Management of hypertriglyceridemia

Simha, Vinaya

doi:10.1136/bmj.m3109

Cited by 123 publications

(138 citation statements)

References 200 publications

(279 reference statements)

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…In familial chylomicronemia syndrome (FCS), an autosomal recessive or compound heterozygous variant in a critical gene regulating chylomicron catabolism is found [1,8,16•], leading to high chylomicron levels and low levels of other lipoprotein species in the plasma [1, 16•]. Chylomicrons deliver triglycerides absorbed from the diet to adipose tissue, skeletal muscle, and cardiac muscle where the enzyme lipoprotein lipase (LPL) breaks down the triglycerides (Fig.…”

Section: Familial Chylomicronemia Syndromementioning

confidence: 99%

“…1) [15,35]. In more than 80% of FCS cases, the disease is caused by an autosomal recessive variant in the LPL gene [1,36]. The remaining FCS cases are due to autosomal recessive or compound heterozygous variants in APOA5, APOC2, GPIHBP1, or LMF1 that all affect LPL function and maturation and thereby interfere with chylomicron levels [8,15].…”

Section: Familial Chylomicronemia Syndromementioning

confidence: 99%

“…The prevalence of FCS is in the range of 1:100,000 to 1:1,000,000 [1,15,37]. The patients typically have severe hypertriglyceridemia (> 10 mmol/L) and high fasting chylomicron levels from a young age [16•, 36].…”

Section: Familial Chylomicronemia Syndromementioning

confidence: 99%

“…Hypertriglyceridemia, defined as plasma triglyceride levels > 1.7 mmol/L (150 mg/dL), affects about 10% of the adult population and it is thus the most common form of dyslipidemia worldwide [1,2]. Patients with hypertriglyceridemia are at an increased risk of stroke and coronary heart disease [3][4][5][6] and, in severe cases, may develop acute pancreatitis [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…Mild-tomoderate hypertriglyceridemia indicates a triglyceride level at which cardiovascular disease risk is increased, and severe hypertriglyceridemia indicates an increased risk of acute pancreatitis [11]. Severe hypertriglyceridemia is uncommon, observed in~0.01% of the general population [14] and~1-2% of all hypertriglyceridemic adults [1,2].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Genetic Basis of Hypertriglyceridemia

Carrasquilla

Christiansen

Kilpeläinen

2021

Curr Atheroscler Rep

View full text Add to dashboard Cite

Purpose of Review Hypertriglyceridemia is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. Severe hypertriglyceridemia may sometimes be a monogenic condition. However, in the vast majority of patients, hypertriglyceridemia is due to the cumulative effect of multiple genetic risk variants along with lifestyle factors, medications, and disease conditions that elevate triglyceride levels. In this review, we will summarize recent progress in the understanding of the genetic basis of hypertriglyceridemia. Recent Findings More than 300 genetic loci have been identified for association with triglyceride levels in large genome-wide association studies. Studies combining the loci into polygenic scores have demonstrated that some hypertriglyceridemia phenotypes previously attributed to monogenic inheritance have a polygenic basis. The new genetic discoveries have opened avenues for the development of more effective triglyceride-lowering treatments and raised interest towards genetic screening and tailored treatments against hypertriglyceridemia. Summary The discovery of multiple genetic loci associated with elevated triglyceride levels has led to improved understanding of the genetic basis of hypertriglyceridemia and opened new translational opportunities.

show abstract

Section: Familial Chylomicronemia Syndromementioning

confidence: 99%

Section: Familial Chylomicronemia Syndromementioning

confidence: 99%

Section: Familial Chylomicronemia Syndromementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Genetic Basis of Hypertriglyceridemia

Carrasquilla

Christiansen

Kilpeläinen

2021

Curr Atheroscler Rep

View full text Add to dashboard Cite

show abstract

Triglyceride‐glucose index's link to cardiovascular outcomes post‐percutaneous coronary intervention in China: a meta‐analysis

Sun,

Hu,

et al. 2024

ESC Heart Failure

View full text Add to dashboard Cite

Percutaneous coronary intervention (PCI) addresses myocardial ischaemia, but a significant subset of patients encounter major adverse cardiovascular events (MACE) post‐treatment. This meta‐analysis investigated the relationship between the post‐PCI triglyceride‐glucose (TyG) index and MACE. Comprehensive searches of the Embase, PubMed, Cochrane Library, and Web of Science databases were conducted up to 3 March 2023, using relevant keywords. The effect size was determined based on I2 statistic using random‐effects models. Cluster‐robust standard errors crafted the dose–response curve, and the GRADE Evaluation Scale was employed to rate the quality of evidence. The group with the highest TyG index had significantly higher post‐PCI MACE rates than the lowest index group, with hazard ratios (HRs) of 2.04 (95% CI 1.65–2.52; I2 = 77%). Each unit increase in TyG index corresponded to HRs of 1.82 for MACE (95% CI 1.34–2.46; I2 = 92%), 2.57 for non‐fatal MI (95% CI 1.49–4.41; I2 = 63%), and 2.06 for revascularization (95% CI 1.23–3.50; I2 = 90%). A linear relationship between TyG index and MACE risk was established (R2 = 0.6114). For all‐cause mortality, the HR was 1.93 (95% CI 1.35–2.75; I2 = 50%), indicating a higher mortality risk with elevated TyG index. The GRADE assessment yielded high certainty for non‐fatal MI but low certainty for all‐cause mortality, revascularization, and MACE. The TyG index may predict risks of post‐PCI MACE, all‐cause mortality, non‐fatal MI, and revascularization, with varied levels of certainty. A potential linear association between the TyG index and MACE post‐PCI was identified. Future research should validate these findings.

show abstract

mTORC2 knockdown mediates lipid metabolism to alleviate hyperlipidemic pancreatitis through PPARα

Wang,

Liu,

Zhou

et al. 2024

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Hyperlipidemic pancreatitis (HP) is an inflammatory injury of the pancreas triggered by elevated serum triglyceride (TG) levels. The mechanistic target of rapamycin (mTOR) signaling pathway plays a crucial role in regulating lipid homeostasis and inflammation. This study aimed to investigate whether the activity of mTOR complex 2 (mTORC2) affects the progression of HP and its underlying mechanisms. In vivo, a high‐fat diet and retrograde administration of sodium taurocholate were employed to establish the HP models in rats, with pancreatic tissue pathology evaluated. The expression of Rictor and peroxisome proliferator‐activator receptor (PPAR) was examined. The serum levels of TG, fatty acid metabolites, inflammatory and lipid metabolism‐related factors were determined. In vitro, pancreatic acinar cells (PACs) were exposed to palmitic acid and cholecystokinin‐8. PAC apoptosis, pyroptosis, and ferroptosis were assessed. In the HP models, rats and PACs exhibited upregulated Rictor and downregulated PPARα, and Rictor knockdown promoted PPARα expression. In vivo, Rictor knockdown decreased the serum levels of TG, α‐amylase, total cholesterol, low‐density lipoprotein cholesterol, lactate dehydrogenase, and inflammatory factors, while increasing high‐density lipoprotein cholesterol levels. Rictor knockdown increased ACOX1 and CPT1α and decreased SREBP‐1, CD36, SCD1, ACLY, and ACACA. Rictor knockdown reduced damage to pancreatic tissue structure. In vitro, Rictor knockdown inhibited PAC apoptosis, pyroptosis, and ferroptosis. Treatment with the PPARα antagonist GW6471 abolished the beneficial effects of Rictor knockdown. Rictor/mTORC2 deficiency reduces serum TG levels, maintains lipid homeostasis, and suppresses inflammation by inhibiting PPARα expression. Weakening mTORC2 activity holds promise as a novel therapeutic strategy for HP.

show abstract

Management of hypertriglyceridemia

Cited by 123 publications

References 200 publications

The Genetic Basis of Hypertriglyceridemia

The Genetic Basis of Hypertriglyceridemia

Triglyceride‐glucose index's link to cardiovascular outcomes post‐percutaneous coronary intervention in China: a meta‐analysis

mTORC2 knockdown mediates lipid metabolism to alleviate hyperlipidemic pancreatitis through PPARα

Contact Info

Product

Resources

About