Cardiovascular Risk and Bone Mineral Density in Children with Familial Mediterranean Fever: The Role of Disease Severity and Genetic Mutations

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Abstract
In the present study, cardiovascular risk indices (Atherogenic Index of Plasma [AIP], Atherogenic Coefficient [AC], Castelli Risk Index-1 [CRI-1], and Castelli Risk Index-2 [CRI-2]) and bone mineral density (BMD SDS) were evaluated in patients with Familial Mediterranean Fever (FMF), and the association of these parameters with disease severity and MEFV gene mutations was investigated. A total of 126 participants (96 FMF patients and 30 healthy controls) were included in the study. FMF patients were classified as mild, moderate, or severe according to the PRAS severity score. Cardiovascular risk indices, biochemical parameters of bone metabolism, and BMD SDS values were compared among the groups. The relationship between BMD SDS and atherogenic indices was assessed by Spearman correlation analysis. The results were also analyzed according to MEFV gene mutations. No significant difference was detected among the groups in terms of sex or age (p > 0.05). FMF patients were found to have substantially higher cardiovascular risk indices than the control group, and these indices increased in parallel with disease severity (p < 0.05). The BMD SDS value of the severe FMF group was significantly lower than that of the other groups (p = 0.025). No difference was detected among the groups with respect to bone metabolism parameters (p > 0.05). No significant correlation was observed between BMD SDS and cardiovascular risk indices (p > 0.05). M694V was the most frequently detected mutation, and the BMD SDS value was lower in patients carrying mutations other than M694V (p = 0.011). The increased cardiovascular risk in FMF patients is associated with disease severity. Severe disease is accompanied by a reduction in bone mineral density. The lack of an association between cardiovascular risk and bone mineral density suggests that these systems may be affected through different mechanisms. It is important that FMF patients are monitored with respect to cardiovascular and bone health.

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