Progress in the care of familial hypercholesterolaemia: 2016

Abstract

● Familial hypercholesterolaemia (FH) is the most common autosomal dominant condition, with a prevalence of between one in 200 and one in 350 people in the general population. ● Untreated FH is associated with premature atherosclerotic cardiovascular disease (CVD). ● The prevalence of homozygous or compound heterozygous FH is now considered to be about one in 300000 people. ● Treating children with FH reduces progression of atherosclerotic CVD and future CVD events. ● Most individuals with FH are undiagnosed, which together with the recent frequency data in the population and in individuals with premature coronary disease creates a public health challenge and mandates a key role for primary care. ● Childhood is the optimal period for detecting FH, since lowdensity lipoprotein cholesterol (LDL-c) concentrations better differentiate affected from unaffected individuals. ● In an Australian community setting, over 70% of adults with an LDL-c level ≥ 6.5mmol/L have clinical FH; of these, 30% have a detectable mutation. ● The community laboratory has an important role in identifying FH, with interpretive comments leading to additional reductions in LDL-c concentrations, and a phone call from the pathologist to the general practitioner improving detection of cases. ● Cascade screening using DNA testing is cost-effective and acceptable to screenees. ● Next generation genetic sequencing may differentiate people with polygenic hypercholesterolaemia alone from those with FH. ● Smoking, hypertension, elevated lipoprotein(a) levels, chronic kidney disease and diabetes are additional atherosclerotic CVD risk factors in FH. ● Equations for assessing absolute risk of CVD in primary prevention underestimate risk in FH. ● The adult LDL-c goal is a greater than 50% reduction in LDL-c levels, followed by a target of <2.5 mmol/L, or <1.8mmol/L for individuals with CVD or other CVD risk factors. ● Proprotein convertase subtilisin/kexin type 9 inhibitors significantly reduce LDL-c and lipoprotein(a) levels in people with FH. ● Registries are essential for improving the care of people with FH.