omacor and Carotid-Artery-Diseases

n-3 polyunsaturated fatty acid (PUFA) treatment may decrease liver fat in non-alcoholic fatty liver disease (NAFLD), but uncertainty exists whether this treatment also decreases cardiovascular disease (CVD) risk in NAFLD. We tested whether 15-18 months n-3 PUFA [docosahexaenoic acid (DHA) and eicosapentaenoic acid] (Omacor/Lovaza, 4 g/day) vs placebo decreased carotid intima-media thickness (CIMT) progression, a surrogate marker of CVD risk. We also evaluated if improvement in markers of NAFLD severity was associated with decreased CIMT progression over time.. In a pre-specified sub-study of the WELCOME (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy) trial (NCT00760513), CIMT was measured using B-mode ultrasound while NAFLD severity was assessed by measuring liver fat percentage (magnetic resonance spectroscopy) and hepatic necro-inflammation (serum cytokeratin-18 (CK-18) concentration), at baseline and end of study.. 92 patients (age 51.5 ± 10.7 years, 57.6% men) completed the study. In the treatment group (n = 45), CIMT progressed by 0.012 mm (IQR 0.005-0.020 mm) compared to 0.015 mm (IQR 0.007-0.025 mm) in the placebo group (n = 47) (p = 0.17). Reduced CIMT progression in the entire cohort was independently associated with decreased liver fat (standardized β-coefficient 0.32, p = 0.005), reduced CK-18 levels (standardized β-coefficient 0.22, p = 0.04) and antihypertensive usage (standardized β-coefficient -0.31, p = 0.009) in multivariable regression analysis after adjusting for all potential confounders. Decreased weight (standardized β-coefficient 0.30, p < 0.001) and increased DHA tissue enrichment during the 18-month study (standardized β-coefficient -0.19, p = 0.027) were both independently associated with decreased liver fat, but not with CK-18.. Improvement in two markers of NAFLD severity is independently associated with reduced CIMT progression.

Topics: Adult; Biomarkers; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Disease Progression; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Predictive Value of Tests; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex

To examine n-3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability.. Patients awaiting carotid endarterectomy (n=121) were randomised to consume control capsules or n-3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher (P<0.0001) in carotid plaque phospholipids in patients in the n-3 PUFA group. Plaques from patients in the n-3 PUFA group had fewer foam cells (P=0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability (P=0.0209), plaque inflammation (P=0.0108), the number of T cells in the plaque (P=0.0097) and a summary score considering a range of plaque features (P=0.0425). Plaques from patients who received n-3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 (P=0.0055), -9 (P=0.0048) and -12 (P=0.0044) and for interleukin-6 (P=0.0395) and intercellular adhesion molecule 1 (P=0.0142).. Atherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Capsules; Carotid Artery Diseases; Chi-Square Distribution; Cytokines; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Endarterectomy, Carotid; England; Female; Foam Cells; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; Male; Matrix Metalloproteinases; Middle Aged; Phospholipids; Preoperative Care; RNA, Messenger; Rupture, Spontaneous; T-Lymphocytes; Treatment Outcome

The objective of this study was to determine the effects of prescription omega-3 (n-3) fatty acid ethyl esters (Omacor®) on blood pressure, plasma lipids, and inflammatory marker concentrations in patients awaiting carotid endarterectomy. Patients awaiting carotid endarterectomy (n = 121) were randomised to Omacor® or olive oil as placebo (2 g/day) until surgery (median 21 days). Blood pressure, plasma lipids, and plasma inflammatory markers were determined. There were significant decreases in systolic and diastolic blood pressure and in plasma triglyceride, total cholesterol, low density lipoprotein-cholesterol, soluble vascular cellular adhesion molecule 1, and matrix metalloproteinase 2 concentrations, in both groups. The extent of triglyceride lowering was greater with Omacor® (25%) compared with placebo (9%). Soluble E-selectin concentration was significantly decreased in the Omacor® group but increased in the placebo group. At the end of the supplementation period there were no differences in blood pressure or in plasma lipid and inflammatory marker concentrations between the two groups. It is concluded that Omacor® given at 2 g/day for an average of 21 days to patients with advanced carotid atherosclerosis lowers triglycerides and soluble E-selectin concentrations, but has limited broad impact on the plasma lipid profile or on inflammatory markers. This may be because the duration of intervention was too short or the dose of n-3 fatty acids was too low.

Topics: Aged; Biomarkers; Blood Pressure; Carotid Artery Diseases; Cholesterol; Docosahexaenoic Acids; Drug Combinations; E-Selectin; Eicosapentaenoic Acid; Endarterectomy, Carotid; Esters; Fatty Acids, Omega-3; Female; Humans; Inflammation; Lipids; Lipoproteins, LDL; Male; Matrix Metalloproteinase 2; Triglycerides; Vascular Cell Adhesion Molecule-1

Topics: Administration, Oral; Capsules; Carotid Artery Diseases; Dietary Supplements; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Endarterectomy, Carotid; Foam Cells; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; Matrix Metalloproteinases; Phospholipids; Preoperative Care; Rupture, Spontaneous; T-Lymphocytes; Treatment Outcome