Systematic review of hypertriglyceridemia-induced acute pancreatitis: A more virulent etiology?

ObjectiveWe sought to define the severity and natural history of hypertriglyceridemia induced acute pancreatitis (HTG-AP), specifically whether HTG-AP causes more severe AP than that caused by other etiologies.MethodsSystematic review of the English literature.ResultsThirty-four studies (15 countries; 1972–2015) included 1340 HTG-AP patients (weighted mean prevalence of 9%). The median admission triglyceride concentration was 2622 mg/dl (range 1160–9769). Patients with HTG have a 14% weighted mean prevalence of AP. Plasmapheresis decreased circulating triglycerides, but did not conclusively affect AP mortality. Only 7 reports (n = 392 patients) compared severity of HTG-AP to that of AP from other etiologies. Of these, 2 studies found no difference in severity, while 5 suggested that HTG-AP patients may have increased severity compared to AP of other etiology.Conclusions1) hypertriglyceridemia is a relatively uncommon (9%) cause of acute pancreatitis; however, patients with hypertriglyceridemia have a high (14%) incidence of acute pancreatitis; 2) plasmapheresis may offer specific therapy unique to this patient population; and 3) data specifically comparing the severity of HTG-AP with AP caused by other etiologies are heterogeneous and scarce.     

高脂血症性急性胰腺炎临床分析

目的 分析高脂血症性急性胰腺炎（HLP）的临床特点及治疗。方法 将2002年9月至2004年4月收集资料完整的249例急性胰腺炎（AP）根据病因分为胆源性AP（142例）、HLP（52例）、酒精性AP（17例）和其他（38例）。着重对HLP与胆源性AP的临床特征、治疗方法进行比较，并分析血甘油三酯与临床指标的相关性。结果 在临床评分相同情况下，HLP与胆源性AP在年龄、性别、血性腹腔积液发生率、复发率、脂肪肝发生率、糖尿病发生率、手术率等方面比较差异均有显著性。甘油三酯与临床评分、CT严重程度评分（CTSI）分级、禁食水时间、住院天数、PLT、HCT、血Ca^2＋相关。结论 HLP以中青年男性患者为主，血甘油三酯高，病情重，住院天数长，以非手术治疗为主。     

Co-occurrence of heterozygous CREB3L3 and APOA5 nonsense variants and polygenic risk in a patient with severe hypertriglyceridemia exacerbated by estrogen administration

We describe a case of a 36-year-old woman with severe hypertriglyceridemia likely caused by double heterozygosity of a known pathogenic APOA5 nonsense variant (p.Q275X) and a novel CREB3L3 nonsense variant (p.C296X) on a background of very strong polygenic susceptibility. Her clinical course worsened with development of eruptive xanthomata after oral administration of 2 mg estradiol twice daily for 2 weeks as part of a medical protocol for intrauterine embryo transfer following in vitro fertilization. Her triglyceride levels decreased to baseline and xanthomata resolved without treatment after discontinuation of hormonal therapy, which also resulted in termination of pregnancy. Before undergoing a second embryo transfer using her natural cycle and no exogenous hormones, the patient started combination therapy with eicosapentaenoic acid ethyl ester and gemfibrozil, leading to an ～80% decrease in triglyceride levels. She continued treatment throughout pregnancy, which progressed to term with the delivery of healthy twins.     

Homozygosity for a partial deletion of apoprotein A-V signal peptide results in intracellular missorting of the protein and chylomicronemia in a breast-fed infant

Deficiency of apoprotein A-V (apoA-V) can cause hypertriglyceridemia. In an 11 months old boy presenting with a severe hypertriglyceridemia, a formerly unknown 24 nucleotide deletion in exon 2 of the APOA5 gene was detected. The homozygous mutation results in an eight amino acid loss in the signal peptide sequence (c.16_39del; p.Ala6_Ala13del). Screening of control persons proved that this deletion is a rare mutation. Hypertriglyceridemia in the patient was only found at the time when he was breast fed, while after weaning, triglyceride levels were close to normal. Under both dietary conditions, apoA-V protein was undetectable in plasma while post-heparin plasma lipoprotein lipase activity was normal.     

Role of omega-3 ethyl ester concentrate in reducing sudden cardiac death following myocardial infarction and in management of hypertriglyceridemia: An Indian consensus statement

IntroductionSudden cardiac death (SCD) is the most lethal manifestation of heart disease. In an Indian study the SCDs contribute about 10% of the total mortality and SCD post ST elevation myocardial infarction (MI) constitutes for about half of total deaths.ObjectiveGiven the limitations of existing therapy there is a need for an effective, easy to use, broadly applicable and affordable intervention to prevent SCD post MI. Leading cardiologists from all over India came together to discuss the potential role of n-3 acid ethyl esters (90%) of eicosapentaenoic acid (EPA) 460 mg & docosahexaenoic acid (DHA) 380 mg in the management of post MI patients and those with hypertriglyceridemia.RecommendationsHighly purified & concentrated omega-3 ethyl esters (90%) of EPA (460 mg) & DHA (380 mg) has clinically proven benefits in improving post MI outcomes (significant 15% risk reduction for all-cause mortality, 20% risk reduction for CVD and 45% risk reduction in SCD in GISSI-Prevenzione trial) and in reducing hypertriglyceridemia, and hence, represent an interesting option adding to the treatment armamentarium in the secondary prevention after MI based on its anti-arrhythmogenic effects and also in reducing hypertriglyceridemia.     

Mechanisms of HDL lowering in insulin resistant,hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity

Hypertriglyceridemia, low plasma concentrations of high density lipoproteins (HDL) and qualitative changes in low density lipoproteins (LDL) comprise the typical dyslipidemia of insulin resistant states and type 2 diabetes. Although isolated low plasma HDL-cholesterol (HDL-c) and apolipoprotein A-I (apo A-I, the major apolipoprotein component of HDL) can occur in the absence of hypertriglyceridemia or any other features of insulin resistance, the majority of cases in which HDL-c is low are closely linked with other clinical features of insulin resistance and hypertriglyceridemia. We and others have postulated that triglyceride enrichment of HDL particles secondary to enhanced CETP-mediated exchange of triglycerides and cholesteryl ester between HDL and triglyceride-rich lipoproteins, combined with the lipolytic action of hepatic lipase (HL), are driving forces in the reduction of plasma HDL-c and apoA-I plasma concentrations. The present review focuses on these metabolic alterations in insulin resistant states and their important contributions to the reduction of HDL-c and HDL-apoA-I plasma concentrations.