ArticleJournal of the American College of Cardiology2016
Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia.
Article in Journal of the American College of Cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06439654 (Atlantic Lipid Lowering Treatment Optimization Program), which is not on this map. Cited by 412 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Atlantic Lipid Lowering Treatment Optimization Program (ALLTOP): A Comprehensive Approach to the Treatment of Familial Hypercholesterolemia and Complex Dyslipidemias
Who cites it
412 citing papers in PubMed, 1 synthesis or guideline pooled it, 919 citations in OpenAlex.
- Efficacy and Safety of Evolocumab and Alirocumab as PCSK9 Inhibitors in Pediatric Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Genetic Cascade Screening for Familial Hypercholesterolemia: A Randomized Clinical Trial.JAMA network open · 2026Trial
- Rethinking familial hypercholesterolemia screening: Quantifying missed diagnoses at the intersection of genetic testing and lipoprotein(a).American journal of preventive cardiology · 2026Article
- Understanding Barriers and Motivators of Familial Hypercholesterolemia Genetic Testing: Insights From the Singapore Public.Journal of genetic counseling · 2026Article
- Genetic screening of children for familial hypercholesterolaemia: the VRONI study.European heart journal · 2026Article
- Putative protective role ofAtherosclerosis plus · 2026Article
- Familial Hypercholesterolemia in Latin America: Unmet Needs, Barriers, and Challenges.Journal of lipid and atherosclerosis · 2026Review
- Article
- Genetic Spectrum of Familial Hypercholesterolemia in Russian North-West Registry: Focus on Correlation Between Clinical and Genetic Diagnosis.Journal of cardiovascular development and disease · 2026Article
- Association between saturated fat intake and low-density lipoprotein cholesterol across the genetic spectrum: Results from the Women's Health Initiative.medRxiv : the preprint server for health sciences · 2026Article
- Article
- Steatotic Liver Disease Predicts Lower Likelihood of LDLR Gene Mutations in Young Korean Patients with Suspected Familial Hypercholesterolemia.Journal of obesity & metabolic syndrome · 2026Article
- Proposal of a familial hypercholesterolemia paediatric diagnostic score (FH-PeDS).European journal of preventive cardiology · 2026Article
- From Phenotype to Genotype and Beyond: Insights into Familial Hypercholesterolemia and Familial Hypertriglyceridemia.Medicina (Kaunas, Lithuania) · 2026Review
- Review
- AAV gene therapy for homozygous familial hypercholesterolemia: a phase 1 trial.Nature medicine · 2026Article
- Simultaneous Assessment of Genetic and Epigenetic Contributions to the Plasma Lipid Levels with Respect to Cardiovascular Risk.Journal of atherosclerosis and thrombosis · 2026Article
- Depletion of renal cortical collecting duct-secreted PCSK9 in early proteinuria prevents sustained nephrotic syndrome-related hypercholesterolemia.American journal of physiology. Renal physiology · 2026Article
- Combining Genomics With Lipid and Inflammatory Biomarkers to Predict Coronary Artery Disease Risk: UK Biobank Study.Journal of the American College of Cardiology · 2026Article
- Monogenic Testing and Polygenic Risk Scores: Who, When, and How It May Shape Future Guidelines.Journal of the American College of Cardiology · 2026Article
352 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Commented on by
- Commented on by
Authors and funding
35 authors at 16 institutions in 8 countries.
Funding
Abstract
backgroundApproximately 7% of American adults have severe hypercholesterolemia (untreated low-density lipoprotein [LDL] cholesterol ≥190 mg/dl), which may be due to familial hypercholesterolemia (FH). Lifelong LDL cholesterol elevations in FH mutation carriers may confer coronary artery disease (CAD) risk beyond that captured by a single LDL cholesterol measurement.
objectivesThis study assessed the prevalence of an FH mutation among those with severe hypercholesterolemia and determined whether CAD risk varies according to mutation status beyond the observed LDL cholesterol level.
methodsThree genes causative for FH (LDLR, APOB, and PCSK9) were sequenced in 26,025 participants from 7 case-control studies (5,540 CAD case subjects, 8,577 CAD-free control subjects) and 5 prospective cohort studies (11,908 participants). FH mutations included loss-of-function variants in LDLR, missense mutations in LDLR predicted to be damaging, and variants linked to FH in ClinVar, a clinical genetics database.
resultsAmong 20,485 CAD-free control and prospective cohort participants, 1,386 (6.7%) had LDL cholesterol ≥190 mg/dl; of these, only 24 (1.7%) carried an FH mutation. Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutation carriers than noncarriers. Compared with a reference group with LDL cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol ≥190 mg/dl and no FH mutation had a 6-fold higher risk for CAD (odds ratio: 6.0; 95% confidence interval: 5.2 to 6.9), whereas those with both LDL cholesterol ≥190 mg/dl and an FH mutation demonstrated a 22-fold increased risk (odds ratio: 22.3; 95% confidence interval: 10.7 to 53.2). In an analysis of participants with serial lipid measurements over many years, FH mutation carriers had higher cumulative exposure to LDL cholesterol than noncarriers.
conclusionsAmong participants with LDL cholesterol ≥190 mg/dl, gene sequencing identified an FH mutation in <2%. However, for any observed LDL cholesterol, FH mutation carriers had substantially increased risk for CAD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.