Risk of Subclinical Atherosclerosis in Patients with Antiphospholipid Syndrome and Subjects With Antiphospholipid Antibody Positivity: A Systematic Review and Meta-analysis

Cardiovascular disease (CVD) in systemic autoimmune disorders has been associated with the underlying autoimmune and inflammatory mechanisms and traditional CVD risk factors. This interconnection leads to a variety of cardiovascular events including ischemic stroke, coronary heart disease, myocardial disease, diastolic and systolic heart dysfunction, arrhythmias, and heart failure.1,2

Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by recurrent vascular events in large, medium or small vessels, often occurring despite an adequate anticoagulation treatment, and the presence of antiphospholipid antibodies (aPL). These include lupus anticoagulant (LA), anticardiolipin (aCL), and anti-beta2glycoprotein I (anti-β2GPI) antibodies.3

Accumulating evidence supports an inflammatory, in addition to classic thrombotic pathophysiology in APS shedding also light on the pathogenesis and management of CVD, a leading cause of morbidity and mortality in APS. Indeed, in a European multicenter registry of 1000 APS patients, ischemic stroke was reported in 19.8% of included patients, myocardial infarction (MI) in 5.5%, while 1.9% of patients developed MI and 2.4% unstable angina during a 10-year follow-up.4

An interaction between traditional and disease-related cardiovascular risk factors is implicated in CVD pathogenesis in APS. Data from several APS registries, suggest that hypertension is reported in 20%-35%,5, 6, 7, 8, 9 hyperlipidemia in 20%-25%,4, 5, 6, 7, 8, 9 smoking in 30%-40%,4,7, 8, 9 and metabolic syndrome in in 17%-38% of APS patients.5,9,10 On the other hand, the disease-related CVD risk factors include the aPL profile and the disease-related medications.11, 12, 13, 14, 15, 16

Carotid intima-media thickness (IMT) assessment constitutes a noninvasive imaging test for subclinical atherosclerosis and has been widely accepted as one of the strongest predictors of CV events.17, 18, 19, 20 Similarly, flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), pulse-wave velocity (PWV), and ankle-brachial index (ABI) are considered surrogate markers of subclinical atherosclerosis and independent predictors of CV events.18,21,22

Hitherto, the association between APS, aPL, and subclinical atherosclerosis, a known marker of CVD,23 is under debate and a field of recently published and ongoing research. In light of the above, the aim of the present systematic review and meta-analysis was to address this gap in clinical knowledge by examining the risk of subclinical atherosclerosis in APS patients and subjects with antiphospholipid antibody postitivity.

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