Elsevier

American Heart Journal

Volume 167, Issue 3, March 2014, Pages 342-349.e17
American Heart Journal

Trial Design
Rationale and design of the familial hypercholesterolemia foundation CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia registry

https://doi.org/10.1016/j.ahj.2013.12.008Get rights and content

Background

Familial hypercholesterolemia (FH) is a hereditary condition caused by various genetic mutations that lead to significantly elevated low-density lipoprotein cholesterol levels and resulting in a 20-fold increased lifetime risk for premature cardiovascular disease. Although its prevalence in the United States is 1 in 300 to 500 individuals, <10% of FH patients are formally diagnosed, and many are not appropriately treated. Contemporary data are needed to more fully characterize FH disease prevalence, treatment strategies, and patient experiences in the United States.

Design

The Familial Hypercholesterolemia Foundation (a patient-led nonprofit organization) has established the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE FH) Registry as a national, multicenter initiative to identify US FH patients, track their treatment, and clinical and patient-reported outcomes over time. The CASCADE FH will use multiple enrollment strategies to maximize identification of FH patients. Electronic health record screening of health care systems will provide an efficient mechanism to identify undiagnosed patients. A group of specialized lipid clinics will enter baseline and annual follow-up data on demographics, laboratory values, treatment, and clinical events. Patients meeting prespecified low-density lipoprotein or total cholesterol criteria suspicious for FH will have the opportunity to self-enroll in an online patient portal with information collected directly from patients semiannually. Registry patients will be provided information on cascade screening and will complete an online pedigree to assist with notification of family members.

Summary

The Familial Hypercholesterolemia Foundation CASCADE FH Registry represents a novel research paradigm to address gaps in knowledge and barriers to comprehensive FH screening, identification, and treatment.

Section snippets

Background

Familial hypercholesterolemia (FH) is a common genetic condition that affects all racial and ethnic groups1 and results in severely elevated levels of low-density lipoprotein cholesterol (LDL-C) from fetal life and concomitant elevated risk of premature cardiovascular disease. It is estimated that >600,000 people in the United States have FH, yet <10% are aware of their condition.2, 3 Of those who are diagnosed, many do not reach recommended treatment targets. A US-based FH registry is needed

Registry objectives

The FH Foundation CASCADE FH Registry has the following 4 specific objectives: (1) To promote awareness of FH prevalence, risk factors, and optimal disease management through education at both the patient and provider level; (2) To identify and enroll heterozygous and homozygous FH patients through clinic- and health care organization–based, community-based, and family-based screening initiatives to track therapy, patient-reported outcomes, and clinical outcomes over time; (3) To evaluate

Discussion

The Centers for Disease Control Office of Public Health Genomics recently categorized FH as a Tier 1 condition for cascade screening, with application of NICE clinical guidelines recommended as the highest level of evidence based on analytic validity and clinical utility.24 As the only active US-based registry for FH, the CASCADE FH Registry aims to promote implementation of cascade screening, more timely disease identification, and optimal therapeutic management to improve the clinical

Conclusions

The unique, innovative features of CASCADE FH will serve to both optimize the FH patient experience and to demonstrate the feasibility and benefit to patients of a large, well-designed registry. The CASCADE FH will use 2 complementary enrollment pathways to maximize inclusivity and create a sustainable model for comprehensive patient screening and identification of all FH patients who wish to participate. Because of the strong genetic component, FH as a disease state represents a unique

Disclosures

The CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia Registry is sponsored by the Familial Hypercholesterolemia Foundation, South Pasadena, CA.

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