POS1352 ANTIINFLAMMATORY, ANTIOXIDANT AND ANTI-ATHEROSCLEROTIC EFFECTS OF A COMBINATION OF NATURAL SUPPLEMENTS ON PATIENTS WITH FMF RELATED AA AMYLOIDOSIS: A NON-RANDOMIZED 24 WEEKS OPEN LABEL INTERVENTIONAL STUDY
Authors: M. Romano, F. Garcia-Bournissen, D. Piskin, R. Cimaz, M. Yilmaz, E. Demirkaya
Journal: Annals of the Rheumatic Diseases (2021)

Background: Few studies have focused on Familial Mediterranean Fever (FMF)-related AA amyloidosis and cardiovascular disease event risk. Systemic inflammation stimulates the development and progression of atherosclerosis which is accelerated by vascular endothelial inflammation and enhanced oxidative stress. Excessive reactive oxygen species (ROS) generation has been reported in FMF, which correlated with attack severity. ROS may also be involved in amyloid formation, and in the pathogenesis of progressive renal injury. Objectives: In this non-randomized, 24 weeks open label interventional study, we aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction and oxidative stress in a cohort of FMF patients with AA amyloidosis. Methods: Morinda citrifolia (anti-atherosclerotic liquid- AAL), omega-3 (anti-inflammatory capsules- AIC) and extract with Alaskan blueberry (anti-oxidant liquid- AOL) were given to patients with FMF related AA amyloidosis. We included patients with biopsy proven AA amyloidosis, older than 18 years who have normal estimated glomerular filtration rate (eGFR) and proteinuria [&gt;3500mg/day]. Flow-mediated dilatation (FMD), asymmetric dimethylarginine (ADMA), hs-CRP, serum PTX3, Carotis intima media thickness (CIMT), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels were studied in baseline and after 24 weeks. Results: 67 FMF-related amyloidosis [52 male (77.6%); median recruitment age 36 years (range 21-66)] were enrolled. M694V mutation was the most common mutation found (74%), with 50.7% of the patients in homozygosity. All patients were treated with colchicine, and most of them (83.6%) has been on colchicine treatment at the time of enrollment. Serum ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies (Table 1). The change of the inflammatory markers PTX3, and hsCRP were negatively correlated with the change in FMD and positively correlated with the change of proteinuria, ADMA, MDA, cholesterol and CIMT. Conclusion: 24 weeks of AAL, AIC and AOL combined supplementation was significantly associated with reduction in serum inflammatory markers (PTX3 and hsCRP), improved endothelial functions (FMD, ADMA), and oxidative state (MDA). Our findings highlight the link among the three pathogenetic mechanisms including inflammation, endothelial function and oxidative status in progression of atherosclerosis and renal injury in patients with FMF related AA amyloidosis. Efficient control of these three mechanisms can have long term benefits from the cardiovascular and renal perspective of the patients with AA amyloidosis. References: [1]Romano M et al. Sci Rep, 2020 [2]Yilmaz M et al. Sci Rep, 2020 Table 1. Comparison of clinical and laboratory characteristics at the baseline and after 24 weeks of AAL, AIC and AOL supplementation Baseline Mean (SD) 24th week Mean (SD) Delta Mean (SD) p Total Cholesterol (mg/dl) 221.2 (60.3) 155.8 (35.4**) -65.3 (55.5) &lt;0.001 eGFR (ml/min/ 1.73 m2) 110.2 (12.8) 104.1 (11.2**) -6.1 (11.9) &lt;0.001 Malondialdehyde (MDA) (nmol/ml) 4.2 (1.8) 1.8 (0.5**) -2.2 (1.8) &lt;0.001 CuZn-SOD (U/ml) 431.5 (154.7) 538.1 (146.4**) 159.7 (211.8) &lt;0.001 GSH-Px (U/ml) 47.8 (13.2) 74.1 (20.3**) 26.3 (21.1) &lt;0.001 ADMA (µmol/l) 4.5 (2.6) 1.3 (0.6**) -3.2 (2.5) &lt;0.001 FMD (%) 5.0 (0.7) 6.4 (0.8**) 1.3 (0.9) &lt;0.001 CIMT (mm) 0.9 (0.2) 0.7 (0.1) -0.2 (0.2) &lt;0.001 Proteinuria (mg/24h) 6855.3 (3116.9) 4079.9 (2359.6) -2775.3 (2874.5) &lt;0.001 hs-CRP (mg/l) 25.5 (4.4-48.0) 3.0 (1.0-9.1)* -20.8 (11.2) &lt;0.001 PTX3 (ng/ml) 13.4 (2.3-67.0) 2.3 (0.4-14.5)* -17.5(17.5) &lt;0.001 Disclosure of Interests: None declared