Specialization
Focus of research
Key research lines for the coming years are:
--Treatment and follow-up of children with familial hypercholesterolemia--
Statins are increasingly considered for certain pediatric conditions to prevent atherosclerosis, but long-term effects are unknown. Yet, these are crucial for a proper clinical approach of children. In 1997, we started a 2-year RCT in familial hypercholesterolemia children to evaluate efficacy and safety of pravastatin. All children continued with a statin, and they now have reached adulthood. This unique cohort enables us to evaluate efficacy, safety, tolerability and compliance of 10-year statin therapy initiated in childhood.
The results will be of value for the development of new evidence based guidelines for treatment of children with hypercholesterolemia. These might also concern conditions other than familial hypercholesterolemia, such as obesity. This research line is Funded by the Dutch Heart Foundation (NHS: 2009B059 Grant Application 2009).
As in other European countries, a nationwide screening programme in the Netherlands tests children for familial hypercholesterolemia when this is requested by the parents. When an adult or child is diagnosed with familial hypercholesterolemia, consultation of a physician is advised. Although treatment guidelines for familial hypercholesterolemia children have been widely published, the clinical follow-up of children diagnosed with familial hypercholesterolemia after genetic testing is unknown. We therefore set out to study this in the paediatric yield of our Dutch nationwide screening program.
--Treatment of adult patients with familial hypercholesterolemia--
In 1994, a screening program was set up in the Netherlands to identify all patients with familial hypercholesterolemia. Currently, 10-15% of the screened persons with FH have normal LDL-c levels. However, the risk of cardiovascular disease (CVD) in these patients is unknown, and it is unclear if or how these subjects should be treated. We aim to determine CVD risk of FH patients with normal or slightly elevated LDL-c levels in order to establish treatment guidelines for these patients.
--Familial hypercholesterolemia and insurances--
Genetic screening for familial hypercholesterolemia in the Netherlands was reported to decrease access to affordable life insurance for mutation carriers. This ‘genetic’ discrimination gave rise to concerns within families with familial hypercholesterolemia and hindered participation in the genetic programme. In order to improve access to insurance for familial hypercholesterolemia mutation carriers, a set of guidelines were issued for insurance companies in 2003. We attempt to determine in a large cohort that had been tested for genetic familial hypercholesterolemia whether the access to insurance has improved since.
--Familial hypercholesterolemia and pregnancy--
It is unknown if treatment of severe hypercholesterolemia should be continued during pregnancy. Several studies suggest that maternal hypercholesterolemia is associated with development of fetal atherosclerosis. However, statins are considered teratogenic and therefore contraindicated during pregnancy. We will investigate whether severe hypercholesterolemia in pregnant women with familial hypercholesterolemia has detrimental consequences for cardiovascular risk of either mother or child. These results will help to formulate evidence-based guidelines for hypercholesterolemic women who wish to become pregnant, ultimately leading to reduced progression of premature atherosclerosis and increased survival.
Furhermore, by means of a systematic review the teratogenic effect of statins during pregnancy in general will be assessed.