Dose-related meta-analysis for Omega-3 fatty acids supplementation on major adverse cardiovascular events.

BACKGROUND & AIMS: Omega-3 supplements are widely used for cardiovascular (CV) protection. We performed an updated meta-analysis for omega-3 and CV outcomes. METHODS: Random-effects meta-analysis including double-blind RCTs with duration ≥1 year, evaluating omega-3 supplements in 4 a priori defined categories (<1, 1, 2, ≥3 of 1g capsules/day) on all-cause mortality, cardiac death, myocardial infarction and stroke, reporting the relative risk (RR) as the measure of interest. Complementary approaches were Trial Sequential Analysis (TSA) and sensitivity analyses for triglycerides, prevention setting, intention-to-treat analysis, eicosapentaenoic acid (EPA), sample size, statin use and study duration. RESULTS: Nineteen randomized controlled trials (RCTs) with 97,709 participants were included. Omega-3 supplements were not statistically significantly associated with reduced all-cause mortality, cardiac death, MI, or stroke, with the exception of reduced cardiac mortality only for the equivalent dose of 2 capsules/day (RR 0.55, 95%CI 0.33, 0.90, p = 0.0169, I2 = 0%). TSA reached the required information size only for the lower doses regarding all-cause and cardiac mortality, where they show no significant association. Meta-regression on EPA dose, as well as the majority of sensitivity analyses did not show any statistically significant association. CONCLUSION: Compared to the robust evidence for low doses, higher doses and particularly for the unique type of omega-3 icosapent ethyl ester should be further addressed.

Prevalence and Determinants of Sex-Specific Dietary Supplement Use in a Greek Cohort.

We describe the profile of dietary supplement use and its correlates in the Epirus Health Study cohort, which consists of 1237 adults (60.5% women) residing in urban north-west Greece. The association between dietary supplement use and demographic characteristics, lifestyle behaviors, personal medical history and clinical measurements was assessed using logistic regression models, separately for women and men. The overall prevalence of dietary supplement use was 31.4%, and it was higher in women (37.3%) compared to men (22.4%; p-value = 4.2-08). Based on multivariable logistic regression models, dietary supplement use in women was associated with age (positively until middle-age and slightly negatively afterwards), the presence of a chronic health condition (OR = 1.71; 95% CI, 1.18-2.46), lost/removed teeth (OR = 0.52; 95% CI, 0.35-0.78) and diastolic blood pressure (OR per 5 mmHg increase =0.84; 95% CI, 0.73-0.96); body mass index and worse general health status were borderline inversely associated. In men, dietary supplement use was positively associated with being employed (OR = 2.53; 95% CI, 1.21-5.29). A considerable proportion of our sample used dietary supplements, and the associated factors differed between women and men.

Omega-3 supplementation and cardiovascular disease: formulation-based systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Omega-3 supplements are popular for cardiovascular disease (CVD) prevention. We aimed to assess the association between dose-specific omega-3 supplementation and CVD outcomes. DESIGN: We included double-blind randomised clinical trials with duration ≥1 year assessing omega-3 supplementation and estimated the relative risk (RR) for all-cause mortality, cardiac death, sudden death, myocardial infarction and stroke. Primary analysis was a stratified random-effects meta-analysis by omega-3 dose in 4 a priori defined categories (<1, 1, 2, ≥3 of 1 g capsules/day). Complementary approaches were trial sequential analysis and sensitivity analyses for triglycerides, prevention setting, intention-to-treat analysis, eicosapentaenoic acid, sample size, statin use, study duration. RESULTS: Seventeen studies (n=83 617) were included. Omega-3 supplementation as ≤1 capsule/day was not associated with any outcome under study; futility boundaries were crossed for all-cause mortality and cardiac death. For two capsules/day, we observed a statistically significant reduction of cardiac death (n=3, RR 0.55, 95% CI 0.33 to 0.90, I2=0%); for ≥3 capsules/day we observed a statistically significant reduction of cardiac death (n=3, RR 0.82, 95% CI 0.68 to 0.99, I2=0%), sudden death (n=1, RR 0.70, 95% CI 0.51 to 0.97) and stroke (n=2, RR 0.74, 95% CI 0.57 to 0.95, I2=0%). CONCLUSION: Omega-3 supplementation at <2 1 g capsules/day showed no association with CVD outcomes; this seems unlikely to change from future research. Compared with the robust scientific evidence available for low doses, the evidence for higher doses (2-4 1 g capsules/day) is weak. The emerging postulated benefit from high-dose supplementation needs replication and further evaluation as to the precise formulation and indication.

Does Supplementation with Omega-3 PUFAs Add to the Prevention of Cardiovascular Disease?

PURPOSE OF REVIEW: Omega-3 fatty acids are increasingly used for the protection of cardiovascular disease. The main but not the sole mechanism of action is the reduction of triglyceride levels. In this review, we summarize the effect of omega-3 supplements on all-cause and cardiovascular mortality, myocardial infarction, and stroke from the relevant randomized controlled trials. RECENT FINDINGS: Twenty-one randomized controlled trials assessed omega-3 supplementation on mortality and cardiovascular-related outcomes. From these studies, as well as from the relevant meta-analyses, we found that omega-3 supplements do not exert a consistent benefit for cardiovascular protection. There is uncertainty of a clear profit from omega-3 supplementation in cardiovascular disease.

The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation.

BACKGROUND: The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the prevention of atrial fibrillation (AF) and the possible underlying mechanisms. METHODS: A literature search based on PubMed listings was performed using "Omega-3 fatty acids" and "atrial fibrilation" as key search terms. RESULTS: n-3 PUFA have been shown to attenuate structural atrial remodeling, prolong atrial effective refractory period through the prevention of reentry and suppress ectopic firing from pulmonary veins. Dietary fish intake has been found to have no effect on the incidence of AF in the majority of studies. Circulating DHA has been consistently reported to be inversely associated with AF risk, whereas EPA has no such effect. The majority of studies investigating the impact of n-3 PUFA supplementation on the incidence of AF following cardiac surgery reported no benefit, though most of them did not use n-3 PUFA pretreatment for adequate duration. Studies using adequate four-week pretreatment with n-3 PUFA before cardioversion of AF showed a reduction of the AF incidence. CONCLUSIONS: Although n-3 PUFA have antiarrhythmogenic properties, their clinical efficacy on the prevention of AF is not consistently supported. Further well-designed studies are needed to overcome the limitations of the existing studies and provide robust conclusions.

Statin use in prediabetic patients: rationale and results to date.

Prediabetes increases the risk for new-onset diabetes mellitus in patients receiving statins and this risk is dose- and time- dependent. Explanations for the conversion of a predisposed individual to diabetes are ambiguous including reductions in ubiquinone and adiponectin levels. However, the risk of new-onset diabetes mellitus is far outweighed by the statin-induced considerable decrease in cardiovascular events. Thus, prediabetic patients at high cardiovascular risk should not be denied high-dose statin therapy due to the small increase in the risk of developing diabetes since statins, especially at higher doses, cause greater reductions in cardiovascular events compared with standard statin doses. Moreover, lifestyle modification or even antidiabetic drugs are highly recommended in these individuals.

Confronting the residual cardiovascular risk beyond statins: the role of fibrates, omega-3 fatty acids, or niacin, in diabetic patients.

Diabetics are regarded a special category of patients known to experience higher rates of cardiovascular complications as compared to the non-diabetic ones. Despite substantial efforts to minimize these risks, with aggressive antiplatelet and lipid lowering therapy, some of the diabetic patients still have a considerable residual risk for cardiovascular adverse events. Important preclinical data with potent lipid-lowering agents, like fibrates, omega-3-fatty acids, and niacin, have shown that they can provide sufficient help in reducing rates of cardiovascular events. In the present review, we are aim to explain their basic mechanisms of action, to present all the available clinical data regarding the efficacy of those agents, and to identify specific diabetic patients' subsets, in whom supplementary therapy with those agents could provide substantial benefit in terms of clinical outcome and not only lipid profile improvement.

Current evidence and future perspectives of omega-3 polyunsaturated fatty acids for the prevention of cardiovascular disease.

Omega-3 fatty acids have been traditionally used for the prevention of major cardiovascular events in patients with or without a history of cardiovascular disease. Their main mechanism of action is to lower triglyceride levels, but they also exert anti-arrythmic and anti-inflammatory properties, they reduce blood pressure levels and stabilize the atherosclerotic plaques. There is a vast amount of evidence derived from randomized studies that seems to question their benefit for the prevention of major cardiovascular events. Upcoming trials will help to better clarify their use in certain indications.

Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis.

CONTEXT: Considerable controversy exists regarding the association of omega-3 polyunsaturated fatty acids (PUFAs) and major cardiovascular end points. OBJECTIVE: To assess the role of omega-3 supplementation on major cardiovascular outcomes. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012. STUDY SELECTION: Randomized clinical trials evaluating the effect of omega-3 on all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke. DATA EXTRACTION: Descriptive and quantitative information was extracted; absolute and relative risk (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I2. Subgroup analyses were performed for the presence of blinding, the prevention settings, and patients with implantable cardioverter-defibrillators, and meta-regression analyses were performed for the omega-3 dose. A statistical significance threshold of .0063 was assumed after adjustment for multiple comparisons. DATA SYNTHESIS: Of the 3635 citations retrieved, 20 studies of 68,680 patients were included, reporting 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions, and 1490 strokes. No statistically significant association was observed with all-cause mortality (RR, 0.96; 95% CI, 0.91 to 1.02; risk reduction [RD] -0.004, 95% CI, -0.01 to 0.02), cardiac death (RR, 0.91; 95% CI, 0.85 to 0.98; RD, -0.01; 95% CI, -0.02 to 0.00), sudden death (RR, 0.87; 95% CI, 0.75 to 1.01; RD, -0.003; 95% CI, -0.012 to 0.006), myocardial infarction (RR, 0.89; 95% CI, 0.76 to 1.04; RD, -0.002; 95% CI, -0.007 to 0.002), and stroke (RR, 1.05; 95% CI, 0.93 to 1.18; RD, 0.001; 95% CI, -0.002 to 0.004) when all supplement studies were considered. CONCLUSION: Overall, omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.