Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Abdelhamid AS
PROVIDER: S-EPMC6517311 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7049091 | biostudies-literature
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| S-EPMC6513571 | biostudies-literature
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| S-EPMC6517012 | biostudies-literature
Project description:OPINION STATEMENT:Early secondary prevention trials of fish and omega-3 polyunsaturated fatty acid (PUFA) capsules reported beneficial effects on cardiovascular disease (CVD) outcomes, including all-cause mortality and sudden cardiac death. These clinical findings, as well as observational and experimental data, demonstrated that omega-3 PUFAs reduced the risk of coronary outcomes and overall mortality and were the basis for recommendations made in the early 2000s to increase omega-3 PUFA intake. In the last 6 years, however, results from both primary and secondary prevention trials have generally failed to show a beneficial effect of omega-3 PUFA supplementation, bringing current recommendations into question. Several possible reasons for these null findings have been proposed, including short treatment periods, relatively low doses of omega-3 PUFAs, small sample sizes, higher background omega-3 intakes, and the concurrent use of modern pharmacotherapy for CVD prevention. At least one of these caveats is being assessed in major clinical trials, with two omega-3 PUFA pharmacological agents being tested at doses of 4?g/day (instead of the more common <1 g/day). These null findings, however, do not necessarily mean that omega-3 PUFAs "are ineffective" in general, only that they were not effective in the context in which they were tested. Accordingly, higher intakes of omega-3 PUFAs, either from fatty fish or from supplements, if continued for decades (as the epidemiological data support) are likely to contribute towards lower risk for CVD. At this time, evidence supports the consumption of a healthy dietary pattern with at least two servings per week of fatty fish. Omega-3 PUFA supplementation is a reasonable alternative for those who do not consume fish, although fish is the preferred source of omega-3 PUFAs because it also provides additional nutrients, some of which are often under-consumed.
| S-EPMC5067287 | biostudies-literature
Project description:Patients with established atherosclerotic cardiovascular (CV) disease remain at increased risk of major adverse cardiovascular events even during optimal lipid-lowering therapy. Recent studies using the methods of Mendelian randomization, as well as analyses of data from large statin trials, have concluded that elevated triglyceride (TG) levels contribute to that increased risk. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish and shellfish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) reduce TG levels when added to the diet in sufficient amounts, and they have favorable effects on several other markers of CV risk. However, trials of omega-3 PUFAs have had inconsistent findings regarding CV risk reduction. Recently, the REDUCE-IT (Reduction of Cardiovascular Events with EPA-Intervention Trial) trial reported that treatment of such high-risk patients with icosapent ethyl, a purified and stabilized ethyl ester of EPA, reduced the risk of the trial's primary CV endpoint by 25% (95% confidence intervals [CI], 32%-17%; P < .001). To appreciate the clinical implications of this result, it is important to understand how the REDUCE-IT trial differed from previous trials, especially with regard to patient enrollment criteria and treatment dosing. We discuss these design features relative to other trials. TG lowering can account for only part of the risk reduction seen with icosapent ethyl; we also consider other potential contributory mechanisms.
| S-EPMC6727875 | biostudies-literature
Project description:Data on omega-3 polyunsaturated fatty acids in relation to cardiovascular disease are limited in women. The aim of this study was to examine longitudinal relations of tuna and dark fish, ?-linolenic acid, and marine omega-3 fatty acid intake with incident major cardiovascular disease in women.This was a prospective cohort study of U.S. women participating in the Women's Health Study from 1993 to 2014, during which the data were collected and analyzed. A total of 39,876 women who were aged ?45 years and free of cardiovascular disease at baseline provided dietary data on food frequency questionnaires. Analyses used Cox proportional hazards models to evaluate the association between fish and energy-adjusted omega-3 polyunsaturated fatty acid intake and the risk of major cardiovascular disease, defined as a composite outcome of myocardial infarction, stroke, and cardiovascular death, in 38,392 women in the final analytic sample (96%).During 713,559 person years of follow-up, 1,941 cases of incident major cardiovascular disease were confirmed. Tuna and dark fish intake was not associated with the risk of incident major cardiovascular disease (p-trend >0.05). Neither ?-linolenic acid nor marine omega-3 fatty acid intake was associated with major cardiovascular disease or with individual cardiovascular outcomes (all p-trend >0.05). There was no effect modification by age, BMI, or baseline history of hypertension.In this cohort of women without history of cardiovascular disease, intakes of tuna and dark fish, ?-linolenic acid, and marine omega-3 fatty acids were not associated with risk of major cardiovascular disease.
| S-EPMC5167636 | biostudies-other
Project description:Whether marine omega-3 fatty acid (n-3 FA) or vitamin D supplementation can prevent cardiovascular disease (CVD) in general populations at usual risk for this outcome is unknown. A major goal of VITAL (Vitamin D and Omega-3 Trial) was to fill this knowledge gap. In this article, we review the results of VITAL, discuss relevant mechanistic studies regarding n-3 FAs, vitamin D, and vascular disease, and summarize recent meta-analyses of the randomized trial evidence on these agents. VITAL was a nationwide, randomized, placebo-controlled, 2×2 factorial trial of marine n-3 FAs (1 g/d) and vitamin D3 (2000 IU/d) in the primary prevention of CVD and cancer among 25?871 US men aged ?50 and women aged ?55 years, including 5106 blacks. Median treatment duration was 5.3 years. Supplemental n-3 FAs did not significantly reduce the primary cardiovascular end point of major CVD events (composite of myocardial infarction, stroke, and CVD mortality; hazard ratio [HR], 0.92 [95% CI, 0.80-1.06]) but were associated with significant reductions in total myocardial infarction (HR, 0.72 [95% CI, 0.59-0.90]), percutaneous coronary intervention (HR, 0.78 [95% CI, 0.63-0.95]), and fatal myocardial infarction (HR, 0.50 [95% CI, 0.26-0.97]) but not stroke or other cardiovascular end points. For major CVD events, a treatment benefit was seen in those with dietary fish intake below the cohort median of 1.5 servings/wk (HR, 0.81 [95% CI, 0.67-0.98]) but not in those above (P interaction=0.045). For myocardial infarction, the greatest risk reductions were in blacks (HR, 0.23 [95% CI, 0.11-0.47]; P interaction by race, 0.001). Vitamin D supplementation did not reduce major CVD events (HR, 0.97 [95% CI, 0.85-1.12]) or other cardiovascular end points. Updated meta-analyses that include VITAL and other recent trials document coronary risk reduction from supplemental marine n-3 FAs but no clear CVD risk reduction from supplemental vitamin D. Additional research is needed to determine which individuals may be most likely to derive net benefit from supplementation. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01169259.
| S-EPMC7001886 | biostudies-literature
Project description:Proteins are often credited as the macromolecule responsible for performing critical cellular functions, however lipids have recently garnered more attention as our understanding of their role in cell function and human health becomes more apparent. Although cellular membranes are the lipid environment in which many proteins function, it is now apparent that protein and lipid assemblies can be organized to form distinct micro- or nanodomains that facilitate signaling events. Indeed, it is now appreciated that cellular function is partly regulated by the specific spatiotemporal lipid composition of the membrane, down to the nanosecond and nanometer scale. Furthermore, membrane composition is altered during human disease processes such as cancer and obesity. For example, an increased rate of lipid/cholesterol synthesis in cancerous tissues has long been recognized as an important aspect of the rewired metabolism of transformed cells. However, the contribution of lipids/cholesterol to cellular function in disease models is not yet fully understood. Furthermore, an important consideration in regard to human health is that diet is a major modulator of cell membrane composition. This can occur directly through incorporation of membrane substrates, such as fatty acids, e.g., n-3 polyunsaturated fatty acids (n-3 PUFA) and cholesterol. In this review, we describe scenarios in which changes in membrane composition impact human health. Particular focus is placed on the importance of intrinsic lipid/cholesterol biosynthesis and metabolism and extrinsic dietary modification in cancer and its effect on plasma membrane properties.
| S-EPMC6185832 | biostudies-literature
Project description:BackgroundGlobal dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.MethodsWe performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).ResultsIn 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.ConclusionsIn pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.
| S-EPMC6582360 | biostudies-literature
Project description:Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case-control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship.
| S-EPMC4418048 | biostudies-literature