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At least 19 recordsLinked to original sources
PubMed2006

Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia.

Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in clinical practice. It is known to induce life-threatening acute pancreatitis, but its role in atherogenesis remains elusive. Hemorheological abnormality was thought to play an important role in pathogenesis of both pancreatitis and atherosclerosis. However, hemorheology in severe HTG was not well investigated. Recently, we established a severe HTG mouse model deficient in lipoprotein lipase (LPL) in which severe HTG was observed to cause a significant increase in plasma viscosity. Disturbances of erythrocytes were also documented, including decreased deformability, electrophoresis rate, and membrane fluidity, and increased osmotic fragility. Scanning electron microscopy demonstrated that most erythrocytes of LPL deficient mice deformed with protrusions, irregular appearances or indistinct concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of membrane lipids may be partially responsible for the hemorheological and morphologic abnormalities of erythrocytes. This study indicated that severe HTG could lead to significant impairment of hemorheology and this model may be useful in delineating the role of severe HTG in the pathogenesis of hyperlipidemic pancreatitis and atherosclerosis.

Animals↗
PubMedDate not supplied

Safety and efficacy of Omacor in severe hypertriglyceridemia.

BACKGROUND: Severe hypertriglyceridemia is a risk factor for acute pancreatitis, therefore decreasing serum triglyceride concentrations is an important component of risk management. Omega-3 fatty acids are well known hypotriglyceridemic agents, but their efficacy in severe forms of the disorder is not well documented. Our objective was to examine the effects of Omacor, a drug composed of 85% omega-3 fatty acid ethyl esters. METHODS: Forty-two patients with triglyceride concentrations between 5.65 and 22.60 mmol/l (500 and 2000 mg/dl) were studied in a prospective, double-blind, placebo-controlled trial of Omacor (4 g/day for 4 months). RESULTS: Compared with baseline values, Omacor significantly reduced mean triglyceride concentrations by 45% (P<0.00001), cholesterol by 15% (P< 0.001), very-low-density lipoprotein cholesterol by 32% (P< 0.0001) and cholesterol:high density lipoprotein (HDL) cholesterol ratio by 20% (P=0.0013), and increased HDL cholesterol by 13% (P=0.014) and low-density lipoprotein cholesterol by 31% (P=0.0014). The placebo had no effect on these parameters. Omacor was well tolerated and no patient discontinued medication because of side effects. CONCLUSIONS: Four capsules of Omacor per day markedly decreased triglyceride concentrations in patients with severe hypertriglyceridemia. The availability of a potent and safe omega-3 fatty acid preparation for this patient population should diminish the risk for acute pancreatitis, and may also reduce the long-term risk for cardiovascular disease.

Cholesterol↗
PubMed1999

Clomiphene-induced severe hypertriglyceridemia and pancreatitis.

Clomiphene has been available for clinical use since 1960 and has been successfully used to aid fertility in women with certain anovulatory disorders. It is a synthetic estrogen analog, of the triphenylethylene derivative group, and its biochemical structure is similar to that of tamoxifen. Estrogen and tamoxifen lower total and low-density lipoprotein cholesterol and increase triglyceride and high-density lipoprotein cholesterol levels. In patients with baseline hypertriglyceridemia, these agents can induce severe hypertriglyceridemia and pancreatitis. The actions of clomiphene on lipid metabolism have not been studied, and to our knowledge, no cases of severe hypertriglyceridemia related to the use of clomiphene have been described. We report the case of a woman who developed 2 episodes of clomiphene-induced hypertriglyceridemia and pancreatitis while receiving this drug for treatment of infertility. Given the striking structural similarity between clomiphene and tamoxifen, it is likely that clomiphene is capable of inducing severe hypertriglyceridemia in patients with certain underlying lipid disorders by a mechanism similar to that of tamoxifen.

Adult↗
PubMed1999

[Comparison of LDL-C values measured with the automated method and the ultracentrifugation method in severe hypertriglyceridemia, and prevalence and life-style of patients with hypertriglyceridemia].

The correlation between LDL-cholesterol (LDL-C) values assayed by the direct method and the ultra-centrifugation method is reported good in normal to moderate hypertriglyceridemia, but it is not clear in severe hypertriglyceridemia. We examined such a correlation in mild (triglycerides, 150-400 mg/dl; n = 3) and severe (> or = 800 mg/dl, n = 9) hypertriglyceridemia. The bias of LDL-C determined by the direct method in comparison with the ultracentrifugation method was from -1.1% to 3.4% and from -49.5% to 15.7% in mild and severe hypertriglyceridemia, respectively. The prevalence of severe hypertriglyceridemia was only 0.2% both in hospital patients and in company workers. Data analyses of company workers indicated that people with severe hypertriglyceridemia have a higher body-mass index, consume more alcohol, smoke more, and exercise less than those with a normal level of triglycerides. These results suggest that there is not a good correlation between LDL-C values assayed by the direct method and the ultracentrifugation method in severe hypertriglyceridemia; but that the direct method can be used for the clinical examination of LDL-C, because of the very low prevalence of severe hypertriglyceridemia. Patients with severe hypertriglyceridemia should improve their life-style as soon as possible.

Adult↗
PubMed2003

An observational study of severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride-lowering therapy when estrogens are given to women with and without familial hypertriglyceridemia.

BACKGROUND: We assessed severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride-lowering therapy when estrogens were given to 56 women with and without familial hypertriglyceridemia. The 56 women had been consecutively referred to our center over a 3-year period because of triglycerides >400 mg/dl despite diet-drug treatment and/or a history of hypertriglyceridemic acute pancreatitis (AP). Of the 56 women, 17 had received estrogen replacement therapy (ERT), hormone replacement (HRT, n=6), or selective estrogen receptor modulators (SERM, n=1). METHODS: After study at entry, in 56 women (median age, 52 years), 36 with familial hypertriglyceridemia, to lower triglycerides, estrogens and SERMs (hormone treatment, HT) were stopped; a very low fat diet (<15% of calories), gemfibrozil (1.2-1.5 mg/day), and omega-3-fatty acid (4-12 g/day) were started, with restudy 2-4 weeks later. RESULTS: Of the 56 women, 24 (43%) were taking HT at entry, with median fasting triglycerides 1270 mg/dl in the HT group and 1087 mg/dl in the no-HT group. Seventeen women (30%) had a history of AP, nine of whom (53%) were/had been on HT at the development of AP. Significant positive correlates of triglycerides at entry in a stepwise regression model were hemoglobin A(1C) (partial r(2)=10.7%, p<0.05) and an interaction between estrogen use and familial hypertriglyceridemia (partial r(2)=15%, p=0.017). After 2-4 weeks on therapy, median triglycerides in the previous-HT group fell from 1270 to 284 mg/dl (p<0.0001) and in the no-HT group from 1087 to 326 mg/dl (p<0.0001). CONCLUSIONS: Before starting HT, to avoid HT induced hypertriglyceridemic AP and exacerbation of overt or covert familial hypertriglyceridemia, triglycerides must be measured. HT is contraindicated in women with preexisting hypertriglyceridemia (triglycerides> or =500 mg/dl). Triglyceride-lowering diets and drugs often fail in the presence of HT and/or poorly controlled diabetes mellitus, but commonly succeed when HT is stopped and diabetes mellitus is tightly controlled.

Adult↗
PubMedDate not supplied

[Insulin therapy in patients with severe hypertriglyceridemia].

A series of seven patients with severe hypertriglyceridemia (triglyceride levels > 1000 mg/dL) is presented. Four of the patients were diabetics, two of them were in treatment with anti-retroviral drugs, and three of them presented acute pancreatitis. In all patients intravenous infusion of insulin was initiated at a rate of 0.05-2 U/kg/day. Two and a half days after this treatment, the serum triglyceride level remained lower than 400 mg/dL. There were no complications during the treatment. The long treatment included basal insulin, fibrates and avoidance of pharmacotherapy. Insulin therapy for diabetic and non-diabetic patients with severe hypertriglyceridemia is an effective and safe treatment.

Female↗
PubMed2004

Inherited apolipoprotein A-V deficiency in severe hypertriglyceridemia.

OBJECTIVE: Mutations in LPL or APOC2 genes are recognized causes of inherited forms of severe hypertriglyceridemia. However, some hypertrigliceridemic patients do not have mutations in either of these genes. Because inactivation or hyperexpression of APOA5 gene, encoding apolipoprotein A-V (apoA-V), causes a marked increase or decrease of plasma triglycerides in mice, and because some common polymorphisms of this gene affect plasma triglycerides in humans, we have hypothesized that loss of function mutations in APOA5 gene might cause hypertriglyceridemia. METHODS AND RESULTS: We sequenced APOA5 gene in 10 hypertriglyceridemic patients in whom mutations in LPL and APOC2 genes had been excluded. One of them was found to be homozygous for a mutation in APOA5 gene (c.433 C>T, Q145X), predicted to generate a truncated apoA-V devoid of key functional domains. The plasma of this patient was found to activate LPL in vitro less efficiently than control plasma, thus suggesting that apoA-V might be an activator of LPL. Ten carriers of Q145X mutation were found in the patient's family; 5 of them had mild hypertriglyceridemia. CONCLUSIONS: As predicted from animal studies, apoA-V deficiency is associated with severe hypertriglyceridemia in humans. This observation suggests that apoA-V regulates the secretion and/or catabolism of triglyceride-rich lipoproteins. Mutations in APOA5 gene might be the cause of severe hypertriglyceridemia in subjects in whom mutations in LPL or APOC2 genes have been excluded. We detected a nonsense mutation in APOA5 gene (Q145X) in a boy with hyperchylomicronemia syndrome. This is the first observation of a complete apoA-V deficiency in humans.

Amino Acid Substitution↗
PubMed1990

Severe hypertriglyceridemia in diabetic ketosis.

In order to learn whether patients with diabetic ketosis who had very severe hypertriglyceridemia had underlying genetic hyperlipidemia, the authors measured plasma lipids in 211 episodes. They report the findings in the 15 patients who had initial plasma triglyceride concentrations above 11.3 mmol/L (1,000 mg/dL). These patients were detected during a prospective study of 155 episodes of ketoacidosis and 56 episodes of ketosis. Eleven of the 15 patients had definite or probable insulin-dependent diabetes mellitus (IDDM), but eight of the 15 were not acidemic despite their ketosis. Twelve of the 15 patients (80%) were men, a far higher percentage of men than the 53.6% in the base population of 211 episodes. Plasma triglyceride concentrations returned to normal levels either during the acute episode (seven cases) or well within a year (two more cases) in most of the patients. From that and other considerations, the authors infer that at least ten, and perhaps 12 of the 15 patients did not have an underlying genetic hyperlipidemia contributing to their original severe hypertriglyceridemia. That contrasts with the findings of others who reported that most patients with severe hypertriglyceridemia associated with noninsulin-dependent diabetes mellitus (NIDDM) (usually without ketosis) did have coexisting familial hypertriglyceridemia.

Adult↗
PubMed2006

Plasma exchange in severe hypertriglyceridemia a clinical study.

BACKGROUND: Hypercholesterolemia and hypertriglyceridemia are independent risk factors for atherosclerotic heart diseases. Moreover acute pancreatitis may occur in patients with severe hypertriglyceridemia. AIM OF THE STUDY: To evaluate the effectiveness of plasma exchange (PE) in patients with severe hypertriglyceridemia. METHODS: Seven patients with severe hypertriglyceridemia (a triglyceride level of more than 1000mg/dl) were treated with PE. After PE, lipid and hematological parameters and side effects were evaluated. RESULTS: Triglyceride levels decreased below 1000mg/dl in all patients. The levels of triglyceride and very low-density lipoprotein cholesterol (p<0.05 for both), and total cholesterol (p<0.005) decreased significantly. PE was well-tolerated. Liver and renal functions, hematological parameters, except for an increase in white blood cell counts, did not change significantly. CONCLUSION: PE may be used safely and effectively in severe hyperlipidemic patients at risk of acute coronary events and acute pancreatitis. Further extended studies may provide more detailed information.

Humans↗
PubMed2001

Severe hypertriglyceridemia with plasma inhibitory factor(s) on lipoprotein lipase activity in a patient with a common Ser(447)-Ter LPL mutation.

Severe hypertriglyceridemia is a major risk for acute pancreatitis. So far, several mutations on the lipoprotein lipase (LPL) gene causing type I hyperlipidemia have been identified. However, the common mutation Ser(447)-Ter has been recently proposed to have a lowering effect on serum triglyceride concentrations in the general population. In this study, we analyzed blood from a patient suffering from severe hypertriglyceridemia and pancreatitis with the mutation on the lipoprotein lipase gene, Ser(447)-Ter. The patient's plasma showed inhibitory effects on the LPL activities from normal subjects. The bottom fraction separated by ultracentrifugation revealed enhanced effects as an inhibitory factor. The inhibitory effect observed in the bottom fraction was dose-dependent, stable at treatment of 65 degrees C for 30 min, and decreased significantly after being dialyzed using membranes with a cut-off molecular weight of 3500 or 6000 Da. The inhibitory effect was significantly higher when the post-heparin plasma was used from the patient or a subject with the same LPL mutation as an LPL source, compared to that from normal subjects. These results suggest that the patient has inhibitory factors in his plasma. Such inhibitory factors might cause severe hypertriglyceridemia in a case with the common mutation, which has been proposed to show the lowing effect on serum triglyceride concentrations in the general population.

Acute Disease↗
PubMed2006

Capecitabine-induced severe hypertriglyceridemia: report of two cases.

OBJECTIVE: To report 2 cases of severe hypertriglyceridemia associated with the use of oral capecitabine. CASE SUMMARIES: The first patient was a 73-year-old woman with metastatic breast carcinoma who received capecitabine 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 324 mg/dL; after 2 cycles of capecitabine, levels increased to 916 mg/dL. Although lipid-lowering treatment was initiated, triglyceride levels peaked at 1782 mg/dL by the end of the seventh cycle. Eight weeks after capecitabine treatment was stopped, triglyceride levels decreased to 118 mg/dL. The second patient was a 59-year-old man with metastatic colorectal carcinoma who was placed on capecitabine treatment at a dosage of 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 244 mg/dL; levels peaked at 1455 mg/dL at the end of the fifth cycle. Capecitabine treatment was discontinued due to disease progression, and triglyceride levels decreased to 154 mg/dL after 11 weeks. DISCUSSION: The most frequently reported adverse effects of capecitabine are gastrointestinal and hematologic effects and palmar-plantar erythrodysesthesia. Drug-induced hyperlipidemia may appear more readily in individuals with hereditary lipoprotein lipase deficiency because decreased lipoprotein lipase activity might make these individuals more susceptible to a rise in triglyceride levels. The Naranjo probability scale indicated a probable relationship between capecitabine and severe hypertriglyceridemia. CONCLUSIONS: Capecitabine should be prescribed with care, especially in patients with preexisting hypertriglyceridemia. The question of whether capecitabine actually causes hypertriglyceridemia needs careful consideration, and the possible mechanism by which it may cause this adverse effect requires further investigation.

Aged↗
PubMed1997

Severe hypertriglyceridemia caused by tamoxifen-treatment after breast cancer surgery.

Tamoxifen, a nonsteroidal estrogen antagonist, has been widely used in a hormonal treatment for breast cancer. The side effects of tamoxifen are generally recognized to be mild. However, we experienced three cases of severe hypertriglyceridemia and/or hyperglycemia induced by tamoxifen. For normalization of their hypertriglyceridemia we need to stop giving tamoxifen. In one of three cases we analyzed her lipoprotein profile in detail with lipoprotein lipase activities and apolipoprotein E phenotype. The case was a 49 year-old woman. After 15 months of tamoxifen administration, she was diagnosed as severe hypertriglyceridemia. Consecutively, severe hyperglycemia was occurred to need insulin therapy. After tamoxifen withdrawal, her triglyceride and glucose levels improved. Her lipolytic enzyme was reduced during tamoxifen treatment. Apolipoprotein E phenotype was uncommon E4/2. Although hypertriglyceridemia was not considered to be a risk factor for coronary heart disease, a marked hypertriglyceridemia might occasionally produce severe lethal pancreatitis. We recommend that a periodic plasma lipid analysis is needed for patients treated with tamoxifen, especially for diabetic and hypertriglyceridemic patients, to avoid such complications.

Antineoplastic Agents, Hormonal↗
PubMed1993

Lipoprotein lipase mass and activity in severe hypertriglyceridemia.

To clarify the role of defective lipoprotein lipase (LPL) in hypertriglyceridemia, the LPL masses and LPL activities in post-heparin plasma (PHP) were studied in severe hypertriglyceridemias. The developed sandwich enzyme immunoassay for the LPL was sensitive from 0.5 to 20 ng/ml of LPL in human PHP. The plasma LPL mass increased by heparin injection (30 USP units/kg) and was found to positively correlate with LPL activity. The mean LPL activity from PHP of normal controls was 2,960 +/- 1,057 nmol/ml/h. The mean LPL masses from human pre- and 15-min post-heparin plasma from normal subjects were 25 +/- 5 ng/ml and 224 +/- 60 ng/ml, respectively. Thus the specific activity of LPL from PHP of normal controls was calculated to be 13.3 mumol FFA released/h/microgram LPL. Among hypertriglyceridemic patients with over 1,000 mg/dl of serum triglyceride, the incidence of patients with LPL masses less than -2 standard deviations (S.D.) of those of average normal control subjects was found to be 27%. Seventy percent of patients showed specific activities within + 2 S.D. of those of average control LPL, and 30% showed significantly low specific activities less than -2 S.D. despite the fact that LPL masses were not less than -2 S.D. of the average normal controls. These results suggest that the evaluation of LPL masses in PHP would be useful for finding functionally defective LPL in patients with hypertriglyceridemia, and that up to 30% severe hypertriglyceridemias may have functionally defective LPL.

Adult↗
PubMed1996

Prevention of recurrent acute pancreatitis in patients with severe hypertriglyceridemia: value of regular plasmapheresis.

The association between acute pancreatitis and severe hypertriglyceridemia has long been recognized. We report two cases of severe primary hypertriglyceridemia (types 1 and V) with recurrent acute pancreatitis. In both patients, observance of appropriate diet and drug therapy was insufficient. Recurrent episodes of pancreatitis were precipitated by dietary fat or alcohol abuse. A plasmapheresis was performed every 4 weeks to decrease the incidence of pancreatitis. It appears that plasmapheresis is a safe and highly effective method for quickly removing serum triglycerides. Moreover, plasma-pheresis may be useful for preventing acute pancreatitis.

Acute Disease↗
PubMed1983

Severe hypertriglyceridemia: role of familial and acquired disorders.

To evaluate the role of familial and secondary factors in the etiology of severe hypertriglyceridemia, family studies were performed and potential secondary causes of hypertriglyceridemia were evaluated in 54 patients with plasma triglyceride levels above 2000 mg/dl. Every subject had hypertriglyceridemic relatives, compatible with a familial form of hyperlipidemia, although plasma triglyceride levels in the relatives were substantially lower than in the index patients. In 5 index patients, both parents had hyperlipidemia. Four of these 5 had no coexisting secondary cause for hypertriglyceridemia. Forty-six of the remaining 49 (94%) also had potential secondary causes of hypertriglyceridemia, most commonly untreated diabetes mellitus. These findings suggest that severe hypertriglyceridemia frequently results from the coexistence of familial and secondary forms of hyperlipidemia.

Adolescent↗
PubMed2006

A novel substitution at the translation initiator codon (ATG-->ATC) of the lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis.

A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes.

Adolescent↗
PubMed2002

Severe hypertriglyceridemia and pancreatitis following hormone replacement prior to cryothaw transfer.

PURPOSE: A case of acute pancreatitis with severe hypertriglyceridemia occurred following use of intramuscular estradiol valerate during endometrial preparation for cryopreserved embryos. METHODS: A 30-year-old woman with primary infertility and a past history of well-controlled hypothyroidism, underwent endometrial development with intramuscular estradiol valerate in preparation for the transfer of cryopreservred embryos. RESULTS: Initial hospitalization, discontinuation of all estrogens, aggressive intravenous fluid hydration, and initiation of low-fat diet with additional gemfibrozil treatment resulted in complete resolution of all symptoms related to the pancreatitis including the hyperlipidemia. A subsequent cryothaw cycle using oral estradiol resulted in a viable pregnancy with only mild increases in the patient's triglyceride and cholesterol levels noted throughout her 38-week gestation. CONCLUSION(S): Estradiol valerate, a commonly used form of estrogen for endometrial preparation during cryothaw cycles, may cause severe hypertriglyceridemia and acute pancreatitis in certain predisposed individuals. Oral and transdermal estrogens should be the preferred method of endometrial preparation in patients at high risk for lipid metabolism disorders, such as patients with polycystic ovarian syndrome and familial hypertriglyceridemia. These estrogens are more rapidly metabolized and have a shorter half life compared to that of estradiol valerate.

Cryopreservation↗