Impaired coronary microvascular function in familial Mediterranean fever
Introduction
Familial Mediterranean fever (FMF) is a genetic disorder inherited as autosomal recessive, which is characterized by recurrent self-limiting episodes of fever and painful polyserositis, affecting mainly the peritoneum, pleura, and synovium [1]. In addition, compared with the general population, vasculitis is seen more frequently in patients with FMF, and coronary vascular involvement in patients with FMF without coronary atherosclerosis has resulted in acute myocardial infarction [2]. Although the pathogenesis of the vascular involvement is unknown, several studies have suggested clinical and subclinical inflammation in FMF and in heterozygous carriers of FMF mutations [3], [4].
FMF is caused by mutations in the MEFV gene [5]. MEFV is located on chromosome 16. About 30 mutations associated with FMF have been defined. The five most common mutations are M694V, M680I, M694I, E148Q, and V726A, most of which are clustered on exon 10. The M694V mutation has been reported to be most common among non-Ashkenazi Jews and Turks. Genetic analyses of 1090 Turkish patients have confirmed that M694V is the most frequent mutation followed by M680I and V726A [6], [7].
After adjusting for coronary heart disease risk factors, one study found that the M694V allele significantly predicted risk of acute myocardial infarction [8]. However, the association between coronary atherosclerosis and FMF remains controversial [9], [10].
Measurement of coronary flow reserve (CFR) is used to assess epicardial coronary arteries and to examine the integrity of coronary microvascular circulation. Impaired endothelial function and reduced CFR, which reflect coronary microvascular function, have been shown to be early manifestations of coronary atherosclerosis. Using transthoracic second harmonic Doppler echocardiography (TTDE) to evaluate CFR has become popular and its feasibility has been validated [11], [12], [13].
We hypothesized that coronary microvascular function might be impaired in patients with FMF.
Section snippets
Methods
We based our clinical diagnoses of FMF on the Tel-Hashomer criteria [14]. Inclusion criteria were 18–50 years of age and no known cardiovascular risk factors. Exclusion criteria were any potential cause of coronary microvascular dysfunction such as coronary artery disease, diabetes mellitus, hypertension, smoking, hyperlipidemia, drinking alcohol, using any vasoactive drug, corticosteroid and/or methotrexate therapy, renal dysfunction, and cardiac rhythm other than sinus. Individuals also were
Clinical characteristics of the study population
The demographic and baseline characteristics of patients in the FMF and control groups are given in Table 1. The two groups were similar regarding age; BMI; blood pressure; and glucose, total cholesterol, HDL cholesterol, and LDL cholesterol levels. However, hsCRP and erythrocyte sedimentation rate (ESR) were significantly higher in the patients with FMF as compared with controls.
IVS thickness, left ventricular PW thickness, LVEDD, LVESD, left ventricular ejection fraction (EF), left atrium
Discussion
Our data demonstrate that coronary microvascular function is impaired in patients with FMF. FMF is prevalent in specific ethnic groups (i.e., non-Ashkenazi Jews, Armenians, Turks, and Arabs). It has been postulated that immunologic abnormalities, which are possibly induced by various pathogens in genetically susceptible individuals, might take part in the pathogenesis of FMF [19]. The pathogenesis of vasculitis in patients with FMF is unknown. The number of cases reported suggests that it is
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