Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia (IFIGhTFH)

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.

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

Participants with suspected FH (LDL-C greater than 220 mg/dL) or a previous clinical diagnosis of FH and randomized to standard of care with lipid testing only.

Participants with suspected FH (LDL-C greater than 220 mg/dL) or a previous clinical diagnosis of FH randomized to genetic testing

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.

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 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

Proband perceptions about their high cholesterol including its etiology, management and heritability at 20 weeks after enrollment compared to baseline

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.

Inclusion Criteria: For probands, inclusion criteria are as follows: LDL cholesterol > 220 mg/dL or a previous clinical diagnosis of FH Aged 18 years or older Ability to provide informed consent 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: Willingness to participate in the study Age 10 or older Ability to give informed consent/assent

IRB approval to share IPD was not obtained for this protocol at the time of the initial protocol submission. If this should be required as part of the peer review process, or after publication of the study results and application will be submitted for a protocol amendment to fulfill this request

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