Antiphospholipid Antibodies Are Major Risk Factors for Non-Thrombotic Cardiac Complications in Systemic Lupus Erythematosus

Abstract

In systemic lupus erythematosus (SLE), cardiovascular complications are among the leading causes of death. Cardiovascular risk in SLE is even higher in the presence of antiphospholipid antibodies or secondary antiphospholipid syndrome (APS). The aim of this retrospective, single-center study was to investigate the occurrence of antiphospholipid antibodies and non-thrombotic cardiac manifestations in 369 SLE patients. We also assessed the clinical and laboratory characteristics of the patients to reveal the risk factors for cardiac manifestations. Patients were divided into two groups based on the presence of antiphospholipid antibodies (APA); 258 (69.9%) patients were APA positive, and 111 (30.1%) patients were APA negative. Mitral and tricuspid insufficiency, aortic stenosis and pulmonary arterial hypertension were more common in APA-positive patients. Anticardiolipin IgG showed the strongest correlation with any non-thrombotic cardiac manifestations. Based on our results, the adjusted global antiphospholipid syndrome score (aGAPSS) above 8.5 is predictive of valvulopathies and ischemic heart disease, while aGAPSS above 9.5 is predictive of cardiomyopathies. The presence of antiphospholipid antibodies may affect the development of cardiac manifestations in SLE. Periodic cardiological and echocardiographic screening of patients without cardiac complaints, as well as regular monitoring of antiphospholipid antibodies, have great importance during the treatment of SLE patients.

Keywords: aGAPSS; antiphospholipid antibodies; non-thrombotic cardiac manifestations; systemic lupus erythematosus.

Figure 1

Frequency of antibody positivity in the APA+ group. The Venn diagram shows the frequency of single, double and triple antibody positivity for aß2GPI, aCL and LA in 258 patients. The frequency of APS is also shown. Abbreviations: APS, antiphospholipid syndrome; LA, lupus anticoagulant; aCL, anticardiolipin antibody; aß2GPI, anti-β2-glycoprotein-1 antibody.

Figure 2

Heat map shows the frequency of aß2GPI IgM/IgG, aCL IgM/IgG and LA in the presence (YES) and absence (NO) of cardiac manifestation. Abbreviations: IHD, ischemic heart disease; AI, aortic insufficiency; MI, mitral insufficiency; MP, mitral prolapse; TI, tricuspidal insufficiency; CM, cardiomyopathy; aß2GPI, anti-β2-glycoprotein-1 antibody; aCL, anticardiolipin antibody; IgM, immunoglobulin M; IgG immunoglobulin G; LA, lupus anticoagulant.

Figure 3

Level of aGAPSS among patients with different cardiac manifestations. On the violin plot black solid line shows the median aGAPSS, and IQR represented by black dotted line. p-values were calculated by Mann–Whitney U test, reported as ** p < 0.01, *** p < 0.001. Abbreviations: IHD, ischemic heart disease; AI, aortic insufficiency; MI, mitral insufficiency; MP, mitral prolapse; TI, tricuspidal insufficiency; CM, cardiomyopathy; aGAPSS, Adjusted Global Antiphospholipid Syndrome Score.

Figure 4

Correlation matrix on the relationship between cardiac manifestations and aGAPPS. The relationship between aGAPPS variables and cardiac manifestations is shown by the Cramer’s V value from Pearson’s chi-squared test, while the relationship between aGAPSS and cardiac manifestations is shown by the rrb coefficient from rank-biserial correlation. * p < 0.05, ** p < 0.01, *** p < 0.001. Abbreviations: IHD, ischemic heart disease; AI, aortic insufficiency; MI, mitral insufficiency; MP, mitral prolapse; TI, tricuspidal insufficiency; CM, cardiomyopathy; aß2GPI, anti-β2-glycoprotein-1 antibody; aCL, anticardiolipin antibody; IgM, immunoglobulin M; IgG, immunoglobulin G; LA, lupus anticoagulant; HLD, hyperlipidemia; HTN, hypertonia; aGAPSS, Adjusted Global Antiphospholipid Syndrome Score.