Clinical outcome and atherothrombogenic risk profile after prolonged wash-out following long-term treatment with high doses of n-3 PUFAs in patients with an acute myocardial infarction (original) (raw)
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The Journal of nutrition, 2006
Many clinical studies report that (n-3) PUFAs decrease the incidence of sudden death in patients with coronary artery disease after myocardial infarction (MI). However, the mechanisms for the beneficial effects of (n-3) PUFAs are unknown. The objectives of the present study were to confirm the findings from clinical trials using an animal model of MI in which dietary intake could be closely controlled and to utilize the model to investigate molecular mechanisms for the beneficial effects of (n-3) PUFAs. Male rats were subjected to coronary ligation to induce MI and were randomly assigned to diets high in (n-6) (58% of lipid) or (n-3) (28% of lipid) PUFAs for 6 mo. A diet high in (n-3) PUFAs was associated with an improvement in 6-mo survival (89.2% vs. 64.9%, P = 0.013) compared with rats consuming a diet high in (n-6) PUFAs (n = 37/group). In a separate study (n = 5 rats/diet group), the (n-3) PUFA diet decreased the (n-6):(n-3) PUFA ratio in plasma (0.6 +/- 0.1 vs. 7.9 +/- 1.8, P ...
European Heart Journal Supplements, 2001
GISSI-Prevenzione was conceived as a population, pragmatic trial on patients with recent myocardial infarction conducted in the framework of the Italian public health sysem. In GISSI-Prevenzione, patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA 1 g daily, but not vitamin E 300 mg daily, was beneficial for death and for combined death, non-fatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden death. At variance from the orientation of a scientific scenario largely dominated by the 'cholesterol-heart hypothesis', GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction. As to the relevance and comparability of GISSI-Prevenzione results, up to 5•7 lives could be saved per 1000 patients with previous myocardial infarction treated with n-3 PUFA (1 g daily) per year. Such a result is comparable to that observed in the LIPID trial, where 5•2 lives could be saved per 1000 hypercholaesterolemic, CHD patients treated with pravastatin for 1 year. The choice in favour of a relatively low-dose regimen (1 g capsule daily) more acceptable for long-term treatment in a population of patients following Mediterranean dietary habits, the pattern of effects seen in GISSI-Prevenzione (namely, reduction of overall mortality with no decrease in the rate of non-fatal myocardial infarction), all suggest that it can confidently be said that n-3 PUFA treatment should be considered a recommended new component of secondary prevention. The importance of this combined/additive effect is further suggested by the preliminary analyses (to be submitted in the final form for publication) of the interplay between diet and n-3 PUFA: there is an interesting direct correlation between size of the effect and 'correctness' of background diets. It can be anticipated that a conceptual barrier must be overcome: a 'dietary drug' should be added to 'dietary advice', which remains fundamental to allow this statement to become true in clinical practice.
Journal of Physiology and Biochemistry, 2019
Several meta-analyses describing the effect of n-3 polyunsaturated fatty acids on the survival rate of the victims of an acute coronary event do not clearly support a beneficial impact of these fatty acids. Yet, animal studies consistently show n-3 PUFAinduced protection against ischemia-reperfusion-induced myocardial injuries. The impact on reperfusion arrhythmias of these PUFAs is more controversial. The literature shows the anti-arrhythmic properties of circulating n-3 PUFAs. However, when these fatty acids are incorporated in the cardiac membrane, they protect the myocardial tissue vis a vis cellular damage but they can be either pro-or anti-arrhythmic during reperfusion, depending on the severity of tissue injuries. The latter elements can explain the lack of beneficial effect observed in the meta-analyses, but a proper use of n-3 PUFAs may provide advantages in terms of survival rate. This review discusses the different results obtained in humans and animals and presents several strategies to enhance the beneficial effects of n-3 PUFAs.
Early Protection Against Sudden Death by n-3 Polyunsaturated Fatty Acids After Myocardial Infarction
Circulation, 2002
Background — Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction. Methods and Results — In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of tre...
n-3 PUFAs and cardiovascular disease prevention
Future Cardiology, 2010
Today, there are several observational and experimental studies, especially clinical randomized trials, that have proven the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs). The most compelling evidence for the cardiovascular benefits of n-3 PUFAs comes from studies of primary prevention in patients following myocardial infarction, and most recently, in patients with heart failure. In this review, we analyze the evidence from epidemiologic studies and from large randomized controlled trials showing the benefits of n-3 PUFAs, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in primary and secondary cardiovascular prevention. Further studies are needed to determine optimal dosing and the relative ratio of DHA and EPA that provide maximal cardioprotection.
Clinical Nutrition, 2011
Background & aims: our aim was to evaluate early initiated one month n-3 polyunsaturated fatty acids (PUFA) supplementation effects on ultrasound indices of endothelial function and serum asymmetric dimethylarginine (ADMA) levels in patients with acute myocardial infarction (AMI). Methods: Forty patients with AMI and successful percutaneous coronary intervention (PCI) were recruited into the study and randomized to the study group (group P; n ¼ 20; standard therapy þ n-3 PUFA 1g daily) or the control group (group C; n ¼ 20; standard therapy). Ultrasound indices of endothelial function: flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NMD) and serum ADMA concentrations (ELISA) were obtained before and after one month (30 AE 1 days) therapy (presented as means AE standard deviations). Results: There was a significant difference between both groups in mean delta (baseline/after one month) FMD (P: 8.1 AE 12.6% vs C: À2.2 AE 11.8%; p ¼ 0.02) with no difference in mean delta NMD (P: 3.3 AE 11.9% vs 0.66 AE 14.3%; p ¼ 0.53). We found also a significant increase in mean FMD (7.4 AE 6.4 to 15.5 AE 10.5%; p ¼ 0.02) with a nonsignificant change in mean NMD values (26.9 AE 12.1 to 30.2 AE 14.0%; p ¼ 0.24) after 1-month therapy with n-3 PUFA. FMD and NMD mean values did not change in control patients (FMD: 11.6 AE 6.1% to 9.4 AE 8.0%; p ¼ 0.5 NMD: 25.1 AE 11.4% to 25.8 AE 14.0%; p ¼ 0.84). The comparison of mean delta ADMA values for both groups revealed no differences (P: 6.2 AE 9.7 mmol/l vs C: 3.6 AE 9.5 mmol/l; p ¼ 0.43). Mean serum ADMA concentrations were significantly increased after 1-month therapy in the group P (P: 2.1 AE 1.8 to 8.3 AE 9.7 mmol/l; p ¼ 0.001; C: 4.5 AE 7.1 to 8.1 AE 9.5 mmol/l; p ¼ 0.09). However, there was a nonsignificant difference in mean baseline serum ADMA levels between both groups (P: 2.1 AE 1.8 mmol/l vs C: 4.5 AE 7.1 mmol/l; p ¼ 0.32). There were no significant correlations between FMD, NMD, ADMA levels and demographic, clinical or biochemical parameters. Conclusions: Early and short-term n-3 PUFA supplementation improved ultrasound indices of endothelial function without affecting serum ADMA levels in patients with AMI and successful primary PCI.
Evidence from observational studies, prospective cohort studies and randomized clinical intervention studies indicate that moderate doses of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) significantly decrease risk of fatal coronary heart disease (CHD). Higher doses and longer duration of intervention may also protect from non-fatal CHD events. The exact mechanisms through which LC n-3 PUFA has an effect on CHD are not well established but may include a decrease in fasting and postprandial triacylglycerol levels, a decrease in arrhythmias, modulation of platelet aggregation and decreased synthesis of pro-inflammatory agents. The mechanistic relation between LC n-3 PUFA and inflammation has attracted great interest, and in vitro studies have revealed that these fatty acids decrease endothelial activation, affect eicosanoid metabolism (including epoxygenation pathways) and induce inflammatory resolution. However, the effects of LC n-3 PUFA on established biomarkers of inflammation and endothelial activation in vivo are not strong. Consequently we need new and more sensitive and systemic biomarkers to reveal the effects of LC n-3 PUFA on localized inflammatory processes.
International heart journal, 2017
A relationship between serum polyunsaturated fatty acids (PUFAs) and cardiovascular disease has been reported; however, the existence of a relationship between serum PUFAs and extent of vessel disease (VD) in patients with ST elevation myocardial infarction (STEMI) remains unclear.Between July 2011 and June 2015, 866 consecutive STEMI patients underwent emergent percutaneous coronary intervention, 507 of whom were enrolled and classified into three groups according to the initial angiograms: 1VD, 294 patients; 2VD, 110 patients; and 3VD/left main trunk disease (LMTD), 103 patients. Serum levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid, and other laboratory data during hospitalization were evaluated.The serum EPA level in the 3VD/LMTD group was significantly lower than that in the 1VD group (55.5 ± 22.1 versus 66.2 ± 28.7, P = 0.002) and was slightly lower than that in the 2VD group (55.5 ± 22.1 versus 65.2 ± 28.9, P = 0.0167)....
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2007
The protective effect of PUFA concentrate prepared from fish oil on isoproterenol-induced myocardial infarction in male albino rats was investigated with respect to changes in the levels of diagnostic marker enzymes, cholesterol, triglycerides, free fatty acids, phospholipids, reduced glutathione (GSH) and lipid peroxides (LPO). Administration of PUFA concentrate significantly prevented the isoproterenol-induced elevation in the levels of plasma diagnostic marker enzymes (ALT [93.5%], AST [95.6%], LDH [94.7%] and CPK [96.1%]). PUFA concentrate feeding exerted a significant antilipidemic effect against isoproterenol-induced myocardial infarction by reducing the levels of lipid components in plasma (cholesterol [71.5%], triglycerides [79.7%] and free fatty acids [70.7%] and heart tissue (cholesterol [81.4%], triglycerides [76.3%] and free fatty acids [78.6%]). A tendency to prevent the isoproterenol-induced phospholipids depletion (74.4%) in the myocardium of experimental rats was also observed. The level of lipid peroxidation was also found to be significantly lower in PUFA treated animals (2.7270.15 nmol/ml in plasma; 1.1870.08 nmol/mg protein in heart tissue) as compared to that of isoproterenol-injected groups (5.7770.43 nmol/ml in plasma; 2.1470.15 nmol/mg protein in heart tissue) of rats. Also the level of reduced GSH significantly higher in the heart tissue of PUFA administered experimental rats (5.6570.98 mg/g) as compared to myocardial infarction induced control rats (2.3970.18 mg/g). The results of the present study indicate that the overall cardioprotective effect of PUFA concentrate is probably related to its ability to inhibit lipid accumulation by its hypolipidaemic property.