Practical definitions of severe versus familial hypercholesterolaemia and hypertriglyceridaemia for adult clinical practice

Diagnostic scoring systems for familial hypercholesterolaemia and familial chylomicronaemia syndrome often cannot differentiate between adults who have extreme dyslipidaemia based on a simple monogenic cause versus people with a more complex cause involving polygenic factors and an environmental component. This more complex group of patients carries a substantial risk of atherosclerotic cardiovascular disease in the case of marked hypercholesterolaemia and pancreatitis in the case of marked hypertriglyceridaemia. Complications are mainly a function of the degree of disturbance in lipid metabolism resulting in elevated lipid levels, so the added value of knowing the precise genetic cause in clinical decision making is unclear and does not lead to clinically meaningful benefit. We propose that for severe elevations of plasma low density lipoprotein cholesterol or triglyceride, the primary factor driving intervention should be the biochemical perturbation rather than the clinical risk score. This underscores the importance of expanding the definition of severe dyslipidaemias and to not rely solely on clinical scoring systems to identify individuals who would benefit from appropriate treatment approaches. We advocate for the use of simple, practical, clinical, and largely biochemically based definitions for severe hypercholesterolaemia (eg, LDL cholesterol >5 mmol/L) and severe hypertriglyceridaemia (triglyceride >10 mmol/L), which complement current definitions of familial hypercholesterolaemia and familial chylomicronaemia syndrome. Irrespective of the precise genetic cause, individuals diagnosed with severe hypercholesterolaemia and severe hypertriglyceridaemia require intensive therapy, including special consideration for new effective but more expensive therapies.