The hinterland of familial hypercholesterolaemia: what do we not know?

Familial hypercholesterolaemia is the commonest autosomal dominant disorder in man, but many questions about familial hypercholesterolaemia remain to be answered. Guidelines are increasing in importance as healthcare becomes standardized. The review suggests areas that require more investigation or where pertinent guidelines may need to be reviewed.

Familial hypercholesterolaemia is commoner than previously thought, but its epidemiology needs further investigation against a background of changing environmental and lifestyle factors that may bear on its phenotypic expression. Screening for familial hypercholesterolaemia may be more difficult than might be thought as cascade testing may not capture all cases effectively and universal screening appears compelling, but requires testing and evaluation. Cardiovascular disease guidelines are moving to being risk based, but familial hypercholesterolaemia stands alone as defined by large database of lipids-cholesterol criteria. A risk-based approach may need to be considered for familial hypercholesterolaemia, but a good evidence base is required. The effects of older therapies on prognosis in familial hypercholesterolaemia are based on surrogate as opposed to cardiovascular disease outcomes. Novel efficacious but expensive therapies are on the horizon, but no specific outcome trials in familial hypercholesterolaemia are planned and they may not be cost-effective outside very severe familial hypercholesterolaemia. Further research is also required to trial and test different models of care for familial hypercholesterolaemia.

Despite familial hypercholesterolaemia being a common genetic condition, aspects of basic epidemiology, risk assessment, treatment, and models of care remain uncertain.