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  • Title: Differences in characteristics and risk of cardiovascular disease in familial hypercholesterolemia patients with and without tendon xanthomas: a systematic review and meta-analysis.
    Author: Oosterveer DM, Versmissen J, Yazdanpanah M, Hamza TH, Sijbrands EJ.
    Journal: Atherosclerosis; 2009 Dec; 207(2):311-7. PubMed ID: 19439299.
    Abstract:
    BACKGROUND: Tendon xanthomas are characteristic of familial hypercholesterolemia (FH). It is not clear whether FH patients with xanthomas have higher risk of cardiovascular disease (CVD) than those without xanthomas. The clinical diagnosis of FH in patients without xanthomas, namely requires the presence of CVD in the patient or in a first-degree relative. This may have masked the association between xanthomas and CVD in a number of studies. A diagnosis of FH based on the presence of a mutation in the low-density lipoprotein receptor (LDLR) gene is free from this selection on CVD. In this systematic review and meta-analysis, we therefore compared the risk of CVD between patients heterozygous for LDLR mutation with and without xanthomas. METHODS AND RESULTS: We conducted a literature search with PubMed and the Web of Science up to January 14, 2009. We selected all articles examining more than 25 human heterozygous FH patients, that provided information about xanthomas. Articles had to be written in a Western European language. A total of 22 articles suited for analyses. A genetic confirmation of FH was compulsory to correctly assess the risk of CVD with presence of xanthomas. Age, male gender, LDL-cholesterol and triglyceride level were associated with the presence of xanthomas (p<0.05 for all). In patients with genetically confirmed FH, xanthomas were associated with a 3.20-fold higher risk of CVD (95% CI 2.12-4.82, p<0.01). CONCLUSIONS: Xanthomas are associated with a 3 times higher risk of CVD among FH patients, suggesting that xanthomas and CVD may share etiology.
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