The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients


John J.P. Kastelein, MD, PhD, Professor of Medicine, Chairman, Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, Room F4-159.2, 1105 AZ Amsterdam, the Netherlands.
(fax: 31 20 566 9343; e-mail:


Objective.  To determine the contribution of classical risk factors to the development of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolaemia (FH).

Design.  A retrospective, multi-centre, cohort study. Extensive data were collected by scrutinizing medical records and the use of questionnaires. Multivariate Cox regression was used to study the relationship between potential risk factors and the occurrence of CVD.

Setting and subjects.  We included 2400 FH patients from 27 Dutch lipid clinics. The diagnosis of FH was based upon the presence of a low-density lipoprotein receptor mutation or upon strict clinical criteria.

Main outcome measures.  Cardiovascular mortality and CVD.

Results.  During 112.943 person-years, 782 (32.6%) patients had had at least one cardiovascular event. Male gender (RR 2.82, 95% CI 2.37–3.36), smoking (RR 1.67, 95% CI 1.40–1.99), hypertension (RR 1.36, 95% CI 1.06–1.75), diabetes mellitus (RR 2.19, 95% CI 1.36–3.54), low HDL-C (RR 1.37, 95% CI 1.15–1.63) and elevated lipoprotein(a) levels (RR 1.50, 95% CI 1.20–1.79) proved to be independent CVD risk factors. These six risk factors explained 18.7% of the variation in the occurrence of CVD.

Conclusions.  Male gender, smoking, hypertension, diabetes mellitus, HDL cholesterol and lipoprotein(a) levels proved to be important risk factors for CVD in FH patients. In addition to the routine instiQJ;tution of statin therapy, controlling these factors needs special attention in the management of this disorder.