Primary objective: in this study, we want to investigate the performance of FH identification with a new approach using existing clinical laboratory data in which patients with severe hypercholesterolemia (LDL-C > 99.5th percentile for age and…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main outcome in this study will be prevalence of genetically confirmed FH
in a preselected population of individuals with severe hypercholesterolemia
(diagnostic yield). DNA genotyping in this study will be performed using a
customized Illumina GSA v3 array.
Secondary outcome
The secundary study parameter will be the diagnostic yield of existing clinical
criteria for genetically confirmed FH.
Background summary
Familial hypercholesterolemia (FH) is an autosomal dominant disorder
characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C)
resulting in an up to 25.8-fold increased risk for premature cardiovascular
disease (CVD) in heterozygous FH (HeFH) patients. Based on an estimated 1:250
prevalence, the number of HeFH patients in the Netherlands is around 70.000.
Unfortunately, over 50% of these patients remain unidentified. Novel screening
methods and optimization of the use of clinical scoring systems are needed to
identify these remaining undiagnosed FH patients.
Study objective
Primary objective: in this study, we want to investigate the performance of FH
identification with a new approach using existing clinical laboratory data in
which patients with severe hypercholesterolemia (LDL-C > 99.5th percentile for
age and sex) are selected.
Our secondary outcome is the comparison of the following FH clinical scoring
systems in their ability to predict the presence of an FH causing mutation:
Dutch Lipid Clinic Network (DLCN) criteria, Familial Hypercholesterolemia Case
Ascertainment (FAMCAT) Tool, Make Early Diagnosis to Prevent Early Deaths
(MEDPED) criteria, criteria of the Simon Broome registry (SB), and the more
recently developed and validated criteria by Besseling et al.
Study design
This is a single-center, cross-sectional observational study.
Study burden and risks
The results of this study will contribute to optimization of the identification
of FH patients, which has been a major issue with this disorder. This study
will teach us whether central laboratories, like Atalmedial, can indeed play a
role in identifying new FH patients, and subsequent cascade testing of first
degree relatives. Early detection of FH patients will result in early benefit
from lipid lowering therapies, greatly reducing CVD risk. In addition, the
identification of these FH patients will enable cascade screening of their
first degree family members, who in turn can be treated (at a young age) as
well. The expected risk for participants in this study is low, as the only
intervention will be a 10 ml venous blood withdrawal.
Jan Tooropstraat 138
Amsterdam 1061 AD
NL
Jan Tooropstraat 138
Amsterdam 1061 AD
NL
Listed location countries
Age
Inclusion criteria
Patients with severe hypercholesterolemia (LDL-cholesterol level above 99,5th
percentile for age and sex).
Exclusion criteria
Three failed blood withdrawal attempts.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL81583.018.22 |