Abstract
BackgroundFamilial hypercholesterolemia (FH) is a genetic disorder that result in abnormally high low-density lipoprotein cholesterol levels, markedly increased risk of coronary heart disease (CHD) and tendon xanthomas (TX). However, the clinical expression is highly variable. TX are present in other metabolic diseases that associate increased sterol concentration. If non-cholesterol sterols are involved in the development of TX in FH has not been analyzed.MethodsClinical and biochemical characteristics, non-cholesterol sterols concentrations and Aquilles tendon thickness were determined in subjects with genetic FH with (n = 63) and without (n = 40) TX. Student-t test o Mann–Whitney test were used accordingly. Categorical variables were compared using a Chi square test. ANOVA and Kruskal–Wallis tests were performed to multiple independent variables comparison. Post hoc adjusted comparisons were performed with Bonferroni correction when applicable. Correlations of parameters in selected groups were calculated applying the non-parametric Spearman correlation procedure. To identify variables associated with Achilles tendon thickness changes, multiple linear regression were applied.ResultsPatients with TX presented higher concentrations of non-cholesterol sterols in plasma than patients without xanthomas (P = 0.006 and 0.034, respectively). Furthermore, there was a significant association between 5α-cholestanol, β-sitosterol, desmosterol, 24S-hydroxycholesterol and 27-hydroxycholesterol concentrations and Achilles tendon thickness (p = 0.002, 0.012, 0.020, 0.045 and 0.040, respectively).ConclusionsOur results indicate that non-cholesterol sterol concentrations are associated with the presence of TX. Since cholesterol and non-cholesterol sterols are present in the same lipoproteins, further studies would be needed to elucidate their potential role in the development of TX.
Highlights
Familial hypercholesterolemia (FH) is a genetic disorder that result in abnormally high low-density lipoprotein cholesterol levels, markedly increased risk of coronary heart disease (CHD) and tendon xanthomas (TX)
In heterozygous FH (HeFH) patients, the clinical expression is highly variable in terms of the severity of hypercholesterolemia, the presence of tendon xanthomas (TX), and the age of onset and severity of CHD, even in subjects sharing the same LDLR gene defect [4]
TX in the presence of severe hypercholesterolemia with autosomal dominant transmission is highly specific of FH [2], and a mutation in one low-density lipoprotein (LDL) receptor-related gene is commonly found in this scenario [7]
Summary
Familial hypercholesterolemia (FH) is a genetic disorder that result in abnormally high low-density lipoprotein cholesterol levels, markedly increased risk of coronary heart disease (CHD) and tendon xanthomas (TX). In HeFH patients, the clinical expression is highly variable in terms of the severity of hypercholesterolemia, the presence of tendon xanthomas (TX), and the age of onset and severity of CHD, even in subjects sharing the same LDLR gene defect [4]. HoFH typically develops TX in the first decade of life, while TXs begin to appear after the third decade of life in 20–50% of affected HeFH [2] It is unknown why some HeFH subjects develop TX and others do not, even sharing the same pathogenic LDLR mutation [4], and it may be related to interindividual variability in the inflammatory response of macrophages to oxidized LDL particles [8]
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