Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management

Clinical management of heterozygous familial hypercholesterolaemia is large ly based on evidence from a small number of observational studies and extra polation from the results of clinical trials of lipid-lowering in patients with polygenic hypercholesterolaemia The objectives of this study were (i) to determine the absolute and relative mortality of patients with treated h eterozygous familial hypercholesterolaemia, (ii) to estimate the effect of changes in treatment efficacy on mortality trends over time, and (iii) to e xamine the implications of these findings for patient management. A cohort of 605 men and 580 women aged 20-79 years with heterozyous familial hyperch olesterolaemia were recruited from 21 out-patient lipid clinics in the UK. Patients were followed prospectively from 1980 to 1995 for 8770 person-year s. Absolute mortality was calculated, and relative risk was expressed as th e ratio of the number of observed deaths to the number expected in the gene ral population of England and Wales. Forty six of the 73 deaths were due to coronary heart disease. In women aged 20-39, despite treatment, the relati ve risk of a fatal coronary event was increased 125-fold (95% confidence in tervals 15-451) and the annual coronary mortality was 0.17%. In men aged 20 -39 the relative risk was increased 48-fold (17-105) and the annual coronar y mortality was 0.46%. The relative risk decreased with age but the absolut e risk increased. For men and women aged 60-79, the annual coronary mortali ty was 1.1% representing a significant excess mortality for women (relative risk 2.6, 1.3-4.5) but not for men (RR 1.1, 0.5-2.3). Non-coronary mortali ty was not increased at any age (RR for all ages 0.68, 0.45-0.99). There wa s a decline in the relative risk for coronary mortality in patients aged 20 -59 from an eight-fold (4.8-7.2) increased risk before 1992 to 3.7 (1.6-7.2 .) thereafter (P = 0.08). The results suggest that the prognosis for patien ts with heterozygous familial hypercholesterolaemia has improved with the i ntroduction of more effective treatment, and that lipid-lowering therapy is not associated with increased non-coronary mortality. These findings and t he excess coronary mortality observed suggest that all affected adult men a nd post-menopausal women should be treated with HMG-CoA reductase inhibitor s. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.