Genomics Implementation

More Detailed Information on Key Tier 1 Applications - Familial Hypercholesterolemia

People with familial hypercholesterolemia (FH) have very high cholesterol levels caused by an inherited genetic condition. High concentrations of low-density lipoprotein (LDL) in the blood are present from birth and may lead to early development of coronary heart disease (CHD) or atherosclerosis. The disease is inherited in an autosomal dominant pattern; siblings and children of an individual with FH have a 50% risk of inheriting the predisposing mutation. Therapeutic lifestyle changes, including changes in diet and exercise, are highly recommended in patients with FH. However, lipid-lowering drug therapy is usually also needed in adult patients and more intensive therapy may also be required. For more information about FH, especially about FH Tier 1 applications, please see the FH education outreach section.

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What is the Tier 1 recommendation?

According to the National Institute for Health and Care Excellence (NICE) FH recommendation

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(NICE Clinical Guideline 71 – Identification and Management of Familial Hypercholesterolemia),
Cascade screening using cholesterol testing with or without DNA analysis should be conducted on relatives of affected persons with FH in order to identify previously unknown cases of FH and provide those people with life-saving treatment. Specifically, the NICE guidelines recommend:

1.2 Identifying people with FH using cascade testing consistent with the NICE recommendation

1.2.1 Healthcare professionals should use systematic methods (that is, cascade testing) for the identification of people with FH.

1.2.2 Healthcare professionals should offer all people with FH a referral to a specialist with expertise in FH for confirmation of diagnosis and initiation of cascade testing.

1.2.3 Healthcare professionals with expertise in FH should explain what is meant by cascade testing, and discuss its implications with all people with FH.

1.2.4 Cascade testing using a combination of DNA testing and LDL-C concentration measurement is recommended to identify affected relatives of those index individuals with a clinical diagnosis of FH. This should include at least the first- and second- and, when possible, third-degree biological relatives.

1.2.5 In families in which a mutation has been identified, the mutation and not LDL-C concentration should be used to identify affected relatives. This should include at least the first- and second- and, when possible, third-degree biological relatives.

1.2.6 In the absence of a DNA diagnosis, cascade testing using LDL-C concentration measurements should be undertaken to identify people with FH.

1.2.7 To diagnose FH in relatives of an index individual, the gender- and age-specific criteria for LDL-C concentration…[provided as an appendix to the guideline]…should be used.

1.2.8 The use of a nationwide, family-based, follow-up system is recommended to enable comprehensive identification of people affected by FH.

1.2.9 Healthcare professionals should be aware of the latest guidance on data protection when undertaking cascade testing.

In addition, the USPSTF recommendation for lipid disorders is useful as a means to ascertain cases of FH even though it does not specifically target FH.

Screening for Lipid Disorders in Adults Recommendation from USPSTF:

Screening Men:
The USPSTF strongly recommends screening men aged 35 or older for lipid disorders.
Grade: A recommendation
The USPSTF recommends screening men aged 20 to 35 for lipid disorders if they are at increased risk for coronary heart disease.
Grade: B recommendation

Screening Women at Increased Risk:
The USPSTF strongly recommends screening women aged 45 or older for lipid disorders if they are at increased risk for coronary heart disease.
Grade: A recommendation
The USPSTF recommends screening women aged 20 to 45 for lipid disorders if they are at increased risk for coronary heart disease.
Grade: B recommendation

Increased risk, for the purposes of this recommendation, is defined by the presence of any one of several risk factors, with the greatest risk for CHD conferred by a combination of multiple risk factors. Included among the risk factors sufficient to indicate increased risk is a family history of cardiovascular disease before age 50 in male relatives or 60 in female relatives.

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What can be gained through public health action?

FH is the most commonly inherited cause of premature CHD among people of European descent. Approximately 1 out of every 500 people in the United States, or an estimated 600,000, has FH due to a mutation in the LDL receptor (LDLR), apolipoprotein B (APOB) or other gene which affects cholesterol clearance. Unfortunately, FH remains significantly underdiagnosed. However, FH cases can be effectively identified using cascade testing, and early detection and treatment can help reduce the risk for CHD and death in these patients.

Research has shown that cascade testing for FH can be highly cost-effective

. This method has a number of other benefits, including decreasing the average age at diagnosis and increasing the percentage of people with FH receiving appropriate treatment.

Interventions relating to Tier 1 FH involve public health working with medical providers and payers to identify relatives through cascade screening so that their health care system can screen relatives and treat affected individuals early before disease progression can occur.

A word about high-risk populations:

Familial hypercholesterolemia occurs more frequently in certain populations, including Afrikaners, French Canadians, Lebanese Christians and Ashkenazi Jews.

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What specifically can state and local public health do?

Public health Interventions for Tier 1 FH applications involve public health departments working with and providing information to medical providers and payers that facilitate actions to identify individuals and families at risk so that their health care system can screen and/or provide medical service options to them early, before the harms and expense of disease progression can occur. Since public health departments operate with limited resources, any actions have a greater chance of success if one or more criteria are met including low or reasonable cost; measurable impact; and evidence- based/cost- effective approach. States can now consider one or more of four major approaches to FH including: 1) providing information to policy makers so that they can make informed decisions about ascertainment and treatment issues; 2) surveillance indicators development and tracking to follow progress; 3) educational outreach targeting the public and health professional groups seeing patients who might be impacted by FH Tier 1 recommendation; and 4) cascade screening from diagnosed FH patients to their first-, second- and, when possible, third- degree relatives. While the challenges and opportunities within each state differ, success of any of these efforts requires the establishment of strong partnerships between public health and providers and payers within each state’s boundaries.

Public health approaches to FH can contribute to general heart disease reduction goals. Likewise, public health work toward general heart disease goals offers ready opportunities for integrating FH. For example, according to the CDC Division of Heart Disease and Stroke Prevention (DHDSP) public health departments can work to prevent and control high blood cholesterol and reduce the burden of heart disease and stroke by promoting activities that can be implemented in healthcare, work sites, communities, and schools.A state program might:

Promote policy development, training, and system changes (e.g., electronic medical records, automated prescription systems, and paper or electronic reminders) to assist health care practitioners to adhere to treatment protocols consistent with national guidelines for preventing and controlling high blood cholesterol;
Partner with organizations to assure that detection and follow-up services are available for controlling high cholesterol in various settings, including health care, work site, and community;
Promote the use of clinical care teams that include health educators to assure consistent screening, detection, risk-factor education, medication monitoring, and follow-up to prevent and control high blood cholesterol;
Educate the public using simple and frequent messages that high blood cholesterol is a major modifiable risk factor for heart disease and stroke, and that having one’s blood cholesterol checked is an important first step in identifying and controlling high blood cholesterol and reducing the risk of heart disease and stroke;
Collaborate on professional medical education, self-care workshops, policy interventions, and incentives to improve detection and control of high blood cholesterol;
Encourage health care insurance coverage for blood cholesterol screening, treatment and control, as well as rehabilitation services for heart attack and stroke survivors;
Partner with other agencies to establish organizational policies and environmental interventions that support healthy lifestyles including access to screening, low-cost healthy food choices, smoke-free facilities, stress management options, and places for physical activity.

Specifically related to FH, public health practitioners may choose to use this information regarding FH to support public health activities in cardiovascular disease prevention programs, public health workforce development, and surveillance, such as:

Incorporating the NICE guidelines into existing public health programs focused on promoting cardiovascular disease awareness and screening, including educational activities for consumers and providers.
Conducting workforce training to increase awareness of the importance of referral for genetic counseling and evaluation for FH genetic testing in appropriate cases, according to the NICE recommendations.
Conducting workforce training to increase awareness of the importance of asking about family history of cardiovascular disease in evaluating risk for FH among healthy individuals in the general population.
Identifying those healthcare facilities with the existing infrastructure to implement genetic counseling and testing for FH for all people with appropriate clinical and family histories. Distribute information about availability of cardiovascular disease-focused board-certified genetic counselors to primary care providers.
Developing curricula for genetic counselors about FH and other cardiovascular disease and developing curricula about genetics/genomics for lipidologists.
Encouraging interaction among geneticists/genetic counselors/lipidologists/preventive cardiologists.
Developing mechanisms to monitor rates of genetic testing being conducted on individuals at risk.
Evaluating disparities in access to genetic counseling and testing for FH.