Metabolic disorders and inflammation are associated with familial combined hyperlipemia
Introduction
Familial Combined Hyperlipidemia (FCH; MIM 144250) is the most frequent genetic hyperlipemia [1,2], and is characterized by the appearance of coronary disease before the age of 60 [3]. The prevalence of this disease is 1–2% in the general population [4] and 10–20% among patients with premature coronary disease. FCH presents a complex phenotype that is not completely understood, and which can vary among patients and affected relatives [5], which complicates diagnosis. FCH is associated with insulin resistance (IR), which is in turn related to different metabolic disorders, such as abdominal obesity, metabolic syndrome and type 2 diabetes mellitus (DM2). A common form of dyslipemia associated with FCH is attributed to the atherogenic lipoprotein phenotype, characterized by elevated levels of triglycerides (TG), small LDL particles and reduced HDL cholesterol levels (HDLc) [[6], [7], [8]], a lipid triad frequently seen in patients with premature coronary disease [9]. Small and dense LDL particles (sdLDL) are formed largely as a response to high levels of TG, and increase the risk of coronary heart disease [10]. The peak size of LDL particles displays a bimodal distribution and can be separated into two phenotypes: pattern A, in which larger, more buoyant LDL predominate, and pattern B, in which smaller, more dense LDL predominate. The National Cholesterol Education Program (ATP III) considers small and dense LDL to be a lipid risk factor [11].
In addition to the above mentioned aspects, it is well known that HDLc does not represent a sum of identical particles, but rather a collection of discrete subfractions that differ in their physicochemical properties; namely, size, density, composition and charge [12]. It seems that HDL atherogenity increases as particle size decreases [13,14], and that small HDL are more atherogenic than large HDL, which has a bearing on treatment [15], as such qualitative alterations in lipoprotein metabolism could account for the increased risk of cardiovascular disease in FCH. However, this is a subject that requires clarification, as there have been few studies of lipoprotein subfractions in FCH, and those to have been published offer conflicting results [16,17].
The inflammation that occurs at all stages of atherosclerosis is also common to the different processes associated with FCH, IR, abdominal obesity, metabolic syndrome and DM2. It has been reported that some molecules are related to inflammation and that adhesion molecules are elevated in FCH patients compared with control populations [18,19] although few studies have analysed the relationship between lipids subfractions and inflammation markers in the context of FCH.
The aim of this study was to evaluate the presence of alterations of hydrocarbonated metabolism and lipid profile, including sdLDL and subfractions of HDL, together with inflammatory parameters and adhesion molecules, in subjects with FCH and to compare them with parameters in a control population.
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Patients
Patients diagnosed with FCH (according to the criteria of Bredie et al. [20]) at the outpatient clinic of the Endocrinology Service of University Hospital Dr. Peset in Valencia were enrolled in the study. As a control group, healthy individuals not related to the patients were matched by age and sex.
Exclusion criteria were DM2 according to ADA criteria [21], triglycerides >400 mg/dl, morbid obesity (BMI ≥ 40 kg/m2), renal disease (glomerular filtration <60 ml / min / 1.73m2), chronic liver
Anthropometric, hydrocarbonated and lipid parameters
A total of 75 patients with FCH with a mean age of 41 ± 14 years and a BMI of 26.9 ± 4.0 kg/m2–30 men (40%) and 45 women (60%) - were matched by age and sex with 75 controls. FCH patients showed higher percentages of excess weight (49% vs 12%), obesity (20% vs 4%), hypertension (28% vs 1%), women's waist ≥80 cm (50% vs 18%) and men's waist ≥94 cm (27% vs 6%) than controls (p < .001 for all). As expected, differences between the FCH and control groups were significant for all lipid and
Discussion
As expected, our results show that FCH patients exhibit a worse lipid profile, which is reflected by IR, increased inflammation parameters and adhesion molecules, and alterations of the subfractions of LDL and HDL. In accordance with previous reports, in our patients FCH was associated with a more pronounced atherogenic lipoprotein profile, evident in reduced HDLc and Apo AI levels and increased LDLc, non-HDLc, Apo B and triglyceride levels [[31], [32], [33]].
FCH exacerbates the deleterious
Conflict of interest
The authors declare that they have no competing interests.
Financial support
This study was financed by grant PI15/1424 from Fund for Health Research (FIS) and co-funded by the European Regional Development Fund of the European Union (ERDF “A way to build Europe”). C.B. is the recipient of a Sara Borrell contract from Carlos III Health Institute (CD14/00043).
Acknowledgments
The authors thank Rosa Falcon (FISABIO) for her technical assistance.
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