POS1375 THE EFFECT OF M694V HOMOZYGOSITY ON THE CAROTID INTIMA-MEDIA THICKNESS AND FLOW MEDIATED DILATATION IN PATIENTS WITH FMF RELATED AMYLOIDOSIS
Authors: S. Sahin, M. Romano, F. Guzel, O. Kasapcopur, D. Piskin, I. Yilmaz, E. Demirkaya
Journal: Annals of the Rheumatic Diseases (2021)

Background: There are limited data in FMF associated AA amyloidosis patients regarding the vascular abnormalities including atherosclerosis and endothelial dysfunction, all of which are contributors of cardiovascular disease (CVD) risk. And, this risk assessment for future CV events have not yet been evaluated between FMF amyloidosis patients with different genotypes. Objectives: We aimed to compare early markers of endothelial dysfunction and atherosclerosis, mortality and other disease characteristics in FMF-related amyloidosis patients with a homozygous M694V genotype and in patients with other genotypes with this cross-sectional comparative study. Methods: For this purpose, patients with FMF-related amyloidosis were assigned according to the MEFV gene mutation to one of the two groups. Group 1: Patients homozygous for M694V (which is the most common genotype associated with the most severe clinical phenotype in FMF) Group 2: Patients homozygous (other than M694V) or compound heterozygous (including M694V) for other MEFV variants. Potential confounders were controlled by excluding the patients with untreated hypertension, diabetes mellitus, obesity, smoking, previous history of CVD low glomerular filtration rate (eGFR &lt;70 mL/min). Flow-mediated dilatation (FMD), pentraxin-3 (PTX3) as early markers of endothelial dysfunction and carotid intima-media thickness (cIMT), fibroblast Growth Factor 23 (FGF23) as an indicator of atherosclerotic vascular disease, all of which are non-invasive tests that are also used to identify subjects at increased risk for future CV events were measured in these 2 groups. Results: We analyzed demographic, clinical, genetic, survival data and these non-invasive markers of endothelial dysfunction (FMD and PTX3) and atherosclerosis (cIMT and FGF23) in 76 FMF amyloidosis patients with homozygous M694V mutations (Group 1) and 93 FMF amyloidosis patients with two pathogenic mutations apart from M694V homozygosity (Group 2) (Table 1). Brachial artery FMD was significantly lower in Group 1 when compared with Group 2 subjects (6.0 vs. 6.5%, p&lt;0.001). cIMT, FGF23 and PTX3 levels were higher in Group 1 when compared with Group 2 (cIMT: 0.84 vs. 0.67 mm, p&lt;0.001; FGF23: 52.4 vs. 38.0 pg/dL, p=0.01; PTX3: 14.0 vs. 3.2 ng/mL, p&lt;0.001). Time to develop amyloidosis was similar in patients homozygous for M694V (median 10.0 years, 95%CI: 8.99-11.0) and in Group 2 (median 10.0 years, 95%CI: 8.97-11.0) (p&gt;0.05). Mortality rate was significantly higher in Group 1 compared to Group 2 (18.4% vs. 1.1%, p&lt;0.001) over a median of 7.8 years of follow-up. FMF amyloidosis patients homozygous for M694V had reduced survival (mean survival: 97 months, 95%CI: 94.9 to 101.0 months) as compared to Group 2 (mean survival: 100.7 months, 95%CI: 100.0 to 101.3 months) (p&lt;0.001) (Figure 1). The proportion of the clinical manifestations including fever, serositis, erysipelas-like erythema, all of which are associated with an FMF attack did not differ between two groups (p&gt;0.05) apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p&lt;0.05) (Table 1). Conclusion: In patients with FMF related amyloidosis, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23 and PTX3 levels. In summary, the data demonstrate that a genotype-phenotype association exists in terms of endothelial dysfunction and atherosclerosis in FMF patients with amyloidosis. Table 1. Group 1 (n=76 ) Group 2 (n=93 ) Total (n=169 ) p Clinical Findings n (% ) n (% ) n (% ) Dialysis 2 (2.6) 3 (3.2) 5 (3.0) 1.00* Kidney transplantation 5 (6.6) 4 (4.3) 9 (5.3) 0.73* Kidney biopsy 68 (89.5) 85 (91.4) 153 (90.5) 0.67 Median (Min-max ) Median (Min-max ) Median (Min-max ) Age (years) 36.5 (19.0-49.0) 35.0 (22.0-49.0) 36.0 (19.0-49.0) 0.16 Age of amyloidosis (years) 20.0 (13.0-31.0) 20.0 (15.0-26.0) 20.0 (13.0-31.0) 0.86 BMI (kg/m 2 ) 26.0 (21.0-32.0) 27.0 (19.0-32.0) 26.6 (29.0-32.0) 0.89 HOMA 2.2 (1.2-7.3) 2.4 (1.1-8.4) 2.4 (1.1-8.4) 0.40 Proteinuria (g/24h) 7.6 4,6 5.4 &lt;0.001 Disclosure of Interests: None declared