516 hot topic(s) found with the query "Familial hypercholesterolemia"
Family cascade screening for equitable identification of familial hypercholesterolemia: study protocol for a hybrid effectiveness-implementation type III randomized controlled trial
(Posted: Apr 19, 2024 10AM)
From the abstract: " Familial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap. In pilot work, we leveraged best practices from behavioral economics and implementation science—including mixed-methods contextual inquiry with clinicians, patients, and health system constituents—to co-design two patient-facing implementation strategies to address this care gap..."
Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States.
Vivienne Souter et al. Circ Genom Precis Med 2024 3 e004457
(Posted: Mar 21, 2024 7AM)
From the abstract: "Familial hypercholesterolemia is a treatable genetic condition but remains underdiagnosed. We reviewed the frequency of pathogenic or likely pathogenic (P/LP) variants in the LDLR gene in female individuals receiving reproductive carrier screening. This retrospective observational study included samples from female patients (aged 18–55 years) receiving a 274-gene carrier screening panel. P/LP LDLR variants were identified in 283 samples (1 in 324). No patients were identified with >1 P/LP variant. LDLR carrier frequency was higher in Asian (1 in 191 [95% CI, 1 in 142–258]) compared with White (1 in 417 [95% CI, 1 in 326–533]; P<0.001) or Black groups (1 in 508 [95% CI, 1 in 284–910]; P=0.004). "
Heart Disease Risk Higher with Genetic Variant Plus Even Slightly Elevated Cholesterol
Inside Precision Medicine, February 2, 2023
(Posted: Feb 03, 2024 8AM)
From the article: " Even people with moderately elevated low-density lipoprotein cholesterol (LDL-C) have higher risk of heart disease if they also had a variant for familial hypercholesterolemia (FH), according to new research. The long-term study included over 20,000 patients and reinforces the value of genetic testing for this condition."
Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol
Y Zhang et al, JAMA Cardio, January 31, 2023
(Posted: Feb 01, 2024 9AM)
From the abstract: "How do familial hypercholesterolemia (FH) genetic variants modify coronary heart disease (CHD) risk among adults with moderate (LDL-C 130-189 mg/dL) and severe (LDL-C=190 mg/dL) hypercholesterolemia? In this pooled cohort study of 21?426 participants followed up with for a median of 18 years, FH variants were associated with a 2-fold higher CHD risk, even among individuals with moderately elevated LDL-C. The increased CHD risk appeared to be largely explained by the substantially higher lifetime cumulative LDL-C exposure in those with an FH variant vs those without. The findings suggest that genetic testing for FH may help refine risk stratification beyond LDL-C alone; clinical research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening. "
Cost-Effectiveness of Screening Strategies for Familial Hypercholesterolaemia: An Updated Systematic Review.
Clara Marquina et al. Pharmacoeconomics 2024 1
(Posted: Jan 30, 2024 10AM)
From the abstract: "A total of 21 studies evaluating 62 strategies were included in this review, most of the studies (95%) adopted a healthcare perspective in the base case, and majority were set in high-income countries. Strategies analysed included cascade screening (23 strategies), opportunistic screening (13 strategies), systematic screening (11 strategies) and population-wide screening (15 strategies). Most of the strategies relied on genetic diagnosis for case ascertainment. Based on reported willingness to pay thresholds for each setting, most CEA studies concluded that screening for FH compared with no screening was cost-effective, regardless of the screening strategy. Cascade screening resulted in the largest health benefits per person tested. "
Secondary (additional) findings from the 100,000 Genomes Project: disease manifestation, healthcare outcomes and costs of disclosure
J Nolan et al, Genetics in Medicine, December 19, 2023
(Posted: Dec 20, 2023 9AM)
From the abstract: "The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia, von Hippel-Lindau. Here we report disclosure processes, manifestation of AF-related disease, outcomes and costs. "
First trial of 'base editing' in humans lowers cholesterol - but raises safety concerns.
Miryam Naddaf et al. Nature 2023 11
(Posted: Nov 14, 2023 9AM)
From the paper: "The first trial in humans of the precise gene-editing technique known as base editing has shown promising results for keeping cholesterol levels in check in patients with familial hypercholesterolemia. The approach injects into people a treatment called VERVE-101, which permanently deactivates a gene in the liver called PCSK9. That gene controls the level of low-density lipoprotein (LDL), or ‘bad’ cholesterol — a key contributor to heart disease. But the findings have also drawn criticism. Two serious adverse events in the trial, including a death, have raised safety concerns. "
Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis.
Nadeem Qureshi et al. Health Technol Assess 2023 11 (16) 1-140
(Posted: Nov 07, 2023 0PM)
From the abstract: "Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective. "
Population screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon
TD O'Brien et al, AJHG, July 27, 2023
(Posted: Jul 30, 2023 10AM)
The Healthy Oregon Project (HOP) is a statewide effort that aims to build a large research repository and influence the health of Oregonians through providing no-cost genetic screening to participants for a next-generation sequencing 32-gene panel comprising genes related to inherited cancers and familial hypercholesterolemia. Overall, we have identified 730 pathogenic/likely pathogenic variants in 710 participants in 24 of the 32 genes on the panel. The carrier rate for pathogenic/likely pathogenic variants in the inherited cancer genes on the panel for an unselected population was 5.0% and for familial hypercholesterolemia was 0.3%.
Still "on the Fence" About Universal Childhood Lipid Screening: The USPSTF Reaffirms an I Statement.
Sarah D de Ferranti et al. JAMA 2023 7 (3) 225-227
(Posted: Jul 21, 2023 9AM)
As in 2007 and in 2016, the task force again finds evidence insufficient to recommend for, or against, screening for lipid disorders in childhood, including both genetic conditions such as FH and secondary multifactorial lipid disorders—an I statement. This USPSTF recommendation is anchored in uncertainty about long-term benefits and safety of screening for, identifying, and treating childhood lipid disorders and uncertainty about the optimal age to start lipid-lowering therapy (ie, in childhood vs adulthood). At the crux of the controversy is the distinction between childhood screening for FH and general childhood lipid screening, as the latter will predominantly identify secondary lifestyle-related lipid abnormalities.
Screening for Lipid Disorders in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
Janelle M Guirguis-Blake et al. JAMA 2023 7 (3) 261-274
(Posted: Jul 21, 2023 9AM)
Lipid screening in childhood and adolescence can lead to early dyslipidemia diagnosis. The long-term benefits of lipid screening and subsequent treatment in this population are uncertain. We reviewed benefits and harms of screening and treatment of pediatric dyslipidemia due to familial hypercholesterolemia (FH) and multifactorial dyslipidemia. We found no direct evidence on the benefits or harms of pediatric lipid screening was identified. While multifactorial dyslipidemia is common, no evidence was found that treatment is effective for this condition. In contrast, FH is relatively rare; evidence shows that statins reduce lipid levels in children with FH, and observational studies suggest that such treatment has long-term benefit for this condition.
Public attitudes challenge clinical practice on genetic risk disclosure in favour of healthcare-provided direct dissemination to relatives
A Rosen et al, EJHG, July 20, 2023
(Posted: Jul 20, 2023 7AM)
Germline genetic testing often has implications not only for the individual patient but also for their genetic relatives. This is especially true for high-penetrance pathogenic variants associated with conditions such as familial hypercholesterolemia and hereditary cancer risk syndromes like Lynch syndrome and the hereditary breast and ovarian cancer syndrome. For these conditions, targeted prevention programs are available, and cascade screening is cost-effective. It is therefore highly relevant to find effective strategies to disclose information from the genetic investigation to healthy relatives at risk. Informing relatives at risk enables equitable access to pre-test genetic counselling and a possibility for them to make an informed decision about genetic testing as well as prevention.
Lipid Disorders in Children and Adolescents: Screening
USPSTF recommendation, July 18, 2023
(Posted: Jul 18, 2023 0PM)
Familial hypercholesterolemia (FH) and multifactorial dyslipidemia are 2 conditions that cause abnormally high lipid levels in children, which can lead to premature cardiovascular events (eg, myocardial infarction and stroke) and death in adulthood. The prevalence of FH in US children and adolescents ranges from 0.2% to 0.4% (1 of every 250 to 500 children and adolescents). Multifactorial dyslipidemia is much more common than FH, with prevalence in children and adolescents ranging from 7.1% to 9.4%. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger.
Familial hypercholesterolaemia
S McErlean, BMJ, July 2023
(Posted: Jul 16, 2023 9AM)
Familial hypercholesterolemia is a common genetic condition affecting 1 in 310 people, resulting in premature coronary artery disease due to elevated cholesterol levels from birth If a parent has familial hypercholesterolemia, there is a 50% chance their child will inherit the condition. Treatment is based on lowering low density lipoprotein (LDL) cholesterol concentration, with a target of at least 50% reduction from baseline.
The Promise of Population-based Genomic Screening for Selected Hereditary Conditions: Contributions of Cost-Effectiveness Analysis
ND Rao et al, CDC Blog Post, July 14, 2023
(Posted: Jul 14, 2023 1PM)
Initial cost-effectiveness research suggests that simultaneous population genomic screening for three CDC Tier 1 genomic applications (hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia) can be cost effective and reduce morbidity and mortality if implemented in adults younger than 40 years old, costs of screening tests are low, and those found carrying a pathogenic variant have access to preventive care.
Yield of Familial Hypercholesterolemia Genetic and Phenotypic Diagnoses After Electronic Health Record and Genomic Data Screening.
Samuel S Gidding et al. J Am Heart Assoc 2023 6 e8572
(Posted: Jun 30, 2023 11AM)
Applying 2 recognized FH screening algorithms to the Geisinger MyCode Community Health Initiative identified 70% of those with a pathogenic or likely pathogenic FH variant. Phenotypic diagnosis was rarely achievable due to missing data.
Summary for Patients: Population Genomic Screening for Three Common Hereditary Conditions.
et al. Ann Intern Med 2023 5 (5) I19
(Posted: Jun 02, 2023 9AM)
Patients who have certain genetic test results are at higher risk for diseases that may be preventable. There is ongoing debate about whether physicians should screen for 3 hereditary conditions: Lynch syndrome (at greater risk for colon cancer), hereditary breast and ovarian cancer, and familial hypercholesterolemia (at greater risk for early heart disease and stroke). This modeling study found that screening for these 3 hereditary conditions is likely cost-effective in U.S. adults younger than 40 years if the testing cost is relatively inexpensive and people have access to preventive care.
Clinician Perspectives on Clinical Decision Support for Familial Hypercholesterolemia
H Bangash et al, J Per Med, May 31, 2023
(Posted: May 31, 2023 7AM)
We deployed CDS for FH at an academic medical center and sought clinician insights using an implementation survey. In November 2020, the FH CDS was deployed in the electronic health record at all Mayo Clinic sites in two formats: a best practice advisory (BPA) and an in-basket alert. Over three months, 104 clinicians participated in the survey (response rate 11.1%). Most clinicians (81%) agreed that CDS implementation was a good option for identifying FH patients; 78% recognized the importance of implementing the tool in practice, and 72% agreed it would improve early diagnosis of FH.
Screening for 3 Genetic Conditions Is Cost-effective in Younger People.
Emily Harris et al. JAMA 2023 5
(Posted: May 24, 2023 9AM)
One-time screening of young adults for 3 conditions—Lynch syndrome, hereditary breast and ovarian syndrome, and familial hypercholesterolemia—would likely be cost-effective compared with only testing patients deemed “high-risk” because of their family histories, according to an analysis of hypothetical cohorts of 100?000 people aged 20 to 60 years. Based on the accepted guideline that interventions priced at no more than $100?000 per quality-adjusted life-year are cost-effective, screening a 30- or 40-year-old person would be worthwhile if the test cost less than $413 or $290, respectively. Assuming a genetic test cost of $250, screening 50-year-old patients would not be cost-effective.
Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.
Gregory F Guzauskas et al. Ann Intern Med 2023 5
(Posted: May 09, 2023 5AM)
The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.
We estimated the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). We found that population genomic screening with a restricted panel of high-evidence genes is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.
Familial Hypercholesterolemia: The Atlantic Divide.
Samuel S Gidding et al. J Pediatr 2022 9
(Posted: May 05, 2023 6AM)
Recommendations have existed since the 1990s to screen for familial hypercholesterolemia and initiate treatment early in life, but uptake has been poor worldwide. Two recent call attention to the fundamental differences in approach to familial hypercholesterolemia care across the Atlantic and barriers to further progress in familial hypercholesterolemia identification globally.
New Family Heart Foundation Study Reveals Systemic Underdiagnosis & Undertreatment of HoFH
Family Heart Foundation, May 2, 2023
(Posted: May 04, 2023 8AM)
A new study showed the diagnosis and treatment of homozygous familial hypercholesterolemia (HoFH) is delayed, and often occurs after a heart attack or early atherosclerotic cardiovascular disease (ASCVD). HoFH is a rare disease and is the most severe form of the common inherited genetic disorder called familial hypercholesterolemia (FH). HoFH leads to severely elevated low density lipoprotein cholesterol (LDL-C) from birth onward. While some with the highest LDL-C are diagnosed with HoFH in childhood, many others are missed, denying them the opportunity for timely initiation of aggressive lipid-lowering therapies (LLT) and resulting in premature cardiovascular disease.
Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry.
Marina Cuchel et al. J Am Heart Assoc 2023 4 e029175
(Posted: May 02, 2023 8AM)
Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.
Cost-effectiveness and Return on Investment of a Nationwide Case-Finding Program for Familial Hypercholesterolemia in Children in the Netherlands.
Zanfina Ademi et al. JAMA Pediatr 2023 5
(Posted: May 02, 2023 8AM)
In this economic evaluation of a hypothetical population of 1000 FH children aged 10 years, nationwide case finding was associated with saved lives and improved quality of life over a lifetime. The incremental cost-effectiveness ratio for cascade screening and initiation of treatment with statins in children vs later detection and treatment was €9220 ($10?050) per quality-adjusted life-year gained, that from a health care perspective and a societal perspective was cost saving and the return on investment for the detection and treatment program for FH in children was €8.37 ($9.12).
Optimizing communication strategies and designing a comprehensive program to facilitate cascade testing for familial hypercholesterolemia.
Gemme Campbell-Salome et al. BMC health services research 2023 4 (1) 340
(Posted: Apr 07, 2023 8AM)
We aimed to optimize communication strategies to support family communication about familial hypercholesterolemia (FH) and improve cascade testing uptake among at-risk relatives. Individuals and families with FH provided feedback on multiple strategies including: a family letter, digital tools, and direct contact.
Feedback from participants was collected via dyadic interviews (n = 11) and surveys (n = 98) on communication strategies and their proposed implementation to improve cascade testing uptake. We conducted a thematic analysis to identify how to optimize each strategy.
Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis.
Noel Peretti et al. The Journal of pediatrics 2022 9
(Posted: Mar 16, 2023 1PM)
How Can Implementation Science Improve the Care of Familial Hypercholesterolaemia?
Mitchell Sarkies et al. Current atherosclerosis reports 2023 2
(Posted: Feb 25, 2023 6AM)
Gaps between evidence and practice, such as underutilization of genetic testing, family cascade testing, failure to achieve LDL-cholesterol goals and low levels of knowledge and awareness, have been identified through clinical registry analyses and clinician surveys. Implementation science theories, models and frameworks have been applied to assess barriers and enablers in the literature specific to local contextual factors (e.g. stages of life).
Know Your Risk for High Cholesterol
CDC Information, February 2023
(Posted: Feb 08, 2023 9AM)
Some people have an inherited genetic condition called FH. This condition causes very high low-density lipoprotein (LDL, or “bad”) cholesterol levels beginning at a young age that, left untreated, continue to worsen with age. An estimated 1 million U.S. adults have confirmed or probable FH.1 Worldwide, about 1 in 313 people are estimated to have FH. If someone in your family has a heart attack early in life, talk with your health care team about your own and your other family members’ risk for FH and whether your family should get tested. Your health care team may talk with you about lifestyle changes you can make to help lower or manage your cholesterol levels. Often, though, FH can’t be treated with lifestyle changes alone. You may need medicine, such as statin therapy or other medicine, to manage your cholesterol levels.
Understanding how educational interventions improve treatment adherence in patients with familial hypercholesterolaemia: a systematic review
H Massey et al, J Community Genetics, December 13, 2022
(Posted: Dec 15, 2022 8AM)
Four themes were identified as important when using education to improve treatment adherence: involving family, patient empowerment, practical problem solving and use of information leaflets. Educational interventions improve short term treatment adherence in patients with FH. Successful interventions are those that involve the whole family, set practical problem solving tasks, and that use techniques to increase the patients self-efficacy.
Familial Hypercholesterolemia Screening in Children and Adolescents in the United States: Where Are We Heading?
M Clyne et al, CDC Blog Post, October 14, 2022
(Posted: Oct 14, 2022 10AM)
Familial Hypercholesterolemia (FH) is a genetic condition that results in elevated levels of low-density lipoprotein cholesterol (LDL-C) from birth, resulting in increased risk of heart disease and myocardial infarction. A 2021 blog from our office highlighted the prevalence of FH, diagnostic strategies, treatment management of those with FH, and the public health importance of identifying people with FH. The blog highlights the benefit of earlier age of diagnosis since recommendations for prevention of atherosclerotic cardiovascular disease (ASCVD) includes treatment to lower LDL-C at a younger age.
A pragmatic clinical trial of cascade testing for familial hypercholesterolemia.
Miller Alexandra A et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 9
(Posted: Sep 30, 2022 7AM)
We compared new cases detected per index case in familial hypercholesterolemia (FH) families with or without an identifiable monogenic etiology.
We enrolled 52 FH probands with a pathogenic variant (FHg+) in LDLR, APOB, or PCSK9 and 73 probands without such a variant (FHg–). New case detection rate was significantly higher in FH families with a monogenic etiology than in those without such an etiology owing to greater uptake and yield of cascade testing.
Personal Stories
Family Heart Foundation, September 2022
(Posted: Sep 24, 2022 7AM)
The Journey to Accepting My FH Diagnosis- “We lost her unexpectedly. From the outside, she had no indication something was wrong.” Charlotte was only 17 when her mother passed away from a heart attack. “She was so petite, and she lived a very stress-free life. She was radiant and active and you would have never known she had heart disease.”
FH Awareness Day is on September 24th
Family Heart Foundation, September 2022
(Posted: Sep 23, 2022 7AM)
Millions of people around the world do not know that they and their families are at severe risk for early heart disease, heart attacks, and even death. Seven out of ten people born today with familial hypercholesterolemia are undiagnosed. Yet, with early diagnosis and treatment, individuals diagnosed with FH can reduce their risk for heart disease by 70%. Together we can raise awareness, find every individual with FH, and prevent early heart disease.
Screening, diagnosis, and treatment of familial hypercholesterolaemia: a call to action.
Crea Filippo et al. European heart journal 2022 9 (34) 3185-3188
(Posted: Sep 09, 2022 8AM)
Familial hypercholesterolaemia (FH) is the most common inherited life-threatening metabolic disorder, affecting 1:300 individuals. In Europe, there are >500?000 children and 2?000?000 adults with FH. However, <5% of these children are identified and only a small fraction of all affected individuals receive life-saving treatment. Elevated LDL-cholesterol (LDL-C) levels in individuals with FH and consequent lifelong LDL-C exposure accelerate the process of atherosclerosis and lead to a 10 times excess risk of premature CVD morbidity and mortality
Universal screening for familial hypercholesterolemia in 2 populations.
Sustar Ursa et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 8
(Posted: Aug 03, 2022 6AM)
In Europe, >2 million individuals with familial hypercholesterolemia (FH) are currently undiagnosed. Effective screening strategies for FH diagnosis in childhood are urgently needed. We assessed the overall performances of 2 different FH screening programs in children: universal screening program with opt-out and opt-in type participation. Our study suggests that universal 3-step FH screening approach in children enabled detection of most children and their parents in every generation screened at reasonable costs. Opt-out screening strategy might be preferable over opt-in screening strategy.
Impact of a Population Genomic Screening Program on Health Behaviors Related to Familial Hypercholesterolemia Risk Reduction.
Jones Laney K et al. Circulation. Genomic and precision medicine 2022 101161CIRCGEN121003549
(Posted: Jul 26, 2022 9AM)
We conducted a retrospective cohort study of MyCode participants with an FH risk variant beginning 2 years before disclosure until January 16, 2019. We analyzed lipid-lowering prescriptions (clinician behavior), medication adherence (participant behavior), and LDL (low-density lipoprotein) cholesterol levels (health outcome impact) pre- and post-disclosure. Data were collected from electronic health records and claims. Despite disclosure of an FH risk variant, nonprescribing and nonadherence to lipid-lowering therapy remained high. However, when clinicians intensified medication regimens and participants adhered to medications, lipid levels decreased.
Lipoprotein (a)
CDC, June 29, 2022
(Posted: Jun 28, 2022 4PM)
High levels of lipoprotein (a) increase your likelihood of having a heart attack, a stroke, and aortic stenosis, especially if you have familial hypercholesterolemia or signs of coronary heart disease. High Lp(a) levels, defined as greater than 50 mg/dL (125 nmol/L),3 are common. Median Lp(a) levels vary by race and sex.4 High Lp(a) is seen in people of all races and ethnicities but appears to be more common in Black people.4 Many people with high Lp(a) have no symptoms. However, your doctor may suspect that you have high Lp(a) if you have one or more risk factors such as family history, familial hypercholesterolemia, peripheral artery disease and others.
A scoping review of interventions increasing screening and diagnosis of familial hypercholesterolemia.
Polanski Amanda et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 6
(Posted: Jun 18, 2022 11AM)
A total of 46 studies across 32 countries were included in the review. All studies were effective in increasing FH detection. In total, 12 different intervention types were extracted with the most used being cascade and electronic medical record screening-based interventions. Given the diversity of effective interventions identified in this review, future efforts could explore approaches that maximize identification through a combination of interventions. Our results support one such strategy that uses electronic medical records to screen for index cases and a 2-step indirect and direct contact method of index cases' relatives.
Incomplete Penetrance of Population-Based Genetic Screening Results in Electronic Health Record
G Elhanan et al, Frontiers in Genetics, April 2022
(Posted: May 26, 2022 7AM)
The clinical value of population-based genetic screening projects depends on the actions taken on the findings. The Healthy Nevada Project (HNP) is an all-comer genetic screening and research project based in northern Nevada. HNP participants with CDC Tier 1 findings of hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), or familial hypercholesterolemia (FH) are notified and provided with genetic counseling. However, the HNP subsequently takes a “hands-off” approach: it is the responsibility of notified participants to share their findings with their healthcare providers, and providers are expected to implement the recommended action plans.
Coronary Heart Disease, Family History and Public Health: From Familial Hypercholesterolemia to Elevated Lipoprotein A
CDC Public Health Genomics Webinar, October 24, 2022
(Posted: May 25, 2022 11AM)
Familial hypercholesterolemia (FH), a genetic disorder of cholesterol metabolism affecting millions of people, has emerged as public health genomics priority for preventing premature morbidity and mortality from heart disease. In addition, elevated lipoprotein (a) (Lp(a)) increases the risk of coronary heart disease, occur in 1 in 5 people, have a strong genetic basis, and accentuate the cardiovascular risk from FH and other risk factors. This seminar will explore advances in FH and Lp(a) and the emerging clinical and public health approaches to reducing the burden of cardiovascular disease using genetics and family history.
Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults
BK Bellows et al, JAHA, May 18, 2022
(Posted: May 19, 2022 10AM)
Individual clinical and genotype data from the UK Biobank were used to estimate the probability of any likely pathogenic familial hypercholesterolemia (FH) genetic variants. Dutch Lipid Clinic Network clinical criteria and the estimated probability of FH were applied to National Health and Nutrition Examination Survey participants to estimate the yield of FH screening in US adults. Clinical criteria-based screening alone could identify 3.7 FH cases per 1000 US adults screened, and adding genetic testing could increase this to 6.6 FH cases per 1000 adults screened.
Applying an LDL-C Threshold-Based Approach to Identify Individuals with Familial Hypercholesterolemia
R Jasani et al, J Clin Lipid, April 2022
(Posted: Apr 14, 2022 9AM)
Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. The optimal electronic health record (EHR) screening strategy for FH is unclear. The objective of this study was to evaluate an LDL-C threshold-based approach of identifying patients with FH from the EHR to determine the optimal LDL-C range for FH consideration. Among those with LDL-C = 190mg/dL, the prevalence of secondary causes increased markedly with higher LDL-C, while the diagnosis of FH has a parabolic relationship. Patients with intermediate LDL-C (220 – 299mg/dL) may be the optimal group to prioritize for FH screening.
Combining familial hypercholesterolemia and statin genetic studies as a strategy for the implementation of pharmacogenomics. A multidisciplinary approach
LR Cela et al, The PGX journal, March 31, 2022
(Posted: Apr 02, 2022 8AM)
We have implemented a new NGS strategy that combines a panel of genes related to familial hypercholesterolemia with genomic regions related to the pharmacogenomics of lipid-lowering drugs described in clinical practice guidelines and in EMA and FDA drug labels. A multidisciplinary team of doctors, biologists, and pharmacists creates a clinical report that provides diagnostic and therapeutic findings using a knowledge management and clinical decision support system, as well as an algorithm for treatment selection.
When You Have Both: Managing FH and High Lp(a)
Family Heart Foundation, March 29, 2022
(Posted: Apr 01, 2022 7AM)
Knowing you have two genetic conditions that can lead to early heart disease is not an easy thing to live with. I have days where I feel invincible, and I have days where I feel like a ticking time bomb. But one way to ease my anxieties is knowing I’m taking every step possible to take my health in my own hands. Luckily, I live in a time where multiple LDL lowering medications are available. In 1966, when my grandfather had his fatal heart attack at 30 years old, there weren’t even statins. I know taking my medicine and regularly seeing my lipid specialist gives me an advantage previous generations didn’t have.
Association of the Interaction Between Familial Hypercholesterolemia Variants and Adherence to a Healthy Lifestyle With Risk of Coronary Artery Disease
AC Fahed et al, JAMA Network Open, March 16, 2022
(Posted: Mar 17, 2022 9AM)
Is adherence to a healthy lifestyle associated with lower risk of coronary artery disease in carriers and noncarriers of pathogenic DNA variants in familial hypercholesterolemia–related genes? In a case-control study of 10?175 participants and cohort study of 39?920 participants, there was a significant risk gradient of coronary artery disease according to variant carrier and lifestyle categories. Estimated risk by the age of 75 years among variant carriers ranged from 35% for those with a favorable lifestyle to 66% for those with an unfavorable lifestyle.
Applying implementation science to improve care for familial hypercholesterolemia.
Jones Laney K et al. Current opinion in endocrinology, diabetes, and obesity 2021 11 (2) 141-151
(Posted: Mar 14, 2022 7AM)
Improving care of individuals with familial hypercholesteremia (FH) is reliant on the synthesis of evidence-based guidelines and their subsequent implementation into clinical care. This review describes implementation strategies, defined as methods to improve translation of evidence into FH care, that have been mapped to strategies from the Expert Recommendations for Implementing Change (ERIC) compilation. There were only 8 of 37 studies that utilized an implementation science theory, model, or framework and two that explicitly addressed health disparities or equity.
Clinical decision support for familial hypercholesterolemia (CDS-FH): Rationale and design of a cluster randomized trial in primary care.
Lindell Olof Persson et al. American heart journal 2022 2
(Posted: Feb 22, 2022 8AM)
Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder with high risk of premature atherosclerotic cardiovascular disease and death. Clinical decision support (CDS) systems have the potential to aid in the identification and management of patients with FH. Prior studies using computer-based systems to screen patients for FH have shown promising results, but there has been no randomized controlled trial conducted. The aim of the current cluster randomized study is to evaluate if a CDS can increase the identification of FH.
Newly Diagnosed: What to do when you’re newly diagnosed with Familial Hypercholesterolemia or High Lipoprotein(a)
Family Heart Foundation February, 2022
(Posted: Feb 20, 2022 7AM)
The diagnosis of familial hypercholesterolemia (FH) or high Lipoprotein (a), or Lp(a), can be very overwhelming. The first thing to do is take a deep breath… then maybe take another one. There are a lot of emotions and questions to sort through but know this – you are not alone. The Family Heart Foundation is here with the tools and resources you need to treat and manage your condition. The good news is that we are living in an extraordinary time of research and understanding of FH and high Lp(a). There are more treatments available now than ever before, and more are on the way. There is hope as we all strive for the same goal: More families. More hearts.
A Mini-Symposium: Implementing Precision and Equitable Public Health in Cascade Testing for Genetic Disorders
CDC event, Feb 10, 2022
(Posted: Dec 13, 2021 2PM)
While there are Tier 1 evidence-based guidelines supporting cascade testing for hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial hypercholesterolemia, and other genetic disorders, the focus is on whether such testing should be done, rather than how to implement cascade testing in practice, both effectively and equitably. Before the full potential health impact of cascade genetic testing can be reached, we must develop a much stronger understanding of which component procedures and practices work best, and then leverage those good practices toward delivering precision public health. This two-hour virtual mini-symposium will explore several efforts to better understand what works well in programs relevant to cascade testing for genetic disorders.
The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification
JR Chora et al, Genetics in Medicine, NOvember 30, 2021
(Posted: Dec 01, 2021 9AM)
The Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified.
Familial Hypercholesterolemia — Hiding in Plain Sight
L Sperling and K Wilemon, MEDSCAPE, October 21, 2021
(Posted: Oct 22, 2021 1PM)
The most common question we hear from the medical community is, if I'm treating someone's cholesterol, does it matter if I diagnose them with FH? And the resounding answer is yes. It matters for three reasons: One, because FH is different. It requires early diagnosis and early treatment to prevent early cardiovascular disease. Two, you never find only an individual with FH; you always find a family if you're looking. Three, FH is a prototype for precision medicine. We can identify those born at the highest risk for the number-one killer around the world before they develop disease. And with early diagnosis and management, we can completely change the trajectory of that individual's life and, really, the story of an entire family.
Case-finding and genetic testing for familial hypercholesterolaemia in primary care.
Qureshi Nadeem et al. Heart (British Cardiac Society) 2021
(Posted: Sep 21, 2021 9AM)
A novel case-finding tool (Familial Hypercholetserolemia Case Ascertainment Tool, FAMCAT1) was applied to the electronic health records of 86?219 patients with cholesterol readings (44.5% of total practices' population), identifying 3375 at increased risk of FH. Of these, a cohort of 336 consenting to completing Family History Questionnaire and detailed review of their clinical data, were offered FH genetic testing in primary care. Genetic testing was completed by 283 patients, newly identifying 16 with genetically confirmed FH and 10 with variants of unknown significance. All 26 (9%) were recommended for referral and 19 attended specialist assessment. In a further 153 (54%) patients, the test suggested polygenic hypercholesterolemia who were managed in primary care.
Perspectives on Identifying and Treating Familial Hypercholesterolemia in Childhood.
et al. Clinical chemistry 2021 9
(Posted: Sep 13, 2021 7AM)
The emphasis in the USA to date has been to screen for lipid disorders in general; there are no recommendations to screen children specifically for FH. Despite the public health importance of FH, and guideline recommendations for pediatric lipid testing, FH screening is not widely performed in pediatric practice, genetic testing has not yet been integrated into screening, and broad pediatric FH screening approaches have not been formally evaluated in the USA.
FH Awareness Day Toolkit 2021
The FH Foundation September 2021
(Posted: Sep 05, 2021 9AM)
FH Awareness Day was established in 2012 by the FH Foundation to raise awareness of familial hypercholesterolemia worldwide. This annual event is held on the September 24th, during National Cholesterol Education Month. Together, we raise our voices to help everyone #KnowFH.
Health Equity and Genetic Disorders
CDC, August 2021
(Posted: Sep 01, 2021 7AM)
Public health efforts to achieve health equity need to include people with genetic disorders. Thousands of inherited genetic disorders affect millions of people in the United States. Genetic disorders include both single-gene disorders, such as cystic fibrosis and sickle cell disease, and conditions that make people more likely to develop common chronic diseases, such as hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia.
Family Sharing Tools
The FH Foundation, July 2021
(Posted: Jul 21, 2021 7AM)
Learning that you have familial hypercholesterolemia (FH) is very different than learning that you simply have high cholesterol. Your diagnosis in not just “your diagnosis.” It is, simply put, your entire family’s diagnosis.
Acceptability, Appropriateness, and Feasibility of Automated Screening Approaches and Family Communication Methods for Identification of Familial Hypercholesterolemia: Stakeholder Engagement Results from the IMPACT-FH study
LK Jones et al, JPM June 21, 2021
(Posted: Jun 22, 2021 8AM)
Guided by the Conceptual Model of Implementation Research, we explored the acceptability, appropriateness, and feasibility of: (1) automated screening approaches utilizing existing health data to identify those who require subsequent diagnostic evaluation for familial hypercholesterolemia (FH) and (2) family communication methods including chatbots and direct contact to communicate information about inherited risk for FH. Focus groups were conducted with 22 individuals with FH (2 groups) and 20 clinicians (3 groups)
Familial hypercholesterolemia related admission for acute coronary syndrome in the United States: Incidence, predictors, and outcomes.
Kheiri Babikir et al. Journal of clinical lipidology 2021
(Posted: Jun 04, 2021 8AM)
Individuals with FH admitted for ACS were younger (median age 57 vs 69 y), had fewer comorbidities (hypertension 74.7% vs 79.6%; diabetes mellitus 30.5% vs 39.0%;p<0.01), were more likely to present with ST-elevation-myocardial infarction (32.8% vs 22.6%;p<0.01) and more likely to undergo multivessel percutaneous coronary intervention (11.4% vs 7.6%;p<0.01) than patients without FH. After propensity-score matching, FH patients more commonly experienced in-hospital VT arrest (11.8% vs 8.0%;p<0.01) and required more mechanical circulatory support (8.6% vs 3.3%; p<0.01). The 30-day readmission in those with FH was more frequently for cardiovascular disease (81.5% vs 46.5%; =p<0.01).
COVID-19 associated risks of myocardial infarction in persons with familial hypercholesterolemia with or without ASCVD
KD Myers et al, AJPM, May 25, 2021
(Posted: May 27, 2021 1PM)
Our analyses confirm that pre-existing ASCVD is associated with increased risk of acute myocardial infarction in the setting of COVID-19. Additionally, we establish that both diagnosed and probable FH are associated with increased risk for AMI in the setting of COVID-19. Critically, our data indicate that those with both ASCVD and FH are at very high risk of AMI if they contract COVID-19.
Limited-Variant Screening vs Comprehensive Genetic Testing for Familial Hypercholesterolemia Diagnosis
AC Sturm et al, JAMA Cardiology, May 26, 2021
(Posted: May 27, 2021 7AM)
In this cross-sectional review of comprehensive genetic test results for individuals with indications for familial hypercholesterolemia, a limited-variant screen was found to have a significantly lower detection rate (8.4%) than the comprehensive diagnostic test (27%).
Knowing More Than the Knowns in Familial Hypercholesterolemia
P Natarajan et al, JAMA Cardiology, May 26, 2021
(Posted: May 27, 2021 7AM)
A negative FH test result from direct-to-consumer array platforms is limited by reduced sensitivity to detect rare variants and poor curation of recurrent non-European mendelian variants. When FH is strongly clinical suspected, even if array-based FH reporting has negative results, a clinical genetic test should still be considered.
A randomized controlled trial of genetic testing and cascade screening in familial hypercholesterolemia
A Ajufo et al, Genetics in Medicine, May 26, 2021
(Posted: May 27, 2021 7AM)
We randomized 240 individuals with a clinical diagnosis of FH to genetic testing for FH (n?=?160) or usual care with lipid testing alone (n?=?80). We observed a low rate of family participation in cascade screening despite repeated recommendations to probands. Compared to usual care, genetic testing did not improve family participation in cascade screening for FH.
Use of commercial genetic testing to help reclassify LDL receptor variants in clinical practice: A case report
E Cabot et al, J Clin Lipidology, April 2021
(Posted: May 10, 2021 8AM)
A Global Call to Action – Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia
The FH Foundation, April 21, 2021
(Posted: Apr 28, 2021 8AM)
Healthcare systems around the world have failed to rescue individuals born with Familial Hypercholesterolemia (FH), even though we have had life-saving therapies for the last 34 years. Without the societal commitment to screen, diagnose, and manage FH, the opportunity to prevent heart disease and stroke for an entire generation has been lost.
New Research to Improve Screening for FH
The FH Foundation, April 27, 2021
(Posted: Apr 28, 2021 8AM)
A strategic imperative is to increase FH diagnosis and improve the rate of cascade screening. In addition to the progress we recently reported from the IMPACT FH study with Geisinger, we are proud to report the latest research that highlights the potential to improve cascade screening by utilizing direct contact of relatives through the FH Foundation.
Genetic basis of hypercholesterolemia in adults
S Saadatagah et al, NPJ Genomic Medicine, April 15, 2021
(Posted: Apr 16, 2021 6AM)
We studied 1682 individuals from southeast Minnesota with primary hypercholesterolemia. An identifiable genetic etiology was present in 17.1% individuals (monogenic in 1.5% and polygenic in 15.6%). Phenotypic and genetic FH showed poor overlap. Only 26% of those who met the clinical criteria of FH had an identifiable genetic etiology and of those with an identifiable genetic etiology only 12.9% met clinical criteria for FH.
Impact of diabetes on coronary severity and cardiovascular outcomes in patients with heterozygous familial hypercholesterolaemia.
Liu Ming-Ming et al. European journal of preventive cardiology 2021
(Posted: Apr 02, 2021 10AM)
Type 2 diabetes mellitus (T2DM) is an independent risk factor for cardiovascular disease. However, the association between T2DM and coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolaemia (HeFH) has not been thoroughly evaluated. Our study aimed to assess the effect of T2DM on CAD severity and hard cardiovascular endpoints in a HeFH cohort of 432 patients.
Massive data screening is a second opportunity to improve the management of patients with familial hypercholesterolemia phenotype.
Zamora Alberto et al. Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis 2021
(Posted: Feb 26, 2021 11AM)
Closing the gap: Identification and management of familial hypercholesterolemia in an integrated healthcare delivery system.
Birnbaum Richard A et al. Journal of clinical lipidology 2021 Feb
(Posted: Feb 19, 2021 10AM)
Despite availability of effective therapy, only 5-10% of affected individuals worldwide are diagnosed.To develop and evaluate a novel approach for identifying and managing patients with FH in a large integrated health system with a diverse patient population, using inexpensive methods. Using Make Early Diagnosis/Prevent Early Death (MEDPED) criteria, we created a method for identifying patients at high risk for FH within the Kaiser Permanente Northern California electronic medical record.
Announcing partnership with Alliance for Million Hearts Campaign
The FH Foundation January, 2021
(Posted: Feb 13, 2021 11AM)
The campaign is a new public-private coalition with the nation’s leading organizations and thought leaders to confront the nation’s leading cause of death – cardiovascular disease. The national campaign will focus on helping more people understand their risk for heart disease and stroke, believe in their power to take steps that lower their risks.
New Drug for Homozygous Familial Hypercholesterolemia Approved by the FDA
The FH Foundation, February 11, 2021
(Posted: Feb 13, 2021 10AM)
This new drug is an angiopoietin-like 3 (ANGPTL3) inhibitor. The target of this drug was discovered in people who have a “loss-of-function” in the gene encoding ANGPTL3, and as a result have very low LDL-C levels and low rates of cardiovascular disease. Evinacumab is a monoclonal antibody therapy that targets ANGPTL3, lowering LDL cholesterol by 47.1% on average (a reduction of more than 130 mg/dL) in a Phase 3 trial in people with HoFH.
How Common is Familial Hypercholesterolemia?
F Swann et al, CDC Blog Post, January 25, 2021
(Posted: Jan 27, 2021 8AM)
Whichever approach to early identification of those with familial hypercholesterolemia (FH) is taken, with over 1 million people in the United States and 25 million globally with FH and many of them undiagnosed, the public health burden of FH is increasingly clear.
Life by the Numbers: Living with Familial Hypercholesterolemia.
Walsh Casey Mulligan et al. Circulation. Genomic and precision medicine 2020 Dec
(Posted: Dec 11, 2020 8AM)
Evinacumab in Patients with Refractory Hypercholesterolemia.
Rosenson Robert S et al. The New England journal of medicine 2020 Dec (24) 2307-2319
(Posted: Dec 10, 2020 8AM)
In this double-blind, placebo-controlled, phase 2 trial, we enrolled 272 patients with or without heterozygous familial hypercholesterolemia who had refractory hypercholesterolemia. We found that the use of evinacumab significantly reduced the LDL cholesterol level, by more than 50% at the maximum dose.
Familial Hypercholesterolemia: A Reportable Disorder
I Kullo, Circulation, November 23, 2020
(Posted: Nov 24, 2020 8AM)
I make the case for designating FH as a reportable condition, allowing HCPs or a public health agency to directly contact at-risk relatives. FH is “point-source outbreak” that is vertically transmitted to related persons. However, the transmittal rate is 50% among children and siblings, the associated risk of adverse cardiovascular events is high, and effective lipid-lowering medications are available.
Performance and clinical utility of supervised machine-learning approaches in detecting familial hypercholesterolaemia in primary care
RK Akyea et al, NPJ Digital Medicine, October 30, 2020
(Posted: Oct 30, 2020 10AM)
We assessed performance of an array of machine-learning approaches for enhancing detection of FH, and their clinical utility, within a large primary care population. A retrospective cohort study was done using routine primary care clinical records of 4,027,775 individuals from the UK. Machine-learning models show similar high accuracy in detecting FH, offering opportunities to increase diagnosis.
Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia.
Santos Raul D et al. The New England journal of medicine 2020 10 (14) 1317-1327
(Posted: Oct 06, 2020 0PM)
In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables. 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean difference was -38.3 percentage points.
The Future of Genetics and Heart Disease
FH Foundation annual inaugural Robert Hegele seminar, September 24, 2020
(Posted: Sep 16, 2020 8AM)
This session includes classification and screening for FH and severe hypercholesterolemia, how human genetic studies have led to important therapeutic advances; the role of patients as a driving force behind Dr. Hegele’s research
Prevention of endothelial dysfunction and thrombotic events in COVID-19 patients with familial hypercholesterolemia.
Vuorio Alpo et al. Journal of clinical lipidology 2020 Jun
(Posted: Aug 28, 2020 1PM)
Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions
AC Fahed et al, Nature Communications, August 20, 2020
(Posted: Aug 21, 2020 9AM)
We study 80,928 individuals to examine whether polygenic background can modify penetrance of disease in tier 1 genomic conditions — familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome. Among carriers of a monogenic risk variant, we estimate substantial gradients in disease risk based on polygenic background — the probability of disease by age 75 years ranged from 17% to 78% for coronary artery disease, 13% to 76% for breast cancer, and 11% to 80% for colon cancer.
Evinacumab for Homozygous Familial Hypercholesterolemia.
Raal Frederick J et al. The New England journal of medicine 2020 Aug (8) 711-720
(Posted: Aug 20, 2020 7AM)
In patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the reduction from baseline in the LDL cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 weeks.
Bypassing the LDL Receptor in Familial Hypercholesterolemia.
Kersten Sander et al. The New England journal of medicine 2020 Aug (8) 775-776
(Posted: Aug 20, 2020 7AM)
Patients with homozygous familial hypercholesterolemia are at increased risk for a cardiovascular event before the age of 20 years, and their condition is very difficult to treat. Because of the absence of fully functional LDL receptors, patients with homozygous familial hypercholesterolemia have only a limited response to the existing drugs.
2020 FH Global Summit
The FH Foundation, August 2020
(Posted: Aug 19, 2020 10AM)
The FH Global Summit is the only conference entirely devoted to the care and treatment of inherited cardiovascular disorders including familial hypercholesterolemia (FH) and high lipoprotein(a). Each year, this invitation only event brings together unique voices to inspire and advent change.
Polygenic Contribution to Low-density Lipoprotein Cholesterol Levels and Cardiovascular Risk in Monogenic Familial Hypercholesterolemia
M Trinder et al. Cir Genomics Precision Medicine, August 2020
(Posted: Aug 14, 2020 7AM)
We constructed a weighted LDL-C polygenic score, composed of 28 single-nucleotide variants, for individuals with monogenic FH from the British Columbia FH; Nutrition, Metabolism and Atherosclerosis Clinic; and UK Biobank cohorts. Polygenic contributions to LDL-C explain some of the heterogeneity in clinical presentation and ASCVD risk for individuals with FH.
Genetic Testing for Inherited Cardiovascular Diseases: A Scientific Statement From the American Heart Association
K Musunuru et al, Circulation: Genomics and Precision Medicine
(Posted: Jul 24, 2020 9AM)
Advances in human genetics are improving the understanding of inherited cardiovascular diseases, including cardiomyopathies, arrhythmic disorders, vascular disorders, and lipid disorders such as familial hypercholesterolemia. This statement summarizes current best practices for genetic testing in inherited cardiovascular diseases.
Genetic Testing in Dyslipidemia
A Scientific Statement from the National Lipid Association
EE Brown et al, NLA, July 9, 2020
(Posted: Jul 12, 2020 7AM)
In selected patients, genetic testing can help in diagnosis and management; Pursuit of genetic testing must weigh potential benefits, risks and patient preference; Genetic counseling is recommended before and after genetic testing.
Understanding limitations of genetic testing is central to deriving the greatest benefit.
Clinical outcomes of a genomic screening program for actionable genetic conditions
AH Buchanan et al, Genetics in Medicine, June 30, 2020
(Posted: Jul 01, 2020 8AM)
A study of electronic health records shows that among individuals with variants in tier1 genes (BRCA, Lynch syndrome, familial hypercholesterolemia, 87% did not have a prior genetic diagnosis. Genomic screening programs can identify individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.
Familial Hypercholesterolemia: Cardiovascular Risk Stratification and Clinical Management
J Kolominsky et al, ACC, June 1, 2020
(Posted: Jun 02, 2020 6AM)
FH is an underdiagnosed yet treatable disorder. Recognizing FH is of utmost importance due to the high risk of premature CAD and major adverse cardiovascular events. After diagnosis of an index case, there is a mandate to perform cascade lipid and/or genetic screening of all first-degree relatives.
Prevalence of Familial Hypercholesterolemia Among the General Population and Patients With Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analysis
P Hu et al, Circulation, May 28, 2020
(Posted: May 30, 2020 7AM)
This systematic review and meta-analysis assessed the prevalence of Familial Hypercholesterolemia in the general population and patients with atherosclerotic cardiovascular disease. With an overall prevalence of 1 in 311, FH is among the most common disorders in the general population.
Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects.
Beheshti Sabina O et al. Journal of the American College of Cardiology 2020 May 75(20) 2553-2566
(Posted: May 26, 2020 5PM)
Health economic evaluation of screening and treating children with familial hypercholesterolemia early in life: Many happy returns on investment?
Z Ademi et al, Atherosclerosis, May 20, 2020
(Posted: May 25, 2020 9AM)
Undiscounted results showed that compared with usual care, cascade screening of ten year-old children for FH and initiation of treatment of affected individuals saved 7.77 LYG and 7.53 QALYs per person over a lifetime. The cascade screening of ten year-old children for FH and initiation of treatment compared to usual case was a cost saving approach.
Association of Rare Pathogenic DNA Variants for Familial Hypercholesterolemia, Hereditary Breast and Ovarian Cancer Syndrome, and Lynch Syndrome With Disease Risk in Adults According to Family History
AP Patel, JAMA Network Open, April 29, 2020
(Posted: Apr 30, 2020 8AM)
In this cohort study of 49?738 participants in the UK Biobank, a pathogenic or likely pathogenic variant associated with the 3 tier 1 genomic conditions (BRCA, Lynch syndrome, FH) was identified in 0.9% of participants. These individuals had an increased risk of disease identified by gene sequencing that was not found through self-reported family history.
Familial hypercholesterolemia: is it time to separate monogenic from polygenic familial hypercholesterolemia?
Brandts Julia et al. Current opinion in lipidology 2020 Apr
(Posted: Apr 29, 2020 7AM)
Through genetic testing, a mutation is found in 60-80% of cases with a clinical diagnosis of definite familial hypercholesterolemia. As individuals with a polygenic basis do not follow the same inheritance pattern observed in monogenic familial hypercholesterolemia, cascade screening in individuals with a polygenic origin is not recommended.
Cardiovascular Complications of COVID-19
M McGowan, The FH Foundation, April 22, 2020
(Posted: Apr 23, 2020 8AM)
Infection with COVID-19 has been associated with multiple cardiac complications including: heart attack, myocarditis (inflammation of the heart muscle), arrhythmias (heart rhythm disturbances) and blood clots. Most people will recover from a COVID-19 infection. Our aim at the FH Foundation is to empower individuals to make the most informed medical choices.
Implementation Research to Improve Case Finding, Cascade Screening, and Treatment for Familial Hypercholesterolemia
NHLBI funding announcement, April 2020
(Posted: Apr 16, 2020 0PM)
This is to support applications that develop innovative strategies for accelerating the uptake and sustainment of evidence-based detection, diagnosis, and treatment of familial hypercholesterolemia: explore barriers and facilitators to implementing case finding and cascade screening; and study adoption, sustainability, and scalability of programs.
Lipoprotein(a) and COVID-19
S Seim, Th FH FOundtaion, April 8, 2020
(Posted: Apr 12, 2020 8AM)
Familial hypercholesterolemia and COVID-19: triggering of increased sustained cardiovascular risk.
Vuorio Alpo et al. Journal of internal medicine 2020 Apr
(Posted: Apr 08, 2020 8AM)
Incorporation of genetic testing significantly increases the number of individuals diagnosed with familial hypercholesterolemia.
Brown Emily E et al. Journal of clinical lipidology 2020 Mar
(Posted: Apr 01, 2020 9AM)
Perspectives from individuals with familial hypercholesterolemia on direct contact in cascade screening.
Schwiter Rachel et al. Journal of genetic counseling 2020 Mar
(Posted: Apr 01, 2020 9AM)
Fifty-eight percent of U.S. index cases (11/19, 57.9%) and all international index cases (8/8, 100%) indicated willingness to provide contact information for certain at-risk relatives to a HCP for the purpose of directly informing relatives of their risk for FH in a hypothetical scenario.
Practice of lipoprotein apheresis and short-term efficacy in children with homozygous familial hypercholesterolemia: Data from an international registry.
Luirink Ilse K et al. Atherosclerosis 2020 Feb 29924-31
(Posted: Mar 25, 2020 9AM)
