Thrombophilia in Patients with Hypertriglyceridemia

Objectives: To investigate a possible relationship between hypertriglyceridemia and the coagulation system, a Cardiovascular Risk Factor Two-township Study was conducted in Taiwan. Design: A case-control study. This longitudinal, prospective study focused on the evolution of cardiovascular disease risk factors with emphasis on haemostatic factors. Subjects: Hypertriglyceridemic subjects (triglyceride <2.26 mmoll+1, n = 327) and age-matched normal controls from a population screening program. Main outcome measures: Haemostatic parameters measured in this study included prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors VIIc and VIIIc, and antithrombin-III and plasminogen levels. Results: In our male hypertriglyceridemic subjects, aPTT was not significantly reduced, while significant elevations of factor VIIIc, factor VIIc, and plasminogen and antithrombin-III levels were noted. In the female hypertriglyceridemic subjects, the elevation of factor VIIc, factor VIIIc, and plasminogen and antithrombin-III levels was highly-significant, whereas aPTT was not significantly reduced. Unexpectedly, the levels of the established coronary risk factor, fibrinogen, did not show a statistically different change. Similar to previous data, our hypertriglyceridemic subjects also presented with hyperinsulinemia, glucose intolerance, upper body obesity, and elevated blood pressure. Conclusions: Despite the fact that in population studies, triglycerides do not consistently appear to be an independent risk factor for coronary heart disease, our data suggest that a pronounced increase in triglycerides warrants aggressive therapy, because this increase may be associated with a hypercoagulable state. This phenomenon contributes another perspective to the study of higher cardiovascular mortality in hypertriglyceridemic subjects.     

Tamoxifen-Induced Severe Acute Pancreatitis: A Case Report

Acute pancreatitis is a condition that leads to destruc-tionand necrosis of pancreatic tissue and frequentdevelopment of multiple organ failure. Most cases arerelated to gallstones or heavy alcohol intake. Amongthe numerous other causes are hypertriglyceridemia,hypercalcemia, abdominal trauma, drugs, vasculitis, viralinfection, peritoneal dialysis, cardiopulmonary bypass,and endoscopic retrograde cholangiopancreatography.Approximately 2 to 5% of cases of acute pancreatitisare drug related, including such drugs as azathioprine,mercaptopurine, asparaginase, pentamidine, didanosine,valproic acid, tetracyclines, estrogen, sulfonamides,thiazides, furosemide, pentamidine, dideoxyinosine, andpossibly glucocorticoids.Tamoxifen is a nonsteroidal estrogen antagonist thathas been widely used in adjuvant hormonal therapy ofprimary breast cancer. The side effects of tamoxifenare generally mild, including effects on lipoproteinmetabolism (1-3). Tamoxifen lowers total and low-densitylipoprotein cholesterol and increases triglycerideand high-density lipoprotein cholesterol levels. However,there are some cases of marked, tamoxifen-induced,hypertriglyceridemia. Hypertriglyceridemia may occa-sionallyproduce severe, lethal pancreatitis (4-8). Here,we report a case of tamoxifen-induced severe, acutepancreatitis. The patient was a woman who had hyper-triglyceridemiaand breast cancer. After mastectomy, bothtamoxifen and antihyperlipidemic agents were adminis-tered.But she withdrew the lipid-lowering agent 2 yearslater on her own. Then she developed tamoxifen-inducedsevere hypertriglyceridemia and pancreatitis.     

A Highly Bioavailable Omega-3 Free Fatty Acid Formulation Improves the Cardiovascular Risk Profile in High-Risk,Statin-Treated Patients With Residual Hypertriglyceridemia (the ESPRIT Trial)

Background

A novel omega-3 formulation in free fatty acid form (OM3-FFA) has as much as 4-fold greater bioavailability than ethyl ester forms and reduces triglyceride (TG) levels in patients with severe hypertriglyceridemia.

Objective

This study was designed to evaluate the efficacy of adding OM3-FFA (2 or 4 g/d) to statin therapy for lowering non–HDL-C and TG levels in subjects with persistent hypertriglyceridemia and at high risk for cardiovascular disease.

Methods

In this double-blind, parallel-group study, 647 diet-stable patients with fasting TG levels ≥200 mg/dL and <500 mg/dL (treated with a maximally tolerated dose of statin or statin with ezetimibe) and at high risk for cardiovascular disease were randomized to 6 weeks of treatment with capsules of control (olive oil [OO]) 4 g/d, OM3-FFA 2 g/d (plus 2 g/d OO), or OM3-FFA 4 g/d. Assessments included fasting serum levels of lipids and apolipoproteins (apo); plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and arachidonic acid; and laboratory safety values and adverse events.

Results

In the 627 subjects in the intention to treat sample, non–HDL-C levels were reduced with OM3-FFA 2 g/d and OM3-FFA 4 g/d (–3.9% and –6.9%, respectively) compared with OO (–0.9%) (both, P < 0.05), as were TG levels (–14.6% and –20.6%, respectively, vs –5.9%; both, P < 0.001). LDL-C levels increased with OM3-FFA 2 g/d (4.6%) compared with OO (1.1%) (P = 0.025) but not with OM3-FFA 4 g/d (1.3%). Total cholesterol and VLDL-C concentrations were reduced compared with OO with both OM3-FFA dosages, and the total cholesterol/HDL-C ratio and apo AI and apo B levels were significantly lowered with OM3-FFA 4 g/d only (all at least P < 0.05). Percent changes from baseline in HDL-C did not differ between OO and either OM3-FFA group. Plasma concentrations of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid were significantly increased and arachidonic acid was significantly reduced in both OM3-FFA treatment groups compared with the OO responses (all, P < 0.001). Withdrawals related to treatment-emergent adverse events ranged from 0.9% with OO to 3.2% with OM3-FFA 4 g/d.

Conclusions

OM3-FFA was well tolerated and lowered non–HDL-C and TG levels at both 2- and 4-g/d dosages in patients with persistent hypertriglyceridemia taking a statin, with the 4-g/d dosage providing incremental improvements compared with 2 g/d. ClinicalTrials.gov identifier: NCT01408303.     

高血脂症性急性胰腺炎临床分析

目的分析高血脂症性急性胰腺炎（HLP）的临床特点及治疗。方法将2002-09-2004-04收集资料完整的249例急性胰腺炎（AP）患者,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（TG）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（CTS1）分级、禁食水时间、住院天数、PLT、HCT、血Ca2＋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。     

内源性高甘油三酯血症者血浆脂蛋白中脂质和载脂蛋白组成及分布的初步研究

对7例内源性高甘油三酯血症者(HTG)及4例血脂正常者血浆的VLDL、IDL、LDL、HDL_2及HDL_3中脂质及载脂蛋白(apo)AI、B100、CⅡ、CⅢ、E的组成和分布进行了比较研究。HTG者VLDL富含甘油三酯、胆固醇及磷酯,其apoCⅡ、CⅢ的含量显著增加;HDL中甘油三酯含量增加,而胆固醇、apoCⅡ及CⅢ含量显著减少;HDL_2中apoA I含量减少。VLDL和HDL这种组成异常可能系胆固醇和apoC由HDL向VLDL转移增加而引起脂质和载脂蛋白分布异常所致。     

Reversible cerebral ischemias: a comparative analysis of risk factors in TIAs and in RINDs

A retrospective study in which 709 patients, 522 with RIND and 187 with TIA, were compared in respect of common risk factors (RFs) for acute cerebro-vascular disease. The two forms of the disease differed significantly in respect of smoking, hematocrit, hypercholesteremia, hypertriglyceridemia and hyperuricacidemia. Although these RFs do not seem to be determinants of or discriminants between the two forms of acute cerebrovascular disease, it is nonetheless highly probable that, together with all the other RFs, they have a facilitatory role.

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Sommario Sono stati confrontati, per i comuni Fattori di Rischio (RF) delle vasculopatie cerebrali acute, 709 soggetti di cui 522 affetti da RIND e 187 affetti da TIA. Il fumo, l'ematocrito, l'ipercolesterolemia, l'ipertrigliceridemia e l'iperuricemia hanno mostrato differenze statisticamente significative nelle due forme di vasculopatie cerebrali ischemiche acute. Anche se i suddetti RF non sembrano poter svolgere un ruolo determinante e/o discriminante tra le due forme cliniche di vasculopatia, è, tuttavia, molto probabile che questi assieme a tutti gli altri RF possano svolgere un ruolo favorevole.

     

Diabete mellito,uricemia e gotta

Riassunto Esistono in letteratura numerosi dati statistici relativi alla associazione tra diabete mellito, livelli di acido urico circolante e gotta. Tali statistiche sono però difficilmente confrontabili tra di loro, in quanto la casística esaminata è spesso disomogenea, in particolare per quanto riguarda i soggetti portatori di dispurinia. Viene infatti spesso trascurato l’aspetto puramente metabolico dell’alterato ricambio nucleo-proteico, per cui solo una percentuale molto bassa di dispurinemici va incontro alla fase articolare della malattia, anche se nel frattempo si sono sviluppati pesanti interessamenti viscerali. Va inoltre ricordata la notevole frequenza di periodi di normouricemia in corso di dispurinemia. Addentrandosi poi nel problema più particolare della correlazione tra diabete mellito ed iperuricemia, l’A., dopo una rapida sintesi del metabolismo dell’acido urico e dei punti di contatto tra metabolismo purinico e metabolismo glico-lipidico, considera l’azione del fruttosio sul metabolismo delle purine e richiama l’attenzione sul problema della ipertrigliceridemia, che può essere considerata il punto di contatto tra le due forme dismetaboliche. L’A. conclude che diabete mellito e dispurinemie, pur nascendo da alterazioni endocrino-metaboliche simili, seguono nel loro sviluppo due binari paralleli, i cui punti di contatto sono, da una parte, in corso di diabete mellito, l’insorgenza di una iperuricemia inapparente perché mascherata da una aumentata dismissione, ma obiettivabile con prove di stimolo, dall’altra, in corso di iperuricemia primaria, una alterazione della cinetica dell’insulina che condiziona un alterato ricambio glicidico.

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Summary The literature contains a wealth of statistical data concerning the relationship between diabetes mellitus, circulating uric acid levels, and gout. But it is difficult to compare these various statistics because the series examined often lack homogeneousness, especially as far as dyspurinemia is concerned. In fact, the purely metabolic expression of the altered nucleo-protein breakdown, i.e. the fact that only a very small percentage of dyspurinemic subjects fall victims to the articular manifestation of the disorder even if in the meantime severe visceral involvement has occurred, is often disregarded. Further, the high prevalence of periods of normal uric acid blood levels in the course of dyspurinemia should be remembered. After a synthetic review of uric acid metabolism and of the points of contact between purine and carbohydrate-lipid metabolism, the author considers the role of fructose in purine metabolism and discusses the problem of the correlation between diabetes and hyperuricemia. Particular stress is laid upon the problem of hypertriglyceridemia which may be considered the connecting link of the two dysmetabolic conditions. The author comes to the conclusion that, while originating from similar hormonal and metabolic disorders, diabetes and dyspurinemia develop along different though parallel lines the points of contact of which are, on the one hand, the appearance of hyperuricemia in diabetes mellitus (this may be inapparent because it is masked by increased excretion but can be shown by tolerance tests), and on the other hand a change in insulin kinetics in the course of primary hyperuricemia with consequent alteration of carbohydrate metabolism.

Traduzione a cura della Redazione.     

NEONATAL HYPERTRIGLYCERIDEMIA A New Index of Antepartum-Intrapartum Fetal Stress?

Abstract. The 95th percentile value of cord serum triglyceride concentration in 82 consecutively live born infants was found to be 0.79 mmol/1. This level was arbitrarily used to define neonatal hypertriglyceridemia. A comparison between 78 normotriglyceridemic and 61 hypertriglyceridemic newborn infants showed a significant association between elevated cord serum triglyceride concentration and insufficiency of the placenta, fetal bradycardia, meconium-stained amniotic fluid and one-minute Apgar score ≤7. A significantly ( p <0.001) greater number of infants with one or several of these four factors, indicating antepartum and/or intrapartum fetal stress were found to be hypertriglyceridemic at birth. This finding suggests that estimation of cord serum triglyceride which is easy and inexpensive might be of value for a more complete evaluation of the newborn infant, and can serve as a supplement to the Apgar Score system.     

两种高脂血症小鼠模型糖代谢及靶组织胰岛素敏感性研究

目的 观察高三酰甘油血症和高胆固醇血症小鼠的糖代谢及靶组织（肝脏和骨骼肌）胰岛素敏感性的变化。方法 采用普通饲料喂养小鼠（对照组,n=8）、脂蛋白脂酶基因敲除杂合子小鼠（LPL+/-）（高三酰甘油血症组,n=8）和高脂饲料喂养小鼠（高胆固醇血症组,n=8）作为实验对象。测量各组小鼠的体质量;检测血清三酰甘油（TG）、胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、血糖浓度和空腹胰岛素水平,计算稳态模型胰岛素抵抗指数（HOMA-IR）和胰岛素敏感指数（ISI）;Western blotting检测肝脏和骨骼肌组织在胰岛素刺激后Akt473位丝氨酸磷酸化水平（p-Aktser473的相对表达量）的变化。结果 高三酰甘油血症组血清TG浓度显著高于对照组和高胆固醇血症组（P<0.05）,高胆固醇血症组血清TC浓度显著高于对照组和高三酰甘油血症组（P<0.05）。与对照组比较,高三酰甘油血症组血糖浓度、空腹胰岛素水平和HOMA-IR有增高趋势,ISI则有所降低,但差异均无统计学意义（P>0.05）;与对照组和高三酰甘油血症组比较,高胆固醇血症组血糖浓度、空腹胰岛素水平和HOMA-IR显著升高,而ISI明显下降（均P<0.05）。高三酰甘油血症组和高胆固醇组肝脏和骨骼肌组织经胰岛素刺激后的p-Aktser473相对表达量及其升高倍数显著低于对照组（P<0.05）;在高胆固醇组,肝脏组织p-Aktser473相对表达量的升高倍数显著低于高三酰甘油血症组,骨骼肌组织在胰岛素刺激后的p-Aktser473相对表达量明显高于高三酰甘油血症组（P<0.05）。结论 高三酰甘油血症和高胆固醇血症均伴有靶组织胰岛素敏感性受损,其中高脂喂养小鼠出现高胆固醇血症时伴有更明显的糖代谢紊乱。