Levitan EB, Wolk A, Mittleman MA. Fish consumption, marine omega-3 fatty acids, and incidence of heart failure: a population-based prospective study of middle-aged and elderly men. Eur Heart J 30, 1495-1500

Cardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, 375 Longwood Avenue, Boston, MA 02215, USA.
European Heart Journal (Impact Factor: 15.2). 05/2009; 30(12):1495-500. DOI: 10.1093/eurheartj/ehp111
Source: PubMed


Fatty fish and marine omega-3 fatty acids were associated with lower rates of heart failure (HF) among US elderly, but this has not been confirmed in broader age ranges or other populations where source and type of fish may differ. We therefore conducted a population-based, prospective study of 39 367 middle-aged and older Swedish men.
Diet was measured using food-frequency questionnaires. Men were followed for HF through Swedish inpatient and cause-of-death registers from 1 January 1998 to 31 December 2004. We used proportional hazards models adjusted for age and other covariates to estimate hazard ratios (HR). Compared with no consumption, men who ate fatty fish once per week had an HR of 0.88 (95% CI 0.68-1.13). Hazard ratios for consumption two times per week and > or =3 times per week were 0.99 and 0.97, respectively. Hazard ratios across quintiles of marine omega-3 were 1, 0.94 (95% CI 0.74-1.20), 0.67 (95% CI 0.50-0.90), 0.89 (95% CI 0.68-1.16), 1.00 (95% CI 0.77-1.29).
In this population, moderate intake of fatty fish and marine omega-3 fatty acids was associated with lower rates of HF, though the association for fish intake was not statistically significant; higher intake was not associated with additional benefit.

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    • "For the human studies described above, there are also others that have shown no association between fish oil supplementation and CVD (Belin et al. 2011; Dijkstra et al. 2009; Jarvinen et al. 2006; Levitan et al. 2009; Nakamura et al. 2005). The inconsistency in results highlights the limitations of randomized controlled trials and prospective cohort studies; thus further studies exploring the therapeutic potential of fish oil supplementation are warranted. "
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    ABSTRACT: The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.
    Archive für Toxikologie 02/2015; 89(9). DOI:10.1007/s00204-015-1477-x · 5.98 Impact Factor
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    • "Results of a few epidemiologic studies demonstrated that fish consumption or fish oil intake was inversely associated with incidence of CHF in general population [30-32]. Furthermore, recently published GISSI-HF trial [9] showed that in patients with CHF on evidence-based therapy, long term treatment with fish oil reduced combined endpoint of mortality or hospitalizations for cardiovascular reasons. "
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    ABSTRACT: Background Effects of fish oil on systematic inflammation in chronic heart failure remain unclear. In this meta-analysis, we aimed to evaluate the influence of fish oil supplementation on circulating levels of inflammatory markers in patients with chronic heart failure. Methods Human randomized controlled trials, which compared the effects of fish oil supplementation with placebo in patients with chronic heart failure, were identified by systematic search of Medline, Embase, Cochrane’s library and references cited in related reviews and studies up to November 2011. Outcome measures comprised the changes of circulating inflammatory markers. Meta-analysis was performed with the fixed-effect model or random-effect model according to the heterogeneity. Results A total of seven trials with eight study arms were included. The pooled results indicated circulating levels of tumor necrosis factor α (SMD = -0.62, 95% CI -1.08 to -0.16, p = 0.009), interleukin 1 (SMD = -1.24, 95% CI -1.56 to -0.91, p < 0.001) and interleukin 6 (SMD = -0.81, 95% CI -1.48 to -0.14, p = 0.02) were significantly decreased after fish oil supplementation; however, high sensitivity C reactive protein, soluble intracellular adhesion molecular 1 and vascular cell adhesion molecular 1 were not significantly affected. Meta-regression and subgroup analysis results suggested the difference in dose of fish oil and follow-up duration might influence the effects of fish oil on tumor necrosis factor α and interleukin 6. Greater reduction of these two markers might be achieved in patients taking fish oil of a higher dose (over 1000 mg/day) or for a longer duration (over 4 months). Conclusions Limited evidence suggests anti-inflammation may be a potential mechanism underlying the beneficial effects of fish oil for chronic heart failure. Further large-scale and adequately powered clinical trials are needed to confirm these effects.
    BMC Cardiovascular Disorders 09/2012; 12(1):77. DOI:10.1186/1471-2261-12-77 · 1.88 Impact Factor
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    • "Increased consumption of omega-3 polyunsaturated fatty acids (ω3-PUFAs) from fish oil (FO) may exert beneficial effects on the heart, as evidenced by a decreased risk of ischemic heart disease , sudden cardiac death (Burr et al., 1989; GISSI-Prevenzione Investigators, 1999), and a lower incidence of heart failure (HF; Mozaffarian et al., 2005; Yamagishi et al., 2008; Levitan et al., 2009; Chen et al., 2011). Various mechanisms for the observed beneficial effects of ω3-PUFAs have been proposed, i.e., decrease in blood pressure, heart rate, and platelet aggregation, antiinflammatory (Kris-Etherton et al., 2002), and ionic remodeling resulting in a decrease of cardiac arrhythmias (den Ruijter et al., 2007; London et al., 2007), but the exact mechanisms are not fully known. "
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    ABSTRACT: Background: Increased consumption of omega-3 polyunsaturated fatty acids (3-PUFAs) from fish oil may have cardioprotective effects during ischemia/reperfusion, hypertrophy, and heart failure (HF). The cardiac Na+/H+-exchanger (NHE-1) is a key mediator for these detrimental cardiac conditions. Consequently, chronic NHE-1 inhibition appears to be a promising pharmacological tool for prevention and treatment. Acute application of the fish oil 3-PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit the NHE-1 in isolated cardiomyocytes. We studied the effects of a diet enriched with 3-PUFAs on the NHE-1 activity in healthy rabbits and in a rabbit model of HF induced by volume- and pressure-overload. Methods: Rabbits were allocated to four groups. The first two groups consisted of healthy rabbits, which were fed either a diet containing 1.25% (w/w) fish oil (3-PUFAs), or 1.25% high-oleic sunflower oil (9-MUFAs) as control. The second two groups were also allocated to either a diet containing 3-PUFAs or 9-MUFAs, but underwent volume- and pressure-overload to induce HF. Ventricular myocytes were isolated by enzymatic dissociation and used for intracellular pH (pHi) and patch clamp measurements. NHE-1 activity was measured in HEPES-buffered conditions as recovery rate from acidosis due to ammonium prepulses. Results: In healthy rabbits, NHE-1 activity in 9-MUFAs and 3-PUFAs myocytes was not significantly different. Volume- and pressure-overload in rabbits increased the NHE-1 activity in 9-MUFAs myocytes, but not in 3-PUFAs myocytes, resulting in a significantly lower NHE-1 activity in myocytes of 3-PUFA fed HF rabbits. The susceptibility to induced delayed afterdepolarizations (DADs), a cellular mechanism of arrhythmias, was lower in myocytes of HF animals fed 3- PUFAs compared to myocytes of HF animals fed9-MUFAs. In our rabbit HF model, the degree of hypertrophy was similar in the 3-PUFAs group compared to the 9-MUFAs group. Concl
    Frontiers in Physiology 04/2012; 3:76. DOI:10.3389/fphys.2012.00076 · 3.53 Impact Factor
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