural heart disease when compared with healthy subjects (p=0.0037). However, whether CRP elevation is a consequence rather than a cause of atrial fibrillation cannot be determined by these results.

These findings require further testing and confirmation in a larger trial. Nevertheless, these results may provide a potential target for pharmacological interruption or reversal of atrial structural remodeling. Currently available pharmacological treatments for atrial fibrillation have limited efficacy and potentially toxic side effects. Inflammatory mechanisms may form a basis for new better tolerated pharmacological approaches for treating atrial fibrillation. Randomized tests of agents such as anti-inflammatory agents or other CRP lowering drugs may be needed6.

Supporting this hypothesis is the observation of inflammatory infiltrates, myocyte necrosis and fibrosis in atrial biopsies of patients with lone atrial fibrillation refractory to anti-arrhythmic therapy10. In an earlier case control study of patients with atrial fibrillation, it was found that CRP levels were higher in patients with atrial fibrillation than a control group of patients in sinus rhythm6.

Conclusion

CRP, a marker of systemic inflammation was independently associated with the presence of atrial fibrillation at baseline, although a causal relationship cannot be established. These findings support a possible association of an inflammatory state and future development of atrial fibrillation.

References

1. Benjamin EJ, Wolf PA, D’Agostino RB. Impact of atrial fibrillation on the risk of death. The Framingham Heart Study. Circulation 1998; 98:946-52.

2. Kannel WB, Abbott RD, Savage DD. CHD and atrial fibrillation. Am Heart J 1983; 106:389-96.

3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as independent risk factor for stroke: The Framingham Study. Stroke 1991; 22:983-88.

4. Fuster V, Ruden LE, Asinger RW. ACC/AHA/ESC Guidelines for management of patients with atrial fibrillation. Circulation 2000; 104:2118-2150.

5. Hutcheon SD and Broad Hurst P. Recent development in the management of atrial fibrillation. JR Coll Physician Edinb 2004; 34:274-79.

6. Chung MK, Martin DO, Sprecher D. CRP elevation in patients with atrial arrhythmias: Inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001; 104:2886-91.

7. Aviles R J, Martin D O and Apperson-Hansen C, . Inflammation, A risk factor for AF. Circulation 2003; 108:3006-10.

8. Volankis JE. Complement-induced stabilization of C-reactive protein – Pneumococcal C–polysaccharide. J Immunol 1982; 128:2745-50.

9. Nikfordjam M, Mullner M, Schreiber W. The association between C-reactive protein on admission and mortality in patients with acute myocardial infarction. J Intern Med 2000; 2117:341-45.

10. Frustaci A, Chimentic C, Bellocci F. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997; 96:1180-84.

11. Aime-Sempe C, Folliguet T, Rucker-Martin C. Myocardial cell death in fibrillating and dilated human right atria. J Am Coll Cardiol 1999; 34:1577-87.

12. Meuorach D. Opsonization of apoptotic cells: Implications for uptake and auto-immunity. Ann NY Acad Sci 2000; 962:226-35.

13. Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovas Res 2002; 54:230-46.

14. Mihm MJ, Yu F, Carnes CA. Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 2001; 104: 174-80.

15. Chew DP, Bhatt DL, Robbins MA. Incremental prognostic value of elevated baseline C-reactive protein among established markers of risk in percutaneous coronary intervention. Circulation 2001; 104: 992-97.

16. Emelia J. Benjamin, Daniel Levy, Sonya M. Independent risk factors for atrial fibrillation in a population-Based cohort. JAMA 1994; 840-44.

17. Aberg H. Atrial fibrillation: A review of 463 cases from Philadelphia General Hospital from 1955 to 1965. Acta Med Scand 1968; 184:425-31.

18. Stroud WD, Laplace LB, Reisinger JA. The etiology, prognosis and treatment of auricular fibrillation. Am J Med Sci 1932; 183:48-60.


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