Korean Circ J.  2013 Dec;43(12):796-803. 10.4070/kcj.2013.43.12.796.

The Impacts of C-Reactive Protein and Atrial Fibrillation on Carotid Atherosclerosis and Ischemic Stroke in Patients with Suspected Ischemic Cerebrovascular Disease: A Single-Center Retrospective Observational Cohort Study

• Ock SY
• Cho KI
• Kim HJ
• Lee NY
• Kim EJ
• Kim NK
• Lee WH
• Yeo GE
• Heo JJ
• Han YJ
• Cha TJ

• KMID: 2224773
• DOI: http://doi.org/10.4070/kcj.2013.43.12.796

Abstract

BACKGROUND AND OBJECTIVES
Carotid intima-media thickness (IMT) is associated with chronic inflammation, and C-reactive protein (CRP) level is elevated in patients with atrial fibrillation (AF). We investigated the impacts of CRP and AF on carotid atherosclerosis and ischemic stroke in patients with suspected ischemic cerebrovascular disease.
SUBJECTS AND METHODS
One-hundred forty patients (78 males) with suspected ischemic cerebrovascular disease underwent carotid ultrasonography. The mean common carotid artery IMT, mean internal carotid artery (ICA) IMT, and plaque score were measured. Patients were divided into four groups according to the presence of AF and elevated CRP level {n=46 for AF(-)CRP(-), n=38 for AF(-)CRP(+), n=43 for AF(+)CRP(-), and n=13 for AF(+)CRP(+)}.
RESULTS
Common carotid artery IMT was significantly higher in the AF(-)CRP(+) (0.98+/-0.51 mm) and AF(+)CRP(+) (0.96+/-0.27 mm) groups compared to the AF(-)CRP(-) (0.80+/-0.32 mm) and AF(+)CRP(-) (0.77+/-0.19 mm) groups (p=0.027). Although there was no significant difference in mean ICA IMT among the groups, plaque score was the highest in the AF(+)CRP(+) (4.18+/-3.84 mm) group, followed by AF(-)CRP(+) (3.87+/-2.78 mm), AF(+)CRP(-) (1.34+/-2.61 mm), and AF(-)CRP(-) (1.17+/-2.02 mm) (p<0.001). The AF(+)CRP(+) group showed significantly higher incidence of ischemic stroke than the other groups (all p<0.05). Binary logistic regression analysis showed that age {odds ratio (OR)=1.033, p=0.001}, elevated CRP (OR=3.884, p=0.001), and the presence of AF (OR=1.375, p=0.018) were significantly correlated with incidence of ischemic stroke.
CONCLUSION
Elevated plasma CRP concentration may be a reliable surrogate marker for predicting carotid atherosclerosis in patients with AF, which may be related to increased risk of ischemic stroke.

Keyword

Atrial fibrillation; C-reactive protein; Carotid atherosclerosis

MeSH Terms

Atrial Fibrillation*
Biomarkers
C-Reactive Protein*
Carotid Artery Diseases*
Carotid Artery, Common
Carotid Artery, Internal
Carotid Intima-Media Thickness
Cohort Studies*
Humans
Incidence
Inflammation
Logistic Models
Plasma
Retrospective Studies*
Stroke*
Ultrasonography
C-Reactive Protein

Reference

1. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002; 105:1135–1143.

2. Shah PK. Plaque disruption and thrombosis. Potential role of inflammation and infection. Cardiol Clin. 1999; 17:271–281.

3. Jonasson L, Holm J, Skalli O, Bondjers G, Hansson GK. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis. 1986; 6:131–138.

4. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999; 340:115–126.

5. Ridker PM, Brown NJ, Vaughan DE, Harrison DG, Mehta JL. Established and emerging plasma biomarkers in the prediction of first atherothrombotic events. Circulation. 2004; 109:25 Suppl 1. IV6–IV19.

6. Danesh J, Wheeler JG, Hirschfield GM, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004; 350:1387–1397.

7. Koenig W, Löwel H, Baumert J, Meisinger C. C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation. 2004; 109:1349–1353.

8. Lombardo A, Biasucci LM, Lanza GA, et al. Inflammation as a possible link between coronary and carotid plaque instability. Circulation. 2004; 109:3158–3163.

9. Winbeck K, Kukla C, Poppert H, Klingelhöfer J, Conrad B, Sander D. Elevated C-reactive protein is associated with an increased intima to media thickness of the common carotid artery. Cerebrovasc Dis. 2002; 13:57–63.

10. Alvarez Garcia B, Ruiz C, Chacon P, Sabin JA, Matas M. High-sensitivity C-reactive protein in high-grade carotid stenosis: risk marker for unstable carotid plaque. J Vasc Surg. 2003; 38:1018–1024.

11. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Cardiovascular Health Study Collaborative Research Group. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med. 1999; 340:14–22.

12. Folsom AR, Pankow JS, Tracy RP, et al. Association of C-reactive protein with markers of prevalent atherosclerotic disease. Am J Cardiol. 2001; 88:112–117.

13. Tracy RP, Psaty BM, Macy E, et al. Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects. Arterioscler Thromb Vasc Biol. 1997; 17:2167–2176.

14. Cai H, Li Z, Goette A, et al. Downregulation of endocardial nitric oxide synthase expression and nitric oxide production in atrial fibrillation: potential mechanisms for atrial thrombosis and stroke. Circulation. 2002; 106:2854–2858.

15. Aviles RJ, Martin DO, Apperson-Hansen C, et al. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003; 108:3006–3010.

16. Bruins P, te Velthuis H, Yazdanbakhsh AP, et al. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation. 1997; 96:3542–3548.

17. Frustaci A, Chimenti C, Bellocci F, Morgante E, Russo MA, Maseri A. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation. 1997; 96:1180–1184.

18. Chung MK, Martin DO, Sprecher D, et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation. 2001; 104:2886–2891.

19. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008; 359:2195–2207.

20. Touboul PJ, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis. 2012; 34:290–296.

21. Nagai Y, Kitagawa K, Yamagami H, et al. Carotid artery intima-media thickness and plaque score for the risk assessment of stroke subtypes. Ultrasound Med Biol. 2002; 28:1239–1243.

22. Blackburn R, Giral P, Bruckert E, et al. Elevated C-reactive protein constitutes an independent predictor of advanced carotid plaques in dyslipidemic subjects. Arterioscler Thromb Vasc Biol. 2001; 21:1962–1968.

23. Burke AP, Tracy RP, Kolodgie F, et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies. Circulation. 2002; 105:2019–2023.

24. Aviles RJ, Martin DO, Apperson-Hansen C, et al. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003; 108:3006–3010.

25. Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994; 271:840–844.

26. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med. 1982; 306:1018–1022.

27. Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood. 1993; 82:513–520.

28. Hadjiev DI, Mineva PP. A reappraisal of the definition and pathophysiology of the transient ischemic attack. Med Sci Monit. 2007; 13:RA50–RA53.