ESPE Abstracts

Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD). Although familial hypercholesterolemia (FH) has an important impact on CVD, most people with FH are undiagnosed or diagnosed only after their first coronary event. Therefore, early identification of affected individuals is crucial. Total cholesterol levels alone are not sufficient to confirm a diagnosis of FH, because of the extensive overlap in LDL–C levels existing between FH-causing mutation carries and non-carries (non-genetic polygenic hypercholesterolemia) and the high prevalence of modestly severe LDLR mutations that hampers the use of LDL-C cut-offs. Therefore, a diagnostic definition of FH, which supports cholesterol measurements with clinical signs and family history, has to be used. Genetic analysis gives a definitive confirmation. The cornerstone of lipid-lowering treatment is a healthy lifestyle, but diet alone fails to lower cholesterol levels to acceptable values namely in patients with genetic hypercholesterolemia needing pharmacological treatment. Statins efficacy is already well established and they are currently the mainstay in the treatment of hypercholesterolemia also in childhood. Statins not only decrease LDL-C, but also have lipid-independent pleiotropic effects, altering inflammatory responses and local atherosclerotic plaque morphology. Considering the safety concerns posed for long-term treatment with statins, screening of liver and muscle enzymes before and during treatment could be envisaged. If liver enzymes are above 3 times the upper limit and/or CK is above 10 times the upper limit and/or patient complains any adverse effects, medication should be stopped. A way to improve the safety of lipid-lowering treatment is to associate different drugs at lower doses. Ezetimibe, decreasing cholesterol absorption through inhibition of Niemann-Pick C1-like 1 protein, could improve the efficacy of statins alone. Moreover, the inhibition of PCSK9 pathway appears one of the most promising novel targets for additional LDL-C reduction. Although we are still far from the complete comprehension of the lipid metabolism, the better understanding of its physiology and pathophysiology has already permitted the introduction of new therapeutic opportunities, namely for patients with severe genetic forms of hypercholesterolemia.