Endothelial Function in Patients with Multiple Sclerosis: The Role of GLP-1 Agonists, Lipoprotein Subfractions, and Redox Balance.

INTRODUCTION: Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma. METHODS: MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated. RESULTS: The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7; p = 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L, p = 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6; p = 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL, p = 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637, p = 0.001), the use of GLP-1a therapy (beta = 0.560, p = 0.003), and small LDL (beta = 0.339, p = 0.043) were the only significant variables in the model that predicted the follow-up RHI. CONCLUSION: Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.

No Difference in Sleep Desaturations Severity between Patients with Wake-Up and Non-Wake-Up Stroke: A PRESS Study Results.

BACKGROUND: Wake-up stroke (WUS) is a certain type of ischemic stroke in which a patient wakes up with a new neurological deficit due to cerebral ischemia. Sleep-disordered breathing is an independent risk factor for stroke, but the role of nocturnal oxygen desaturation in the pathophysiology of WUS is still insufficiently explored. According to several studies, patients with WUS have a significantly more severe sleep apnea syndrome and lower mean blood oxygen saturation. This study aimed to assess the severity of nocturnal desaturations in acute WUS and non-WUS patients using nocturnal pulse oximetry. MATERIAL AND METHODS: The cohort of 225 consecutive patients with neuroimaging-verified acute cerebral ischemia was prospectively enrolled. For further analyses, 213 subjects with known WUS/non-WUS status were selected (111 males and 102 females, average age 70.4 ±12.9, median baseline NIHSS = 5, median baseline mRS = 3). Patients were divided into the WUS group (n = 45) and the non-WUS group (n = 168). Overnight pulse oximetry was performed within 7 days of the stroke onset and data of both of the studied groups were compared. RESULTS: We found oxygen desaturation index (ODI) in the WUS group was 14.5 vs. 16.6 (p = 0.728) in the non-WUS group, basal O2 saturation was 92.2% vs. 92.5% (p = 0.475), average low O2 saturation was 90.3% vs. 89.6% (p = 0.375), minimal O2 saturation was 79.5% vs. 80.6% (p = 0.563), and time with O2 saturation <90% (T90) was 4.4% vs. 4.7% (p = 0.729). CONCLUSIONS: In the studied sample, monitored respiratory parameters including ODI, basal O2 saturation, average low O2 saturation, minimal O2 saturation, and T90 did not significantly differ between groups of WUS and non-WUS patients.

Lipoprotein Subfractions Associated with Endothelial Function in Previously Healthy Subjects with Newly Diagnosed Sleep Apnea-A Pilot Study.

BACKGROUND: Obstructive sleep apnea (OSA) activates several pathophysiological mechanisms which can lead to the development of vascular diseases. Endothelial dysfunction (ED) is an initial step in the development of atherosclerosis. The association between ED and OSA has been described in several studies, even in previously healthy subjects. High-density lipoproteins (HDL) were generally considered to be atheroprotective, and low-density lipoprotein (LDL) to be an atherogenic component of lipoproteins. However, recent findings suggest a pro-atherogenic role of small HDL subfractions (8-10) and LDL subfractions (3-7). This study aimed to evaluate the relationship between endothelial function and lipid subfractions in previously healthy OSA subjects. MATERIAL AND METHODS: We prospectively enrolled 205 subjects with sleep monitoring. Plasma levels of triacylglycerols, total cholesterol, LDL, HDL, and their subfractions were assessed. Endothelial function was determined using peripheral arterial tonometry, and reperfusion hyperemia index (RHI) was assessed. RESULTS: Plasma levels of small and intermediate HDL subfractions have statistically significant pro-atherogenic correlations with endothelial function (p = 0.015 and p = 0.019). In other lipoprotein levels, no other significant correlation was found with RHI. In stepwise multiple linear regression analysis, small HDL (beta = -0.507, p = 0.032) was the only significant contributor in the model predicting RHI. CONCLUSIONS: In our studied sample, a pro-atherogenic role of small HDL subfractions in previously healthy subjects with moderate-to-severe OSA was proven.