Abstract:
Cardiovascular disease (CVD) remains underestimated in familial Mediterranean feverassociated
AA amyloidosis (FMF-AA).We aimed to compare early markers of endothelial dysfunction
and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the
Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients).
Measures of increased risk for future CVD events and endothelial dysfunction, including flowmediated
dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and
fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared
between groups. The frequency of clinical FMF manifestations did not differ between the two groups
apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower
in Group 1 when compared with Group 2 (MD [95% CI]: 0.6 [(0.89)–(0.31)]). cIMT, FGF23,
and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08–0.16]; FGF23 MD [95% CI]:
12.8 [5.9–19.6]; PTX3 MD [95% CI]: 13.3 [8.9–17.5]). In patients with FMF-AA, M694V homozygosity
is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased
CVD risk profiles. These data suggest that a genotype–phenotype association exists in terms of
endothelial dysfunction and atherosclerosis in patients with FMF-AA.