The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients

Nomura, Shosaku; Inami, Norihito; Shouzu, Akira; Omoto, Seitaro; Kimura, Yutaka; Takahashi, Nobuyuki; Tanaka, Atsushi; Urase, Fumiaki; Maeda, Yasuhiro; Ohtani, Hajime; Iwasaka, Toshiji

doi:10.1080/09537100802409921

Cited by 94 publications

(70 citation statements)

References 43 publications

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“…13) Nomura, et al clearly showed that platelet-derived microparticles, indicating platelet activation, signifi cantly decreased with EPA treatment in hyperlipidemic and diabetic patients. 14) Conversely, several studies failed to show any antiplatelet effects of EPA. Davi, et al studied the add-on effect of EPA with ticlopidine on platelet function in patients with CAD.…”

Section: Discussionmentioning

confidence: 99%

Effects of Eicosapentaenoic Acid on Platelet Function in Patients Taking Long-Term Aspirin Following Coronary Stent Implantation

et al. 2014

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SummaryEicosapentaenoic acid (EPA) has been widely accepted to have antiatherosclerotic effects. The aim of this study was to investigate the antiplatelet effect of EPA combined with acetylsalicylic acid (ASA) following stent implantation. Eighteen patients who had undergone coronary stent implantation at least 8 months previously were included. All patients were given EPA ethyl ester (EPA-E) 1.8 g/day in addition to ASA 100 mg/day for 12 weeks. After the treatment, the plasma EPA/arachidonic acid (AA) ratio increased signifi cantly from 0.40 ± 0.2 to 1.08 ± 0.39 (P < 0.001). There were no changes in the maximum platelet aggregation (MPA) induced by adenosine diphosphate (5 and 20 µmol/L), AA (0.3 and 0.5 mg/mL), or collagen (2 and 4 µg/mL). Furthermore, no signifi cant differences were observed in the expression of PAC-1 and CD62P on the platelet surface membranes or in the soluble P-selectin concentration. With further analysis, a signifi cant negative correlation was found between collagen (2 µg/mL)-induced MPA and plasma EPA/AA ratio (r = -0.507, P = 0.032). The patients were then divided into 2 groups according to the median EPA/AA ratio value of 0.92. In the high EPA/AA ratio group (n = 10), collagen-induced MPA was signifi cantly suppressed after EPA-E administration (45.3 ± 15.9 versus 39.0 ± 16.3, P = 0.033). In contrast, there were no signifi cant changes in platelet aggregation (56.0 ± 9.8 versus 57.1 ± 11.4, P = 0.745) in the low EPA/AA ratio group (n = 8). EPA treatment had a potential to suppress collagen-induced platelet aggregation in patients with a high plasma EPA/AA ratio. (Int Heart J 2014; 55: 228-233) Key words: Omega-3 polyunsaturated fatty acids, Coronary artery disease C oronary revascularization with drug-eluting stents (DES) has become a widespread technique for treating coronary artery disease (CAD). The guidelines recommend that patients with DES should receive dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and thienopyridine for at least 1 year in order to prevent stent thrombosis.1,2) When the risk of stent thrombosis decreases in the chronic phase following DES implantation, secondary prevention becomes a primary target of patient care. In fact, in the chronic phase, the risks of CAD or cerebrovascular disease are much higher than that of stent thrombosis.3,4) Therefore, lifelong treatment with ASA is also recommended for the secondary prevention of atherothrombotic events following DAPT termination. 1,2)Eicosapentaenoic acid (EPA) has been widely accepted to have antiatherosclerotic effects. 5,6) In relation to secondary prevention, the use of eicosapentaenoic acid ethyl ester (EPA-E) in combination with statins successfully reduced the recurrence of cardiovascular events in the Japan EPA lipid intervention study (JELIS). 7) In particular, in patients who underwent coronary artery intervention, the JELIS sub-study showed that the incidence of major coronary events was significantly reduced by 41% in the EPA treatment group. 8) EPA is known to improve vascula...

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Section: Discussionmentioning

confidence: 99%

Effects of Eicosapentaenoic Acid on Platelet Function in Patients Taking Long-Term Aspirin Following Coronary Stent Implantation

et al. 2014

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“…Supplementary EPA has successfully suppressed the expression of platelet activation markers and the release of platelet-derived microparticles capable of generating thrombin (a potent platelet aggregator), thereby retarding further platelet activation [17,18]. There is evidence that EPA and DHA also reduce platelet aggregation [19].…”

Section: Introductionmentioning

confidence: 95%

Effects of Seal Oil and Tuna‐Fish Oil on Platelet Parameters and Plasma Lipid Levels in Healthy Subjects

Mann

O’Connell

Baldwin

et al. 2010

Lipids

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Fish are a rich source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two long-chain polyunsaturated n-3 fatty acids (LC n-3 PUFA) with cardiovascular benefits. A related but less-investigated LC n-3 PUFA, docosapentaenoic acid (DPA), is more common in seal oil and pasture-fed red meats. This study compared indicators of platelet function and plasma lipids in healthy volunteers given supplements containing these different fatty acids (FA) for 14 days. Subjects, randomised into three groups of ten, consumed capsules of tuna oil (210 mg EPA, 30 mg DPA, 810 mg DHA), seal oil (340 mg EPA, 230 mg DPA, 450 mg DHA) or placebo (sunola) oil. Supplementary LC n-3 PUFA levels were approximately 1 g/day in both fish and seal oil groups. Baseline dietary FA and other nutrient intakes were similar in all groups. Both fish and seal oil elevated platelet DHA levels (P < 0.01). Seal oil also raised platelet DPA and EPA levels (P < 0.01), and decreased p-selectin (P = 0.01), a platelet activation marker negatively associated with DPA (P = 0.03) and EPA (P < 0.01) but not DHA. Plasma triacylglycerol decreased (P = 0.03) and HDL-cholesterol levels increased (P = 0.01) with seal oil only. Hence, seal oil may be more efficient than fish oil at promoting healthy plasma lipid profiles and lowering thrombotic risk, possibly due to its high DPA as well as EPA content.

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“…EPA alone decreased insulin reactivity and increased adiponectin levels in obese Japanese, without affecting leptin levels (114) . In type 2 diabetics, EPA had no effect on adiponectin levels but an additive positive effect when combined with statin treatment (194) . To date, only three studies investigated the independent effects of EPA and DHA on insulin sensitivity in human subjects.…”

Section: Insulin Sensitivity and Glycaemic Controlmentioning

confidence: 99%

The differential effects of EPA and DHA on cardiovascular risk factors

2011

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Compelling evidence exists for the cardioprotective benefits resulting from consumption of fatty acids from fish oils, EPA (20 :5n-3) and DHA (22 :6n-3). EPA and DHA alter membrane fluidity, interact with transcription factors such as PPAR and sterol regulatory element binding protein, and are substrates for enzymes including cyclooxygenase, lipoxygenase and cytochrome P450. As a result, fish oils may improve cardiovascular health by altering lipid metabolism, inducing haemodynamic changes, decreasing arrhythmias, modulating platelet function, improving endothelial function and inhibiting inflammatory pathways. The independent effects of EPA and DHA are poorly understood. While both EPA and DHA decrease TAG levels, only DHA appears to increase HDL and LDL particle size. Evidence to date suggests that DHA is more efficient in decreasing blood pressure, heart rate and platelet aggregation compared to EPA. Fish oil consumption appears to improve arterial compliance and endothelial function; it is not yet clear as to whether differences exist between EPA and DHA in their vascular effects. In contrast, the beneficial effect of fish oils on inflammation and insulin sensitivity observed in vitro and in animal studies has not been confirmed in human subjects. Further investigation to clarify the relative effects of consuming EPA and DHA at a range of doses would enable elaboration of current understanding regarding cardioprotective effects of consuming oily fish and algal sources of long chain n-3 PUFA, and provide clearer evidence for the clinical therapeutic potential of consuming either EPA or DHA-rich oils.

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The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients

Cited by 94 publications

References 43 publications

Effects of Eicosapentaenoic Acid on Platelet Function in Patients Taking Long-Term Aspirin Following Coronary Stent Implantation

Effects of Eicosapentaenoic Acid on Platelet Function in Patients Taking Long-Term Aspirin Following Coronary Stent Implantation

Effects of Seal Oil and Tuna‐Fish Oil on Platelet Parameters and Plasma Lipid Levels in Healthy Subjects

The differential effects of EPA and DHA on cardiovascular risk factors

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