Serum Levels Of Eicosapentaenoic Acid Research Articles

Eicosapentaenoic Acid and the Outcomes in Older Patients Undergoing Atrial Fibrillation Ablation.

A lower serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (EPA/AA) level correlates with cardiovascular events. Nevertheless, elevated serum EPA levels increase the risk of new-onset atrial fibrillation (AF) in older patients. The relationship between the EPA/AA and outcomes post-AF ablation remains unclear. This study investigated the impact of the EPA/AA on AF recurrence and cardiovascular events after AF ablation in older patients. This retrospective cohort study examined consecutive patients with AF aged ≥65 years who underwent a first-time AF ablation. We compared the 3-year AF recurrence and 5-year major adverse cardiovascular event (MACE) rates between patients divided into high and low EPA/AA levels defined as above and below the median EPA/AA value before ablation. MACE was defined as heart failure hospitalizations, strokes, coronary artery disease, major bleeding, and cardiovascular death. Among the 673 included patients, the median EPA/AA value was 0.35. Compared with the low EPA/AA group, the high EPA/AA group had a significantly higher cumulative incidence of AF recurrence (39.3% versus 27.6%; log-rank P=0.004) and lower cumulative incidence of MACE (13.8% versus 25.5%, log-rank P=0.021). A high EPA/AA level was determined as an independent predictor of AF recurrence (hazard ratio [HR], 1.75 95% CI, 1.24-2.49; P=0.002) and MACE (HR, 0.60 [95% CI, 0.36-0.99]; P=0.046). The EPA/AA was associated with AF recurrence and MACE after ablation in patients with AF aged ≥65 years.

Interaction of Vitamin D Supplements and Marine n-3 Fatty Acids on Digestive Tract Cancer Prognosis.

A meta-analysis suggested that marine n-3 polyunsaturated fatty acids (PUFAs), e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), might reduce cancer mortality. However, a randomized clinical trial of marine n-3 PUFA and vitamin D supplementation failed to verify this benefit. This study aimed to investigate the potential interaction between vitamin D supplementation and serum EPA and DHA levels. This post hoc analysis of the AMATERASU trial (UMIN000001977), a randomized controlled trial (RCT), included 302 patients with digestive tract cancers divided into two subgroups stratified by median serum levels of EPA + DHA into higher and lower halves. The 5-year relapse-free survival (RFS) rate was significantly higher in the higher half (80.9%) than the lower half (67.8%; hazard ratio (HR), 2.15; 95% CI, 1.29-3.59). In the patients in the lower EPA + DHA group, the 5-year RFS was significantly higher in the vitamin D (74.9%) than the placebo group (49.9%; HR, 0.43; 95% CI, 0.24-0.78). Conversely, vitamin D had no effect in the higher half, suggesting that vitamin D supplementation only had a significant interactive effect on RFS in the lower half (p for interaction = 0.03). These results suggest that vitamin D supplementation may reduce the risk of relapse or death by interacting with marine n-3 PUFAs.

Impact of serum eicosapentaenoic acid/arachidonic acid ratio on overall survival in lung cancer patients treated with pembrolizumab: a pilot study

This pilot study analyzed the dietary patterns of patients with non-small cell lung cancer undergoing initial pembrolizumab, an immune checkpoint inhibitor (ICI), treatment in the month before treatment. Serum fatty acid fractions and their associations with ICI treatment efficacy were also investigated. The results showed that long-term survivors (those who survived for ≥ 3 years) consumed significantly more seafood than short-term survivors (those who survived for < 3 years). Furthermore, the serum levels of eicosapentaenoic acid (EPA) as well as the ratio of EPA to arachidonic acid (EPA/AA) were higher in the long-term survivors than those in the short-term survivors. The group with a high serum EPA/AA ratio had a significantly higher overall survival rate after ICI treatment than the group with a low serum EPA/AA ratio. In conclusion, higher dietary seafood consumption may improve OS in lung cancer patients treated with ICI and the serum EPA/AA ratio may be a useful biomarker for determining the efficacy of ICI treatment. Thus, supplements that increase the serum EPA/AA ratio could serve as new nutritional interventions for enhancing the efficacy of ICI treatment. However, further large-scale case and intervention studies are required.

Abstract 13573: Association of Increased Eicosapentaenoic Acid to Arachidonic Acid Ratio With Early Restoration of Coronary Blood Flow in ST-Elevation Myocardial Infarction

Background: Early restoration of coronary blood flow is important to reduce myocardial damage in patients with ST-elevation myocardial infarction (STEMI). Cardiovascular protection of increased levels of eicosapentaenoic acid (EPA) to arachidonic acid (AA) has been shown in recent clinical trials. Therefore, this study examined whether increased EPA / AA ratio was related to early restoration of coronary blood flow in STEMI patients underwent primary percutaneous coronary intervention (PCI). Methods: Serum levels of EPA, AA, and EPA/AA ratio were measured in consecutive 216 STEMI patients. The angiographic findings of TIMI-flow grade in the infarct related artery before PCI were compared between patients with and without increased EPA / AA ratio (&amp;gt;0.291). Results: TIMI-flow grade 3 before PCI were obtained in 25 (11.6%) of all study patients. Smaller enzymatic infarct size was obtained in patients with TIMI-flow grade 3 before PCI compared with TIMI-flow grade 0-2 before PCI (Peak CK-MB; 358 &amp;plusmn; 252 mg/dL, vs. 280 &amp;plusmn; 260 mg/dL, p &amp;lt;0.05). There were significant differences between 2 groups in the distribution of TIMI-flow grade (p&amp;lt;0.05). Moreover, multivariate logistic regression analysis showed that patients with increased EPA/AA ratio was significantly associated with the presence of TIMI-flow grade 3 before PCI after adjustment for conventional risk factors (OR 5.0, 95% CI 1.92-12.8, p&amp;lt;0.01). Conclusions: Increased levels of EPA /AA ratio is independently associated with early restoration of coronary blood flow, leading to reduced myocardial damage in patients with STEMI. These results might support the new strategy of administration of EPA before PCI in STEMI care.

Imbalanced serum levels of resolvin E1 (RvE1) and leukotriene B4 (LTB4) may contribute to the pathogenesis of atherosclerosis

Persistent and chronic unresolved inflammation exerts a critical role in developing atherosclerosis; however, mechanisms that prevent the resolution of inflammation in atherosclerosis are poorly delineated. This study aims to evaluate the serum levels of inflammatory high-sensitivity C-reactive protein (hsCRP), pro-inflammatory leukotriene B4 (LTB4), besides anti-inflammatory compounds, including eicosapentaenoic acid (EPA) and its derivative resolvin E1 (RvE1) in patients with atherosclerosis. Thirty-four atherosclerosis patients and thirty-two age- and sex-matched healthy individuals were included in this study. The serum levels of hsCRP, LTB4, EPA, and RvE1 were measured using the enzyme-linked immunosorbent assay (ELISA) technique. Our results showed that the hsCRP serum levels in the three-vessel disease (3VD) subgroup of patients are significantly lower than those in the mild and single-vessel disease (SVD) subgroups (P < 0.05). Besides, the serum levels of LTB4 were meaningfully greater in patients with atherosclerosis compared to healthy controls (P < 0.05). Also, the serum EPA and RvE1 levels were significantly higher in patients than in controls (P < 0.01 and P < 0.05, respectively). However, the ratio of RvE1 to LTB4 (RvE1:LTB4) in patients was significantly reduced to that in controls (P < 0.0001). These findings illustrate that imbalanced pro-resolving RvE1 and pro-inflammatory LTB4 might contribute to failing vascular inflammation resolution and subsequent progression toward chronic inflammation in atherosclerosis.

Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina

Backgroundn-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA. Methods and resultsWe enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ± 37.7 μg/mL vs. 49.4 ± 28.8 μg/mL, p = 0.015) and DHA (135.7 ± 47.6 μg/mL vs. 117.4 ± 37.6 μg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively. ConclusionOur results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population.

Association of blood eicosapentaenoic acid levels with intracerebral hemorrhage during the COVID-19 pandemic: preliminary experience from a single-center in Japan

BackgroundThe COVID-19 pandemic has forced lockdowns and declarations of states of emergency, resulting in marked changes to daily life such as dietary habits in many countries. Though serum omega-3 polyunsaturated fatty acids levels have been shown to be useful markers for recurrent vascular events or worse prognosis in cardiovascular diseases and ischemic stroke, the relationship between serum omega-3 PUFA levels and the occurrence of intracerebral hemorrhage has essentially been unknown. We explored the association of serum omega-3 polyunsaturated fatty acids with intracerebral hemorrhage during the COVID-19 pandemic.MethodsParticipants comprised patients admitted to Juntendo University Hospital (Tokyo, Japan) with intracerebral hemorrhage between January 1, 2016 and April 30, 2020. Clinical characteristics including serum omega-3 polyunsaturated fatty acid levels were compared between patients developing intracerebral hemorrhage during the period from January 1, 2016 to February 29, 2020, and the subsequent COVID-19 pandemic period (March 1 to April 30, 2020). Clinical characteristics independently related to intracerebral hemorrhage during the COVID-19 pandemic were analyzed by comparing these two cohorts of intracerebral hemorrhage patients in different periods.ResultsA total of 103 patients (age, 67.0 ± 13.9 years; 67 males) with intracerebral hemorrhage were enrolled. Intracerebral hemorrhage developed in 91 patients before and 12 patients during the COVID-19 pandemic. Monthly averages of intracerebral hemorrhage patients admitted to our hospital during and before the COVID-19 pandemic were 6 and 1.82, respectively. Serum eicosapentaenoic acid levels were significantly lower in intracerebral hemorrhage patients during the COVID-19 pandemic than before (31.87 ± 12.93 μg/ml vs. 63.74 ± 43.29 μg/ml, p = 0.007). Multiple logistic regression analysis showed that, compared to before the COVID-19 pandemic, dyslipidemia (odds ratio 0.163, 95% confidence interval 0.031–0.852; p = 0.032) and eicosapentaenoic acid levels (odds ratio 0.947, 95% confidence interval 0.901–0.994; p = 0.029) were associated with intracerebral hemorrhage during the COVID-19 pandemic.ConclusionsFrom our preliminary results, low eicosapentaenoic acid levels were linked with intracerebral hemorrhage during the COVID-19 pandemic. Low levels of eicosapentaenoic acid might be an endogenous surrogate marker for intracerebral hemorrhage during the COVID-19 pandemic.

Effects of eicosapentaenoic acid on serum levels of selenoprotein P and organ-specific insulin sensitivity in humans with dyslipidemia and type 2 diabetes.

ABSTRACTAimSelenoprotein P (SeP, encoded by SELENOP in humans) is a hepatokine that causes insulin resistance in the liver and skeletal muscle. It was found that polyunsaturated fatty acid eicosapentaenoic acid (EPA) downregulates Selenop expression by inactivating SREBP‐1c. The present study aimed to examine the effect of EPA for 12 weeks on circulating SeP levels and insulin sensitivity in humans with type 2 diabetes.MethodsA total of 20 participants with dyslipidemia and type 2 diabetes were randomly assigned to an EPA (900 mg, twice daily) group and a control group. The primary endpoint was a change in serum SeP levels. Organ‐specific insulin sensitivity in the liver (HGP and %HGP), skeletal muscle (Rd), and adipose tissue (FFA and %FFA) were assessed using a hyperinsulinemic‐euglycemic clamp study with stable isotope‐labeled glucose infusion.ResultsSerum SeP levels were not changed in either group at the end of the study. In the EPA group, the changes in SeP levels were positively correlated with the change in serum EPA levels (r = 0.709, P = 0.022). Treatment with EPA significantly enhanced %FFA but not %HGP and Rd. The change in serum EPA levels was significantly positively correlated with the change in %HGP, and negatively correlated with changes in Rd.ConclusionsThe change in serum EPA levels was positively correlated with serum SeP levels, hepatic insulin sensitivity, and negatively with skeletal muscle insulin sensitivity in humans with type 2 diabetes. The EPA‐induced enhancement of hepatic insulin sensitivity might be associated with a mechanism independent of serum SeP levels.

Serum Eicosapentaenoic and Arachidonic Acids Concentration and Cognitive Function in Patients With Coronary Artery Disease.

Introduction:Recent studies have shown that Polyunsaturated Fatty Acids (PUFAs), including Eicosapentaenoic Acid (EPA), and Arachidonic Acid (AA), are associated with cognitive functions in patients with Coronary Artery Disease (CAD). Nevertheless, controversial results have been reported, too. The current study aimed to clarify the association of serum EPA and AA levels with cognitive decline in an Iranian sample with CAD.Methods:We evaluated cognitive function with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), in relation to serum levels of EPA and AA, in 179 CAD patients. The associations between the MMSE and MoCA scores and the other demographic parameters were evaluated.Results:Patients with CAD generally had mild cognitive impairment. But we could not find any significant correlation between PUFAs and cognitive function. However, BMI was associated with EPA/MoCA; age was associated with MMSE/MoCA and BMI. Finally, the correlation between sex and MMSE/MoCA was significant.Conclusion:Subjects generally had mild cognitive impairment, but we could not find any significant correlation between serum EPA and AA levels with cognitive function.

Abstract 14687: Achieved Eicosapentaenoic Acid (EPA) Levels Predicts Regression of Coronary Plaque Volumes by Coronary Computed Tomography Angiography (CCTA) in the EVAPORATE Trial

Background: Despite the beneficial effects of statins on progression of coronary atherosclerosis and cardiovascular (CV) events, significant CV risk persists in patients with hypertriglyceridemia. In REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) added to statins reduced initial and total CV events by 25% and 30%, but the mechanisms of benefit are unclear. In a follow-up analysis, degree of CV benefit from IPE was predominantly related to achieved serum EPA levels. Methods: EVAPORATE is a randomized, placebo-controlled trial, using CCTA to evaluate the effects of IPE as an adjunct to statins on coronary plaque volumes in a cohort with elevated triglycerides. Here, we present the 18-month, pre-specified secondary end-point analysis on association of achieved serum EPA levels, and change in coronary plaque volumes in the pooled cohort. Results: 80 patients were enrolled, and 68 completed the 18-month visit. Median (IQR) level of serum EPA for the pooled cohort was 20.6 (13.8) ug/ml at baseline and 25.3 (55.5) ug/ml at follow up. At 18 months, EPA levels &gt; 26 ug/ml predicted regression of fibro-fatty plaque (logβ: - 0.75± 0.36), total non-calcified plaque (TNCP) (logβ: - 0.77± 0.33), and total plaque (TP) (logβ: - 0.63± 0.28) volumes (mm3), after adjustment for age, sex, diabetes, hypertension, and baseline TGL levels (p &lt; 0.05 for all). Conclusions: Higher serum EPA levels predict regression of prognostically relevant coronary plaque volumes, TNCP, and TP on CCTA. This provides important mechanistic correlation to the CV benefits of IPE.

Antarctic Krill Oil Attenuates Oxidative Stress via the KEAP1-NRF2 Signaling in Patients with Coronary Heart Disease.

Background Antarctic krill oil (AKO) has strong antioxidant activities and is effective for alleviating coronary heart disease (CHD). Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) axis is a crucial antioxidant signaling pathway. Thus, AKO may exert its antioxidant effects on CHD patients via KEAP1-NRF2 signaling. Methods AKO fatty acid (FA) profiles were analyzed by using gas chromatography (GC). One hundred CHD patients were divided into the intervention (IG, AKO) and control (CG, placebo) groups. Before and after 1, 2, and 3 months of intervention, we measured serum levels of reactive oxygen species (ROS), 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione peroxidase (GPx), and KEAP1 and NRF2 levels in peripheral blood leukocytes (PBLs). Serum FAs were measured by GC at baseline and after 3-month intervention. Results AKO contains rich eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which is more than 27% of total FA. The levels of EPA and DHA, KEAP1, and NRF2 in the IG group were higher than those in the CG group (p < 0.05). Serum levels of ROS, 8-OHdG, NO, and MDA in the IG group were lower than those in the CG group, whereas the levels of SOD, GSH, and GPx in the IG group were higher than those in the CG group (p < 0.05). Serum levels of saturated fatty acids (UFA) in the IG group were higher than those in the CG group, whereas reverse results were obtained for the levels of saturated fatty acids (SFA). Serum levels of EPA and DHA had a strong negative relationship with the level of ROS, whereas the ROS level had a strong negative relationship with the levels of KEAP1-NRF2. Conclusion AKO increases antioxidant capacities of CHD patients via the KEAP1-NRF2 signaling in the PBL.

Fatty Acid Treatment with Pure Omega-3 Eicosapentaenoic Acid Ethyl Ester for Patients with Cardiovascular Diseases: Differences between Branded (EPADEL&amp;amp;#174;) and Generic Products

Background: Omega-3 polyunsaturated fatty acids (PUFAs) have some protective benefits for patients with coronary artery and cerebrovascular diseases. Eicosapentaenoic acid (EPA) drugs are prescribed as branded (B: EPADEL?) or generic products but no data exist concerning the differences in treatment outcomes between these products. Methods and Results: We investigated the differences in the serum levels of EPA, docosahexaenoic acid (DHA) and arachidonic acid (AA), and the EPA/AA ratios through blood sampling six months after daily administration of 1800 mg of EPADEL? and a generic EPA drug was initiated for 96 patients with cardiovascular diseases. All patients received these PUFA treatments while continuing with baseline therapy. After 6 months of administration, EPADEL? produced better results than the generic (G) product (EPA; baseline: 59.4 ± 25.5 μg, B: 215.5 ± 58.8 μg, G: 199.7 ± 63.8 μg, B vs G, p μg, B: 158.3 ± 36.3 μg, G: 163.6 ± 38.9 μg, B vs G, p Conclusions: There were clear differences between EPA branded and the generic products. Further study is required to determine whether the benefits from the branded product justify the higher price compared to the generic drug cost.

Eicosapentaenoic acid/arachidonic acid ratio and weight loss during hospitalization for glycemic control among overweight Japanese patients with type 2 diabetes: a retrospective observational study

BackgroundThe study aimed to examine the relationship between levels of serum eicosapentaenoic acid (EPA), arachidonic acid (AA), as well as EPA/AA ratio and weight loss during hospitalization in participants considered to be overweight, with type 2 diabetes.MethodsThe study participants included 142 patients who were hospitalized for treatment of type 2 diabetes. We divided the participants into two groups depending on the achievenemt in reduction of bodyweight 3% or more during hospitalization and examined the relationship between serum levels of EPA and AA, as well as ratio of EPA/AA on admission and effectiveness of weight loss under strict dietary therapy during hospitalization, using Cox proportional hazard models.ResultsAfter adjustment was made for several confounders, the hazard ratio of effective weight loss for logarithmical serum EPA was 1.59 (95% CI 1.02–2.49, P = 0.04) and for logarithmical EPA/AA ratio 1.64 (1.03–2.61, P = 0.04), whereas the hazard ratio for effective weight loss for logarithmical serum AA was 1.11 (0.45–2.78, P = 0.82). In addition, after dividing EPA/AA ratio and serum EPA into quartiles based on participant number, the hazard ratio for the highest quartile of EPA/AA ratio was 2.33 (1.14–4.77, P = 0.02), and for the highest quartile of serum EPA 1.60 (0.80–3.19, P = 0.18) compared with the lowest quartile.ConclusionThese results suggest the possibility that EPA is involved in bodyweight change under a caloric-restriction regimen. In addition, EPA/AA ratio was found to be a better predictor of medical intervention for weight loss among overweight patients with type 2 diabetes, compared with serum EPA level.

Relationship Between Serum Eicosapentaenoic Acid Levels and J-Waves in a General Population in Japan.

We previously showed that J-waves were found more frequently in patients with low levels of serum eicosapentaenoic acid (EPA) in the acute phase of myocardial infarction, and were associated with the incidence of ischemia-related ventricular arrhythmias. However, the relationship between J-waves and serum EPA levels in a general population remains to be elucidated.The Iwaki Health Promotion Project is an ongoing community-based health promotion study in Iwaki, Hirosaki, which is in northern Japan. A total of 1,052 residents (mean age, 53.9 ± 15.4 years; 390 men) who participated in this project in 2014 were studied. A standard 12-lead electrocardiogram (ECG) was recorded and serum EPA levels were measured to evaluate the relationship between J-waves and serum EPA levels. J-waves were found in 52 (5%) subjects and were observed more frequently in male than female subjects (44 [11%] versus 8 [1%], P < 0.0001). More than half of the J-waves were the notched type (60%), and J-waves were detected most frequently in inferior leads on ECG (52%). The RR interval was longer and QTc duration shorter in subjects with J-waves than those without. No significant difference was found in serum EPA levels between subjects with and without J-waves (70 [49-116] versus 65 [41-106] μg/mL, P = 0.40). In multivariate analysis, male gender and RR interval were independent factors associated with the presence of J-waves.There was no significant relationship between J-waves and serum EPA levels in this general population in Japan. Various mechanisms for manifestation of the J-waves are suggested.

Age Stratification and Impact of Eicosapentaenoic Acid and Docosahexaenoic Acid to Arachidonic Acid Ratios in Ischemic Stroke Patients.

Aim: We focused on the ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to arachidonic acid (AA) and explored the significance of these ratios relative to clinical characteristics by age in ischemic stroke patients.Methods: We enrolled patients with acute ischemic stroke who underwent radiological investigations and laboratory examinations, including measurement of serum EPA, DHA, and AA levels, and controls. Patients were classified according to age (< 65, 65–74, and ≥ 75 years) and the tertile of EPA/AA and DHA/AA ratios, and clinical aspects were compared with these factors.Results: We analyzed 373 patients (age 70.2 ± 13.4 years; 245 males) and 105 controls. Among stroke patients, patients aged < 65 years had the lowest EPA/AA (0.35 ± 0.23, p = 0.006) and DHA/AA (0.73 ± 0.27, p < 0.001) ratios. Compared with controls, patients aged < 65 years showed lower EPA/AA (vs. 0.49 ± 0.25, p < 0.001) and DHA/AA (vs. 0.82 ± 0.26, p = 0.009) ratios. From logistic regression analysis, the EPA/AA (odds ratio 0.18, 95% confidence interval 0.04–0.81, p = 0.026) and DHA/AA (odds ratio 0.09, 95% confidence interval 0.02–0.33, p < 0.001) ratios were inversely related to patients aged < 65 years. According to age-stratified analyses, we found an association of aortic arch calcification with a lower EPA/AA ratio for patients aged ≥ 75 years and an association of multiple infarctions and cerebral white matter lesions with a lower EPA/AA ratio for patients aged 65–74 years (p < 0.05).Conclusions: The ratios of EPA/AA and DHA/AA could be specific markers for younger stroke patients. The EPA/AA ratio may be related to aortic arch calcification for elderly stroke patients and to multiple infarctions and cerebral white matter disease for middle-aged stroke patients.

A cross-sectional and longitudinal study between association of n-3 polyunsaturated fatty acids derived from fish consumption and high-density lipoprotein heterogeneity

Decreased high-density lipoprotein (HDL) particle size, cholesterol poor, apolipoprotein A-I-rich HDL particles leading to smaller HDL particle size, may be associated with an anti-atherosclerotic effect. The data are sparse regarding the relationship between n-3 polyunsaturated fatty acids [n-3 PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and HDL particle size. This study was designed as a hospital-based cross-sectional study to investigate the relationship between the serum levels of n-3 PUFAs and the HDL-cholesterol/apolipoprotein A-1 ratio, as estimated by the HDL particle size, in patients with the presence of one or more risk factors for atherosclerotic cardiovascular disease (ASCVD). Six hundred and forty sequential patients were enrolled in this study. The serum levels of EPA and DHA showed a strong correlation (r = 0.736, p < 0.0001). However, in a multivariate regression analysis after adjustment for ASCVD risk factors, increased serum DHA (β = − 0.745, p = 0.021), but not serum EPA (β = − 0.414, p = 0.139) or EPA + DHA (β = 0.330, p = 0.557) level, was identified as an independent indicator of decreased HDL particle size. In 476 patients followed up for at least 6 months, the absolute change (Δ) in the HDL-cholesterol/apolipoprotein A-1 ratio decreased significantly as the quartile of the Δ DHA level increased (p = 0.014), whereas no significant difference in the Δ HDL-cholesterol/apolipoprotein A-1 ratio was noted with the increase in the quartile of the Δ EPA level. Moreover, a multivariate regression analysis identified increased DHA level and decreased estimated low-density lipoprotein (LDL) particle size measured relative to the mobility value of LDL with polyacrylamide gel electrophoresis (i.e., relative LDL migration: LDL-Rm value), as independent predictors of decreased HDL-cholesterol/apolipoprotein A-1 ratio (β = − 0.171, p = 0.0003 and β = − 0.142, p = 0.002). The results suggest that increased serum DHA level, but not EPA level, might be associated with decreased HDL-cholesterol/apolipoprotein A-1 ratio, an indicator of estimated HDL particle size. Further studies are needed to investigate the useful clinical indices and outcomes of these patients.Clinical Trial Registration Information UMIN (http://www.umin.ac.jp/), Study ID: UMIN000010603.

Eicosapentaenoic acid prevents arterial calcification in klotho mutant mice.

BackgroundThe klotho gene was identified as an “aging-suppressor” gene that accelerates arterial calcification when disrupted. Serum and vascular klotho levels are reduced in patients with chronic kidney disease, and the reduced levels are associated with arterial calcification. Intake of eicosapentaenoic acid (EPA), an n-3 fatty acid, reduces the risk of fatal coronary artery disease. However, the effects of EPA on arterial calcification have not been fully elucidated. The aim of this study was to determine the effect of EPA on arterial calcification in klotho mutant mice.Methods and resultsFour-week-old klotho mutant mice and wild-type (WT) mice were given a diet containing 5% EPA (EPA food, klotho and WT: n = 12, each) or not containing EPA (control food, klotho and WT: n = 12, each) for 4 weeks. Calcium volume scores of thoracic and abdominal aortas assessed by computed tomography were significantly elevated in klotho mice after 4 weeks of control food, but they were not elevated in klotho mice after EPA food or in WT mice. Serum levels of EPA and resolvin E1, an active metabolite of EPA, in EPA food-fed mice were significantly increased compared to those in control food-fed mice. An oxidative stress PCR array followed by quantitative PCR revealed that NADPH oxidase-4 (NOX4), an enzyme that generates superoxide, gene expression was up-regulated in arterial smooth muscle cells (SMCs) of klotho mice. Activity of NOX was also significantly higher in SMCs of klotho mice than in those of WT mice. EPA decreased expression levels of the NOX4 gene and NOX activity. GPR120, a receptor of n-3 fatty acids, gene knockdown by siRNA canceled effects of EPA on NOX4 gene expression and NOX activity in arterial SMCs of klotho mice.ConclusionsEPA prevents arterial calcification together with reduction of NOX gene expression and activity via GPR120 in klotho mutant mice.

Clinical implications of eicosapentaenoic acid/arachidonic acid ratio (EPA/AA) in adult patients with congenital heart disease.

Recent studies showed that a low ratio between the levels of eicosapentaenoic acid and those of arachidonic acid (EPA/AA) is associated with higher incidence of coronary artery disease and poor prognosis of heart failure, arrhythmia, and cardiac sudden death. However, the clinical implications of EPA/AA in adult patients with congenital heart disease remain unclear. We aimed to assess the prognostic value of EPA/AA regarding cardiac events in adult patients with congenital heart disease. We measured the serum levels of eicosapentaenoic acid and arachidonic acid in 130 adult patients (median age, 31years) stratified into two groups according to their EPA/AA (low, ≤0.22; high, >0.22). We prospectively analyzed the association between EPA/AA and incidence of cardiac events during a mean observation period of 15months, expressed in terms of hazard ratio (HR) with 95% confidence interval (95% CI). In the subgroup of patients with biventricular circulation (2VC) (n=76), we analyzed the same clinical endpoints. In our study population, EPA/AA was not associated with the incidence of arrhythmic events (HR, 1.52; 95% CI, 0.82-2.85; p=0.19), but low EPA/AA was a predictor of heart failure hospitalization (HR, 2.83; 95% CI, 1.35-6.30; p<0.01). Among patients with 2VC, an EPA/AA of ≤0.25 was associated with a significantly higher risk of arrhythmic events (HR, 2.55; 95% CI, 1.11-6.41; p=0.03) and heart failure hospitalization (HR, 5.20; 95% CI, 1.78-18.1; p<0.01). EPA/AA represents a useful predictor of cardiac events in adult patients with congenital heart disease.

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

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, 2014

The effect of fish oil supplementation on maternal and neonatal outcomes: a triple-blind, randomized controlled trial.

To evaluate the effect of fish oil supplementation on pregnancy outcomes in mother and newborn. This randomized, triple-blind, placebo-controlled trial was conducted on 150 pregnant women aged 18-35 years from Feburary 2014 to April 2015 in Tabriz, Iran. Participants were assigned to receive either 1000 mg fish oil supplements containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexanoic acid or placebo from week 20 of gestation to birth. The primary outcome measure was birth weight. Gestational duration, preterm labor low birth weight (LBW), length, head circumference, and maternal serum docosahexaenoic acid (DHA) and EPA level at 35-37 weeks were also examined. The statistical analysis was on an intention-to-treat basis. Demographic characteristics were similar in both groups (P>0.05). The mean (SD) birth weight values in the fish oil and placebo groups were 3256 (362) g and 3172 (447) g, respectively (adjusted mean difference (MD)=84.1 g, 95% confidence interval [CI]=-24.8 to 193.2). Five (7.6%) neonates in the placebo versus no case in the fish oil group were born with LBW (P=0.02). The rate of preterm labor was lower in the fish oil group (adjusted OR=0.74, 95% CI=0.16-3.42). However, there were no statistically significant differences in the maternal outcomes (P>0.05) with the exception of the proportion of maternal serum DHA fatty acid at 35-37 weeks (P<0.001). Although low dose fish oil supplementation increased birth weight, its effect was not statistically significant. The frequency of LBW was significantly reduced in the intervention group, but the observed reduction needs to be confirmed in future larger investigations using different doses of omega-3.