Beyond the Guidelines: Perspectives on Management of Pediatric Patients with Hypertriglyceridemia.

PURPOSE OF REVIEW: To provide a comprehensive overview of hypertriglyceridemia (HTG) in youth, identifying gaps in categorizing triglyceride (TG) levels and management strategies, and exploring new therapies for TG reduction. RECENT FINDINGS: Non-fasting TG levels as important cardiovascular (CV) risk indicators, with HTG's pathophysiology involving genetic and secondary factors affecting TG metabolism. Emerging treatments, including those affecting the lipoprotein lipase complex and inhibiting proteins like apoC3 and ANGPTL3, show promise. The review highlights the need for specific management approaches for youth, the significance of non-fasting TG levels, and the potential of new therapies in reducing CV and pancreatitis risks, advocating for further research on these treatments' efficacy and safety.

2024 KSoLA consensus on secondary dyslipidemia.

Elevated blood cholesterol and triglyceride levels induced by secondary causes are frequently observed. The identification and appropriate handling of these causes are essential for secondary dyslipidemia treatment. Major secondary causes of hypercholesterolemia and hypertriglyceridemia include an unhealthy diet, diseases and metabolic conditions affecting lipid levels, and therapeutic side effects. It is imperative to correct secondary causes prior to initiating conventional lipid-lowering therapy. Guideline-based lipid therapy can then be administered based on the subsequent lipid levels.

Lipid apheresis in the management of severe hypertriglyceridaemia in an adolescent girl with global developmental delay.

Hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) remains one of the common metabolic causes of acute pancreatitis in the paediatric population and the third most common cause after alcohol and gallstones in the adult population. We report a case of an early adolescent girl with global developmental delay and moderate cognitive impairment of unknown aetiology who presented with recurrent acute pancreatitis and uncompensated hypovolaemic shock. She was found to have serum triglyceride level of 7877 mg/dL (reference range<150 mg/dL) and hyperglycaemia with ketosis (no prior history of diabetes mellitus) that was successfully treated with lipid apheresis. This sometimes is an early modality for treatment in adults; however, it remains a last resort in children, used only for severe cases. A brief literature review on severe HTG-AP and its management is also provided.

Lipid Disorders and Pregnancy.

Practicing endocrinologists are likely to confront 2 major issues that occur with dyslipidemias during pregnancy. The most dramatic is the development of severe hypertriglyceridemia leading to acute pancreatitis. The second is the approach to treatment of familial hypercholesterolemia, a common genetic disorder. This article reviews the normal physiology and the pathophysiology of lipoproteins that occurs with pregnancy and then discusses the approaches to prevention and/or treatment of dyslipidemia in pregnancy with a focus on lifestyle and acceptable drug therapies.

Moderate-intensity continuous training reduces triglyceridemia and improves oxygen consumption in dyslipidemic apoCIII transgenic mice.

This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (V̇O2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P<0.0001) and higher concentrations of total plasma cholesterol (P<0.05), low-density lipoprotein (LDL) cholesterol (P<0.01), and very low-density lipoprotein (VLDL) cholesterol (P<0.0001) in the animals. Furthermore, the transgenic mice exhibited increased adipose mass (P<0.05) and higher V̇O2peak compared to their NTG controls (P<0.0001). Following the exercise protocol, MICT decreased triglyceridemia and cholesterol levels in dyslipidemic animals (P<0.05), and reduced adipocyte size (P<0.05), increased muscular glycogen (P<0.001), and improved V̇O2 in all trained animals (P<0.0001). These findings contribute to our understanding of the effects of moderate and continuous exercise training, a feasible non-pharmacological intervention, on the metabolic profile of genetically dyslipidemic subjects.

Comparative analysis of therapeutic plasma exchange vs. standard management in hypertriglyceridemia-induced acute pancreatitis: triglyceride reduction and clinical outcomes.

BACKGROUND AND AIM: The use of therapeutic plasma exchange (TPE) for treatment of hypertriglyceridemia-induced acute pancreatitis (HTGP) remains controversial in the literature. This study compared the clinical outcomes of TPE versus conventional therapy in patients with HTGP. METHODS: Fifty-five patients with HTGP were included. Patients were retrospectively compared in pairs: those who received TPE treatment and those who did not, those whose triglyceride level fell below 500 mg/dL within 48 h, and those who did not, those with and without persistent organ failure. The primary outcome was the percentage of triglyceride reduction within 48 h. Secondary outcomes were the length of hospital stay, mortality, cost-effectiveness, and persistent organ failure. RESULTS: Percentage decrease in triglyceride levels, medical hospitalization costs, and length of hospital stay were higher in the TPE group compared to the non-TPE group (p < 0.05, for each). However, there was no difference regarding persistent organ failure and mortality (p > 0.05, for each). The length of hospital stay, average cost, persistent organ failure, and mortality were similar in both groups whose triglyceride level fell below 500 mg/dL within 48 h and those who did not (p > 0.05, for each). Among patients with persistent organ failure, average cost was higher in the TPE group compared to the non-TPE group (p < 0.05). An independent relation was found between the average cost and persistent organ failure, TPE, length of hospital stay, albumin, and urea values in all patients (p < 0.05, for each). CONCLUSIONS: The approach of using TPE for treatment of HTGP was not found to be superior to the conventional treatment. Randomized controlled studies with larger number of patients are needed to gain better understanding of this issue.

Pancreatic and cardiometabolic complications of severe hypertriglyceridaemia.

PURPOSE OF REVIEW: This review endeavours to explore the aetiopathogenesis and impact of severe hypertriglyceridemia (SHTG) and chylomicronaemia on cardiovascular, and pancreatic complications and summarizes the novel pharmacological options for management. RECENT FINDINGS: SHTG, although rare, presents significant diagnostic and therapeutic challenges. Familial chylomicronaemia syndrome (FCS), is the rare monogenic form of SHTG, associated with increased acute pancreatitis (AP) risk, whereas relatively common multifactorial chylomicronaemia syndrome (MCS) leans more towards cardiovascular complications. Despite the introduction and validation of the FCS Score, FCS continues to be underdiagnosed and diagnosis is often delayed. Longitudinal data on disease progression remains scant. SHTG-induced AP remains a life-threatening concern, with conservative treatment as the cornerstone while blood purification techniques offer limited additional benefit. Conventional lipid-lowering medications exhibit minimal efficacy, underscoring the growing interest in novel therapeutic avenues, that is, antisense oligonucleotides (ASO) and short interfering RNA (siRNA) targeting apolipoprotein C3 (ApoC3) and angiopoietin-like protein 3 and/or 8 (ANGPTL3/8). SUMMARY: Despite advancements in understanding the genetic basis and pathogenesis of SHTG, diagnostic and therapeutic challenges persist. The rarity of FCS and the heterogenous phenotype of MCS underscore the need for the development of predictive models for complications and tailored personalized treatment strategies. The establishment of national and international registries is advocated to augment disease comprehension and identify high-risk individuals.

Assessment of triglyceride clearance of haemoperfusion from three cases of hypertriglyceridaemia-induced acute pancreatitis: a case series.

Rapid reduction of plasma triglycerides (TG) is believed to improve the outcome of pancreatitis in the context of hypertriglyceridaemia (HTG)-induced acute pancreatitis (HTG-AP). Previous studies have suggested that haemoperfusion (HP) with the Jafron cartridge series could be effective for reducing TG concentrations in patients with HTG-AP. However, the clearance capacity (CC) for TG removal has not been reported. This case series reports on data from three patients with HTG-AP who underwent HP with HA230 or HA330 cartridges. Blood samples were collected from both before and after the cartridge circuit every 30 min and the CC was calculated. Twelve pairs of blood samples were collected for each type of HP cartridge. The mean ± SD CC of the HA230 cartridge for TG removal in this case series was 0.009781 ± 1.117235 ml/min (95% confidence interval [CI], -0.7000762, 0.7196384 ml). The mean ± SD CC of the HA330 cartridge for TG removal in this case series was 0.344914 ± 1.412183 ml/min (95% CI, -0.5523448, 1.2421721 ml). Based on the findings of this small case series, special caution is advised when considering the use of the HA230 and HA330 cartridges for reducing blood TG concentration pending further conclusive evidence from larger studies.

Factors affecting clinical outcomes of continuous and intermittent plasmapheresis in patients with severe hypertriglyceridemia.

INTRODUCTION: Acute hypertriglyceridemia is considered a category III indication for plasmapheresis. The use of plasma as replacement fluid (RF) has been suggested to replace the consumed lipoprotein lipase. Heparin when used as an anticoagulant could possibly release lipoprotein lipase, thereby increasing triglyceride clearance. METHODS: The impact of RF (albumin vs fresh frozen plasma (FFP) and anticoagulant (ACD-A vs. heparin) on triglycerides following plasmapheresis in 27 patients with severe hypertriglyceridemia (SHTG) was investigated. A paired study of four patients with recurrent SHTG was conducted, evaluating continuous (Optia) versus intermittent flow plasmapheresis (Haemonetics). RESULTS: Shorter procedures positively impacted triglycerides (TG) drop post-sessions p < 0.05. In albumin sessions, patients who used heparin demonstrated significantly greater drop in TG and required less sessions than did those with citrate p < 0.05. In heparin sessions, patients who used albumin demonstrated significantly greater drop in triglycerides and required less sessions than did those with FFP p < 0.05. Three of six patients who used FFP and heparin showed a triglyceride drop of 11.7% following three sessions and a 50% drop with one albumin session. Compared with Haemonetics, Optia removed comparable volumes of plasma in less time, processing smaller blood volumes and using less citrate p < 0.05. Patients demonstrated significantly lower drop in TG and required more sessions with Haemonetics than they did with Optia p < 0.05. CONCLUSION: Shorter procedure was the main predictor for effective TG clearance. This can be achieved by continuous apheresis technology, particularly when using albumin as RF. TG removal via Optia seems to be optimized by using heparin.

Application of Lipid Apheresis in Acute Lipogenic Pancreatitis.

INTRODUCTION: Recently, the incidence of hypertriglyceridemia-associated pancreatitis (HTG-AP) has been increasing. The pathogenesis of lipogenic pancreatitis is not fully understood. This study aimed to retrospectively analyze the laboratory data, clinical manifestations, and prognosis of patients with lipid-derived pancreatitis who received lipid purification, to explore whether lipid purification is a better treatment for acute hyperlipidemic pancreatitis. METHODS: In this study, we enrolled five subjects diagnosed with HTG-AP at the Second Xiangya Hospital of Central South University between 2021 and 2022. We collected demographic data, medical histories, clinical manifestations, and laboratory data. All patients received routine therapy. Blood lipid purification was conducted using the double filtration plasmapheresis (DFPP) method. Plasma was separated from blood cells and purified to remove cholesterol, triglycerides, and low-density lipoprotein (LDL). SPSS was used for statistical analyses. RESULTS: Following a single lipoprotein apheresis (LA) treatment, significant improvements in serum lipid levels were observed. Three patients achieved triglyceride levels below 5.65 mmol/L within 24 h, while the remaining 2 patients experienced reductions of 82% and 78%, respectively. The average triglyceride level decreased from 36.82 to 7.27 mmol/L, representing an 80% reduction from baseline. Total cholesterol decreased by 59% on average, and LDL levels decreased by 69%. Statistically significant differences were observed in triglyceride and cholesterol levels before and after treatment. Four patients exhibited increased HDL levels posttreatment, while 1 patient showed a decrease. The average HDL/TC level was 21% higher after treatment. CONCLUSION: LA in HTG-AP effectively improves clinical symptoms, rapidly lowers lipid levels, and achieves good therapeutic outcomes.

The Role of Triglycerides in Atherosclerosis: Recent Pathophysiologic Insights and Therapeutic Implications.

Triglycerides have long been recognized as a cardiovascular disease risk factor. However, their precise role in atherosclerosis and potential utility as a therapeutic target remains debated topics. This review aims to shed light on these aspects by exploring the complex relationship between triglycerides and atherosclerosis from pathophysiological and pharmacological perspectives. Triglycerides, primarily carried by chylomicrons and very low-density lipoproteins, play an essential role in energy storage and utilization. Dysregulation of triglyceride homeostasis and triglyceride- rich lipoproteins metabolism often leads to hypertriglyceridemia and subsequently increases atherosclerosis risk. Triglyceride-rich lipoproteins remnants interact with arterial wall endothelial cells, get retained in the subendothelial space, and elicit inflammatory responses, thereby accelerating atherogenesis. Despite the clear association between high triglyceride levels and increased cardiovascular disease risk, intervention trials targeting triglyceride reduction have produced mixed results. We discuss a range of triglyceride-lowering agents, from fibrates to omega-3 fatty acids, with a focus on their mechanism of action, efficacy, and major clinical trial outcomes. Notably, the role of newer agents, such as angiopoietin-like protein 3 and apolipoprotein C3 inhibitors, is also explored. We highlight the challenges and controversies, including the ongoing debate on the causal role of triglyceride in atherosclerosis and the discordant outcomes of recent clinical trials. The potential confounding effects of associated risk factors, such as elevated apolipoprotein B, insulin resistance, and metabolic syndrome, are considered. In conclusion, this review underscores the importance of a nuanced approach to understanding the role of triglycerides in atherosclerosis and their potential as a therapeutic target. Further research is needed to unravel the complex interplay between triglycerides, triglyceride-rich lipoproteins, and associated factors in atherosclerosis pathogenesis and refine triglyceride-targeted therapeutic strategies.

AAV-mediated hepatic LPL expression ameliorates severe hypertriglyceridemia and acute pancreatitis in Gpihbp1 deficient mice and rats.

GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPLs). However, Gpihbp1 knockout mice did not develop hypertriglyceridemia (HTG) during the suckling period but developed severe HTG after weaning on a chow diet. It has been postulated that LPL expression in the liver of suckling mice may be involved. To determine whether hepatic LPL expression could correct severe HTG in Gpihbp1 deficiency, liver-targeted LPL expression was achieved via intravenous administration of the adeno-associated virus (AAV)-human LPL gene, and the effects of AAV-LPL on HTG and HTG-related acute pancreatitis (HTG-AP) were observed. Suckling Gpihbp1-/- mice with high hepatic LPL expression did not develop HTG, whereas Gpihbp1-/- rat pups without hepatic LPL expression developed severe HTG. AAV-mediated liver-targeted LPL expression dose-dependently decreased plasma TG levels in Gpihbp1-/- mice and rats, increased post-heparin plasma LPL mass and activity, decreased mortality in Gpihbp1-/- rat pups, and reduced the susceptibility and severity of both Gpihbp1-/- animals to HTG-AP. However, the muscle expression of AAV-LPL had no significant effect on HTG. Targeted expression of LPL in the liver showed no obvious adverse reactions. Thus, liver-targeted LPL expression may be a new therapeutic approach for HTG-AP caused by GPIHBP1 deficiency.

Sirolimus-induced Hypertriglyceridemia Leads to Acute Pancreatitis and Diabetic Ketoacidosis Post Stem Cell Transplant for Sickle Cell Disease.

Sirolimus (mammalian target of rapamycin inhibitor) is a potent immunosuppressive agent, used in patients receiving hematopoietic stem cell transplant (HSCT) for Graft vs Host disease prophylaxis. Compared to calcineurin inhibitors, sirolimus has no neurotoxicity or nephrotoxicity, but sirolimus causes dose-dependent thrombocytopenia, leukopenia, delayed wound healing, hyperlipidemia, and hypertriglyceridemia. Here we report a case of acute pancreatitis and diabetic ketoacidosis in a patient with sickle cell disease post haploidentical family donor HSCT which was managed conservatively without plasmapheresis. Based on our review of the literature, this is the first reported case of developing acute pancreatitis as an adverse effect of sirolimus-induced hypertriglyceridemia leading to diabetic ketoacidosis in a recipient of HSCT.

Evaluation of the Needs and Experiences of Patients with Hypertriglyceridemia: Social Media Listening Infosurveillance Study.

BACKGROUND: Hypertriglyceridemia is a risk factor for cardiovascular diseases. Internet usage in China is increasing, giving rise to large-scale data sources, especially to access, disseminate, and discuss medical information. Social media listening (SML) is a new approach to analyze and monitor online discussions related to various health-related topics in diverse diseases, which can generate insights into users' experiences and expectations. However, to date, no studies have evaluated the utility of SML to understand patients' cognizance and expectations pertaining to the management of hypertriglyceridemia. OBJECTIVE: The aim of this study was to utilize SML to explore the disease cognition level of patients with hypertriglyceridemia, choice of intervention measures, and the status quo of online consultations and question-and-answer (Q&A) search platforms. METHODS: An infosurveillance study was conducted wherein a disease-specific comprehensive search was performed between 2004 and 2020 in Q&A search and online consultation platforms. Predefined single and combined keywords related to hypertriglyceridemia were used in the search, including disease, symptoms, diagnosis, and treatment indicators; lifestyle interventions; and therapeutic agents. The search output was aggregated using an aggregator tool and evaluated. RESULTS: Disease-specific consultation data (n=69,845) and corresponding response data (n=111,763) were analyzed from 20 data sources (6 Q&A search platforms and 14 online consultation platforms). Doctors from inland areas had relatively high voice volumes and appear to exert a substantial influence on these platforms. Patients with hypertriglyceridemia engaging on the internet have an average level of cognition about the disease and its intervention measures. However, a strong demand for the concept of the disease and "how to treat it" was observed. More emphasis on the persistence of the disease and the safety of medications was observed. Young patients have a lower willingness for drug interventions, whereas patients with severe hypertriglyceridemia have a clearer intention to use drug intervention and few patients have a strong willingness for the use of traditional Chinese medicine. CONCLUSIONS: Findings from this disease-specific SML study revealed that patients with hypertriglyceridemia in China actively seek information from both online Q&A search and consultation platforms. However, the integrity of internet doctors' suggestions on lifestyle interventions and the accuracy of drug intervention recommendations still need to be improved. Further, a combined prospective qualitative study with SML is required for added rigor and confirmation of the relevance of the findings.