Familial Hypercholesterolemia in the United States: Evaluating a Centralized Cascade Screening Model to Improve Early Diagnosis
Abstract
FY20 PRMRP Topic Area and Area of Encouragement: The proposed project relates to the topic area of Familial Hypercholesterolemia and Area of Encouragement of “Research to improve early diagnosis of familial hypercholesterolemia (FH) and the implementation of diagnostic tools, including in the pediatric population.” The diagnostic tool being implemented in this proposal is cascade screening. Cascade screening is the process of screening family members once a person is diagnosed with FH in order to identify others who may be affected. This approach can identify both adults and children early in life, allowing for earlier treatment with cholesterol lowering therapies and reductions in the risk of heart disease. Problem to Be Addressed: FH is a genetic condition, affecting about 1 in every 250 individuals. Because FH is caused by a dominant gene, it runs in families. If a person has FH, there is a 50% chance that each of their children will also inherit the gene. People with FH have extremely high low density lipoprotein-cholesterol (LDL-C, aka “bad cholesterol”) from birth, which dramatically increases their risk of atherosclerotic cardiovascular disease (ASCVD) at a young age. ASCVD is cardiovascular disease as a result of cholesterol deposits in the arteries and includes heart attack, angina, the need for stents and bypass surgery, stroke, and even sudden cardiac death. Fortunately, treatment with cholesterol-lowering drugs can significantly reduce this risk. Unfortunately, less than 15% of people with FH in the U.S. have been identified, despite the efforts of the Centers for Disease Control and Prevention (CDC) to prioritize FH for early detection, cascade screening, and proactive treatment with cholesterol-lowering drugs. Furthermore, people with FH and their families have recognized the missed opportunities when families are not screened for FH: • “3 of my family members would be alive,” – woman with FH. • “I would like to think if my husband was tested after his father had a stroke/died that we wouldn’t be dealing with the level of damage he has now @ 47. Instead, he didn’t start meds till about 33. His brother still hasn’t been tested as he doesn’t want to know!” – spouse of an FH patient. • “I would have sought treatment sooner and I would have had my children tested sooner if I d known. My father had never heard of FH. He was just told he had high cholesterol like a lot of men in their 50s when he was first diagnosed. I also tested high 10 years ago but figured it was a fluke and did nothing. It s only recently that I was retested and was diagnosed with FH…. I feel like there have been a lot of missed opportunities on behalf of medical professionals who should know better.” – woman with FH. In contrast, a successful national FH screening approach in the Netherlands detected over 70% of people with FH. We refer to this approach as the Dutch model. The key components of the Dutch model were centralized coordination of family outreach and patient engagement outside of usual healthcare settings by their “Foundation for Tracing FH.” These efforts were found to be cost-effective and led to early treatment for individuals with FH, reducing their risk of heart attack to levels similar to the general population. The centralized Dutch model is promising but has not yet been tested widely in the U.S. There is an urgent need to establish an effective cascade screening approach in the U.S. in order to systematically identify affected family members once a person has been diagnosed with FH. Otherwise, upwards of 1 million FH individuals will remain undiagnosed and undertreated, leaving them at high risk for heart attacks, the need for stents or bypass surgery, and early death. These consequences are not only devastating for families, but they are costly in terms of healthcare dollars and lost productivity, especially since heart disease caused by FH often strikes younger men, women, and even children. Research at a v
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110645
Entities
People
- Zahid Ahmad
Organizations
- United States Army
- University of Texas Southwestern Medical Center