LAUSR

BACKGROUND AND AIMS Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited condition characterized by elevated plasma low-density lipoprotein-cholesterol (LDL-C) levels, severe, accelerated atherosclerosis and premature coronary heart disease. We evaluated cardiovascular complications in HoFH patients over extended follow-up and investigated their association with changes in cholesterol over time, as well as total cholesterol burden. METHODS In this retrospective single-centre study, 53 patients (baseline mean ± standard deviation [SD], total cholesterol 15.5 ± 3.7 mmol/L and LDL-C 13.2 ± 2.6 mmol/L) were followed for up to 38 years (21.2 ± 10 years). The primary outcome was an adverse clinical event, defined as cardiovascular death, nonfatal myocardial infarction, or angina. RESULTS Twenty-eight patients experienced an event, of whom 8 died due to complications of major surgery (4), myocardial infarction (3) or stroke (1). While total cholesterol levels were comparable in patients with and without an event at baseline (20 mmol/L), those who subsequently experienced an event showed a slower decline in total cholesterol. Cumulative total cholesterol (i.e. total-cholesterol year score) was highly associated with the incidence of an adverse clinical event in a linear dose-response relation. A 100 mmol/L increase in cumulative total cholesterol (i.e. an average exposure of 10 mmol/L per 10 years or 20 mmol/L per 5 years) was associated with a doubling of the risk of a cardiovascular event (age-adjusted incidence rate ratio: 1.99, 95% CI, 1.16-3.41). CONCLUSIONS Our findings reinforce the importance of early diagnosis and initiation of maximal treatment, including lipoprotein apheresis, to ensure long-term reduction in the cholesterol burden, expressed as the total-cholesterol year score, and risk of cardiovascular complications in HoFH.