Background Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic events and/or pregnancy morbidity in the persistent presence of antiphospholipid antibodies (aPL). The mechanisms by which aPLs cause thrombosis have not been completely elucidated. Recent studies suggest that thrombosis may be linked to diminished production of nitric oxide (NO) in endothelial cells. Endothelium-derived NO normally exerts anti-thrombotic and vasodilator effects. Diminished NO production in APS patients may therefore result not only in thrombosis but also blunted vasodilator responses. Whether patients with APS display blunted NO-stimulated vasodilation has not been directly determined.
Objectives We determined endothelium-dependent and endothelium-independent vasodilator response in cutaneous microvasculature of APS patients and healthy controls.
Methods Patients with primary or secondary APS (all positive for at least two different aPL) and healthy controls were enrolled between May 2014 and May 2015. Participants were asked to avoid coffee, tea or energy drinks on the day the measurements were performed. During the 2-hour measurement protocol electrocardiogram, arterial blood pressure and laser Doppler flux of cutaneous microvessels were monitored. Iontophoresis of acetylcholine, which stimulates NO production in endothelial cells, was used to assess endothelium-dependent vasodilation. Iontophoresis of sodium nitroprusside, a direct NO donor, was used to assess endothelium-independent vasodilation. Finally, local warming (42°C) of skin on the left forearm skin was used to assess heat-stimulated vasodilator response. Data were analyzed using independent samples t-test or repeated measures ANOVA followed by Dunnett's test.
Results Thirty four APS patients and 34 healthy age and sex-matched controls completed the study (24 female and 10 male in each group, age range 22–74). Participants were divided into three age groups, 22–38 years (12 female per group), 39–49 (5 female, 6 male per group) and ≥50 (7 female, 4 male per group). Acetylcholine iontophoresis, sodium nitroprusside iontophoresis or local heating stimulated vasodilation in all participants. Endothelium-dependent vasodilator response to acetylcholine was blunted in APS patients aged ≥50 (P<0.050 vs. healthy controls), but remained unaltered in younger participants. Conversely, vasodilator response to local heating was blunted in APS patients from the 22–38 age group (P<0.050 vs. healthy controls). Endothelium-independent vasodilation stimulated by NO donor sodium nitroprusside was similar in all groups.
Conclusions Here we show that endothelium-dependent vasodilator response in cutaneous microvasculature is diminished in older APS patients, while changes in vasodilator response to local heating affect mainly younger APS female patients. Our results indicate that cutaneous microvasculature in APS is functionally altered. This study supports diminished endothelial NO production in patients with APS.
Disclosure of Interest None declared