Treatment with omega-3 polyunsaturated fatty acids does not improve endothelial function in patients with type 2 diabetes and very high cardiovascular risk: A randomized, double-blind, placebo-controlled study (Omega-FMD).

BACKGROUND AND AIMS: Numerous recent studies conducted in different clinical settings have focused on the benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of cardiovascular diseases. There is limited evidence that patients with type 2 diabetes (T2D) and very high cardiovascular risk can also benefit from a high dose of n-3PUFAs, especially those on optimal medical therapy as recommended by the guidelines. The aim of the present study was to assess the impact of high-dose n-3 PUFA treatment on endothelial function in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD). METHODS: We conducted a prospective randomized double-blind, placebo-controlled, 2-center study, in which endothelial function was measured using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD). Serum fatty acids composition was measured by gas chromatography. All measurements were done at baseline and after 3 months of treatment with PUFAs at a dose of 2 g/d (n = 36) or placebo (n = 38). RESULTS: The majority of the study population was treated with optimal medical therapy. Despite significantly higher concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid in the n-3 PUFA group after 3-month treatment, we did not observe significant changes in endothelial function indices (FMD and NMD). However, in regression analysis, only baseline FMD was associated with EPA concentration before 3 months of n-3 PUFA treatment. CONCLUSIONS: Three months of high-dose n-3 PUFA treatment in very high-risk patients with ASCVD and T2D did not improve the endothelial function indices.

Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes.

BACKGROUND: Despite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in patients with type 2 diabetes (DM2) and established atherosclerosis. PURPOSE: To investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function, coagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients with atherosclerotic vascular disease and DM2 who receive optimal medical therapy. METHODS: We conducted a prospective, double-blind, placebo-controlled, randomized, double-center study, in which thrombin generation (plasma thrombogenic potential from automated thrombogram), fibrin clot properties (plasma fibrin clot permeability; lysis time), platelet aggregation (light transmission aggregometry with adenosine diphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid profiles, leptin and adiponectin levels, as well as markers of systemic inflammation (i.e., hsCRP, IL-6, TNF-α, ICAM-1, VCAM-1, and myeloperoxidase) were determined at baseline and at 3 months after treatment with 2 g/day of n-3 PUFAs (n = 36) or placebo (n = 38). Moreover, we assessed serum fatty acids of the phospholipid fraction by gas chromatography both at baseline and at the end of the study. RESULTS: Majority of patients were treated with optimal medical therapy and achieved recommended treatment targets. Despite higher serum levels of eicosapentaenoic acid (EPA) (by 204%; p < 0.001) and docosahexaenoic acid (DHA) (by 62%; p < 0.0001) in n-3 PUFA group at the end of treatment no changes in platelet aggregation, thrombin generation, fibrin clot properties or markers of systemic inflammation were observed. No intergroup differences in the insulin, HbA1c and lipid levels were found at the end of the study. There was no change in adiponectin and leptin in interventional group, however leptin increased in control group (p = 0.01), therefore after study period leptin levels were lower in the interventional group (p = 0.01). Additionally, resolvin D1 did not differ between interventional and control group. CONCLUSIONS: In conclusion, our study demonstrated that in patients with long-standing, well-controlled DM2 and atherosclerotic disease the treatment with a high dose of n-3 PUFAs (namely, 1 g/day of EPA and 1 g/day of DHA for 3 months) does not improve coagulation, metabolic, and inflammatory status when measured with the specified tests. The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014.

Effects of n-3 polyunsaturated fatty acids on depressive symptoms, anxiety and emotional state in patients with acute myocardial infarction.

BACKGROUND: Our aim was to assess whether an early introduced n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation affects depression symptoms, anxiety and emotional state in patients with acute myocardial infarction (AMI) and no history of mental disorders. METHODS: Fifty two patients with AMI were enrolled into the study and randomized to the study group (group P; n=26; standard therapy+n-3 PUFA 1 g daily) or the control group (group C; n=26; standard therapy). The following psychological tests were used at the baseline (3rd day of AMI) and after one month (30±1 days): Beck Depression Inventory (BDI), State-Trait Anxiety Inventory in a specific situation (STAI-S) and as a general trait (STAI-T), Emotional State Questionnaire (ESQ). RESULTS: The baseline characteristics, pharmacotherapy and BDI, STAI-S/T and ESQ were similar between both groups. The mean test scores assessed for all patients (group P and C) during the one-month observation were significantly lower for BDI (p=0.04), STAI-T (p=0.03), STAI-S (p=0.01) and harm/loss emotions (p=0.005). After adjusting for age, sex, body mass index, coronary artery disease severity, ejection fraction, serum troponin level and the baseline tests results, n-3 PUFA intervention revealed additional significant decrease in BDI (p=0.046), STAI-S (p=0.03) and harm/loss emotions (p=0.04). CONCLUSIONS: Our study provides novel and preliminary observations--n-3 PUFA supplementation reveals additional decreasing effects on depressive and anxiety symptoms in early post-MI patients.

N-3 polyunsaturated fatty acids do not influence the efficacy of dual antiplatelet therapy in stable angina pectoris patients after percutaneous coronary intervention.

BACKGROUND: We aimed to prospectively assess the influence of the recommended dose, 1.0 g of polyunsaturated fatty acids (N-3 PUFA) daily, on platelet reactivity in patients with stable angina pectoris (SAP) after elective percutaneous coronary intervention (PCI). METHODS: Forty consecutive patients with SAP and successful PCI were randomized to the study group (group PUFA: n = 20; age 65 ± 8; standard therapy + 75 mg acetylsalicylic acid + 75 mgclopidogrel + N-3 PUFA/Omacor 1 g daily) and the control group (group C: n = 20; age 65 ± 9; standard therapy + 75 mg acetylsalicylic acid + 75 mg clopidogrel). Platelet reactivity tests (COL, TRAP, ASPI, ADP) were performed using whole blood aggregometry (multiplate platelet [PLT] function analysis) on the 2,nd and 30th day after PCI. RESULTS: Baseline patients' characteristics and clinical outcomes were comparable between the groups. There were no differences between both groups in the mean values of the PTL tests measured 30 days after PCI (PUFA vs. C ASPI: 18.5 ± 17 vs. 27 ± 29 U, COL: 30.4 ± 14.3 vs. 30.3 ± 13.4 U, ADP: 25.4 ± 16.1 vs. 20 ± 10.7 U, TRAP: 65.8 ± 25.6 vs. 57.1 ± 20.4 U, p = NS). The mean delta values of the PTL tests (18-24 h post-PCI/30 days post-PCI) were also comparable between the groups. The PTL aggregometry results were related to time - the baseline values of the ADP (p = 0.003), COL (p = 0.037) and TRAP (p < 0.001) tests were smaller and the ASPI (p = 0.027) test was higher than those measured after 1-month. CONCLUSIONS: N-3 PUFA supplementation does not affect the efficacy of dual antiplatelettherapy in patients with SAP after PCI.

N-3 polyunsaturated fatty acids early supplementation improves ultrasound indices of endothelial function, but not through NO inhibitors in patients with acute myocardial infarction: N-3 PUFA supplementation in acute myocardial infarction.

BACKGROUND & AIMS: Our aim was to evaluate early initiated one month n-3 polyunsaturated fatty acids (PUFA) supplementation effects on ultrasound indices of endothelial function and serum asymmetric dimethylarginine (ADMA) levels in patients with acute myocardial infarction (AMI). METHODS: Forty patients with AMI and successful percutaneous coronary intervention (PCI) were recruited into the study and randomized to the study group (group P; n = 20; standard therapy + n-3 PUFA 1 g daily) or the control group (group C; n = 20; standard therapy). Ultrasound indices of endothelial function: flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NMD) and serum ADMA concentrations (ELISA) were obtained before and after one month (30 ± 1 days) therapy (presented as means ± standard deviations). RESULTS: There was a significant difference between both groups in mean delta (baseline/after one month) FMD (P: 8.1 ± 12.6% vs C: -2.2 ± 11.8%; p = 0.02) with no difference in mean delta NMD (P: 3.3 ± 11.9% vs 0.66 ± 14.3%; p = 0.53). We found also a significant increase in mean FMD (7.4 ± 6.4 to 15.5 ± 10.5%; p = 0.02) with a nonsignificant change in mean NMD values (26.9 ± 12.1 to 30.2 ± 14.0%; p = 0.24) after 1-month therapy with n-3 PUFA. FMD and NMD mean values did not change in control patients (FMD: 11.6 ± 6.1% to 9.4 ± 8.0%; p = 0.5 NMD: 25.1 ± 11.4% to 25.8 ± 14.0%; p = 0.84). The comparison of mean delta ADMA values for both groups revealed no differences (P: 6.2 ± 9.7 µmol/l vs C: 3.6 ± 9.5 µmol/l; p = 0.43). Mean serum ADMA concentrations were significantly increased after 1-month therapy in the group P (P: 2.1 ± 1.8 to 8.3 ± 9.7 µmol/l; p = 0.001; C: 4.5 ± 7.1 to 8.1 ± 9.5 µmol/l; p = 0.09). However, there was a nonsignificant difference in mean baseline serum ADMA levels between both groups (P: 2.1 ± 1.8 µmol/l vs C: 4.5 ± 7.1 µmol/l; p = 0.32). There were no significant correlations between FMD, NMD, ADMA levels and demographic, clinical or biochemical parameters. CONCLUSIONS: Early and short-term n-3 PUFA supplementation improved ultrasound indices of endothelial function without affecting serum ADMA levels in patients with AMI and successful primary PCI.