Left-sided heart valve abnormalities and risk of ischemic cerebrovascular accidents in patients with systemic lupus erythematosus

Abstract

The aim of the study was to assess the relationship between ischemic cerebrovascular accidents (ICVAs), that is, transient ischemic attack (TIA) or stroke, and left-sided heart valve abnormalities (LHVAs) in patients with systemic lupus erythematosus (SLE). In total, 71 consecutive SLE patients were studied.At baseline, history, clinical and laboratoryevaluations, as well as trans-thoracic echocardiography (TTE) were performed. From the original population, so patients were followed up for a mean time of 5.80 + 1.53 years. After a mean period of 5.39 + 1.42 years; 40 patients underwent a repeat TTE.

Previous ICVA history was present at baseline in 16 patients (22.5%). Of these, 13 (81.2%) had evidence of LHVAs on TTE. Previous ICVAs were significantly associated to diagnosis of secondary anti-phospholipid syndrome (SAPS), positivity for anti-cardiolipin antibodies (aCl), and LHVAs. Multivariate analysis confirmed the correlation between previous ICVAs and LHVAs. LHVAs were not more commonly observed in patients with SAPS compared to patients without SAPS. At the end of follow-up, irrespective of any differences in antithrombotic treatment, ICVAs had occurred in 13 patients.During follow-up, ICVAs had recurredin seven patients, while a first eventTIA occurredin one patient. Multivariate analysis confirmed the relationship between ICVAs and LHVAs, and a trend towards a positive correlation of the former with SAPS. This study demonstratesthat LHVAs represent a compelling risk factor for the development of ICVAs in SLE patients. Conversely, SAPS and aCl positivity, although associated with ICVAs, did not clearly correlate with LHVAs in our study. These results provide insight on the pathogenesis of ICVAs and may give clues on the potential efficacy of preventive/therapeutic strategies in different SLE subpopulations.

Keywords

heart valve abnormalities SLE stroke TIA

Get full access to this article

View all access options for this article.

References

Boumpas DT , Austin HA 3rd , Fessler BJ , Balow JE , Klippel JH , Lockshin MD. Systemic lupus erythematosus: emerging concepts. Part 1: Renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease . Ann Intern Med 1995; 122: 940-950 .

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes . Arthritis Rheum 1999; 42: 599-608 .

Gladman DD. Prognosis and treatment of systemic lupus erythematosus . Curr Opin Rheumatol 1995; 7: 402-408 .

Reveille JD , Bartolucci A , Alarcon GS. Prognosis in systemic lupus erythematosus. Negative impact of increasing age at onset, black race, and thrombocytopenia, as well as causes of death . Arthritis Rheum 1990; 33: 37-48 .

Ward MM. Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus . Arthritis Rheum 1999; 42: 338-346 .

Harris EN , Gharavi AE , Asherson RA , Boey ML , Hughes GR. Cerebral infarction in systemic lupus: association with anticardiolipin antibodies . Clin Exp Rheumatol 1984; 2: 47-51 .

Toubi E , Khamashta MA , Panarra A , Hughes GR. Association of antiphospholipid antibodies with central nervous system disease in systemic lupus erythematosus . Am J Med 1995; 99: 397-401 .

Kitagawa Y , Gotoh F , Koto A , Okayasu H. Stroke in systemic lupus erythematosus . Stroke 1990; 21: 1533-1539 .

Levine SR , Brey RL , Sawaya KL et al. Recurrent stroke and thromboocclusive events in the antiphospholipid syndrome . Ann Neurol 1995; 38: 119-124 .

10.

Hojnik M , George J , Ziporen L , Shoenfeld Y. Heart valve involvement (Libman -Sacks endocarditis) in the antiphospholipid syndrome . Circulation 1996; 93: 1579-1587 .

11.

Asherson RA , Gibson DG , Evans DW , Baguley E , Hughes GR. Diagnostic and therapeutic problems in two patients with antiphospholipid antibodies, heart valve lesions, and transient ischemic attacks . Ann Rheum Dis 1988; 47: 947-953 .

12.

Asherson RA , Lubbe WF. Cerebral and valve lesions in SLE: association with antiphospholipid antibodies . J Rheumatol 1988; 15: 539-543 .

13.

Young SM , Fisher M , Sigsbee A , Errichetti A. Cardiogenic brain embolism and lupus anticoagulant . Ann Neurol 1989; 26: 390-392 .

14.

Libman E , Sacks B. A hitherto undescribed form of valvular and mural endocarditis . Arch Intern Med 1924; 33: 701-737 .

15.

Gleason CB , Stoddard MF , Wagner SG , Longaker RA , Pierangeli S , Harris EN. A comparison of cardiac valvular involvement in the primary antiphospholipid syndrome versus anticardiolipin-negative systemic lupus erythematosus . Am Heart J 1993; 125: 1123-1129 .

16.

Roldan CA , Shively BK , Crawford MH. An echocardiographic study of valvular heart disease associated with systemic lupus erythematosus . N Engl J Med 1996; 335: 1424-1430 .

17.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271-1277 .

18.

Wilson WA , Gharavi AE , Koike T et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop . Arthritis Rheum 1999; 42: 1309-1311 .

19.

Harris EN , Gharavi AE , Patel SP , Hughes GR. Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986 . Clin Exp Immunol 1987; 68: 215-222 .

20.

Sahn DJ , DeMaria A , Kisslo J , Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements . Circulation 1978; 58: 1072-1083 .

21.

Helmcke F , Nanda NC , Hsiung MC et al. Color Doppler assessment of mitral regurgitation with orthogonal planes . Circulation 1987; 75: 175-183 .

22.

Perry GJ , Helmcke F , Nanda NC , Byard C , Soto B. Evaluation of aortic insufficiency by Doppler color flow mapping . J Am Coll Cardiol 1987; 9: 952-959 .

23.

Futrell N , Millikan C. Frequency, etiology, and prevention of stroke in patients with systemic lupus erythematosus . Stroke 1989; 20: 583-591 .

24.

Khamashta MA , Cervera R , Asherson RA et al. Association of antibodies against phospholipids with heart valve disease in systemic lupus erythematosus . Lancet 1990; 335: 1541-1544 .

25.

Devinsky O , Petito CK , Alonso DR. Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura . Ann Neurol 1988; 23: 380-384 .

26.

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

27.

Hanly JG , Walsh NM , Sangalang V. Brain pathology in systemic lupus erythematosus . J Rheumatol 1992; 19: 732-741 .

28.

Menon S , Jameson-Shortall E , Newman SP , Hall-Craggs MR , Chinn R , Isenberg DA. A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus . Arthritis Rheum 1999; 42: 735-741 .

29.

Caronti B , Calderaro C , Alessandri C et al. Serum anti-beta2- glycoprotein I antibodies from patients with antiphospholipid antibody syndrome bind central nervous system cells . J Autoimmun 1998; 11: 425-429 .

30.

Cabral AR , Amigo MC , Cabiedes J , Alarcón-Segovia D. The antiphospholipid/cofactor syndromes: a primary variant with antibodies to β2-glycoprotein I but no antibodies detectable in standard antiphospholipid assays . Am J Med 1996; 101: 472-481 .

31.

Levine SR , Kim S , Deegan MJ , Welch KM. Ischemic stroke associated with anticardiolipin antibodies . Stroke 1987; 18: 1101-1106 .

32.

Barbut D , Borer JS , Wallerson D , Ameisen O , Lockshin M. Anticardiolipin antibody and stroke: possible relation of valvular heart disease and embolic events . Cardiology 1991; 79: 99-109 .

33.

Vianna JL , Khamashta MA , Ordi-Ros J et al. Comparison of the primary and secondary antiphospholipid syndrome: a European Multicenter Study of 114 patients . Am J Med 1994; 96: 3-9 .

34.

The Antiphospholipid Antibodies in Stroke Study Group . Clinical and laboratory findings in patients with antiphospholipid antibodies and cerebral ischemia . Stroke 1990; 21: 1268-1273 .

35.

Levine SR , Deegan MJ , Futrell N , Welch KM. Cerebrovascular and neurologic disease associated with antiphospholipid antibodies: 48 cases . Neurology 1990; 40: 1181-1189 .

36.

Verro P , Levine SR , Tietjen GE. Cerebrovascular ischemic events with high positive anticardiolipin antibodies . Stroke 1998; 29: 2245-2253 .

37.

The Antiphospholipid Antibodies and Stroke Study Group (APASS) . Anticardiolipin antibodies and the risk of recurrent thrombo-occlusive events and death . Neurology 1997; 48: 91-94 .

38.

Levine JS , Branch DW , Rauch J. The antiphospholipidsyndrome . N Engl J Med 2002; 346: 752-763 .