Familial Combined Hyperlipidemia: metabolic features and new diagnostic criteria.

Abstract

Contains fulltext : 59038.pdf (publisher's version ) (Open Access)Familial Combined Hyperlipidemia (FCH) is the most common inherited hyperlipidemia in humans with an increased risk of cardiovascular disease (CVD). Therefore, it is of great importance to identify and treat subjects with FCH appropriately. The exact pathophysiology of FCH is still unknown, also the genetic basis for FCH has remained obscure. The search for metabolic and genetic origin of this lipid disorder has some fundamental problems. Not all research groups use the same criteria to establish the diagnosis FCH, and the lipid phenotype can vary substantially within any individual. The main aim of this thesis was to evaluate this intra-individual variation in lipid phenotype over a period of 5 year and to come to more consistent and unequivocal diagnostic criteria for FCH which can be used in clinical practice. The diagnosis FCH based on plasma total cholesterol and triglycerides, both adjusted for age and gender was consistent in only 74% of the subjects over a 5-year period. It appeared that the combination of absolute apoB level, triglyceride concentration and total cholesterol concentration, both adjusted for age and gender most adequately predict FCH. To facilitate the implementation of these new diagnostic criteria in clinical practice we developed a nomogram to simply and accurately diagnose FCH. Furthermore, we investigated the contribution of other metabolic parameters and factors (like homocysteine, insulin resistance and leptin) in relation to FCH phenotype and the increased risk of CVD and presented a review about the pathogenesis of FCH with emphasis on the role of insulin resistance, adipose tissue metabolism and fatty acids.KUN Katholieke Universiteit Nijmegen, 8 december 2004Promotor : Stalenhoef, A.F.H. Co-promotor : Graaf, J. de165 p