An overview of persistent chylomicronemia: much more than meets the eye

Current Opinion in Endocrinology Diabetes and Obesity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Purpose of review The aim this is to provide an overview severe hypertriglyceridemia presenting in the form chylomicronemia that persists despite treatment secondary causes and use conventional lipid-lowering treatment. Recent findings Persistent a rare syndromic disorder affects carriers bi-allelic combinations pathogenic gene variants impairing lipoprotein lipase (LPL) activity, as well significant number individuals who do not meet genetic criterion. It associated with high risk acute pancreatitis other morbidities. Effective innovative treatments for are being developed becoming available. Patients persistent any cause respond equally next-generation therapies LPL-independent mechanisms action generally LPL-dependent treatments. Summary Not all carry proven combination impair LPL activity. Documenting clinical characteristics people their response emerging essential correctly establish trajectory ensure equitable access personalized

Language: Английский

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Epidemiology and longitudinal course of chylomicronemia: Insights from NHANES and a large health care system

Journal of clinical lipidology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Chylomicronemia is characterized by fasting triglyceride (TG) ≥1000 mg/dL; its longitudinal course not well studied. Using National Health and Nutrition Examination Survey (NHANES) data (1999-2018; n = 21,998), we determined chylomicronemia prevalence temporal trend. Mayo Clinic (4,524,506 TG measurements for 1,294,044 individuals), studied the ascertained persistent (PC), defined as mg/dL in more than half individuals with ≥3 measurements. We used logistic regression to assess factors associated PC. In NHANES, of was 0.20% overall, higher men (0.32%) Hispanics (0.33%). declined from 0.34% 1999-2004 0.11% 2013-2018, while lipid-lowering pharmacotherapy use patients increased 5.3% 51.9%. data, 5618 (0.43%) had at least 1 episode chylomicronemia. Of these, 8.8% (390 4443 measurements) met operational definition <150 mg/dL, 1.3% a diagnosis acute pancreatitis, 0.6% chronic pancreatitis. Respective figures nonpersistent were 12.5% 5.1%, PC 26.2% 11.5%. Younger age, Hispanic ethnicity, prior levels US, ∼500 adults has ∼5500 Individuals have high occurrence pancreatitis may need effective treatment.

Language: Английский

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Current and Emerging Treatment Options for Hypertriglyceridemia: State-of-the-Art Review

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 147 - 147

Published: Jan. 23, 2025

Hypertriglyceridemia (HTG) is associated with a residual risk of atherosclerotic cardiovascular disease. Extremely elevated triglyceride (TG) concentrations, particularly due to familial chylomicronemia syndrome (FCS), pose for acute pancreatitis. Standard therapies statins, fibrates, omega-3 fatty acids, and niacin may be insufficient reduce TG levels improve clinical outcomes in patients HTG. Novel antisense oligonucleotides small interfering ribonucleic acids target the key modulators TG-rich lipoprotein catabolism. Among apolipoprotein C-III (apoC-III) inhibitors, olezarsen plozasiran appear safer alternatives volanesorsen regarding drug-induced thrombocytopenia FCS or severe After failure vupanorsen, new angiopoietin-like protein 3 (ANGPTL3) inhibitor, zodasiran, demonstrated potential decrease moderate Meanwhile, fibroblast growth factor 21 (FGF21) analog, pegozafermin, became another candidate treatment This comprehensive review outlines pharmacological targets metabolism, discusses international guidelines, summarizes latest evidence from trials provide insight into current emerging options primary

Language: Английский

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Novel RNA-Based Therapies in the Management of Dyslipidemias

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1026 - 1026

Published: Jan. 25, 2025

Pharmaceutical advancements and an improved understanding of pathophysiology have enabled innovative therapies for chronic conditions like dyslipidemia. This condition is marked by abnormalities in lipid homeostasis. Nucleic acid therapeutics, including antisense oligonucleotides small interfering RNAs, are novel management strategies that silence genes targeting mRNA. Antisense modify mRNA to inhibit protein production, whereas RNAs induce degradation via the RNA-induced silencing complex (RISC), thus offering promising treatments dyslipidemia atherosclerotic cardiovascular disease. Chemical modifications improve their stability targeting. RNA-based PCSK9, Lp(a), ApoC-III, ANGPTL3 hold transformative potential treating effectively. article discusses latest data from completed ongoing trials on RNA dyslipidemia, inclisiran, pelacarsen, olpasiran, zerlasiran, lepodisiran, volanesorsen, olezarsen, plozasiran, zodasiran, solbinsiran. Each therapy targets specific molecules while also significantly impacting other parameters. The results these indicate improvements risk reduction, with studies expected further refine role agents effective management.

Language: Английский

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Familial chylomicronemia syndrome and treatments to target hepatic APOC3 mRNA

Atherosclerosis, Journal Year: 2025, Volume and Issue: unknown, P. 119114 - 119114

Published: Jan. 1, 2025

Language: Английский

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Olezarsen, a liver-directed APOC3 ASO therapy for hypertriglyceridemia

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 21, 2024

Apolipoprotein (apo)C-III, a key regulator of plasma triglyceride (TG) levels, is prime candidate for the treatment hypertriglyceridemia (HTG), prevention acute pancreatitis, and reduction future atherosclerotic cardiovascular disease (ASCVD) events.

Language: Английский

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Differential Effects of Volanesorsen on ApoC-III, Triglycerides and Pancreatitis in Familial Chylomicronemia Syndrome Diagnosed by Genetic or Non-Genetic Criteria

Journal of clinical lipidology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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Reducing the Risk of Pancreatitis by Inhibiting APOC3

New England Journal of Medicine, Journal Year: 2025, Volume and Issue: 392(2), P. 197 - 199

Published: Jan. 8, 2025

Language: Английский

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Exploring emerging pharmacotherapies for type 2 diabetes patients with hypertriglyceridemia

Expert Opinion on Pharmacotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 11

Published: Jan. 11, 2025

Introduction Atherogenic dyslipidemia with increased triglycerides, low high-density lipoprotein cholesterol levels and small dense low-density (LDL) particles is a major risk factor contributing to the cardiovascular (CV) in patients type 2 diabetes (T2D). This regarded as residual after achieving target of LDL cholesterol.

Language: Английский

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Diagnosis, Evaluation, and Management of Severe Hypertriglyceridemia

Current Cardiovascular Risk Reports, Journal Year: 2025, Volume and Issue: 19(1)

Published: Jan. 21, 2025

Language: Английский

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