C-reactive protein in antiphospholipid syndrome: relationship with cardiovascular pathology

Objective. To assess relationship of high sensitivity C reactive protein (hsCRP) level in pts with antiphospholipid syndrome (APS) with clinico-laboratory features and cardiovascular pathology. Material and methods. 206 pts were included. 58 from them had primary APS (PAPS), 72 –systemic lupus erythematosus (SLE) with APS and 76 – SLE. 29 from 76 pts of the latter group were positive on anticardiolipin antibodies (ACA) – SLE with antiphospholipid antibodies (APhL) and 47 – low positive or negative on ACA – SLE without APhL. 72 persons without autoimmune diseases were included into control group. CRP (with high sensitivity immuno-nephelometric assay), APhL (with solid phase immuno-enzyme assay), plasma lipids were evaluated, sonography with measurement of intima-media complex (IMC) thickness of common carotid arteries, carotid artery bulbs and internal carotid arteries, electrocardiography (ECG), echocardiography (EchoCG), Holter ECG monitoring were performed. Results. HsCRP serum level in pts was significantly higher than in control: 2,55 [0,71; 7,04] mg/l (varied from 0,15 to 39,85) vs 0,68 [0,26; 1,97] mg/l (varied from 0,1 to 9,61), p<0,001. Most high hsCRP concentration was found in SLE with APS (p=0,02). HsCRP level in pts with PAPS with history of combined or isolated arterial thrombosis was significantly higher than in pts with SLE and APS having the same localization of thrombosis. HsCRP concentration less than 3 mg/l correlated with duration of postthrombotic period in pts with PAPS. HsCRP level also correlated with triglyceride concentration, body mass index, summated coronary risk and magistral arteries IMC thickness. Conclusion. HsCRP elevation in pts with APS was associated with development of combined and arterial thrombosis as well as with traditional risk factors of atherosclerosis.

C-reactive protein, antiphospholipid syndrome, systemic lupus erythematosus, thrombosis, atherosclerosis

1. <div><p>Pepys M. B., Baltz M. L. Acute phase proteins with special reference to C-reactive protein and related pro- teins (pentaxins) and serum amyloid A protein. Adv. Immunol., 1983, 34, 141-212</p><p>Ridker P. M. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation, 2003, 107, 363–69</p><p>Насонов Е. Л., Панюкова Е. Н., Александрова Е. Н. С-реактивный белок – маркер воспаления при атеросклерозе (новые данные). Кардиология, 2002, 7, 53-9</p><p>Насонов Е. Л. Антифосфолипидный синдром. М: Литтера, 2004, 379</p><p>Hunt B. J. The endothelium in atherogenesis. Lupus, 2000, 9, 189-93</p><p>Meroni P. L. Endothelial cell perturbation by antiphos- pholipid antibodies in systemic lupus erythematosus. Lupus, The 8th International Congress on SLE, 2007, 16, 17-9</p><p>Pierangeli S. S. New targeted therapies for treatment of thrombosis in antiphospholipid syndrome: lessons from In Vitro and In Vivo studies. Lupus, The 8th International Congress on SLE, 2007, 16, 19-20</p><p>Pierangeli S. S., Harris E. N. Probing antiphospho- lipid-mediated thrombosis: the interplay between anti- cardiolipin antibodies and endothelial cells. Lupus, 2003, 12(7), 539-45</p><p>Amigo M. C., Carcia-Torres R. Morphology of vas- cular, renal, and heart lesions in the antiphospho- lipid syndrome: relationship to pathogenesis. Curr. Rheumatol. Rep., 2000, 2 (3), 262-70</p><p>Shoenfeld Y., Gerli R., Doria A. et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation, 2005, 112, 3337-47</p><p>Szekanecz Z., Shoenfeld Y. Lupus and cardiovascular disease: the facts. Lupus, 2006, 15, 3-10</p><p>Toloza S. M., Uribe A. G., McGwin G. Jr. et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXIII. Baseline predictors of vas- cular events. Arthritis Rheum., 2004, 50, 3947-57</p><p>Baron M. A., Khamashta M. A., Hughes G. S. et al. Prevalence of an abnormal ankle-brachial index in patients with primary antiphospholipid syndrome. Ann. Rheum. Dis., 2005, 64, 144–6</p><p>Doria A., Shoenfeld Y., Wu R. et al. Risk factors for subclinical atherosclerosis in a prospective cohorts of patients with systemic lupus erythemathosus. Ann. Rheum. Dis., 2003, 62, 1071–7</p><p>Roman M. J., Salmon J. E., Spobel R. et al. Prevalence and correlates of accellerated atherosclerosis in sys- temic lupus erythematosus. N. Engl. J. Med., 2003, 349, 2399–406</p><p>Ames P. R. J., Tommasino C., Brancaccio V. et al. C-Reactive protein in primary antiphospholipid syn- drome. J. Rheumatol., 2007, 34 (3), 650-1</p><p>Becarevic M., Majkic-Singh N. High-sensitivity C-reactive protein: discriminator between patients with primary and secondary antiphospholipid syndrome. Clin. Biochem., 2008, 41 (18), 1449-53</p><p>Myakis S., Lockshin M. D., Atsumi A. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syn- drome. J. Thromb. Haemost., 2006, 4, 295–306</p><p>Hochberg M. C. Updating the American College of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum., 1997, 40 (9), 1725</p><p>De Leeuw K., Freire B., Smit A. J. et al. Traditional and non-traditional risk factors contribute to the development of accelerated atherosclerosis in patients with systemic lupus erythematosus. Lupus, 2006, 15, 675-82</p><p>Sherer Y., Shoenfeld Y. Atherosclerosis. Ann. Rheum. Dis., 2002, 61 (2), 97-9</p><p>Перова Н. В. Суммарный коронарный риск ИБС и показания к лечению гиперхолестеринемии (при- менение европейских рекомендаций 1994г. к рос- сийским условиям). Кардиология, 1996, 3, 47-53</p><p>Barter P., Brewer B., Brown G. et al. Pocket guide to prevention of coronary heart disease. Downloaded from www.chd-taskforce.com in January 2003</p><p>Александрова Е. Л., Насонов Е. Л., Ковалев В. Ю. Количественный иммуноферментный метод опре- деления антител к кардиолипину в сыворотке крови. Клин. ревматол., 1995, 4, 35-9</p><p>Ianuzzi A., Michele M. D., Panico S. et al. Radical Trapping Activity, Blood Pressure and Carotid Enlargement in women. Hypertension, 2003, 41, 289-96</p><p>Kazmierski R., Watala C., Lukasik M. et al. Common carotid artery remodeling studied by sonomorphologi- cal criteria. J. Neuroimaging, 2004, 14 (3), 258 – 64</p><p>Александрова А. Е., Новиков А. А., Решетняк Т. М. и соавт. Клинико-иммунологическая оцен- ка высокочувствительного метода определения С-реактивного белка при антифосфолипидном синдроме. Научно-практич. ревматол., 2007, 1, 9-15</p><p>Pepys M. B., Lanham J. G., De Beer F. C. C-reactive protein in SLE. Clin. Reum. Dis., 1982, 8, 91-103</p><p>Barnes E. V., Narain S., Naranjo A. et al. High sensitivity C-reactive protein in systemic lupus erythematosus: relation to disease activity, clinical presentation and implications for cardiovascular risk. Lupus, 2005, 14, 576 – 82</p><p>Ridker P. M. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation, 2003, 107, 363–9</p><p>Ridker P. M., Hennekens C. H., Buring J. E. et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N. Engl. J. Med., 2000, 342, 836–43</p><p>Pearson T. A., Mensah G. A., Alexander R. W. et al. Markers of inflammation and cardiovascular disease- application to clinical and public health practice. Circulation, 2003, 107, 499–511</p><p>Jialal I., Devaraj S., Venugopol S. K. C-reactive protein: risk marker or mediator in atherothrombosis? Hypertension, 2004, 44 (1), 6-11</p><p>Jialal I., Devaraj S. Role of C-reactive protein in the assessment of cardiovascular risk. Am. J. Cardiol., 2003, 91, 200–2</p><p>Shamsuzzaman A. S., Winnicki M., Lanfranchi P. et al. Elevated C-reactive protein in patients with obstruc- tive sleep apnea. Circulation, 2002, 105, 2462–4</p><p>Ridker P. M., Buring J. E., Cook N. R. et al. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14719 initially healthy American women. Circulation, 2003, 107, 391–7</p><p>Клюквина Н. Г., Баранов Е. Л., Александрова Е. Н. и соавт. С-реактивный белок при системной красной волчанке у мужчин: связь с тромботическими осложнениями. Клин. мед., 1997, 8, 24-6</p><p>Svenungsson E., Jensen-Urstad K., Heimbürger M. et al. Risk Factors for Cardiovascular Disease in Systemic Lupus Erythematosus. Circulation, 2001, 104, 1887-93</p><p>Ильина А. Е., Клюквина Н. Г., Александрова Е. Н. и соавт. Атеросклеротическое поражение сосудов при системной красной волчанке и антифосфоли- пидном синдроме у мужчин. Научно-практич. ревматол., 2005, 5, 4-10</p><p>Sailer T., Vormittag R., Pabinger I. Et al. Inflammation in patients with lupus anticoagulant and implications for thrombosis. J. Rheumatol., 2005, 32, 462-8</p><p>Jiménez S, García-Criado M. A., Tàssies D. et al. Preclinical vascular disease in systemic lupus ery- thematosus and primary antiphospholipid syndrome. Rheumatology (Oxford), 2005, 44(6), 756-61</p><p>Ames P. R. J., Tommasino C., Brancaccio V. et al. C-Reactive protein in primary antiphospholipid syn- drome. J. Rheumatol., 2007, 34 (3), 650-1</p><p>Bobba R., Landolt-Marticorena C., Fortin P. R. Thrombosis and inflammation: a question in need of an answer. J. Rheumatol., 2005, 32 (3), 397-400</p></div><br />