Association between antiphospholipid antibodies and cardiac abnormalities in patients with systemic lupus erythematosus

doi:10.1016/0002-9343(90)90368-N

The American Journal of Medicine

Volume 89, Issue 4, October 1990, Pages 411-419

https://doi.org/10.1016/0002-9343(90)90368-N Get rights and content

Abstract

purpose: Although the antiphospholipid antibodies are well recognized to be associated with thrombosis, recurrent abortion, and thrombocytopenia in patients with systemic lupus erythematosus (SLE), their relationship with cardiac disease is less clear. The purpose of this study was to evaluate the association between antiphospholipid antibodies and cardiac abnormalities in patients with SLE.

patients and methods: A total of 75 consecutive SLE patients and 60 healthy sex- and age-matched control subjects were evaluated in a case-control study. All participants underwent M-mode, two-dimensional, and Doppler echocardiography. Antiphospholipid antibodies levels were assayed in each patient. The prevalence of antiphospholipid antibodies in patients with and without echocardiographic abnormalities was compared.

results: Compared with the control group, SLE patients had significantly more pericardial abnormalities, left ventricular hypertrophy, left atrial enlargement, left ventricular dysfunction and verrucous valvular thickening, global valvular thickening with dysfunction, and mitral and aortic regurgitation. Among these abnormalities, antiphospholipid antibodies were significantly associated with isolated left ventricular (global or segmental) dysfunction (four of five positive; p <0.05), verrucous valvular (mitral or aortic) thickening (seven of nine positive; p <0.005), global valvular (mitral or aortic) thickening and dysfunction (five of six positive; p <0.02), as well as mitral regurgitation (16 of 19 positive; p <0.001) and aortic regurgitation (five of six positive; p <0.02).

conclusion: Valvular lesions and myocardial dysfunction are associated with elevated antiphospholipid antibodies. This study has important implications for the pathogenic role of antiphospholipid antibodies in relation to these cardiac abnormalities.

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Pulmonary hypertension (PH) is a life-threatening condition that may affect outcomes in patients with systemic lupus erythematosus (SLE). The role of antiphospholipid antibodies (aPL) on the risk of PH is controversial. Therefore our objective was to estimate the risk of PH (WHO groups 1–5) including associated pulmonary arterial hypertension (APAH, WHO group 1 only) related to aPL in patients with SLE.
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Of 984 identified abstracts, 31 primary studies (five cohorts, 13 case-control, 13 cross-sectional) met inclusion criteria, including 4480 SLE patients. Prevalence of PH in aPL-positive vs. aPL-negative SLE patients was 12.3% vs. 7.3%, respectively. The overall pooled odds ratio (OR) for PH was 2.28 (95% CI, 1.65 to 3.15) (I² = 39%). The risk of APAH was also significantly increased (OR = 2.62 [95% CI, 1.11–6.15]). The risk of PH was the highest for lupus anticoagulant (OR = 1.96 [95% CI, 1.31–2.92]) and IgG anticardiolipin antibodies (OR = 2.64 [95% CI, 1.30–5.36]) while other antibodies were not significantly associated with PH.
Among SLE patients, aPL can identify patients at risk for PH and APAH. These findings warrant implementation of effective screening and early treatment strategies.
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Ischemia due to atherosclerosis, although occurring earlier in SLE patients than in the normal population, affects more frequently older SLE patients, with long-standing disease, long period of corticosteroid intake, and, usually, quiescent disease at the time of the cardiovascular event. Ischemic cardiopathy could be due to APS (Asherson et al., 1989; Murpy and Leach, 1989; Leung et al., 1990a,b; MacGregor et al., 1992; Kattwinkel et al., 1992), and in this case could develop at any age and in any stage of the disease course. Urowitz et al. (1976) described a bimodal distribution of the causes of death in SLE: an “early” peak due to SLE severity/activity or infections and a “late” peak due to atherosclerotic CAD; this trend has been confirmed in other studies too (Rubin et al., 1985; Abu-Shakra et al., 1995).
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology, characterized by the production of autoantibodies by autoreactive B cells, which are capable of inducing inflammatory changes in various organs and systems by several mechanisms. In patients with SLE, all the cardiac structures can be involved. Pericarditis is the most common cardiac abnormality, but lesions of the valves, myocardium, and coronary vessels may also occur. Nowadays, cardiac manifestations can be frequently recognized by echocardiography and other noninvasive tests, such as cardiac computed tomography or cardiac magnetic resonance imaging. Echocardiography is a nonexpensive, sensitive, and specific technique in detecting cardiac abnormalities, particularly mild pericarditis, valvular lesions, and myocardial dysfunction. Premature atherosclerosis is the most frequent cause of coronary artery disease in SLE patients. Efforts should be made to control traditional risk factors as well as all other factors, which could contribute to atherosclerotic plaque development.
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The heart is one of the main target organs in antiphospholipid syndrome (APS). Cardiac involvement has been found in up to 40% of patients with this syndrome, but significant morbidity appears in only 4–6% of these patients. APS cardiac manifestations range from asymptomatic valvular lesions to life-threating diffuse myocardial microthrombosis involvement described in catastrophic APS setting. However, the attribution of some of these clinical manifestations to the APS is still under debate. This chapter will discuss each cardiac manifestation related to antiphospholipid separately.
Prevalence and predictors of valvular heart disease in patients with systemic lupus erythematosus
2016, Autoimmunity Reviews
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In this study we found a one-in-four prevalence of significant valvulopathy in patients with SLE. In previous studies, the prevalence of VHD has ranged between 12% and 73%; the different criteria to define valvular lesions and the different diagnostic methods may account for the large variability in the results [1–4,21–24,27–34]. Despite the fame of verrucous endocarditis described by Libman and Sacks [5], most echocardiographic studies have shown that thickening is by large the most frequent valvular lesion [4,15,16,22,24,25].
We aimed to study the frequency, severity and predictors of valvular heart disease (VHD) in our lupus cohort.
211 patients were included. A transthoracic echocardiogram was used for this study. Significant valvular lesions were classified into two groups: valvular thickening and valvular dysfunction. Univariate logistic regression was performed in order to find associations with valvular thickening and dysfunction. Those variables with a p value ≤ 0.1 in the univariate analysis were subsequently included in multiple logistic regression models.
Significant valve lesions were found in 53 patients (25%). The independent predictors of valvular thickening were the age at the time of the echocardiogram (OR 1.05, 95% CI 1.02–1.7), lymphopenia (OR 3.6, 95%CI 1.4–9.5), thrombocytopenia (OR 2.65, 95%CI 1.24–5.72), and anti-Sm antibodies (OR 3.28, 95%CI 1.44–7.33). The independent predictors of valvular dysfunction were age at the time of the echocardiogram (OR 1.045, 95%CI 1.009–1.083), thrombocytopenia (OR 5, 95%CI 1.66–14.86), hypertension (OR 6.2, 95%CI 2.1–18.4) and aPL (OR 6.2, 95%CI 2.1–18.4). Regarding the latter, the independent relation with valvular dysfunction was only seen for the double positivity aCL/LA, (OR 13.2, 95%CI 3.8–45.2, p < 0.0001).
Our study confirms the high prevalence of significant VHD in SLE patients. Clinical variables related with persistent inflammatory activity were associated with VHD. The association between VHD and aPL positivity was confirmed. Double-positive aCL/LA patients were most likely to suffer from valvular dysfunction.
Evolution of cardiac dysfunction in patients with antiphospholipid antibodies and/or antiphospholipid syndrome: A 10-year follow-up study
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In contrast, other studies did not observe any difference among the above groups [19,42]. An association between aPL and valve abnormalities was described by most transthoracic echocardiography studies examining SLE patients with and without aPL [5,6,11,12,33,43,44], while data from the transesophageal ehocardiographic studies did not support this association [4,33,45,46] (Supplementary Table 2). The valvular disease was persistent or progressive over time in most prospective echocardiographic studies in SLE [3,10,11].
To describe the evolution of valve involvement and myocardial dysfunction over time in patients with systemic lupus erythematosus (SLE) with or without antiphospholipid antibodies (aPL) and/or antiphospholipid syndrome (APS).
From an initial cohort of 150 patients assessed by transthoracic echocardiography 10 years ago, 17 patients with primary APS (PAPS), 23 with SLE-associated APS (SLE/APS), 19 with SLE positive for aPL without APS, and 23 with SLE negative for aPL were re-evaluated in the present echocardiography study.
Valvulopathy was detected in 65% of PAPS and 62% of SLE patients with or without aPL. Disease duration [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.13–2.36; p = 0.009 for every 5 years of increase] and presence of SLE/APS (OR, 3.51; 95% CI, 1.27–9.67; p = 0.015) were the only factors associated with the progression of valvular disease in univariate and multivariate analyses. Left ventricular diastolic dysfunction similarly progressed over time, with deceleration time (DT) and isovolumic relaxation time (IVRT) being equally prolonged in each of the four groups (p < 0.05). Right ventricular DT was significantly prolonged in each of the three SLE patient groups (p < 0.001), whereas IVRT increased only in SLE/APS patients (p = 0.040).
Among patients with APS and SLE (with or without aPL), SLE/APS and disease duration were independent factors for valvular disease progression in the present 10-year follow-up echocardiography study. Anticoagulation did not arrest valvular disease progression. Ventricular diastolic dysfunction, primarily of the left ventricle, also progressed over the 10-year period.
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Clinical studyAssociation between antiphospholipid antibodies and cardiac abnormalities in patients with systemic lupus erythematosus

Abstract

Am J Med

Am J Cardiol

Clin Immunol Immunopathol

Int J Cardiol

Am Heart J

Am Heart J

Semin Arthritis Rheum

Am Heart J

Am J Cardiol

Am J Med

Anticardiolipin antibodies—clinical associations

Postgrad Med J

Thrombosis in systemic lupus despite circulating anticoagulants

J Lab Clin Med

Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating anticoagulants

Br Med J

IgG and IgM anticardiolipin antibody associated clinical syndromes

J Rheumatol

Thrombosis, abortion, cerebral disease and the lupus anticoagulant

Br Med J

Association of lupus anticoagulant with severe valvular heart disease in systemic lupus erythematosus

J Rheumatol

Recurrent cerebral ischemia and mitral valve vegetation in a patient with antiphospholipid antibodies

J Rheumatol

Multiple transient ischemic attacks, lupus anticoagulant and verrucous endocarditis

Stroke

Diagnostic and therapeutic problems in two patients with antiphospholipid antibodies, heart valve lesions, and transient ischemic attacks

Ann Rheum Dis

Clinical study
Association between antiphospholipid antibodies and cardiac abnormalities in patients with systemic lupus erythematosus