Notice bibliographique
Résumé
Background: Familial Hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease caused by excessive accumulation of LDL-C in circulation. Early treatment can normalize life expectancy. There are many barriers to care in FH that may lead to low diagnosis rates and unfavourable patient outcomes. For example, despite recommendations of genetic screening for diagnosis of FH by several national organizations, it is not routinely available as part of clinical care in Canada. Additionally, sex has been identified as a potential barrier to optimal care in cardiovascular diseases, which needs to be further explored in FH specifically.Methods/Results: First, the impact of unbiased genetic testing on re-classification of patients with a clinical diagnosis of FH in a single centre cohort in Québec was determined. Next-generation sequencing of the LDLR, APOB and PCSK9 genes and multiplex ligation-dependent probe amplification of the LDLR gene to detect genetic variants, including copy number variants was performed. All mutations were reviewed by a geneticist and cross-referenced in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/). Among 335 FH cases seen at the lipid clinic of the McGill University Health Centre (55% men, 45% women), baseline LDL-C was 7.0 ± 1.8 mmol/L. Women were diagnosed 6 years later than men and presented with higher LDL-C and apoB levels. In 229 patients who underwent genetic testing, a pathogenic FH-causing variant was identified in 169 (74%) individuals. A majority had variants in the LDLR (86%) or ABOP (14%) genes. Interestingly, the genetic panels currently available in Québec, which includes 11 common variants in French Canadians, only accounted for 49% of identified mutations. Importantly, 67% of patients initially defined as “probable FH” were re-classified as “definite FH” following genetic screening. Next, we investigated how sex can act as a barrier to care in FH, potentially leading to less-than-optimal patient outcomes. A preliminary retrospective registry analysis of 292 patients with FH at from the lipid clinic at the McGill University Health Centre was performed. In this cohort, less women were on high-intensity statins compared to men (35% vs. 74%, P=0.002) and less women reached an LDL-C target of ≤ 2.5 mmol/L compared to men (32% vs. 55%, P=0.02). To further investigate sex differences in treatment of FH, a global scale systematic review was performed. Publicly available databases were searched for peer-reviewed, English publications. Publications went through two rounds of screening in duplicate and were kept if the population was labelled as FH and data demonstrating a sex comparison in treatment was available. A thorough data extraction was performed. After duplicates were excluded, the search identified 3,979 records. After screening all items for inclusion criteria, 50 records remained. Conclusion: Genetic testing in patients suspected of having FH provided diagnostic certainty and permitted re-classification of many individuals with a probable diagnosis of FH. The limited genetic panel offered by Québec, focusing only on common French Canadian variants provided incomplete data in half of the cases. Our data supports unbiased genetic testing for a diagnosis of FH. The preliminary results of our single centre registry analysis revealed important sex differences in treatment and lipid level achievement in FH. The final selection of records of our systematic review will allow us to compare and contrast existing data on sex differences in treatment of FH. This review has the potential to reveal sex as a barrier to optimal treatment in FH. Identifying these imbalances will allow us to reduce barriers in care through educational initiatives, adequate training, and public advocacy to improve the quality of life and life expectancy of all individuals with FH
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,017 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,003 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,002 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».