Triglyceride reduction in secondary atherosclerotic cardiovascular disease prevention: core concepts in contemporary therapeutic targeting
Notice bibliographique
Résumé
This commentary refers to ‘Real-world risk of cardiovascular outcomes associated with hypertriglyceridaemia among individuals with atherosclerotic cardiovascular disease and potential eligibility for emerging therapies’, by P.R. Lawler et al., 2020;41:86–94. Elevated plasma triglyceride (TG), including in optimally treated patients, is a marker of future cardiovascular event risk in patients with prevalent atherosclerotic cardiovascular disease (ASCVD), occurring in as many as one in four patients.1 Triglyceride may be associated with residual ASCVD risk in at least several ways (Figure 1). First, TG reflects the concentration of circulating atherogenic remnant cholesterol. Second, higher TG is associated with higher atherogenic small, dense low density lipoproteins (LDL).2 (apoB—a clinically measurable marker found in a 1:1 ratio on all atherogenic lipoproteins—may quantify these effects in aggregate, reflecting both more TG-rich lipoproteins as well as an increased number of small, dense LDL.3) Beyond lipid and lipoprotein risk pathways, however, elevated TG may also herald the presence of insulin resistance. Insulin resistance is characterized by a complex, integral interplay between dyslipidaemia, adiposity, hypertension, and inflammation. Insulin resistance promotes increased fatty acid secretion from adipose tissues, driving up plasma TG. Glucose levels rise due to impaired stimulation of glucose transport, as does blood pressure due to deficient nitric oxide release. Hence, plasma TG is linked to several inter-related ASCVD risk pathways, and thus may identify at-risk patients for targeted therapy. Overview of pathways associated with triglyceride-related atherosclerotic cardiovascular disease risk. Prior and ongoing trials of TG-reducing pharmacotherapies have focused primarily on (i) peroxisome proliferator-activated receptor (PPAR) modulation (e.g. fibrates) and (ii) reducing hepatic generation of TG-rich lipoproteins (e.g. omega-3 fatty acids such as icosapent ethyl; as well as statins).2 , 4 Neutral fibrate trials (FIELD, ACCORD, and BIP), juxtaposed against the large benefit associated with statins, muted enthusiasm for fibrates for ASCVD event reduction (in the absence of very high TG), and these therapies are infrequently used in clinical practice. In contrast, building on the positive JELIS trial (NCT00231738), the REDUCE-IT trial (NCT01492361) observed large reductions in ASCVD events in high-risk primary and secondary prevention settings with icosapent ethyl among statin-treated patients with residually elevated TG. However, interest in fibrates has been renewed in part through the ongoing PROMINENT trial (NCT03071692) of pemafibrate, a potent selective PPAR-α modulator, in high-risk primary and secondary prevention patients with hypertriglyceridaemia. As Dr Spence points out, further evidence for PPAR modulation of TG-associated cardiometabolic risk is evolving.5 While we share Dr Spence’s renewed enthusiasm for targeting PPAR in ASCVD risk reduction,5 further trials are awaited before broadly embracing fibrate therapy in contemporary secondary prevention, outside of patients with very high TG.4 We hence did not focus on these therapies in our study. The authors thank freelance medical illustrator Gail Rudakevich for generation of the figure. Conflict of interest: R.S.R. receives research support from Amgen, Novartis, Regeneron, serves on advisory boards for Amgen, C5, CVS Caremark, Corvidia; receives honoraria for non-promotional speaking from Amgen, Kowa, Pfizer and Regneron; has stock holdings in MediMergent LLC; and receives royalties from UpToDate, Inc. Other authors declared no conflicts of interest to disclose.
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 | 0,004 | 0,014 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,004 |
| Communication savante | 0,003 | 0,004 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,014 | 0,027 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,002 |
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 ».