Hypercholesterolemia, Familial
Conditions
Keywords
Familial Hypercholesterolemia, Genetics, Cascade screening
Brief summary
To test the hypothesis that in patients with a clinical diagnosis of familial hypercholesterolemia (FH), genetic testing and identification of a causative mutation might enhance the success of family-based cascade screening.
Detailed description
To examine the impact of genetic testing on the efficiency of cascade screening for FH, patients with suspected FH or a clinical diagnosis of FH have been randomized to genetic testing or standard of care with lipid testing alone. After systematic encouragement of family enrollment, as a primary endpoint, the compared the number of probands with relatives enrolled in each group one year after results were returned to probands. The secondary endpoints examined include the number of relatives enrolled within 52 weeks of the genetic counseling call and the number of relatives diagnosed with FH through the study. Exploratory subgroup analyses were conducted stratifying the cohort by randomization/genetic test result. Further exploratory analyses compared probands' perceptions about high cholesterol diagnosis at baseline and at 20 weeks from enrollment
Interventions
OTHERStandard of Care
Randomized to standard of care with lipid testing only.
OTHERGenetic Testing
Randomized to genetic testing.
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Probands were randomized 2:1 to genetic testing for FH plus lipid testing or lipid testing alone
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For probands, inclusion criteria are as follows: 1. LDL cholesterol \> 220 mg/dL or a previous clinical diagnosis of FH 2. Aged 18 years or older 3. Ability to provide informed consent 4. Willingness/ability to contact a minimum of 2 biological relatives about the study
Exclusion criteria
* For family members of probands, inclusion criteria are as follows: 1. Willingness to participate in the study 2. Age 10 or older 3. Ability to give informed consent/assent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of probands with relatives enrolled | 52 weeks after genetic/lipid testing results are returned to probands | The primary outcome of this study was the number of probands with family members enrolled in the study within 52 weeks of results being returned to probands. Investigators compared the proportion of probands with a relative enrolled in the genetic testing group with the proportion of probands with a relative enrolled in the usual care group (lipid testing only). Relative enrolment was defined as the return of a test kit within the study time frame. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The number of relatives enrolled in the study 52 weeks after results were returned to probands | 52 weeks after results are returned to probands | The number of relatives enrolled in the study within 52 weeks of results being returned to probands. Investigators compared the number of relatives enrolled in the genetic testing group with the number of relatives enrolled in the usual care group (lipid testing only). Relative enrolment was defined as the return of a test kit within the study time frame. |
| The number of family members diagnosed with FH 52 weeks after results were returned to probands | 52 weeks after results are returned to probands | The number of family members diagnosed with FH within 52 weeks of results being returned to probands. Investigators compared the number of enrolled relatives diagnosed with FH in the genetic testing group with the number of enrolled relatives diagnosed with FH in the usual care group (lipid testing only). This diagnosis had to be made through the study. The number of enrolled relatives diagnosed with FH in each group was expressed as the new case per index case ratio (relatives diagnosed with FH/total number of index case). Relative enrolment was defined as the return of a test kit within the study time frame. The diagnosis of FH was based on meeting either genetic or the Make Early Diagnosis To Prevent Early Deaths (MEDPED) clinical criteria |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proband perceptions about their high cholesterol including its etiology, management and heritability at 20 weeks after enrollment compared to baseline | 20 weeks after enrollment | Proband perceptions about their high cholesterol including its etiology, management and heritability were examined at baseline and 20 weeks after enrollment, using a questionnaire administered at these time points. Investigators examined proband agreement/disagreement with statements about the etiology of their high cholesterol, its management and heritability in these questionnaires. Using this approach, investigators were able to determine the proportion of probands that agreed/disagreed with these statements, and could compare how these proportions differed between the groups of interest at baseline/follow-up and how these changed from baseline to follow-up. |
Outcome results
None listed