Η μεταγευματική λιπαιμία σε ασθενείς με ετερόζυγη μορφή της οικογενούς υπερχοληστερολαιμίας: σύγκριση με ασθενείς με οικογενή συνδυασμένη δυσλιπιδαιμία και με υγιείς μάρτυρες

Abstract

Introduction Familial combined hyperlipidaemia (FCH) was originally described by Goldstein et al. as a new inheritable lipid disorder 182. It is the most common genetic cause of dyslipidaemia, with an estimated prevalence of 0.5-5.7 % in the general population and 10-14% among patients who suffer an early myocardial infarction 184,186,189. Individuals with FCH have a 10-fold higher risk for developing premature coronary artery disease (CAD) 186. It accounts for approximately 100,000 myocardial infarctions per year in the United States and the European Union 187. FCH is characterised by intraindividual and intrafamilial variability of the lipid profile, expressed as periodical increase of triglyceride (TG) and/or total cholesterol (TC) levels, and the presence of premature cardiovascular disease before the age of 60 years 182. Elevated levels of apolipoprotein B (apoB) and small dense low density lipoproteins (sdLDL) are the two most consistent metabolic findings in FCH, while other metabolic disturbances such as insulin resistance, impaired chylomicron (CM) clearance, hypertension, abdominal obesity and low high density lipoprotein levels (HDL) often coexist 186-187. It is estimated that 65% of individuals with FCH fulfil the National Cholesterol Education Program (NCEP) - Adult Treatment Panel III (ATP III) criteria for the diagnosis of the metabolic syndrome (Mets) 121,189. Gene mutations of lipoprotein lipase (LPL), hepatic lipase, apolipoprotein C-II and/or apolipoprotein A5 have been implicated in the pathogenesis of FCH 637. Familial hypercholesterolaemia (FH) is an autosomal, condominant, monogenic disorder of lipoprotein metabolism, characterised by very high levels of low density lipoprotein (LDL), tendon xanthomas and increased risk of premature atherosclerosis. The heterozygote frequency has been reported in most populations as 1:500, while the homozygote frequency as 1/1.000.000 638. FH results from inherited mutations of the LDL receptor (LDLr) gene and to date more than 1000 mutations have been reported 10. Coronary events occur before the age of 65 years in up to 85% of males and 50% of females with untreated heterozygous FH, while in homozygous FH CAD generally appears during the teenage years 14. FH has also been linked to premature valvulopathy and peripheral vascular disease 47,51-52. Postprandial lipaemia is a physiological polygenic metabolic process, following ingestion of dietary fat, mainly characterised by a marked increase in TG rich lipoprotein levels, such as CM, very low density lipoproteins (VLDL) and their remnants 291. The hypertriglyceridaemic state is accompanied by sdLDL particles that are more susceptible to oxidation and low HDL cholesterol levels 191. Hypertriglyceridaemia is also considered as a prothrombotic state, by provoking activation of nuclear factor B, a key mediator of atherosclerosis 639-640. Elevated fasting plasma TG concentrations are well established as an independent risk factor for the development of CAD 276-277. Although it is known that postprandial TG levels can be highly discriminatory between CAD patients and healthy subjects, it is not yet clear whether postprandial lipaemia, itself, is an independent risk factor for atherosclerosis 279. In the present study we evaluated the postprandial TG response in untreated patients with FCH and FH and a group of healthy subjects, as well as among different subgroups of FH and FCH patients, according to their lipid phenotype. ........................................................................................................