251 articles - 08.09.10
1: Am J Cardiol. 2010 May 15;105(10):1409-12. Epub 2010 Mar 30.
Maki KC, Dicklin MR, Davidson MH, Doyle RT, Ballantyne CM; COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators.
Provident Clinical Research, Glen Ellyn, Illinois, USA. kmaki@providentcrc.com
The present post hoc analysis of data from the COMBination of prescription Omega-3 with Simvastatin (COMBOS) study investigated the predictors of the low-density lipoprotein (LDL) cholesterol response to prescription omega-3 acid ethyl ester (P-OM3) therapy in men and women with high (200 to 499 mg/dl) triglycerides during diet plus simvastatin therapy. Subjects (n = 256 randomized) received double-blind P-OM3 4 g/day or placebo for 8 weeks combined with diet and open-label simvastatin 40 mg/day. The percentage of changes from baseline (with diet plus simvastatin) in lipids was evaluated by tertiles of baseline LDL cholesterol and triglyceride concentrations. The baseline LDL cholesterol tertile was a significant predictor of the LDL cholesterol response (p = 0.022 for the treatment by baseline tertile interaction). The median LDL cholesterol response in the P-OM3 group was +9.5% (first tertile, <80.4 mg/dl), -0.9% (second tertile), and -6.4% (third tertile, > or =99.0 mg/dl). Non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride responses did not vary significantly by baseline LDL cholesterol tertile. The reductions in very-low-density lipoprotein cholesterol concentrations were greater than the increases in LDL cholesterol, where present, resulting in a net decrease in the concentration of cholesterol carried by atherogenic particles (non-high-density lipoprotein cholesterol) in all baseline LDL cholesterol tertiles. In conclusion, these results suggest that the increase in LDL cholesterol that occurred with the addition of P-OM3 to simvastatin therapy in subjects with mixed dyslipidemia was confined predominantly to those with low LDL cholesterol levels while receiving simvastatin monotherapy. Copyright 2010 Elsevier Inc. All rights reserved.
Publication Types: Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20451686&dopt=ExternalLink
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PMID: 20451686 [PubMed - indexed for MEDLINE]2: Clin Exp Hypertens. 2010 Jan;32(2):137-44.
Cicero AF, Derosa G, Di Gregori V, Bove M, Gaddi AV, Borghi C.
Lipid Research Unit, Department of Internal Medicine, Aging and Kidney Diseases, Alma Mater Studiorum University of Bologna, Bologna, Italy. afgcicero@cardionet.it
Recent evidence suggests that at least a part of the polyunsaturated fatty acids (PUFAs) heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. We retrospectively evaluated the long-term effect of a PUFA supplementation on the blood pressure level of 111 hypertriglyceridemic subjects with untreated normal-high blood pressure that were prescribed a 2 grams PUFA supplementation in order to improve their plasma lipid pattern. After 12 months of treatment, systolic blood pressure (SBP) meanly decreased by 2.7 +/- 2.5 mmHg (p = 0.001) and diastolic blood pressure (DBP) by 1.3 +/- 3.3 mmHg (p < 0.001), while basal heart rate decreased by 4.0 +/- 4.4 bpm (p < 0.001). Both SBP and DBP reduction were significantly related to the baseline SBP (p < 0.001) and DBP (p < 0.001), respectively. Diastolic blood pressure change was also inversely related to the patient's age (p = 0.004). No significant difference was perceived in the metabolic syndrome subgroup. In our retrospective study, highly purified omega-3 PUFA long-term supplementation is associated with a significant reduction in SBP, DBP, Pulse pressure (PP), and basal heart rate in hypertriglyceridemic patients with normal-high blood pressure. No significant difference was perceived in the metabolic syndrome subgroup. The main determinants of the PUFA anti-hypertensive effect appear to be the basal blood pressure level and age.
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PMID: 20374188 [PubMed - indexed for MEDLINE]3: Curr Med Res Opin. 2010 Apr;26(4):907-15.
Bays HE, Maki KC, McKenney J, Snipes R, Meadowcroft A, Schroyer R, Doyle RT, Stein E.
Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA. HBaysMD@aol.com
OBJECTIVE: Assess the long-term efficacy and safety of prescription omega-3-acid ethyl esters (P-OM3) coadministered with simvastatin in an extension of the Combination of Prescription Omega-3 Plus Simvastatin (COMBOS) trial. METHODS: COMBOS included hypertriglyceridemic patients (triglyceride [TG] >or=200 mg/dL and <500 mg/dL or >or=2.26 mmol/L and <5.64 mmol/L) with low density lipoprotein cholesterol (LDL-C) level no greater than 10% above the National Cholesterol Education Program, Adult Treatment Panel III treatment goal. After an 8-week lead-in phase with simvastatin 40 mg/day (which continued throughout the trial), subjects were randomized to 8 weeks of P-OM3 4 g/day or placebo. Completers were eligible to participate in a 24-month extension study. Those who received placebo + simvastatin in COMBOS switched to open-label P-OM3 + simvastatin ('Switchers'); those who received P-OM3 + simvastatin during COMBOS continued the same regimen (open-label) in the extension phase ('Non-switchers'). The primary endpoint was the difference between Non-switchers and Switchers in median percent change in non-high-density lipoprotein-cholesterol (non-HDL-C) from COMBOS end of treatment to Month 4 of the extension phase. RESULTS: At Month 4 from COMBOS end of treatment, non-HDL-C was reduced by a median of 9.4% in Switchers and increased by 0.9% in Non-switchers (p < 0.001). For the total population (combined Non-switcher + Switcher population), the median percent change from COMBOS baseline to Months 4, 12, and 24 was -8.3%, -7.3%, and -8.9%, respectively (all p < 0.001). This extension study revealed no unexpected safety findings. A limitation of this study was a gap between completion of COMBOS and enrollment in the extension phase for some patients; however, a post-hoc non-HDL-C sensitivity analysis performed at the 4-month primary endpoint revealed no influence of gap on study results. CONCLUSIONS: In this 24-month extension study, P-OM3 was generally well tolerated, and produced sustained reductions in non-HDL-C levels in simvastatin-treated patients with TG levels between 200 and 500 mg/dL (2.26 mmol/L and 5.64 mmol/L). CLINICAL TRIAL REGISTRY NUMBER: NCT00903409.
Publication Types: Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20156032&dopt=ExternalLink
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PMID: 20156032 [PubMed - indexed for MEDLINE]4: Ann Nutr Metab. 2010;56(3):170-5. Epub 2010 Feb 12.
Hauenschild A, Bretzel RG, Schnell-Kretschmer H, Kloer HU, Hardt PD, Ewald N.
Third Medical Department and Policlinic, University Hospital of Giessen and Marburg, Giessen, Germany.
BACKGROUND: Patients with highly increased plasma triglyceride levels are at risk of developing serious complications such as pancreatitis, coronary heart disease and stroke. Therefore it is important to rapidly decrease plasma triglyceride levels. A sufficient control of triglyceride levels with drugs like fibrates, statins or nicotinic acid can usually only be attained after a couple of weeks. Plasma exchange appears to be a fast but expensive method to reduce triglyceride levels. In this study we describe the use of a new omega-3 fatty acid and medium-chain triglyceride-rich formula diet as a therapeutic concept to reduce plasma triglyceride levels fast and effectively. METHODS: Thirty-two patients with severe hypertriglyceridemia were treated with the especially composed formula diet for a period of 7 days. RESULTS: Within this period of time, plasma triglycerides decreased from 1,601 (402-4,555) to 554 (142-2,382) mg/dl (p < 0.05). Total cholesterol levels were reduced from 417 (211-841) to 287 (165-457) mg/dl (p < 0.001). Fasting glucose and uric acid levels also slightly decreased (-8%; -12%). The formula diet as a 1-week treatment was well tolerated and accepted by the patients. CONCLUSION: This diet was successfully used as an acute treatment in severe hypertriglyceridemia and showed effectiveness in rapidly and safely lowering plasma triglyceride levels. (c) 2010 S. Karger AG, Basel.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20150726&dopt=ExternalLink
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PMID: 20150726 [PubMed - indexed for MEDLINE]5: Circ J. 2010;74(3):510-7. Epub 2010 Feb 9.
Origasa H, Yokoyama M, Matsuzaki M, Saito Y, Matsuzawa Y; JELIS Investigators.
Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Japan. horigasa@las.u-toyama.ac.jp
BACKGROUND: Despite the risk of critical heart disease, poor adherence to treatment is common in patients with lifestyle-related diseases such as hypercholesterolemia. The association between adherence to treatment and clinical outcome was examined in JELIS (Japan EPA Lipid Intervention Study) and strategies for avoiding poor adherence were explored. METHODS AND RESULTS: Patients taking 80% or more of the study medications were considered to exhibit good adherence. The primary endpoint was either sudden cardiac death or myocardial infarction. Adherence was lower in the eicosapentaenoic acid (EPA) + statin group (66.5%) than in the statin alone group (72.5%). In good adherers with previous coronary artery disease, EPA substantially reduced the risk compared with statin alone (hazard ratio 0.55, 95% confidence intervals 0.34-0.88, P<0.014). Furthermore, the clinical benefit of EPA + statin was significantly larger in patients with good adherence than in those with poor adherence (P=0.041). Finally, a 5-year risk prediction model constructed from the data indicated that complete adherence would lead to 51% reduction of risk compared with non-adherence. CONCLUSIONS: Good adherence to medication was associated with a lower cardiovascular risk than with poor adherence, and the assistance of a pharmacist is of great importance in achieving persistent adherence during treatment.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20145342&dopt=ExternalLink
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PMID: 20145342 [PubMed - indexed for MEDLINE]6: Mayo Clin Proc. 2010 Feb;85(2):122-8.
Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E.
Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Ave, Louisville, KY 40213, USA. hbaysmd@aol.com
OBJECTIVE: To evaluate the effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol (HDL-C) levels in atorvastatin-treated patients with elevated non-HDL-C and triglyceride levels. PATIENTS AND METHODS: This study, conducted between February 15, 2007, and October 22, 2007, randomized patients with elevated non-HDL-C (>160 mg/dL) and triglyceride (>or=250 mg/dL and <or=599 mg/dL) levels to double-blind treatment with prescription omega-3-acid ethyl esters, 4 g/d, or placebo for 16 weeks. Patients also received escalating dosages of open-label atorvastatin (weeks 0-8, 10 mg/d; weeks 9-12, 20 mg/d; weeks 13-16, 40 mg/d). RESULTS: Prescription omega-3-acid ethyl esters plus atorvastatin, 10, 20, and 40 mg/d, reduced median non-HDL-C levels by 40.2% vs 33.7% (P<.001), 46.9% vs 39.0% (P<.001), and 50.4% vs 46.3% (P<.001) compared with placebo plus the same doses of atorvastatin at the end of 8, 12, and 16 weeks, respectively. Prescription omega-3-acid ethyl esters plus atorvastatin also reduced median total cholesterol, triglyceride, and very low-density lipoprotein cholesterol levels and increased HDL-C levels to a significantly greater extent than placebo plus atorvastatin. Percent changes from baseline low-density lipoprotein-cholesterol, apolipoprotein A-I, and apolipoprotein B levels were not significantly different between groups at the end of the study. CONCLUSION: Prescription omega-3-acid ethyl esters plus atorvastatin produced significant improvements in non-HDL-C and other lipid parameters in patients with elevated non-HDL-C and triglyceride levels.
Publication Types: Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20118387&dopt=ExternalLink
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PMID: 20118387 [PubMed - indexed for MEDLINE]7: Phys Sportsmed. 2009 Apr;37(1):37-43.
Leaf DA, Hatcher L.
Division of General Internal Medicine, Greater Los Angeles V.A. Healthcare System, Los Angeles, CA 90073, USA. david.leaf@med.va.gov
Marine omega-3 fatty acids have an important role in reducing the risk of coronary artery disease (CAD). The American Heart Association recommends 1 g/day of omega-3 fatty acids for patients with CAD, and for those without CAD, the consumption of a variety of fish (preferably fatty fish) at least twice a week is recommended. Greater amounts of omega-3 fatty acids (4 g per day) are recommended to treat hypertriglyceridemia. Fish oil capsules are often needed to provide the greater quantities of omega-3 fatty acids necessary to treat hypertriglyceridemia, which should not obscure the important triglyceride-lowering effects of seafood consumption. The effects of fish consumption on plasma lipids and lipoproteins are well described in studies that have generally been conducted with fatty fish and fish oil capsules. This study of a group of men and women in a strictly controlled dietary setting showed that compared with a cholesterol-free diet, both lean fish and beef diets raised plasma low-density lipoprotein cholesterol levels, but the fish diet resulted in lower levels of plasma total cholesterol, very-low-density lipoprotein (VLDL) triglycerides, and VLDL cholesterol, while the beef diet resulted in higher plasma high-density lipoprotein cholesterol levels. These findings can help practitioners to extend their dietary recommendations to incorporate significant quantities of low-fat fish to reduce triglyceride levels.
Publication Types: Randomized Controlled Trial
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20048486&dopt=ExternalLink
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PMID: 20048486 [PubMed - indexed for MEDLINE]8: Phys Sportsmed. 2009 Apr;37(1):11-9.
Plaisance EP, Grandjean PW, Mahurin AJ.
Department of Anatomy Physiology and Pharmacology, Boshell Diabetes and Metabolic Diseases Research Program, Auburn University, Auburn, AL 36849, USA. plaisep@auburn.edu
Elevated fasting and postprandial serum triglyceride concentrations are associated with cardiovascular disease morbidity and mortality. Aerobic exercise reduces serum triglyceride concentrations in the presence or absence of weight loss. Although pharmacological interventions are often used in combination with aerobic exercise to achieve target triglyceride concentrations, information on the combined effects of aerobic exercise and lipid-modifying agents on serum triglycerides is limited. This review examines the independent and combined effects of both interventions on serum fasting and postprandial triglyceride concentrations from the available literature. Reductions in serum triglycerides after aerobic exercise are associated with an increase in skeletal muscle lipoprotein lipase activity and a decrease in hepatic triglyceride and very-low-density lipoprotein (VLDL) synthesis and secretion. Lipid-modifying agents such as niacin, omega-3 fatty acids, and statins also decrease fasting and postprandial triglycerides by increasing lipoprotein lipase (LPL) activity and/or decreasing VLDL synthesis. When combined, lipid-modifying agents may reduce fasting and postprandial triglyceride secretion to an extent in which aerobic exercise cannot provide any additional benefit. These observations indicate that aerobic exercise and pharmacological strategies reduce serum triglycerides by similar mechanisms, which may attenuate the triglyceride-lowering capacity of the concordant treatment.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20048483&dopt=ExternalLink
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PMID: 20048483 [PubMed - indexed for MEDLINE]9: Can J Physiol Pharmacol. 2009 Dec;87(12):1074-82.
Dlugosova K, Weismann P, Bernatova I, Sotnikova R, Slezak J, Okruhlicova L.
Institute for Heart Research, Slovak Academy of Sciences, 840 05 Bratislava, Slovak Republic.
Statins and omega-3 polyunsaturated fatty acids (n-3 PUFA) reduce cardiovascular disease incidence during hypertriglyceridemia (HTG). To elucidate possible cardioprotective mechanisms, we focused on gap junction protein connexin 43 (Cx43). Its expression is disturbed during atherogenesis, but little information is available on its expression during HTG. Experiments were performed on adult male hereditary HTG (hHTG) rats treated with n-3 PUFA (30 mg/day) and atorvastatin (0.5 mg/100 g body weight per day) for 2 months. Cx43 expression and distribution in the aorta were investigated by using Western blotting and immunolabeling, followed by quantitative analysis. Transmission electronmicroscopy was used to study ultrastructure of endothelial contact sites. In contrast to age-matched Wistar, Cx43 expression in aorta of hHTG rats was significantly higher (p < 0.05), and prominent Cx43 immunospots were seen in tunica media and less in endothelium of hHTG rats. Changes in Cx43 expression were accompanied by local qualitative subcellular alterations of interendothelial connections. Treatment of hHTG rats with n-3 PUFA and atorvastatin markedly lowered Cx43 expression in aorta and modified connexin distribution in endothelium and media (p < 0.05 vs. untreated hHTG). The protective effect of treatment of HTG was observed on the structural integrity of the endothelium and was readily visible at the molecular level. Results indicate the involvement of altered Cx43 expression in vascular pathophysiology during HTG and during HTG treatment.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20029544&dopt=ExternalLink
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PMID: 20029544 [PubMed - indexed for MEDLINE]10: Histol Histopathol. 2010 Feb;25(2):141-51.
Cayli S, Sati L, Seval-Celik Y, Tuncer MA, Yaymaci B, Berkman Z, Altug T, Demir R.
Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.
The preventive and therapeutic effects of eicosapentaenoic acid (EPA) on diet-induced hyperlipidemia in rabbits have been investigated. Eighteen New Zealand rabbits were randomly divided into three groups of 6 subjects each; experimental group-I (EG-I) was administered a cholesterol rich diet, experimental group-II (EG-II) was treated with EPA (300 mg/kg/d) following a cholesterol-rich diet and the control group (CG) had a standard diet. Blood samples were collected at day 0 and at the 4th and 12th weeks of EG-II to obtain serum levels of total cholesterol (TC), high density lipid-cholesterol (HDL-C), low density lipid-cholesterol (LDL-C) and triglyceride (TG). From each group tissue samples were collected from the carotid artery for immunohistochemistry and electron microscopy. Our results showed that EPA could significantly lower (p<0.001) serum TC, LDL-C, HDL-C and TG levels with a reduction of 35%; 55%; 44% and 51%, respectively. Scanning and transmission electron microscopy results revealed that endothelial damage was more prominent in EG-I when compared to EG-II. The ruptured endothelial lining and damaged cellular surface was increased in EG-I when compared to EG-II. Ultrastructural observations showed that after EPA treatment, the degeneration and cellular surface damage on the endothelium were also decreased. These biochemical and ultrastructural results suggest that EPA is a potential drug which significantly lowers the serum lipid profile and partially repairs endothelial dysfunction due to hyperlipidemia.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20017101&dopt=ExternalLink
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PMID: 20017101 [PubMed - indexed for MEDLINE]11: Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E429-39. Epub 2009 Dec 1.
Hein GJ, Bernasconi AM, Montanaro MA, Pellon-Maison M, Finarelli G, Chicco A, Lombardo YB, Brenner RR.
Departamento de Ciencias Biologicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
A sucrose-rich diet (SRD), compared with a starch diet, induces time-dependent metabolic disorders and insulin resistance with hypertriglyceridemia, similar to type 2 diabetes. In this study, we examined the effect of SRD, after 8 mo, on nuclear receptors peroxisome proliferator-activated receptor-alpha (PPARalpha), and liver X receptor-alpha (LXRalpha), stearoyl-CoA desaturase-1 (SCD-1), and Delta6 and Delta5 desaturases mRNA and activity, hepatic enzymes involved in lipid metabolism, and fatty acid (FA) composition as well as the reversal produced by cod liver oil. SRD induced triglyceride increase in plasma and liver, increasing the anabolic FA synthase, malic enzyme, and glucose-6-phosphate dehydrogenase, but not the prooxidative enzymes FA oxidase and carnitine palmitoyltransferase I, and correspondingly decreased PPARalpha and increased LXRalpha expressions. Results suggest a contribution of both nuclear receptors' interaction on these enzymatic activities. SRD depressed SCD-1 without altering oleic acid proportion and increased Delta6 and Delta5 desaturases and the proportion of n-6 arachidonic acid. Therefore, the data do not support that SRD hypertriglyceridemia is produced by increased SCD-1-dependent oleic acid biosynthesis. The administration of 7% cod liver oil for 2 mo depressed LXRalpha, enhancing PPARalpha in control and SRD-fed rats, reversing the activity of the hepatic enzymes involved in lipid metabolism and therefore the hyperlipidemia produced by the SRD. Fish oil increased n-3 PUFA and depressed n-6 PUFA of liver lipids without altering the 18:1/18:0 ratio, suggesting that its effects were produced mainly by competition of dietary n-6 and n-3 FA and not through desaturase activity modification.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19952344&dopt=ExternalLink
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PMID: 19952344 [PubMed - indexed for MEDLINE]12: Postgrad Med. 2009 Sep;121(5):145-50.
Bays HE, Maki KC, Doyle RT, Stein E.
Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA. hbaysmd@aol.com
BACKGROUND: Prescription omega-3-acid ethyl ester (P-OM3; Lovaza) therapy is indicated for treating very high triglyceride levels (>or= 500 mg/dL) at a dose of 4 g/day. The caloric content associated with each 1-g capsule of P-OM3 is approximately 11 Cal (Cal = kilocalories) - approximately 9 Cal from the oil in the capsule that contains omega-3 fat and approximately 2 Cal attributed to the components of the capsule shell. Thus, the 4-g/day dose contributes approximately 44 Cal/day, with approximately 36 Cal/day derived from the oil. METHODS: This analysis evaluated 167 dyslipidemic (triglycerides: >or= 500 mg/dL and < 1300 mg/dL), overweight/obese (body mass index [BMI] >or= 25 kg/m(2) and <or= 43 kg/m(2)) patients aged 18 to 79 years. Data were derived from an 8-week, randomized, double-blinded, placebo-controlled, parallel-group trial comparing P-OM3 4 g/day + fenofibrate 130 mg/day (n = 84) versus placebo (4 g/day of corn oil) + fenofibrate 130 mg/day (n = 83), and an 8-week open-label extension (n = 117), during which all subjects received P-OM3 + fenofibrate. Subjects who received P-OM3 + fenofibrate continued the same treatment in the extension phase (non-switchers; n = 59). Those who initially received corn oil placebo + fenofibrate received P-OM3 + fenofibrate in the extension phase (switchers; n = 58). RESULTS: During the 8-week double-blind phase in subjects receiving fenofibrate, the addition of P-OM3 (versus placebo) did not significantly change median (minimum, maximum) body weight (P-OM3 = 0 [-4.6, +4.2] kg, placebo = 0 [-3.6, +5.5] kg; P = 0.088) or waist circumference (P-OM3 = +0.1 [-12.1, +17.5] cm, placebo = +0.5 [-9.9, +12.2] cm; P = 0.162). In the 8-week extension phase, non-switchers and switchers did not differ in median change from the end of the double-blind phase in body weight (non-switchers = +0.2 [-3.2, +5.6] kg, switchers = +0.1 [-6.9, +7.9] kg; P = 0.982), or waist circumference (non-switchers = +0.1 [-9.8, +41.8] cm, switchers = +0.2 [-12.0, +7.0] cm; P = 0.685). CONCLUSION: When coadministered with fenofibrate for up to 16 weeks, the modest daily caloric contribution of P-OM3 (4 g/day) did not alter body weight or waist circumference compared with baseline or compared with fenofibrate plus placebo in patients with very high triglyceride levels.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19820283&dopt=ExternalLink
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PMID: 19820283 [PubMed - indexed for MEDLINE]13: J Med Food. 2009 Aug;12(4):809-13.
Park Y, Harris WS.
Department of Food and Nutrition, College of Human Ecology, Hanyang University, Seoul, Republic of Korea. yongsoon@hanyang.ac.kr
The purpose of this study was to determine dose effects of n-3 polyunsaturated fatty acids (PUFAs) on mean platelet volume (MPV) and platelet count (PLT-CT) in mildly hypertriglyceridemic subjects. Subjects with a serum triglyceride level between 100 and 300 mg/dL were placed on a corn oil placebo for 4 weeks and then randomly assigned to groups taking seven capsules per day of placebo (n = 47) or one of the following doses of n-3 PUFAs for 20 weeks: 0.5 g (n = 50), 1 g (n = 23), or 2 g (n = 12). At the end of both the placebo period and the treatment period, MPV and PLT-CT were measured without stimulation (baseline 1 following placebo period, baseline 2 following n-3 supplement period) and after ex vivo stimulation with collagen (10 microg/mL), cold (4 degrees C), and heat (37 degrees C). Collagen and cold significantly increased MPV, whereas heat lowered MPV regardless of treatment. All stimuli decreased PLT-CT. Only the 2 g/day dose of n-3 PUFAs increased MPV at baseline 2 (7.2 +/- 0.5 vs. 7.5 +/- 0.5 fL) and after the cold stimulus (7.5 +/- 0.5 vs. 7.8 +/- 0.5 fL). There was no dose-dependent effect of n-3 PUFAs on platelet activation; rather, 2 g of n-3 PUFAs increased MPV slightly in mildly hypertriglyceridemic subjects.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19735181&dopt=ExternalLink
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PMID: 19735181 [PubMed - indexed for MEDLINE]14: J Med Food. 2009 Aug;12(4):803-8.
Park Y, Harris WS.
Department of Food and Nutrition, College of Human Ecology, Hanyang University, Seoul, Republic of Korea. yongsoon@hanyang.ac.kr
The n-3 polyunsaturated fatty acids (PUFAs) are known to reduce risk for coronary heart disease partly by altering blood lipids. The purpose of this study was to determine the effect of low doses of n-3 PUFAs on the lipid profile and their tolerability in mildly hypertriglyceridemic subjects. Subjects with a serum triacylglycerol (TG) level between 100 and 300 mg/dL were placed on a corn oil placebo (seven capsules per day; single-blind) for 4 weeks and then randomized to continue seven capsules per day of placebo (n = 49) or one of the following doses of n-3 PUFAs for 20 weeks: 0.5 g (n = 51), 1 g (n = 23), or 2 g (n = 12). During the treatment period, 48-50% of the 1-g and 2-g dose groups reported noticing burping (P < .05), and only about half as many in the 0.5-g group noticed burping. Interestingly, 2% of those assigned to the placebo did report a fishy burping during the study, but this dropped back to nearly 0% by week 20. There was no significant effect for any dosage group on fasting and postprandial serum TG, chylomicron TG, very-low-density lipoprotein-cholesterol, or high-density lipoprotein-cholesterol concentration. However, 1-g and 2-g n-3 PUFA treatments significantly increased total cholesterol and low-density lipoprotein-cholesterol concentration. In addition, all doses of n-3 PUFA treatments significantly increased plasma phospholipid n-3 PUFAs. We conclude that doses of n-3 PUFAs of 0.5-2 g/day in healthy volunteers with above average TG levels did not have beneficial effects on their lipid profiles.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19735180&dopt=ExternalLink
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PMID: 19735180 [PubMed - indexed for MEDLINE]15: J Nutr Biochem. 2009 Dec;20(12):927-39. Epub 2009 Sep 3.
Micallef MA, Garg ML.
Nutraceuticals Research Group, School of Biomedical Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia.
Phytosterols and omega-3 fatty acids are natural compounds with potential cardiovascular benefits. Phytosterols inhibit cholesterol absorption, thereby reducing total- and LDL cholesterol. A number of clinical trials have established that the consumption of 1.5-2.0 g/day of phytosterols can result in a 10-15% reduction in LDL cholesterol in as short as a 3-week period in hyperlipidemic populations. Added benefits of phytosterol consumption have been demonstrated in people who are already on lipid-lowering medications (statin drugs). On the other hand, omega-3 fatty acid supplementation has been associated with significant hypotriglyceridemic effects with concurrent modifications of other risk factors associated with cardiovascular disease, including platelet function and pro-inflammatory mediators. Recent studies have provided evidence that the combination of phytosterols and omega-3 fatty acids may reduce cardiovascular risk in a complementary and synergistic way. This article reviews the health benefits of phytosterols and omega-3 fatty acids, alone or in combination with statins, for the treatment/management of hyperlipidemia, with particular emphasis on the mechanisms involved.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19733044&dopt=ExternalLink
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PMID: 19733044 [PubMed - indexed for MEDLINE]16: Lipids. 2009 Sep;44(9):817-26. Epub 2009 Aug 5.
Ryan AS, Bailey-Hall E, Nelson EB, Salem N Jr.
Martek Biosciences Corporation, 6480 Dobbin Road, Columbia, MD 21045, USA. alryan@martek.com
Preclinical and clinical studies demonstrate that the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as a triacylglycerol (TAG) or an ethyl ester are protective against cardiovascular disease. Both have significant TAG-lowering effects. We developed a concentrated ethyl ester of DHA (MATK-90, 900 mg/g) using microalgae as its source. This study evaluated the effects that different doses of MATK-90 had on lipid levels and clinical parameters in male Wistar rats fed a high-fructose diet used to induce hypertriglyceridemia (TAG > or = 300 mg/dL). Effects of MATK-90 were compared to those produced by a pharmaceutical product (Lovaza, formerly Omacor, P-OM3; 465 mg EPA + 375 mg DHA), a TAG oil used in food (DHASCO, algal-DHA, 40% DHA by weight), and a control (corn oil). Doses of MATK-90 (0.6, 1.3, 2.5, 5.0 g kg(-1) day(-1)), algal-DHA (2 g DHA kg(-1) day(-1)), and P-OM3 (5.0 g kg(-1) day(-1)) were administered by oral gavage for 28 days. A significant dose-related decrease was observed in TAG and cholesterol levels in all but the lowest dose of MATK-90 treatment group vs. control. The high-dose group of MATK-90 and the P-OM3 group produced similar reductions in TAG levels.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19655188&dopt=ExternalLink
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PMID: 19655188 [PubMed - indexed for MEDLINE]17: Postgrad Med. 2009 Jul;121(4):145-53.
Sadovsky R, Kris-Etherton P.
SUNY Downstate Medical Center, Brooklyn, NY 11203, USA. richard.sadovsky@downstate.edu
Triglyceride (TG) levels can increase for numerous reasons, including a sedentary lifestyle, an unhealthy diet, especially one rich in refined carbohydrates, and comorbidities. According to the National Cholesterol Education Program (NCEP), the normal TG level is < 150 mg/dL. Patients with very high TG (VHTG) levels (> or = 500 mg/dL) should be promptly managed and treated to reach lipid treatment goals, as determined by the NCEP. Lowering TG levels is the primary management goal in these patients, while lowering low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol levels are secondary goals. Therapeutic lifestyle changes are often recommended initially for patients with elevated TGs; however, concomitant drug therapy is often required. Data show that intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can significantly decrease serum TGs, along with plasma concentrations of certain lipoproteins. Omega-3-acid ethyl esters are available by prescription or as dietary supplements. Clinical trials in adult patients with VHTGs show that four 1 g capsules of prescription omega-3 fatty acids, which contain 465 mg of EPA and 375 mg of DHA per capsule, can effectively decrease TG levels by up to 45%, and is generally well tolerated.
Publication Types: Research Support, Non-U.S. Gov't Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19641280&dopt=ExternalLink
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PMID: 19641280 [PubMed - indexed for MEDLINE]18: Adv Ther. 2009 Jul;26(7):675-90. Epub 2009 Jul 27.
Rupp H.
Experimental Cardiology Laboratory, Heart Center, Department of Internal Medicine and Cardiology, Philipps University of Marburg, 35043 Marburg, Germany. Rupp@staff.uni-marburg.de
Despite progress made in post-myocardial infarction (MI) revascularization and background therapy for the failing heart, the prevention of adverse cardiac remodeling associated with severe rhythm disorders remains an important drug target. Part of the remodeling can be counteracted by modulating the activity of ion channels and exchangers by omega-3 acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the GISSI-Prevenzione and GISSI-HF trials, omega-3 fatty acids were administered as ethyl esters (Omacor Solvay Pharmaceuticals) and not as triglycerides present in fish oil. Ethyl esters result in a sustained intestinal absorption of EPA and DHA and require various purification steps during production, thereby minimizing the content of environmental toxins. Also the rather high (38%) DHA content of Omacor should not be ignored since in rats with low dose intake of omega-3 acids, DHA but not EPA inhibited ischemia-induced arrhythmias. In patients on multiple tablets, 840 mg EPA+DHA in one capsule is preferred to increase compliance. It is not justified to refer to Omacor as "n-3 polyunsaturated fatty acid supplementation" or even "fish oil" and, based on controlled clinical trials, there is no evidence that fish oil could be a substitute of Omacor. To avoid further confusion, guidelines should be precise and refer to the medication, eg, as in NICE guideline CG48: "Omega-3-acid ethyl esters treatment licensed for secondary prevention post-MI." The anti-arrhythmogenic action of Omacor should be seen in the context of implantable cardioverter-defibrillator trials (DINAMIT, IRIS) where non-sudden death was increased and total mortality unaltered. However, Omacor administered in the GISSI-HF trial reduced the incidence of severe arrhythmic events and mortality. Also in the GISSI-Prevenzione trial, arrhythmic death and mortality were reduced. At higher dosages (daily, 3-4 g) Omacor exhibits more pronounced cardiovascular benefits and, as a licensed indication, improves hypertriglyceridemia and related lipid parameters.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19629408&dopt=ExternalLink
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PMID: 19629408 [PubMed - indexed for MEDLINE]19: Int J STD AIDS. 2009 Aug;20(8):580-1.
Falasca K, Ucciferri C, Mancino P, Pizzigallo E, Calza L, Vecchiet J.
Infectious Diseases Clinic, Department of Medicine and Aging, 'G. d'Annunzio' University, Chieti, Italy.
Compared with healthy controls, HIV patients already have abnormal lipoprotein concentrations before the initiation of highly active antiretroviral therapy (HAART), which worsen with the therapy. HAART-associated dyslipidaemia features fundamental proatherogenic changes such as increased plasma triglycerides (TGs), increased total cholesterol and low-density lipoprotein cholesterol as well as decreased high-density lipoprotein cholesterol (HDL-C). The current guidelines for managing HIV-associated dyslipidaemia recommend diet and exercise counselling, alteration of HAART regimen or addition of lipid-lowering medications such as statins, fibrates and omega-3 (OM-3) fatty acids. Given that cardiovascular risk significantly increases with elevated lipid levels, selecting a drug to manage dyslipidaemia is particularly important. A case is described of an HIV patient who had severe hypertriglyceridaemia and bad metabolic parameters treated with rosuvastatin and OM-3 fatty acids. So we obtained a more marked reduction of TG levels than has never been described before in the literature, associated with a significant increase in HDL-C levels.
Publication Types: Case Reports
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19625595&dopt=ExternalLink
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PMID: 19625595 [PubMed - indexed for MEDLINE]20: J Cardiovasc Pharmacol. 2009 Sep;54(3):196-203.
Roth EM, Bays HE, Forker AD, Maki KC, Carter R, Doyle RT, Stein EA.
Sterling Research Group, University of Cincinnati, Cincinnati, Ohio, USA.
BACKGROUND/RATIONALE: Treatment of severe hypertriglyceridemia is indicated to reduce the risk of pancreatitis in patients with triglyceride (TG) levels > or =500 mg/dL. Hypertriglyceridemia is also a risk factor for atherosclerotic coronary heart disease. Prescription omega-3 fatty acids (P-OM3) and fenofibrate (FENO) are among the most effective lipid-altering agents that reduce TG levels. Given that some patients may not achieve optimal TG levels with a single agent, we hypothesized that concomitant use of P-OM3 or addition of P-OM3 to FENO would result in a TG reduction greater than that with FENO alone. METHODS: This randomized, 8-week, double-blind, placebo-controlled study was designed to compare the safety and efficacy of P-OM3 4 g QD plus concomitant FENO 130 mg with FENO 130 mg QD plus placebo in subjects with very high TG levels (> or =500 mg/dL). Subjects who completed the double-blind study were given the option to continue into an open-label, 8-week extension study, wherein they all received P-OM3 4 g plus FENO 130 mg QD. On completion of the first extension study, subjects were eligible to continue into an open-label 24-month extension of the treatment with P-OM3 4 g plus FENO 130 mg QD. RESULTS: Concomitant P-OM3 + FENO (n = 81) and FENO monotherapy (n = 82) reduced median TG values from 649.5 to 267.5 mg/dL (60.8%) and from 669.3 to 310 mg/dL (53.8%), respectively (P = 0.059). When subjects who had received 8 weeks of stable FENO monotherapy were given P-OM3 during the 8-week, open-label extension study (n = 58), TG levels were reduced 17.5% (P = 0.003) over the course of the extension. The second extension phase was terminated early (n = 93)-not because of a safety signal but because of the lack of a substantial incremental change in the primary endpoint lipid values above that reached in either the original study or the first extension in subjects receiving the combination of fenofibrate and P-OM3. CONCLUSIONS: Both FENO monotherapy and P-OM3 + FENO significantly reduced TGs in subjects with very high TGs, with a trend to greater reduction in the P-OM3 + FENO group. The addition of P-OM3 to stable FENO therapy in the same subjects in an open-label extension study resulted in a statistically significant reduction in TG levels. Subjects who received P-OM3 + FENO for 16 weeks and subjects in which P-OM3 was added to FENO monotherapy during the open-label phase of the study did not differ in their final lipid responses. In the second open-label extension, within the combined group taking P-OM3 and FENO, analysis of change from the second extension baseline to end of treatment revealed no clinically important change.
Publication Types: Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19597368&dopt=ExternalLink
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PMID: 19597368 [PubMed - indexed for MEDLINE]