The addition of omega-3 ethyl esters to the combination of aspirin and clopidogrel significantly potentiates platelet response to clopidogrel after percutaneous coronary intervention.

BackgroundDespite 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.PurposeTo 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.MethodsWe 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.ResultsMajority 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.ConclusionsIn 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, 2014Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0523-9) contains supplementary material, which is available to authorized users.

Objective-The goal of this study was to investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) are able to alter plasma fibrin clot properties and reduce thrombin formation in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI). Methods and Results-In an investigator-initiated, prospective, double-blind, placebo-controlled, randomized study, patients undergoing PCI who received standard pharmacotherapy were assigned to the treatment with 1 g/day n-3 PUFA (nϭ30) or placebo (nϭ24) for 1 month. Plasma fibrin clot permeability (K s ); lysis time (t 50% ); prothrombin fragment 1.2; and peak thrombin generation from automated thrombogram, 8-isoprostaglandin F 2␣ (8-iso-PGF 2␣ , an oxidative stress marker), and C-reactive protein were determined at baseline, 3 to 5 days after randomization, and 30 days after randomization. At baseline, both treatment groups did not differ significantly. A 1-month treatment with n-3 PUFA compared with placebo was associated with 15.3% higher K s , indicating larger pores in the fibrin network (Pϭ0.0005); 14.3% shorter t 50% , indicating increased susceptibility to fibrinolysis (PϽ0.0001); 33.8% lower prothrombin fragment 1.2 (Pϭ0.0013); 13.4% lower peak thrombin generation (Pϭ0.04); and 13.1% lower 8-iso-PGF 2␣ (Pϭ0.009). Treatment with n-3 PUFA had no effect on fibrinogen and C-reactive protein. After 1 month of treatment, fibrinogen (rϭϪ0.53, PϽ0.0001), treatment assignment (rϭ0.29, Pϭ0.006) and 8-iso-PGF 2␣ (rϭϪ0.27, Pϭ0.015) were independently associated with clot permeability (PϽ0.0001, R 2 ϭ0.66). Conclusion-Adding n-3 PUFA to standard therapy in stable patients undergoing PCI significantly decreases thrombin formation and oxidative stress and favorably alters fibrin clot properties. These findings indicate novel antithrombotic effects induced by n-3 PUFA in humans. (Arterioscler Thromb Vasc Biol. 2011;31:1696-1702.)Key Words: angioplasty Ⅲ fibrin Ⅲ fish oils Ⅲ thrombin Ⅲ oxidative stress A ntiplatelet and antithrombotic agents are one of the cornerstones of successful therapy of coronary artery disease (CAD). Despite antiplatelet treatment with acetylsalicylic acid and clopidogrel, some patients undergoing percutaneous coronary intervention (PCI) and after acute coronary syndromes (ACS) still experience thrombotic events, including stent thrombosis and recurrent myocardial infarction. 1,2 Platelet activation is closely associated with blood coagulation activation, resulting in a surge of thrombin generation that leads ultimately to fibrin clot formation. 2 As thrombin is also a potent platelet activator, inhibition of thrombin generation, thrombin activity, or both might improve treatment outcomes of CAD patients.A relationship between the structure/function of a fibrin clot and the presence of cardiovascular disease was first demonstrated in patients with advanced CAD in 1992. 3 Fibrin clots composed of dense fiber networks, which display lower clot permeability (by approximately 30% compared with control subjects), have been...

Data of the European Cancer Registries indicate that the incidence of breast cancer, which is the most common cancer among women, tends to increase not only in postmenopausal but also in very young women. The potential causes of breast cancer are genetic predisposition, long -term hormonal replacement therapy, alcohol, environmental pollution, and possibly modern lifestyle. The controversial results of several studies suggest that certain everyday-use products (including cosmetic ingredients) may be linked to breast cancer. Some of these ingredients, such as ethylene oxide, have recently been classified by the International Agency for Research for Cancer as carcinogenic and mutagenic to humans, with sufficient evidence of carcinogenicity for breast cancer. Other ingredients, such as xenoestrogens, are chemicals which have an estrogen -like effect or disrupt the normal metabolism of the natural estrogen and thus act as carcinogens. Some of them have been shown to result in DNA damage in animal and human mammary epithelial cells and, therefore, have the potential to generate genomic instability in the breast tissue. Examples of xenoestrogens with such properties include parabens, aluminium salts, phthalates, or bisophenol A. No sufficient epidemiological data on humans have been published so far, and the effects of a mixture of chemicals to which women are exposed during lifetime on the incidence of breast cancer have not been investigated. However, the results of the available studies emphasize the need for analysis of adverse environmental factors, which, in addition to a genetic predisposition and natural aging, may contribute to the increased incidence of breast cancer.

The aim of the study is to evaluate the prevalence and incidence of myocardial dysfunction (MD) and heart failure (HF) in long-lasting (≥10 years) type 1 diabetes without cardiovascular disorders or with hypertension or coronary heart disease (CHD). The study included 1,685 patients with type 1 diabetes (mean baseline age, 51 years; diabetes duration, 36 years). In all patients, echocardiography was performed, NT-proBNP levels were measured, and clinical symptoms were evaluated. A 7-year follow-up was conducted to monitor systolic and diastolic manifestations of MD and HF. At the end of the follow-up period, the prevalence of HF in the entire group was 3.7 %, and the incidence was 0.02 % per year. The prevalence of MD was 14.5 % and the incidence –0.1 % per year. MD and HF were observed only in hypertensive or CHD patients. At baseline, subjects with diastolic HF constituted 85 % of the HF population and those with systolic HF the remaining 15 %. Baseline HF predictors included age, diabetes duration, HbA1c levels, CHD, systolic blood pressure >140 mmHg, and GFR <60 mL/min/1.73 m2. In patients with type 1 diabetes, MD and HF occurred only when diabetes coexisted with cardiovascular disorders affecting myocardial function. The prevalence and incidence of HF in patients with hypertension and CHD were relatively low. While the cause of this observation remains uncertain, it could probably be explained, at least partially, by the cardioprotective effect of concomitant treatment.

BackgroundGrowing evidence suggests a cardioprotective role of omega-3 polyunsaturated fatty acids (PUFA). However, the exact mechanisms underlying the effects of omega-3 PUFA in humans have not yet been fully clarified.PurposeWe sought to evaluate omega-3 PUFA-mediated effects on adipokines in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI).MethodsWe conducted a prospective, double-blind, placebo-controlled, randomized study, in which adiponectin, leptin and resistin were determined at baseline, 3–5 days and 30 days during administration of omega-3 PUFA 1 g/day (n = 20) or placebo (n = 28).ResultsAs compared to controls administration of omega-3 PUFA resulted in increase of adiponectin by 13.4 % (P < 0.0001), reduction of leptin by 22 % (P < 0.0001) and increase of adiponectin to leptin (A/L) ratio by 45.5 % (P < 0.0001) at 30 days, but not at 3–5 days. Compared with placebo adiponectin was 12.7 % higher (P = 0.0042), leptin was 16.7 % lower (P < 0.0001) and A/L ratio was 33.3 % higher (P < 0.0001) in the omega-3 PUFA group at 30 days. Resistin decreased similarly in both groups after 1 month, without intergroup differences (P = 0.32). The multivariate model showed that the independent predictors of changes in adiponectin at 1 month (P < 0.001) were: omega-3 PUFA treatment, baseline platelet count, total cholesterol and those in leptin (P < 0.0001) were: omega-3 PUFA treatment and waist circumference. Independent predictors of A/L ratio changes (P < 0.0001) were: assigned treatment, current smoking and hyperlipidemia.ConclusionsIn high risk stable coronary patients after PCI omega-3 PUFA supplementation improves adipokine profile in circulating blood. This might be a novel, favourable mechanism of omega-3 PUFA action.Electronic supplementary materialThe online version of this article (doi:10.1007/s10557-013-6457-x) contains supplementary material, which is available to authorized users.

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BackgroundThere are inconsistent data about the role of serum phospholipid fatty acid composition in patients with type 2 diabetes (T2DM) and atherosclerotic cardiovascular disease (ASCVD). The aim of the study was to investigate the relationship between serum phospholipid fatty acid composition, systemic low-grade inflammation, and glycemic control in high-risk T2DM patients.MethodsSeventy-four patients (26% women, mean age 65.6 ± 6.8 years) with T2DM (median diabetes duration 10 years) and documented ASCVD (74 with coronary artery disease, 26 with peripheral arterial disease) were enrolled in the study. Baseline HbA1c was estimated using turbidimetric inhibition immunoassay. According to the median value of HbA1c the patients were grouped into those with HbA1c < 7.0% (< 53 mmol/mol) (n = 38) and those with HbA1c ≥ 7.0% (≥ 53 mmol/mol) (n = 36). Serum phospholipid fatty acids were measured with gas chromatography.ResultsPatients with HbA1c ≥ 7.0%, compared with those with HbA1c < 7.0% had similar composition of saturated and monounsaturated fatty acids in serum phospholipids, but had higher concentrations of linoleic acid (LA) and higher n-6/n-3 polyunsaturated fatty acid (PUFA) ratio as well as lower levels of eicosapentaenoic acid (EPA), total n-3 PUFAs, and the EPA/arachidonic acid ratio. We found that LA (r = 0.25; p = 0.03) and n-6/n-3 PUFA ratio (r = 0.28; p = 0.02) were positively correlated with HbA1c. Multivariate logistic regression analysis showed that n-6/n-3 PUFA ratio, hsCRP and T2DM duration were independent predictors of worse glycemic control in patients with T2DM and ASCVD.ConclusionsThis study showed that glycemic control in high-risk T2DM patients with ASCVD was significantly associated with unfavorable serum phospholipid n-6/n-3 PUFA ratio and greater systemic inflammation.