Bilberry Supplementation after Myocardial Infarction Decreases Microvesicles in Blood and Affects Endothelial Vesiculation.

SCOPE: Diet rich in bilberries is considered cardioprotective, but the mechanisms of action are poorly understood. Cardiovascular disease is characterized by increased proatherogenic status and high levels of circulating microvesicles (MVs). In an open-label study patients with myocardial infarction receive an 8 week dietary supplementation with bilberry extract (BE). The effect of BE on patient MV levels and its influence on endothelial vesiculation in vitro is investigated. METHODS AND RESULTS: MVs are captured with acoustic trapping and platelet-derived MVs (PMVs), as well as endothelial-derived MVs (EMVs) are quantified with flow cytometry. The in vitro effect of BE on endothelial extracellular vesicle (EV) release is examined using endothelial cells and calcein staining. The mechanisms of BE influence on vesiculation pathways are studied by Western blot and qRT-PCR. Supplementation with BE decreased both PMVs and EMVs. Furthermore, BE reduced endothelial EV release, Akt phosphorylation, and vesiculation-related gene transcription. It also protects the cells from P2X7 -induced EV release and increase in vesiculation-related gene expression. CONCLUSION: BE supplementation improves the MV profile in patient blood and reduces endothelial vesiculation through several molecular mechanisms related to the P2X7 receptor. The findings provide new insight into the cardioprotective effects of bilberries.

Association Between Chocolate Consumption and Severity of First Infarction

Abstract Background: Cardiovascular diseases, such as acute myocardial infarction, are the main causes of death in the world. The flavonoids present in chocolate can have benefits for people who have risk factors to the development of cardiovascular diseases and have a coadjuvant effect on known therapies. Objective: To analyze the association between chocolate consumption, severity of coronary lesions, risk factors and severity of the first infarction in patients attended at the Cardiology Institute of Santa Catarina and other hospitals in the State of Santa Catarina. Methods: Subanalysis of the Catarina Heart Study cohort, evaluated 350 patients with first myocardial infarction. We evaluated clinical, echocardiographic, hemodynamic laboratorial variables. We used chi square test to evaluate qualitative variables, t student test in the case of parametric variables and U Mann Whitney test in non-parametric variables. We considered significant p < 0,05. Results: Lower prevalence of hypertension (43.2% % vs. 62.3% p = 0.003), diabetes mellitus (13.5% vs. 25.7%, p = 0.027) and smoking (24.3% vs. 37.7%, p = 0.032) among those who consume chocolate. Higher use of alcohol (40.5% vs. 26.4%, p = 0.018) and drugs (9.5% vs. 3.3%, p = 0.023) among those who consumed chocolate. Among the patients who consumed chocolate, there was a negative correlation between amount consumed and Syntax (r = -0.296, p = 0.019). Conclusion: There was association between chocolate consumption and lower prevalence of hypertension, diabetes and smoking. There was no association between amount of chocolate consumed and post-infarction ventricular function and TIMI frame count. Higher prevalence of alcohol and drug use among those who consume chocolate. Negative correlation between Syntax and the amount of chocolate consumed.

Influence of intermittent fasting on myocardial infarction-induced cardiac remodeling.

BACKGROUND: Information on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival. METHODS: Wistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL - fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF - fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations. RESULTS: Before surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 µm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and ß-myosin heavy chain did not differ between groups. CONCLUSION: Intermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.

Omega-3 Fatty Acid and Cardiovascular Outcomes: Insights From Recent Clinical Trials.

PURPOSE OF REVIEW: Omega-3 fatty acids (ω-3 FA) are among the most well-recognized health supplements but their cardiovascular benefits have long been controversial owing to inconsistent results from previous cardiovascular outcomes trials (CVOT). In this article, we provide a short review of existing literature followed by recent randomized clinical trial data, with a discussion of the potential clinical implications of these new findings. RECENT FINDINGS: Data from the randomized, controlled trial REDUCE-IT, when viewed within the context of other recently published trials ASCEND and VITAL, add to a growing body of evidence on the use of ω-3 FA therapies in the treatment of atherosclerotic cardiovascular disease (ASCVD). Given the different formulations, dosages, and patient populations studied, CVOTs of ω-3 FA have provided valuable insight into the use of these agents in cardioprotection. Current data suggest that higher dosages of pure eicosapentaenoic acid ω-3 FA formulations provide additional benefit in reduction of ASCVD events.

Effectiveness of the physical activity intervention program in the PREDIMED-Plus study: a randomized controlled trial.

BACKGROUND: The development and implementation of effective physical activity (PA) intervention programs is challenging, particularly in older adults. After the first year of the intervention program used in the ongoing PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial, we assessed the initial effectiveness of the PA component. METHODS: PREDIMED-Plus is an ongoing randomized clinical trial including 6874 participants randomized to an intensive weight-loss lifestyle intervention based on an energy-restricted Mediterranean diet (MedDiet), physical activity promotion and behavioral support and to a control group using MedDiet recommendations but without calorie restriction or PA advice. Body mass index (BMI) and waist circumference (WC) are measured by standard clinical protocols. Duration and intensity of PA is self-reported using the validated REGICOR Short Physical Activity Questionnaire. The primary endpoint of the PREDIMED-Plus trial is a combined cardiovascular outcome: myocardial infarction (acute coronary syndromes with positive troponin test), stroke, or cardiovascular mortality. The present study involved secondary analysis of PA data (n = 6059; mean age 65 ± 4.9 years) with one-year changes in total, light, and moderate-to-vigorous PA within and between intervention groups as the outcome. Generalized estimating equation models were fitted to evaluate time trends of PA, BMI, and WC within groups and differences between intervention and control groups. RESULTS: After 12 months, average daily MVPA increased by 27.2 (95%CI 5.7;48.7) METs-min/day and 123.1 (95%CI 109.7-136.6) METs-min/day in the control and intervention groups, respectively. Total-PA, light-PA, and MVPA increased significantly (p < 0.01) in both groups. A significant (p < 0.001) time*intervention group interaction was found for Total-PA and MVPA, meaning the PA trajectory over time differed between the intervention and control groups. Age, sex, education level, and BMI did not moderate the effectiveness of the PA intervention. BMI and WC decreased significantly with increasing MVPA, compared with participants who reported no changes in MVPA. CONCLUSION: After one year of follow-up, the PREDIMED-Plus PA intervention has been effective in increasing daily PA in older adults. TRIAL REGISTRATION: Retrospectively registered at the International Standard Randomized Controlled Trial ( http://www.isrctn.com/ISRCTN89898870 ), registration date: 24 July 2014.

Omega-3 PUFA attenuate mice myocardial infarction injury by emerging a protective eicosanoid pattern.

Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation is a recommended preventive approach against cardiovascular diseases, but its mechanism of protection against myocardial infarction (MI) injury is not fully understood. Eicosanoid metabolomics demonstrated an abnormal eicosanoid profile was in the plasma of mice receiving MI surgery. 19,20-EDP, 17,18-EEQ, 14,15-EET and 9,10-EpOME were decreased, and PGE2 was increased by the surgery. N-3 PUFA-rich diets feeding or transgene of Fat-1 shifted the eicosanoid profile to an n-3 PUFA dominant style and attenuated the myocardial infarction injury. Multiple logistic regression analysis suggested the degree of MI injury was related with an eicosanoid pattern, composed by eicosanoids derived from both n-3 and n-6 PUFA in the three enzymatic pathways. These results suggested the benefits of n-3 PUFA on MI was achieved synergistically.

Plasma Circulating Extracellular RNAs in Left Ventricular Remodeling Post-Myocardial Infarction.

Despite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associated with post-MI LVRm phenotypes. RNA sequencing of exRNAs was performed on plasma samples from patients with "beneficial" (decrease LVESVI ≥ 20%, n = 11) and "adverse" (increase LVESVI ≥ 15%, n = 11) LVRm. Selected differentially expressed exRNAs were validated by RT-qPCR (n = 331) and analyzed for their association with LVRm determined by cardiac MRI. Principal components of exRNAs were associated with LVRm phenotypes post-MI; specifically, LV mass, LV ejection fraction, LV end systolic volume index, and fibrosis. We then investigated the temporal regulation and cellular origin of exRNAs in murine and cell models and found that: 1) plasma and tissue miRNA expression was temporally regulated; 2) the majority of the miRNAs were increased acutely in tissue and at sub-acute or chronic time-points in plasma; 3) miRNA expression was cell-specific; and 4) cardiomyocytes release a subset of the identified miRNAs packaged in exosomes into culture media in response to hypoxia/reoxygenation. In conclusion, we find that plasma exRNAs are temporally regulated and are associated with measures of post-MI LVRm.

Effects of the "plate model" as part of dietary intervention on modification of selected cardiometabolic risk factors in post-myocardial infarction patients: study protocol for a randomized controlled trial.

BACKGROUND: Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, and there is a rising global burden. The effects of diet on cardiometabolic risk factors have been studied extensively. Healthy eating as a cost-effective approach to risk reduction in post-myocardial infarction patients is proven to be beneficial, and the "plate model" is one of the practical methods to achieve this objective. METHODS/DESIGN: The study will be conducted as a randomized, single-blind, controlled clinical trial for a period of 3 months. A total of 120 overweight (body mass index >23 kg/m2) inpatients (aged 20-70 years) with a history of troponin-positive acute coronary syndrome (ACS) within the 1 month preceding the study will be recruited. Simple randomization will be used in participant allocation. The intervention group will receive the model plate diet. The control group will be provided with routine dietary advice. Other domains, such as advice on exercise and lifestyle modification, will be equalized among patients in both the groups. The visits and evaluations will be done at recruitment (visit 0), 4 weeks, and 12 weeks after the intervention. The primary outcome will be a mean body weight reduction of 10%, and the secondary outcomes will include mean reduction of systolic and diastolic blood pressure, improvement of anthropometric parameters, and improvement of lipid profile and liver enzymes in the test group compared with the control group at 12 weeks following the plate model diet. DISCUSSION: This study protocol is designed to establish the effects of the plate model diet on modification of cardiometabolic risk factors in patients with ACS. This will also be a pioneering study designed to investigate the practicality of the model plate in local settings and in the South Asian region. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry identifier: SLCTR/2016/22. Registered on 22 September 2016 ( http://www.slctr.lk/trials/483 ).

Tomato (Lycopersicon esculentum) or lycopene supplementation attenuates ventricular remodeling after myocardial infarction through different mechanistic pathways.

The objective of this study was to evaluate the influence of tomato or lycopene supplementation on cardiac remodeling after myocardial infarction (MI). Male Wistar rats were assigned to four groups: the sham group (animals that underwent simulated surgery) that received a standard chow (S; n=18), the infarcted group that received a standard chow (MI; n=13), the infarcted group supplemented with lycopene (1 mg of lycopene/kg body weight/day) (MIL; n=16) and the infarcted group supplemented with tomato (MIT; n=16). After 3 months, morphological, functional and biochemical analyses were performed. The groups MIL and MIT showed decreased interstitial fibrosis induced by infarction. Tomato supplementation attenuated the hypertrophy induced by MI. In addition, tomato and lycopene improved diastolic dysfunction evaluated by echocardiographic and isolated heart studies, respectively. The MI group showed higher levels of cardiac TNF-α compared to the MIL and MIT groups. Decreased nuclear factor E2-related factor 2 was measured in the MIL group. Lipid hydroperoxide levels were higher in the infarcted groups; however, the MIT group had a lower concentration than did the MI group [S=223±20.8, MI=298±19.5, MIL=277±26.6, MIT=261±28.8 (nmol/g); n=8; P<.001]. We also examined left ventricle miRNA expression; when compared to the S group, the MIL group uniquely down-regulated the expression of eight miRNAs. No miRNA was found to be up-regulated uniquely in the MIT and MIL groups. In conclusion, tomato or lycopene supplementation attenuated the cardiac remodeling process and improved diastolic function after MI. However, the effect of lycopene and tomato supplementation occurred through different mechanistic pathways.

Supplementation with omega-3 acids after myocardial infarction and modification of inflammatory markers in light of the patients' diet: a preliminary study.

BACKGROUND: Neuroendocrine activation, activation of proinflammatory cytokines and platelets, and endothelial dysfunction play a significant role in the development of heart failure (HF). AIM: The aim of the work was to assess the effect of supplementation with EPA and DHA in a daily dose of 1 g on selected inflammatory markers and platelet activation in patients with HF after recent myocardial infarction in light of their diet. METHODS: This preliminary study was a randomised, double-blind trial involving 30 patients with post-infarction HF. One group received a product containing 1 g of omega-3 acids, while the other received placebo, i.e. corn oil 1 g daily for 12 weeks. At baseline and at week 12, venous blood was obtained in the fasted state in order to determine the following parameters: NT-proBNP, fibrinogen, INR, creatinine clearance, serum lipid profile, hsCRP, troponin, glucose, transaminases, GGTP, MCP-1, pentraxin 3, and CD-40. To evaluate the patient's diet and dietary intake of omega-3 acids, a 24-h dietary interview and the Block's Food Frequency Questionnaire (FFQ) were applied. RESULTS: Supplementation of omega-3 acids in a dose of 1 g per day had no effect on lipid or inflammatory parameters, with the exception of pentraxin 3. In both groups, after three months of supplementation, overall consumption of energy and saturated fatty acids was significantly higher (p < 0.05). CONCLUSIONS: Potential benefits associated with supplementation were nullified by a highly atherogenic diet. Apparently, supplementation of omega-3 acids without simultaneous dietary education and nutrition control does not bring the expected effect. Further research involving a larger group of patients is needed to better understand the relationship between patient's diet and the effectiveness of omega-3 supplementation.

[Effect of a new low-cholesterol meat and vegetal product on correction of simulated lipid metabolism disorders in rats].

The paper presents the biomedical evaluation of meat and cereal spread from low-cholesterol raw material with vegetable ingredients, recommended as a functional food. The experimental model with myocardial infarction like changes in hearts of the animals, accompanied by vascular changes similar to atherosclerotic changes in humans, as well as the modeling of the metabolic imbalance of lipids have been carried out by intramuscular injection of epinephrine and unbalanced feeding the animals with food rich in cholesterol, with a high content of carbohydrates and fats. Wistar rats were divided into 4 groups of 12 animals each. The rats in groups 1-3 were induced the cardio distress with intramuscular injection of epinephrine; group IV consisted of intact (healthy) animals. Dramatic changes in biochemical blood status that indicated heart disease have been observed within 2 days after the injection of epinephrine (0.2 ml per 1 kg of animal body weight) to the tested animals. During the experiment a sharp increase in activity of indicator enzymes of alanine aminotransferase (ALT) and aspartate aminotransferases (AST), with a predominance of AST over ALT, along with an increase in LDH activity have been observed. The 1.4-1.6 fold increase in blood serum creatinine has also been found. Later the animals in groups 1, 2, 3 with simulated cardio pathology were fed a ration with intervention of food rich in cholesterol, with a high content of carbohydrates and fats (50% of the diet) for a month for induction of lipid metabolism disorders. An increase in the concentration of cholesterol and triglycerides by 3 fold or more has been observed. In addition, an accumulation of sulfhydryl groups has been noted, as evidenced by increased rates of thymol. For further normalization of lipid metabolism, the animals in tested group I were fed the diet with intervention of spread, developed in accordance with GOST 12318-91 "Canned meat "Meat spread"; the rats of group 2 were fed with spread with vegetable supplements (pumpkin by-products and alginates), and group 3 received a standard diet within the next month. The results of biochemical blood serum studies have shown that the level of cholesterol, triglycerides, creatinine and sulphydryl groups in the experimental groups 1 and 2 decreased, indicating a positive influence on lipid metabolism and prevention of peroxides formation in the organism. These changes were more pronounced when meat product with plant additives and alginate was used in the diet. Only under the application of the meat-vegetable pate cholesterol level ceased to differ from that of the control group of animals. Based on the significant reduction of blood malondialdehyde level, antioxidant properties of vegetable supplements have been proven. The experimental data showed that the spread, developed on the basis of low-cholesterol raw meat with vegetable ingredients (pumpkin by-products and alginates) can be used to correct metabolic disorders of lipids, reducing the risk of cardio pathology in the body.

Role of melatonin, melatonin receptors and STAT3 in the cardioprotective effect of chronic and moderate consumption of red wine.

We have recently discovered that melatonin, given acutely and directly to the isolated heart at the concentration found in wine, confers cardioprotection against ischemia-reperfusion (I/R). However, whether the presence of melatonin in wine contributes to the cardioprotective effect of chronic and moderate consumption of wine and its signalling mechanisms of protection are unknown. We therefore used both in vivo and in vitro models of I/R to investigate whether the presence of melatonin in red wine may contribute to the cardioprotective effect of chronic and moderate consumption of red wine. Wistar rats and C57black6 mice (WT) received drinking water supplemented daily with a moderate amount of red wine or melatonin given at the concentration found in the red wine. Rats were also pretreated with luzindole, a specific inhibitor of melatonin receptors 1 and 2 (2.3 mg/kg/day, intraperitoneally) or prazosin, a specific inhibitor of melatonin receptor type 3 (2.5 mg/kg/day, intraperitoneally). After 14 days, hearts were subjected to I/R in vivo or ex vivo. Red wine reduced the infarct size in both rats and WT mice (p < 0.001). Luzindole did not affect wine-induced cardioprotection, while prazosin reduced the infarct sparing effect of red wine (p < 0.05). Furthermore, red wine or melatonin failed to protect tumor necrosis factor alpha (TNF) receptor 2 knockout or cardiomyocyte specific signal transducer and activator of transcription 3 (STAT3) deficient mice (n.s. vs. control). Our novel findings suggest that the presence of melatonin in red wine contributes to the cardioprotective effect of chronic and moderate consumption of red wine against lethal I/R injuries. This effect is most likely mediated, at least in part, via melatonin receptor 3 and the activation of TNF and STAT3, both key players of the prosurvival and well described SAFE pathway.

Hypolipidemic influence of dietary fenugreek (Trigonella foenum-graecum) seeds and garlic (Allium sativum) in experimental myocardial infarction.

The cardioprotective influence of dietary fibre-rich fenugreek seeds and the well-established hypolipidemic spice garlic was evaluated both individually and in combination in isoproterenol induced myocardial infarcted rats. It was particularly examined whether pretreatment with dietary fenugreek, garlic or fenugreek + garlic would be beneficial under hypercholesterolemic conditions by their influence on the tissue lipid profile. Four groups each of male Wistar rats were maintained on either a basal diet or a high cholesterol diet for 8 weeks. Dietary interventions with fenugreek, garlic and the combination of fenugreek and garlic were made by including 10% fenugreek seed powder, 2% freeze-dried garlic powder, and 10% fenugreek seed powder + 2% garlic powder. At the end of the diet regimen, myocardial infarction was induced with isoproterenol (i.p. 80 mg kg(-1)) twice at intervals of 12 h. The disturbed activities of cardiac marker enzymes in serum and the heart confirmed isoproterenol induced myocardial infarction. Dietary fenugreek, garlic or fenugreek + garlic was found to ameliorate the pathological changes in heart tissue and lipid abnormalities in serum and the heart, the beneficial effect being higher with the combination of fenugreek and garlic, invariably amounting to an additive effect. The results also indicated that the hypercholesterolemic situation aggravated the myocardial damage during isoproterenol-induced myocardial infarction. This dietary intervention study suggested that the combination of fenugreek seeds and garlic offers a higher beneficial influence in exerting the cardioprotective effect.

Effects of high and low salt intake on left ventricular remodeling after myocardial infarction in normotensive rats.

The dietary-sodium restriction is a standard approach following an acute myocardial infarction (MI). We examined the hypothesis in which the use of a high or low-sodium diet would worsen post-infarction left ventricular remodeling in rats and facilitate the development of heart failure. Left coronary artery ligation or sham-operated (SO) was produced in male Wistar rats (250-290 g). After surgery, animals were assigned to one of the three diets: standard amount of sodium (0.3% NaCl, SO and MI groups), a high-sodium diet (0.6% NaCl, SO-High and MI-High groups), or a low-sodium diet (0.03% NaCl, SO-Low and MI-Low groups). Diets were provided for 8 weeks post-surgery. Mortality rate was elevated in high-salt group (MI-Low, 21.4%; MI, 35.3%; MI-High, 47.6%). Contractility parameter was seen to be impaired in MI-Low animals (3195 ± 211 mm Hg/s) compared with MI (3751 ± 200 mm Hg/s). Low-salt diet did not prevent myocardial collagen deposition (MI-Low, 5.2 ± 0.5%; MI, 5.0 ± 0.4%) nor myocyte hypertrophy (MI-Low, 608 ± 41µ(2); MI, 712 ± 53 µm(2)) in left ventricle after MI. High-salt intake increases collagen volume fraction (SO, 3.3 ± 0.4%; SO-High, 4.7 ± 0.4%) in animals sham, but no major changes after MI. Our results show that ventricular remodeling was not altered by immediate introduction of low sodium after MI, and it may be a safe strategy as a therapeutic intervention to avoid volume retention. However, high sodium can be harmful, accelerating the post-infaction ventricular remodeling.

Subcutaneous nerve activity and spontaneous ventricular arrhythmias in ambulatory dogs.

BACKGROUND: Stellate ganglion nerve activity (SGNA) is important in ventricular arrhythmogenesis. However, because thoracotomy is needed to access the stellate ganglion, it is difficult to use SGNA for risk stratification. OBJECTIVE: The purpose of this study was to test the hypothesis that subcutaneous nerve activity (SCNA) in canines can be used to estimate SGNA and predict ventricular arrhythmia. METHODS: We implanted radiotransmitters to continuously monitor left stellate ganglion and subcutaneous electrical activities in 7 ambulatory dogs with myocardial infarction, complete heart block, and nerve growth factor infusion to the left stellate ganglion. RESULTS: Spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) was documented in each dog. SCNA preceded a combined 61 episodes of VT and VF, 61 frequent bigeminy or couplets, and 61 premature ventricular contractions within 15 seconds in 70%, 59%, and 61% of arrhythmias, respectively. Similar incidence of 75%, 69%, and 62% was noted for SGNA. Progressive increase in SCNA [48.9 (95% confidence interval [CI] 39.3-58.5) vs 61.8 (95% CI 45.9-77.6) vs 75.1 (95% CI 57.5-92.7) mV-s] and SGNA [48.6 (95% CI 40.9-56.3) vs 58.5 (95% CI 47.5-69.4) vs 69.0 (95% CI 53.8-84.2) mV-s] integrated over 20-second intervals was demonstrated 60 seconds, 40 seconds, and 20 seconds before VT/VF (P <.05), respectively. The Pearson correlation coefficient for integrated SCNA and SGNA was 0.73 ± 0.18 (P <.0001 for all dogs, n = 5). Both SCNA and SGNA exhibited circadian variation. CONCLUSION: SCNA can be used as an estimate of SGNA to predict susceptibility to VT and VF in a canine model of ventricular arrhythmia and sudden cardiac death.

No effect of n-3 fatty acids supplementation on NT-proBNP after myocardial infarction: the Alpha Omega Trial.

BACKGROUND: heart failure is a major risk factor for cardiovascular mortality, for which n-3 fatty acids may have beneficial effects. We examined the effect of marine eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and plant-derived alpha-linolenic acid (ALA) on N-Terminal-pro Brain Natriuretic Peptide (NT-proBNP), a biomarker of heart failure. METHODS: we randomly assigned 4837 post-myocardial infarction patients, aged 60-80 years (82% men), to margarines supplemented with a targeted additional intake of 400 mg/day EPA and DHA, 2 g/day ALA, EPA-DHA plus ALA, or placebo for 40 months. In a random selection of 639 patients, NT-proBNP was determined both at baseline and at the end of follow-up. NT-proBNP was loge-transformed and analysed by type of treatment using analysis of covariance adjusting for baseline NT-proNBP. RESULTS: patients consumed on average 19.8 g margarine/day, providing an additional amount of 238 mg/day EPA with 158 mg/day DHA, 1.98 g/day ALA, or both, in the active-treatment groups. In the placebo group, the geometric mean level NT-proBNP increased from 245 ng/l (95%-confidence interval [CI]: 207-290) to 294 ng/l (95%-CI: 244-352) after 40 months (p = 0.001). NT-proBNP levels were not affected by ALA (+8% versus placebo; 95%-CI: -8% to +25%; p = 0.34), EPA-DHA (+2% versus placebo; 95%-CI: -14% to +18%; p = 0.78), nor EPA-DHA plus ALA (+9% versus placebo; 95%-CI: -8% to +25%; p = 0.31) treatment. CONCLUSIONS: supplementation with modest amounts of EPA-DHA, with or without ALA, did not have a significant effect on NT-proBNP levels in patients with a history of myocardial infarction.

Effect of omega-3 fatty acids on kidney function after myocardial infarction: the Alpha Omega Trial.

BACKGROUND AND OBJECTIVES: Kidney function gradually decreases with age, and myocardial infarction accelerates this deterioration. Omega-3 (n-3) fatty acids may slow down the decline of kidney function. The effect of marine and plant-derived n-3 fatty acids on kidney function in patients after myocardial infarction was examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the Alpha Omega Trial, 2344 patients with history of myocardial infarction ages 60-80 years old (81% men) were randomized to one of four trial margarines. The patients received an additional targeted amount of 400 mg/d eicosapentaenoic acid and docosahexaenoic acid, 2 g/d α-linolenic acid, eicosapentaenoic acid-docosahexaenoic acid plus α-linolenic acid, or placebo for 40 months. Serum cystatin C and serum creatinine were assessed at baseline and after 40 months. Creatinine-cystatin C-based GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: Patients consumed 19.9 g margarine/d, providing an additional 239 mg/d eicosapentaenoic acid with 159 mg/d docosahexaenoic acid, 1.99 g/d α-linolenic acid, or both in the active treatment groups. After 40 months, compared with baseline, mean (±SD) creatinine-cystatin C-based GFR was -6.9 (±12.6), -4.8 (±13.4), -6.2 (±12.8), and -6.0 (±13.0) ml/min per 1.73 m(2) in the placebo, eicosapentaenoic acid-docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid-docosahexaenoic acid plus α-linolenic acid groups, respectively. After 40 months, in patients receiving eicosapentaenoic acid-docosahexaenoic acid compared with placebo, the decline in creatinine-cystatin C-based GFR was 2.1 less (95% confidence interval, 0.6 to 3.6; P<0.01) ml/min per 1.73 m(2); other comparisons were not statistical significant. Odds ratios (95% confidence intervals) of incident CKD (<60 ml/min per 1.73 m(2)) and rapid decline of kidney function (≥3 ml/min per year) for eicosapentaenoic acid-docosahexaenoic acid compared with placebo were 0.83 (0.58 to 1.18) and 0.85 (0.67 to 1.08), respectively. CONCLUSIONS: Long-term supplementation with 400 mg/d eicosapentaenoic acid-docosahexaenoic acid provides a small beneficial effect on kidney function in patients with a history of myocardial infarction.