EAS 2010 - Session Planner

EFFICACY OF 15 YEARS OF GENETIC CASCADE SCREENING FOR FAMILIAL HYPERCHOLESTEROLEMIA IN THE NETHERLANDS IN PREVENTION OF CORONARY ARTERY DISEASE

Roeland Huijgen¹, J. Versmissen², D.M. Oosterveer², I. Kindt³, E.J.G. Sijbrands², J.J.P. Kastelein¹

¹Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, ²Dept of Cardiovascular Genetics & Dept of Pharmacology, Vascular and Metabolic Diseases, Erasmus Medical Center, Rotterdam, ³Foundation for Identification of Persons with Inherited Hypercholesterolemia (StOEH), Amsterdam, The Netherlands

Objective: Familial hypercholesterolemia (FH) is associated with a severely increased risk of coronary artery disease (CAD). Genetic screening for FH is ongoing in the Netherlands since 1994 and after such diagnosis 85% used cholesterol-lowering medication (Huijgen PLoS ONE 2010). Statin treatment reduces the risk of a first CAD event by 80% in clinically diagnosed FH patients (Versmissen BMJ 2008). If CAD risk attributable to FH is similar in clinically and genetically diagnosed patients, one could predict the treatment-induced risk reduction after genetic diagnosis.
Methods: We compared CAD event free survival in 1,338 patients clinically diagnosed with FH and 11,136 relatives identified with FH through genetic screening to that of 20,057 screened relatives without FH before 1990 (pre-statin era). We used a Cox-proportional hazard model, adjusted for traditional cardiovascular risk factors. We estimated the number of CAD events after genetic FH diagnosis until expected age of death.
Results: The risk of CAD was significantly increased, in both clinically and genetically diagnosed FH patients, compared to unaffected relatives, peaking at the age of 35 (RR 11.9; 95%CI 5.2 to 27.1 and RR 11.8; 95%CI 6.4 to 21.8, respectively). In 6,366 subjects that were untreated and free of CAD at FH diagnosis, 2,892 CAD events would occur if they would remain untreated, whereas 2,045 events (71%) can be prevented if 85% would be treated.
Conclusion: Genetic screening for FH is currently effective in preventing CAD in the Netherlands, with 3 untreated subjects required to be identified with FH to avert CAD in 1.