Assessment of Surrogate Markers for Cardiovascular Disease in Familial Mediterranean Fever-Related Amyloidosis Patients Homozygous for M694V Mutation in MEFV Gene

Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated 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 flow-mediated 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.

Automated summary

This study finds that FMF-AA patients with a homozygous M694V mutation have a higher risk of cardiovascular disease compared to patients with other genotypes. They also have higher levels of fibroblast growth factor 23 (FGF23), carotid intima-media thickness (cIMT), and pentraxin-3 (PTX3).