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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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168 hot topic(s) found with the query "Cholesterol"

It is Time to Screen for Homozygous Familial Hypercholesterolemia in the United States
(Posted: May 07, 2024 10AM)

From the abstract: "Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9–11. "

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. "

Dose-Response Associations of Lipid Traits With Coronary Artery Disease and Mortality.
Guoyi Yang et al. JAMA Netw Open 2024 1 (1) e2352572 (Posted: Jan 20, 2024 10AM)

From the abstract: "Do apolipoprotein B (apoB), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) increase risk of coronary artery disease (CAD), all-cause mortality, or cause-specific mortality, and if so, what are the shapes of these associations? In this genetic association study using mendelian randomization including 347?797 participants of European ancestry from UK Biobank, genetically predicted apoB and LDL-C were positively associated with CAD, all-cause mortality, and cardiovascular mortality, all in a dose-dependent way. Genetically predicted TG was positively associated with CAD, although the presence of pleiotropy was suggested. "

Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes: A Mendelian Randomization Study.
Tormod Rogne et al. JAMA Netw Open 2024 1 (1) e2351166 (Posted: Jan 12, 2024 6AM)

From the abstract: " Which pathways mediate the inequity in pregnancy health associated with low educational attainment? In this cohort study of more than 3 million individuals, an association between genetically estimated lower educational attainment and increased risk of ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring low birth weight was observed. A sizeable portion of these associations were explained by targetable risk factors. These findings suggest that the association of socioeconomic inequalities with adverse pregnancy outcomes may be reduced by intervening for type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure."

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. "

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.

Contemporary Polygenic Scores of Low-Density Lipoprotein Cholesterol and Coronary Artery Disease Predict Coronary Atherosclerosis in Adolescents and Young Adults.
Rodrigo Guarischi-Sousa et al. Circ Genom Precis Med 2023 7 e004047 (Posted: Jul 10, 2023 8AM)

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.

Novel and future lipid-modulating therapies for the prevention of cardiovascular disease.
Julia Brandts et al. Nat Rev Cardiol 2023 4 (Posted: Apr 15, 2023 8AM)

Key proteins involved in lipoprotein metabolism, such as PCSK9, angiopoietin-related protein 3, cholesteryl ester transfer protein and apolipoprotein(a), have been identified as viable targets for therapeutic intervention through observational and genetic studies. These proteins can be targeted using a variety of approaches, such as protein inhibition or interference, inhibition of translation at the mRNA level. These novel and upcoming strategies are complementary to and could work synergistically with existing therapies, or in some cases could potentially replace therapies, offering unprecedented opportunities to prevent ASCVD.

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 Brand (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.

Association of Rare Protein-Truncating DNA Variants in APOB or PCSK9 With Low-density Lipoprotein Cholesterol Level and Risk of Coronary Heart Disease.
Jacqueline S Dron et al. JAMA cardiology 2023 2 (Posted: Feb 02, 2023 6AM)

What is the prevalence of protein-truncating variants (PTVs) in the apolipoprotein B (APOB) or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes and their association with low-density lipoprotein (LDL) cholesterol levels and coronary heart disease (CHD)? In this genetic association study including 19?073 US participants and 190?464 UK participants, a PTV was identified in 0.4% of individuals. Estimated untreated LDL cholesterol concentrations were 32% to 37% lower in PTV carriers vs noncarriers, and PTVs were associated with a 49% reduction in CHD risk.

Association between genetically proxied PCSK9 inhibition and prostate cancer risk: A Mendelian randomisation study.
Fang Si et al. PLoS medicine 2023 1 (1) e1003988 (Posted: Jan 04, 2023 6AM)

Using genetic variants associated with LDL cholesterol, liver-derived gene expression, and plasma protein levels, the researchers applied drug target Mendelian randomization (MR) and colocalization to examine the association between lipid-lowering drug targets and the risk of overall, early-onset, and advanced prostate cancer. Additional MR analyses were conducted to explore putative mediators of drug effects. This study provided evidence of an association between genetically proxied PCSK9 inhibition and lower risk of overall and early-onset prostate cancer supported by both MR and colocalization approaches.

Workshop on Considerations for Returning Individual Genomic Results from Population-Based Surveys: Focus on the National Health and Nutrition Examination Survey
National Academy of Medicine Workshop, December 2022 (Posted: Oct 20, 2022 10AM)

Population surveys collect information from participants by asking questions. Today, many surveys also collect biologic specimens that can be used to analyze a respondent's DNA and other biomarkers. The National Health and Nutrition Examination Survey (NHANES) administers a physical examination, collects biospecimens, and reports some test results (e.g., cholesterol levels) to the participant. Traditionally, NHANES participants have been told that they will not be contacted with personal genetic results. However, clinical science is evolving to encourage more return of individual research results. Therefore, NHANES will revisit the issue of if, when, and how to return genetic results to study participants.

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 Brand (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.

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

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.

Everyone deserves a diagnosis
The Family Heart Foundation, July 18, 2022 (Posted: Jul 20, 2022 0PM)

“Runs in the family” is not a diagnosis- Over the past 10 years, we have heard from thousands of people who have heart disease or had a stroke caused by an inherited cholesterol disorder. Unfortunately, they did not learn of their genetic condition until it was too late. The damage was done. They were told that heart disease or high cholesterol “runs in the family” but were never given the name of the genetic cause that leads to so much heartache across generations. We believe families deserve a diagnosis so they can get the care they deserve. That is why we have launched this campaign. We hope you will join us to help reach people who have never heard of FH or elevated Lipoprotein(a).

Transferability of genetic risk scores in African populations
AB Kamiza et al, Nature Medicine, June 2, 2022 (Posted: Jun 03, 2022 10AM)

Using summary statistics from the Million Veteran Program (MVP), we showed that GRSs derived from data of African American individuals enhance polygenic prediction of lipid traits in SSA compared to European and multiancestry scores. However, our GRS prediction varied greatly within SSA between the South African Zulu (low-density lipoprotein cholesterol (LDL-C), R2?=?8.14%) and Ugandan cohorts (LDL-C, R2?=?0.026%). We postulate that differences in the genetic and environmental factors between these population groups might lead to the poor transferability of GRSs within SSA. More effort is required to optimize polygenic prediction in Africa.

Coronary Heart Disease, Family History and Public Health: From Familial Hypercholesterolemia to Elevated Lipoprotein A
CDC Public Health Genomics Webinar, October 24, 2022 Brand (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.

Heterogeneity in statin responses explained by variation in the human gut microbiome
T Wilmansky et al, Med, May 11, 2022 (Posted: May 12, 2022 8AM)

the authors identify a novel blood-based biomarker for monitoring statin effects in two large, independent human cohorts. They identify gut microbiome features robustly associated with variable statin responses, both in terms of on-target (cholesterol lowering) and adverse (insulin resistance) effects. Furthermore, these microbiome-statin associations are independent of human genetic variation associated with statin response variability. These results support the potential clinical utility of monitoring the gut microbiome for optimizing drug therapy.

The Potential Clinical Benefit of Lowering Lipoprotein(a)
BA Ference et al, JAMA Cardiology, April 3, 2022 (Posted: Apr 04, 2022 11AM)

Lipoprotein(a) (Lp[a]) is a cholesterol-carrying, apolipoprotein B (apo B)–containing lipoprotein that has an apolipoprotein(a) (apo[a]) moiety covalently attached to its apo B100 molecule.1 The attached apo(a) moiety interferes with the interaction between Lp(a) and the apo B100–dependent low-density lipoprotein receptor, resulting in a long circulating half-life and accumulation of oxidized phospholipids within Lp(a).

Major cholesterol study reveals benefits of examining diverse populations
Nature research briefing, December 9, 2021 (Posted: Dec 12, 2021 9AM)

Researchers performed the largest genetic study of cholesterol levels so far by combining data from 201 studies in 35 countries involving 1.65 million people. Diversifying research participants improved the ability to identify genes controlling cholesterol levels and to predict levels across all ancestries.

Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen.
Montasser May E et al. Science (New York, N.Y.) 2021 12 (6572) 1221-1227 (Posted: Dec 08, 2021 8AM)

A current goal in genomics is to identify genetic variation associated with actionable traits of clinical concern. Through exome sequencing of an Old Order Amish population, This study identified a genetic variant that results in an amino acid change in the beta-1,4-galactosyltransferase 1 protein and is correlated with lower levels of cardiovascular disease. Investigation of the mutant protein showed that it affects genes associated with low-density lipoprotein cholesterol (LDL-C), and mice engineered to express the mutant protein exhibited a 38% decrease in blood LDL-C levels. The study suggests that such genomic sequencing and analysis can link genotype to phenotype and identify potentially clinically actionable pathways to treat disease.

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
W van Rheenen et al, Nature Genetics, December 6, 2021 (Posted: Dec 07, 2021 7AM)

We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels.

Trans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease.
Zheng Jie et al. International journal of epidemiology 2021 10 (Posted: Oct 24, 2021 6PM)

51, 672 CKD cases and 958 102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13 093 CKD cases and 238 118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo were included. Eight risk factors showed reliable evidence of causal effects on CKD in Europeans, including genetically predicted body mass index (BMI), hypertension, systolic blood pressure, high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein(a), type 2 diabetes (T2D) and nephrolithiasis. In East Asians, BMI, T2D and nephrolithiasis showed evidence of causality on CKD.

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.

Long-term Benefits and Harms Associated With Genetic Cholesteryl Ester Transfer Protein Deficiency in the General Population.
Nordestgaard Liv Tybjærg et al. JAMA cardiology 2021 10 (Posted: Oct 08, 2021 5AM)

This cohort study of the Danish general population found that genetic CETP deficiency was associated with lower risk of cardiovascular morbidity and mortality but higher risk of age-related macular degeneration (AMD). The lower risk of cardiovascular end points was associated with genetically lower levels of non–high density lipoprotein (HDL) cholesterol, while the higher risk of AMD was associated with genetically higher levels of HDL cholesterol.

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.

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.

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.

A Chinese host genetic study discovered type I interferons and causality of cholesterol levels and WBC counts on COVID-19 severity
H Zhu et al, MEDRXIV, June 9, 2021 (Posted: Jun 10, 2021 6AM)

Cholesterol-lowering oligonucleotides pass preclinical milestone
K O'Leary, Nature Medicine, May 20, 2021 (Posted: May 21, 2021 0PM)

PCKS9 is a protein that regulates low-density lipoprotein (LDL) cholesterol in the liver and is a promising therapeutic target for the treatment of dyslipidemia and atherosclerosis. Monoclonal antibodies directed against PCSK9 are available for clinical use, but these must be administered by injection. To overcome this limitation, a recent study developed a potent antisense oligonucleotide–based PCSK9 inhibitor (known as AZD8233) suitable for oral delivery.

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.

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.

Effect of Pharmacogenetic Testing for Statin Myopathy Risk vs Usual Care on Blood Cholesterol A Randomized Clinical Trial
JL Vassy et al, JAMA Network Open, December 2, 2020 (Posted: Dec 04, 2020 11AM)

In this randomized clinical trial including 408 patients, statin-naive patients whose physicians knew their SLCO1B1 genotype results at baseline did not have poorer low-density lipoprotein cholesterol reductions after 1 year, compared with patients who received usual care.

Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study
N Aung et al, Front in Genetics, November 11, 2020 (Posted: Nov 12, 2020 8AM)

Using Mendelian randomization in the UK biobank, we identified causal associations between BMI, LDL cholesterol and susceptibility to COVID-19. In particular, individuals in higher genetic risk categories were predisposed to SARS-CoV-2 infection. These findings support the integration of BMI into the risk assessment of COVID-19 and allude to a potential role of lipid modification in the prevention and treatment.

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.

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.

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.

Statin drugs might boost healthy gut microbes
P Libby, Nature News, May 6, 2020 (Posted: May 08, 2020 9AM)

An analysis of faecal samples reveals that obese people who take cholesterol-lowering statin drugs have a ‘healthier’ community of gut microorganisms than would be expected. What are the implications of this surprising finding?

From GWAS to GEMMs: Sestrin1 and cholesterol biosynthesis
EJ Gallagher, Sci Trans Med, April 15, 2020 (Posted: Apr 17, 2020 9AM)

Heart Disease Family Health History, and Familial Hypercholesterolemia
CDC, March 2020 Brand (Posted: Mar 05, 2020 8AM)

Having a family health history of heart disease makes you more likely to develop heart disease yourself. In some cases, having family members with heart disease at a young age (age 50 or younger) can be a sign of familial hypercholesterolemia, a genetic disease that causes high cholesterol. Take time to collect your family health history of heart disease.

Making Informed CHOICES: The Launch of a "Big Data" Pragmatic Trial to Improve Cholesterol Management and Prevent Heart Disease in Ontario.
Ferreira-Legere Laura E et al. Healthcare quarterly (Toronto, Ont.) 2020 Jan 22(4) 6-9 (Posted: Feb 26, 2020 8AM)

The study is a pragmatic, registry-based, cluster randomized controlled trial that aims to improve cholesterol management through appropriate statin use in adults and to ultimately reduce cardiovascular events in high-risk communities. It uses an innovative, multicomponent intervention approach that includes audit and feedback reports and educational materials.

Aspirin for Prevention of Cardiovascular Disease
AT Peters et al, JAMA Patient Page, February 18, 2020 (Posted: Feb 23, 2020 0PM)

Which patients may benefit? Some adults between ages 40 and 70 years at high risk of developing cardiovascular disease and at low risk of bleeding may consider taking low-dose aspirin. Factors that put someone at risk of developing cardiovascular disease include smoking, a strong family history of heart attack, and uncontrolled blood pressure, cholesterol, or diabetes.

Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease
M Trinder et al, JAMA Cardiology, February 11, 2020 (Posted: Feb 13, 2020 8AM)

In this cohort study of 48?741 adults recruited by the UK Biobank, individuals with comparable levels of low-density lipoprotein cholesterol, monogenic hypercholesterolemia were found to have a greater risk of CVD compared to those with polygenic hypercholesterolemia.

Step aside CRISPR, RNA editing is taking off: Making changes to the molecular messengers that create proteins might offer flexible therapies for cancer, pain or high cholesterol, in addition to genetic disorders.
S Reardon, Nature, February 4, 2020 (Posted: Feb 05, 2020 9AM)

Reducing the Global Public Health Burden of Familial Hypercholesterolemia: More Work Ahead
MJ Khoury et al, CDC Blog, January 21 2020 Brand (Posted: Jan 21, 2020 1PM)

Historically, FH has served as a paradigm for the role of cholesterol in heart disease. FH now also serve as a paradigm for bringing together the strengths of both public health and precision medicine approaches to health. The recommendations of this international group highlight the importance of integrating FH care in health systems with a lifelong approach to care

Association of Genetically Predicted Lipid Levels With the Extent of Coronary Atherosclerosis in Icelandic Adults
E Bjornsson et al, JAMA Cardiology, November 20, 2019 (Posted: Nov 21, 2019 7AM)

Using mendelian randomization in a study of Icelandic adults, the results show that elevated non–high-density lipoprotein cholesterol is associated with the development of coronary atherosclerosis and may be a better marker for atherogenic lipoproteins than low-density lipoprotein cholesterol.

Familial Hypercholesterolemia as a Prototype for Precision Public Health
MJ Khoury et al, CDC Blog, November 19, 2019 Brand (Posted: Nov 20, 2019 9AM)

In the absence of population screening guidelines specific to FH, and in the midst of all people with cholesterol-related health problems, how do we find and treat persons with FH? One answer to this question may be precision public health. Precision public health leverages emerging data by time, place, and persons, coupled with machine learning methods.

Many Adults with Familial Hypercholesterolemia Are Not Meeting Goal LDL-Cholesterol Level
RF Green et al, CDC Blog Post, November 15, 2019 Brand (Posted: Nov 15, 2019 0PM)

Among patients in the CASCADE FH registry, 73.7% were on statins, Even among the study population, which was selected from specialty clinics and likely receiving more aggressive cholesterol-lowering therapies than the general FH population, only 48% achieved LDL-cholesterol <100 mg/dL, and only 22% reached LDL-cholesterol <70 mg/dL.

Long-neglected gene plays a bigger role in Alzheimer’s than suspected, study shows
S Begley, StatNews, November 11, 2019 (Posted: Nov 12, 2019 8AM)

Just days after news that an ultra-rare form of a cholesterol-related gene called APOE protected a Colombian woman from developing early-onset Alzheimer’s disease (as one of her other genes supposedly fated her to), a second study is providing even stronger evidence that APOE might be the basis for preventing or treating Alzheimer’s.

Looking back and thinking forwards - 15 years of cardiology and cardiovascular research.
Kalman Jonathan M et al. Nature reviews. Cardiology 2019 Sep (Posted: Oct 21, 2019 10AM)

Several practice-changing breakthroughs are described, such as those that target risk factors such as inflammation and elevated LDL-cholesterol levels. Furthermore, these key opinion leaders predict that machine learning technology and data derived from wearable devices will pave the way towards the coveted goal of personalized medicine.

Deadly condition more common than once thought-Familial hypercholesterolemia raises risk of heart disease, death
K Corso, ABC News, September 30, 2019 (Posted: Oct 01, 2019 8AM)

Familial hypercholesterolemia is a genetic problem where the gene for clearing out LDL cholesterol is actually mutated, it's broken, so what happens is LDL cholesterol, the bad cholesterol, builds up in the bloodstream and then causes plaque or atherosclerosis to form. Diet and exercise aren't enough to address FH.

Personalized Nutrition: The Latest on DNA-Based Diets
Scientific American, September 27, 2019 (Posted: Oct 01, 2019 8AM)

Since the sequencing of the human genome, there's been a lot of interest in nutrigenomics. It’s long been clear that we don’t all respond the same way to the same dietary interventions. Some people do really well on a higher fat diet. Others develop high triglycerides or cholesterol on the same diet.

High cholesterol can be life-threatening genetic disorder. It's more common than you think.
A Shanes, North Jersey Record, September 17, 2019 (Posted: Sep 18, 2019 9AM)

Longitudinal low density lipoprotein cholesterol goal achievement and cardiovascular outcomes among adult patients with familial hypercholesterolemia: The CASCADE FH registry.
Duell P Barton et al. Atherosclerosis 2019 Aug 85-93 (Posted: Sep 18, 2019 9AM)

Longitudinal data on familial hypercholesterolemia patients in The FH Foundation CASCADE registry shows that less than half achieve target LDL cholesterol & atherosclerotic events are high: Unmet public health challenge for early and more aggressive treatment.

Low-density lipoprotein cholesterol goal achievement in patients with familial hypercholesterolemia in countries outside Western Europe: The International ChoLesterol management Practice Study.
Blom Dirk J et al. Journal of clinical lipidology (4) 594-600 (Posted: Sep 13, 2019 9AM)

Data from an international practice survey of familial hypercholesterolemia: 1) low cholesterol goal attainment (32%); 2) statin doses were often inadequate, and 3) cholesterol absorption inhibitor use was low.

Risk Categorization Using New American College of Cardiology/American Heart Association Guidelines for Cholesterol Management and Its Relation to Alirocumab Treatment Following Acute Coronary Syndromes
MT Roe et al, Circulation, September 2, 2019 (Posted: Sep 03, 2019 8AM)

The US 2018 US cholesterol management guidelines identify patients with recent acute coronary syndrome and dyslipidemia who are at very high risk for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab.

New European Lipid Guidelines Take Aggressive Approach
S Hughes, Medscape, September 1, 2019 (Posted: Sep 02, 2019 6AM)

New lipid guidelines from the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) have adopted an aggressive approach with new lower targets for low-density lipoprotein (LDL) reduction than seen before for most risk categories.

Recovering From a Stroke Can Be a Long Road, But Don’t Give Up
CDC Information, 2019 Brand (Posted: Aug 28, 2019 7AM)

Clark ate healthy and was in good physical condition before the stroke, but he also had high blood pressure and high cholesterol, which may have been a part of his family history; his grandmother passed away from a stroke.

A gene-diet interaction-based score predicts response to dietary fat in the Women's Health Initiative
K Westerman et al, MedXRIV, August 2019 (Posted: Aug 23, 2019 8AM)

The study sought to leverage the Women's Health Initiative cohort to generate and test genetic scores for the response of six cardiometabolic risk factors (body mass index, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and fasting glucose) to dietary fat.

Risk of Ischemic Stroke and Peripheral Arterial Disease in Heterozygous Familial Hypercholesterolemia: A Meta-Analysis.
Akioyamen Leo E et al. Angiology 2019 Sep 70(8) 726-736 (Posted: Aug 21, 2019 8AM)

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder predisposing affected individuals to lifelong low-density lipoprotein cholesterol (LDL-C) elevation and coronary heart disease. However, whether HeFH increases the risk of peripheral arterial disease (PAD) and ischemic stroke is undetermined.

Cholesterol: Fact or Fiction?
Test your cholesterol smarts with this quiz. CDC, 2019 Brand (Posted: Aug 19, 2019 9AM)

Positive Topline Results from Phase 3 Trial of Evinacumab in Patients with Severe, Inherited Form of High Cholesterol
Regeneron, August 14, 2019 (Posted: Aug 17, 2019 9AM)

Editorial: PCSK9 Inhibitors Prior Authorization- Redundant Process Due for a Redesign
K Nasir et al, Circulation, Cardiovascular Quality and Outcomes, July 23, 2019 (Posted: Jul 24, 2019 8AM)

In 2015, the cardiovascular community enthusiastically welcomed FDA approval of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors) as an additional add-on therapeutic option for managing cholesterol-related cardiovascular disease risk. However, the celebrations were short-lived.

Causal associations between potentially modifiable risk factors and the Alzheimer's phenome: A Mendelian randomization study
SJ Andrews et al, BioRXIV preprints, July 2 , 2019 (Posted: Jul 03, 2019 8AM)

This study uses mendelian randomization to demonstrate a possible causal relationship between blood pressure, cholesterol levels, BMI, depression, insomnia symptoms, physical activity and educational attainment on Alzheimer's disease. These findings support public health programs to educate the public about preventable causes of AD.

Nevada Health Study Using Genetics To Fight Disease Statewide
N Glick, KUNR, June 28, 2019 (Posted: Jul 01, 2019 1PM)

The Healthy Nevada Project kicked off in 2016, and so far, has around 50,000 participants. Its aim is to eventually reach 1 million people across Nevada. Anyone can sign up, which is what makes it the largest community-based population health study of its kind in the world. For now, the study is looking for three gene variants that are linked to colon cancer, high cholesterol and breast and ovarian cancer.

Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study
C Depommier et al,. Nature Medine, July 1, 2019 (Posted: Jul 01, 2019 11AM)

Microbiome manipulation may be promising in tackling metabolic syndrome in humans. This is a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity and reduced insulinemia and plasma total cholesterol.

Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights.
Stein Ricardo et al. Current cardiology reports 2019 Jun (8) 68 (Posted: Jun 27, 2019 8AM)

In the last two decades, significant advances have been made in understanding the genetic basis of dyslipidemias. This review discusses current knowledge of the genetics and pathophysiology of disorders that predispose to dyslipidemia. The authors also discuss new cholesterol-lowering medications, including PCSK9 inhibitors.

Low LDL Cholesterol by PCSK9 Variation Reduces Cardiovascular Mortality.
Benn Marianne et al. Journal of the American College of Cardiology 2019 Jun (24) 3102-3114 (Posted: Jun 25, 2019 8AM)

Genetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of cardiovascular mortality in 109,566 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study

10-year-old’s cholesterol was over 800. Can CRISPR fix the problem?
T Avril, Philadelphia Inquirer, June 10, 2019 (Posted: Jun 11, 2019 7AM)

2018 Cholesterol Clinical Practice Guidelines: Synopsis of the 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline.
Grundy Scott M et al. Annals of internal medicine 2019 May (Posted: May 31, 2019 10AM)

Life-threatening genetic cholesterol condition could be found through blood donations
UT Wouthwestern, Eureka Alert, May 22, 2019 (Posted: May 23, 2019 8AM)

LDL-C goal achievement in patients with familial hypercholesterolaemia in countries outside Western Europe: The International ChoLesterol management Practice Study (ICLPS)
Blom DJ, et al. Journal of Clinical Lipidology. May 14, 2019 (Posted: May 16, 2019 8AM)

AHA News: A Father's Death at 37 Reveals a Hidden History of Cholesterol
US News, April 30, 2019 (Posted: May 05, 2019 11AM)

Cholesterol Myths and Facts
CDC, February 2019 Brand (Posted: Feb 12, 2019 11AM)

Cholesterol Management
Million Hearts, 2019 Brand (Posted: Feb 10, 2019 1PM)

New Cholesterol Guidelines Personalize Risk and Add Treatments
J Abbasi, JAMA, February 7, 2019 (Posted: Feb 08, 2019 9AM)

A New Personalized, Patient-Centric, and Cost-Conscious Guideline for Contemporary Cholesterol Management.
Peterson Eric et al. JAMA 2019 Feb (Posted: Feb 06, 2019 8AM)

Effects of Genetic Variants Associated with Familial Hypercholesterolemia on Low-Density Lipoprotein-Cholesterol Levels and Cardiovascular Outcomes in the Million Veteran Program
Y San et al. Circulation Genomics Prec Medicine, December 2018 (Posted: Jan 04, 2019 8AM)

New 2018 Guideline on the Management of Blood Cholesterol from the American College of Cardiology / American Heart Association Task Force on Clinical Practice Guidelines
What does it mean for FH, the FH Foundation, December 6, 2018 (Posted: Dec 08, 2018 1PM)

New ACC/AHA Cholesterol Guideline Allows For More Personalized Care; New Treatment Options
American College of Cardiology, November 10, 2018 (Posted: Nov 13, 2018 9AM)

Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease.
Benito-Vicente Asier et al. International journal of molecular sciences 2018 Nov 19(11) (Posted: Nov 07, 2018 11AM)

These Cholesterol-Reducers May Save Lives. So Why Aren’t Heart Patients Getting Them?
G Kolata, NY Times, October 2, 2018 (Posted: Oct 02, 2018 0PM)

When high cholesterol and heart disease runs in the family: Familial Hypercholesterolemia
American Heart Association, Podcast, September 2018 (Posted: Sep 08, 2018 10AM)

She tried diet and exercise. But her high cholesterol came from her genes.
N Brown, American Heart Association, September 4, 2018 (Posted: Sep 04, 2018 0PM)

Genetic testing pushed for hereditary high cholesterol disease,
(Posted: Aug 17, 2018 10AM)

Do More Genetic Testing for Familial High Cholesterol —Expert panel makes recommendations on cascade screening, specific genes to test
C Phend, Medpage Today, July 30, 2018 (Posted: Jul 31, 2018 1PM)

Sex differences in cholesterol levels from birth to 19 years of age may lead to increased cholesterol burden in females with FH.
Holven Kirsten B et al. Journal of clinical lipidology (3) 748-755.e2 (Posted: Jul 07, 2018 5PM)

Balancing Affordability And Access: Lessons From New Cholesterol-Lowering Drugs
JA Doshi et al, Health Affairs, June 5, 2018 (Posted: Jun 06, 2018 8AM)

PCSK9 genetic variants, life-long lowering of LDL-cholesterol and cognition: a large-scale Mendelian randomization study
D Lyall et al, BioRxIV preprints, May 31, 2018 (Posted: Jun 02, 2018 11AM)

Severely elevated cholesterol often goes untreated
L Rapaport, Reuters news, Mar 26, 2018 (Posted: Mar 26, 2018 7PM)

Primary prevention of cardiovascular disease: The past, present, and future of blood pressure- and cholesterol-lowering treatments
MJG Leening et al, PLOS Medicine, Mar 20, 2018 (Posted: Mar 20, 2018 4PM)

Fighting Genetic High Cholesterol: A Mother's Story: After a heart attack at only 38, Katherine Wilemon was inspired to start a foundation and help raise awareness.
MR Vann, Everyday Health (Posted: Jan 25, 2018 11AM)

Is it time to retire cholesterol tests?
M Leslie, Science, Dec 6, 2017 (Posted: Dec 08, 2017 10AM)

HDL Cholesterol Metabolism and the Risk of CHD: New Insights from Human Genetics.
Vitali Cecilia et al. Current cardiology reports 2017 Nov (12) 132 (Posted: Dec 08, 2017 10AM)

A Daughter's Diagnosis, A Mother's Wake-up Call: She knew cholesterol was a family problem, but didn’t take it seriously until it affected her daughter.
J Caswell, Heart Insight, Nov 2017 (Posted: Nov 29, 2017 2PM)

CaRe high - Cascade screening and registry for high cholesterol in Germany.
Schmidt Nina et al. Atherosclerosis. Supplements 2017 Nov 3072-76 (Posted: Nov 08, 2017 9AM)

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Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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