Antiphospholipid syndrome _ a rare latent cause of cardiovascular disease

Natia Archaia, Vakhtang Chumburidze, Nona Kakauridze


Background: Antiphospholipid syndrome (APS) is a multisystem autoimmune disease, characterised by thrombotic  and/or obstetric complications in the presence of persistently positive antiphospholipid antibodies (aPL). Due to its vascular nature, various organs and tissues may be affected, including the cardiac system. The cardiac involvement in APS is multifactorial: thrombosis plays an important role as well as immune-mediated injury. The most common manifestations include valve abnormalities, occlusive arterial disease, intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. Many investigators favor a two-hit hypothesis to explain how aPL causes injury: the presence of aPL (first hit) induces endothelial injury and another condition (second hit), such as pregnancy, infection, trauma, surgery or malignancy, triggers thrombosis. The two-hit hypothesis may explain why patients persistently positive for aPL suffer thrombosis only occasionally. 

Aim: This article reviews cardiac involvement in APS, including criteria and non-criteria cardiac manifestations..

Methods and Materials: The literature search was conducted through some online database, such is Pubmed, Sciencelib, Researchgate, Frontiers, Google Scholar, Willey online library. Key words for searching were used APS and atherosclerosis, APS and Cardiac manifestation, APS and myocardial infarction, Autoantibodies and atherosclerosis. Among 90 publications from high rated journals, were identified 33 relevant articles Published between 2002 and February 2021.

Conclusion: As multiple traditional and nontraditional autoimmune-inflammatory risk factors initiate cardiovascular diseases (CVD) in APS, it is imperative to increase the efforts in early 

diagnosis, control risk factors and close follow-up, to minimize CVD development in APS.  Hence multidisciplinary therapeutic approach has important role  in these patients.


Antiphospholipid syndrome, Cardiovascular disease, Autoantibodies, Myocardial Infarction


Kolitz, Tamara Shiber, Shachaf Sharabi, Itzhak Winder, Asher Zandman-Goddard, Gisele. Cardiac manifestations of antiphospholipid syndrome with focus on its primary form., Frontiers in Immunology 2019 May; 10(5):941. Frontiers Media S.A.

Zara Sayara,b, Rachel Mollc, David Isenbergd,e, Hannah Cohena,c. Thrombotic antiphospholipid syndrome: A practical guide to diagnosis and management. Thrombosis Research . 2021; 198 :213–221

Tenedios, Felicia Erkan, Doruk Lockshin, Michael D. Cardiac Manifestations in the Antiphospholipid Syndrome.Rheumatic Disease Clinics of North America. 2006, 32(3): 491-507

Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306. pubmed/16420554.

Sammaritano, L. R. Antiphospholipid syndrome. Best Practice and Research: Clinical Rheumatology.2020, 34(1):70–81.

L.Lóczi, J. Kappelmayer, T. Tarr, Z. Bagoly. Antiphospholipid syndrome and the risk of myocardial infarction: current evidence and uncertainties. Kardiologia Polska,2020, 78(1): 6-14,doi:10.33963/KP.15090

Rand JH, Wolgast LR, Marder VJ, Aird WC, Bennett JS, Schulman S, White II GC, eds. The antiphospholipid syndrome. Hemostasis and Thrombosis. 6th ed.: Philadelphia, PA: Lippincott Williams and Wilkins; 2013;1216‑1231.

Mok CC, Tang SSK, To CH, Petri M. Incidence and risk factors of thromboembolism in systemic lupus erythematosus: a comparison of three ethnic groups. Arthritis Rheum. 2005; 52:2774–82. doi: 10.1002/art.21224

Shoenfeld Y, Meroni PL, Toubi E. Antiphospholipid syndrome and systemic lupus erythematosus: are they separate entities or just clinical presentations on the same scale? Curr Opin Rheumatol. 2009;21:495–500. doi: 10.1097/BOR.0b013e32832effd

Cervera R, Piette JC, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002; 46: 1019‑1027.

Andreoli L, Chighizola CB, Banzato A, et al. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res (Hoboken). 2013; 65: 1869‑1873

Pons-Estel GJ, Andreoli L, Scanzi F, Cervera R, Tincani A. The antiphospholipid syndrome in patients with systemic lupus erythematosus. J Autoimmun. 2017; 76:10–20. doi: 10.1016/j.jaut.2016.10.004

Corban MT, Duarte ‑Garcia A, McBane RD, et al. Antiphospholipid syndrome: role of vascular endothelial cells and implications for risk stratification and target‑ ed therapeutics. J Am Coll Cardiol. 2017; 69: 2317‑2330.

Celińska ‑Lowenhoff M, Iwaniec T, Padjas A, et al. Altered fibrin clot structure/ function in patients with antiphospholipid syndrome: association with thrombotic manifestation. Thromb Haemost. 2014; 112: 287‑296.

Asztabski M, Wypasek E, Ząbczyk M, Undas A. Reduced plasma fibrin clot permeability and susceptibility to fibrinolysis are associated with increased intima‑media thickness in patients with primary antiphospholipid syndrome. Thromb Res. 2014; 134: 945‑951.

Kenji OKU. The scoring system for the risk-stratification in patients with the antiphospholipid syndrome.Japanese Journal of Clinical Immunology, 2017; 40(6):435-441, Doi:

Limper, M., de Leeuw, K., Lely, A. T., Westerink, J., Teng, Y. K. O., Eikenboom, J., Otter, S., Jansen, A. J. G., Ree, M. V.D., Spierings, J., Kruyt, N. D., van der Molen, R., Middeldorp, S., Leebeek, F. W. G., Bijl, M., & Urbanus, R. T. Diagnosing and treating antiphospholipid syndrome: A consensus paper. Netherlands Journal of Medicine, 2019; 77(3):98–108.

Radin M, Schreiber K, Costanzo P, et al. The adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) for risk stratification in young APS patients with acute myocardial infarction. Int J Cardiol. 2017; 240: 72‑77.

Otomo K, Atsumi T, Amengual O, et al. Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum. 2012; 64: 504‑512.

Roman MJ, Shanker B, Davia A, Lockshin MD, Crow MK, Schwartz JE, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. New Engl J Med. 2003; 349:2399–406. doi: 10.1056/NEJMoa035471

Bilora F, Boccioletti V, Girolami B, Zanon E, Armani M, Petrobelli F, et al. Are antiphospholipid antibodies an independent risk factor for atherosclerosis? Clin Appl Thromb Hemost. 2002; 8:103–13. doi: 10.1177/107602960200800205

Stepien K, Nowak K, Wypasek E, et al. High prevalence of inherited thrombophilia and antiphospholipid syndrome in myocardial infarction with non‑obstructive coronary arteries: comparison with cryptogenic stroke. Int J Cardiol. 2019; 290: 1‑6

Nazir S, Tachamo N, Lohani S, et al. Acute myocardial infarction and an‑ tiphospholipid antibody syndrome: a systematic review. Coron Artery Dis. 2017; 28: 332‑335.

Vlachoyiannopoulos PG. Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study. Rheumatology. 2003; 42:645–51. doi: 10.1093/rheumatology/keg182

Artenjak A, Lakota K, Frank M, Cuˇcnik S, Rozman B, BoŽiˇc B, et al. Antiphospholipid antibodies as non-traditional risk factors in atherosclerosis based cardiovascular diseases without overt autoimmunity. a critical updated review. Autoimmun Rev. 2012; 11:873–82. doi: 10.1016/j.autrev.2012.03.002

Lauwerys BR, Lambert M, Vanoverschelde JL, Cosyns JP, Houssiau FA. Myocardial microangiopathy associated with antiphospholipid antibodies. Lupus. 2001;10:123–5. doi: 10.1191/096120301666383277

Cervera R, Tektonidou MG, Espinosa G, Cabral AR, González EB, Erkan D, et al. Task force

on catastrophic antiphospholipid syndrome (APS) and Non-criteria APS Manifestations (I):

catastrophic APS, APS nephropathy and heart valve lesions. Lupus. 2011; 20:165–73. doi: 10.1177/0961203310395051

Tenedios F, Erkan D, Lockshin MD. Cardiac manifestations in the antiphospholipid syndrome. Rheum Dis Clin North Am. 2006;32:491– 507. doi: 10.1016/j.rdc.2006.05.008

Erdogan D, Goren MT, Diz-Kucukkaya R, Inanc M. Assessment of cardiac structure and left atrial appendage functions in primary antiphospholipid syndrome: a transesophageal echocardiographic study. Stroke. 2005; 36:592–96. doi: 10.1161/01.STR.0000154858.27353.df

Colorio CC, Martinuzzo ME, Forastiero RR, Pombo G, Adamczuk Y, Carreras LO. Thrombophilic factors in chronic thromboembolic pulmonary hypertension . Blood Coagul Fibrinoly. 2001; 12:427–32.

WolfM, Boyer-Neumann C, Parent F, Eschwege V, Jaillet H, Meyer D, et al. Thrombotic risk factors in pulmonary hypertension. ERJ. 2000; 15:395–9.

Krause I, Lev S, Fraser A, Blank M, Lorber M, Stojanovich L, et al. Close association between valvular heart disease and central nervous system manifestations in antiphospholipid syndrome. Ann Rheum Dis. (2005) 7:P12. doi: 10.1186/ar1535

Osula S, Bell GM, Hornung RS. Acute myocardial infarction in young adults: causes and management. Postgrad Med J. (2002) 78:27–30. doi: 10.1136/pmj.78.915.27


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