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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

View Article: PubMed Central - PubMed

ABSTRACT

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.

Conclusions: The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014

Electronic supplementary material: The online version of this article (doi:10.1186/s12933-017-0523-9) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

Permeation coefficient (Ks), before (a) and after intervention (b); endogenous thrombin potential (ETP), before (c) and after intervention (d); platelet aggregation—5 mmol/L of arachidonic acid (PR AA) before (e) and after intervention (f) in placebo and n-3 PUFAs group. Horizontal line median; upper and lower margin of rectangle interquartile range, vertical line observation away from 1.5 quartiles
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Fig2: Permeation coefficient (Ks), before (a) and after intervention (b); endogenous thrombin potential (ETP), before (c) and after intervention (d); platelet aggregation—5 mmol/L of arachidonic acid (PR AA) before (e) and after intervention (f) in placebo and n-3 PUFAs group. Horizontal line median; upper and lower margin of rectangle interquartile range, vertical line observation away from 1.5 quartiles

Mentions: At baseline there were no significant intergroup differences in the markers of thrombin generation and fibrin clot properties. After 3 months of n-3 PUFA treatment, no intergroup differences were found in fibrin clot properties and most markers of thrombin generation, except for F1.2. A within-group analysis showed that there was a trend towards an increase in F1.2 levels in the placebo group (p = 0.05) during the study period, while this parameter remained unaltered in the n-3 PUFA group (p = 0.53). As a result, F1.2 levels were lower in the n-3 PUFA group (p = 0.04) at the end of the study, but the differences were of borderline significance (Table 2; Fig. 2).Fig. 2


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
Permeation coefficient (Ks), before (a) and after intervention (b); endogenous thrombin potential (ETP), before (c) and after intervention (d); platelet aggregation—5 mmol/L of arachidonic acid (PR AA) before (e) and after intervention (f) in placebo and n-3 PUFAs group. Horizontal line median; upper and lower margin of rectangle interquartile range, vertical line observation away from 1.5 quartiles
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5391604&req=5

Fig2: Permeation coefficient (Ks), before (a) and after intervention (b); endogenous thrombin potential (ETP), before (c) and after intervention (d); platelet aggregation—5 mmol/L of arachidonic acid (PR AA) before (e) and after intervention (f) in placebo and n-3 PUFAs group. Horizontal line median; upper and lower margin of rectangle interquartile range, vertical line observation away from 1.5 quartiles
Mentions: At baseline there were no significant intergroup differences in the markers of thrombin generation and fibrin clot properties. After 3 months of n-3 PUFA treatment, no intergroup differences were found in fibrin clot properties and most markers of thrombin generation, except for F1.2. A within-group analysis showed that there was a trend towards an increase in F1.2 levels in the placebo group (p = 0.05) during the study period, while this parameter remained unaltered in the n-3 PUFA group (p = 0.53). As a result, F1.2 levels were lower in the n-3 PUFA group (p = 0.04) at the end of the study, but the differences were of borderline significance (Table 2; Fig. 2).Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

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.

Conclusions: The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014

Electronic supplementary material: The online version of this article (doi:10.1186/s12933-017-0523-9) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus