Tissue Omega-6/Omega-3 Fatty Acid Ratio and Risk for Coronary Artery Disease (original) (raw)

Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease

Journal of Atherosclerosis and Thrombosis, 2011

The Japan EPA Lipid Intervention Study (JELIS) was the first prospective randomized clinical trial to demonstrate prevention of coronary events by pure eicosapentaenoic acid (EPA). The aim of this study was to examine the relationships between various plasma fatty acid concentrations and the risk of coronary events in JELIS participants. Methods: In 15,534 participants, we calculated the hazard ratio for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris, and angioplasty/ stenting or coronary artery bypass grafting) relative to the on-treatment average level of plasma fatty acids with the Cox proportional hazard model. Results: As a result of EPA intervention, the plasma EPA concentration increased, but the docosahexaenoic acid (DHA) concentration did not. The other fatty acids measured decreased slightly. The higher plasma level of EPA (hazard ratio 0.83, p 0.049, in all participants and hazard ratio 0.71, p 0.018, in the EPA intervention group), but not of DHA, was inversely associated with the risk of major coronary events. The associations between other fatty acids and the risk of major coronary events were not significant. In all JELIS participants, the risk of major coronary events was significantly decreased (20%) in the group with high (150 g/mL or more) on-treatment plasma EPA concentration compared with that in the low (less than 87 g/mL) group. Conclusion: The risk of coronary artery disease is influenced by variations in plasma fatty acid composition. Among n-3 polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation with the risk of major coronary events.

Fatty Acids and Associated Cardiovascular Risk

Food and Nutrition Sciences, 2013

A fatty acid (FA) is a carboxylic acid with a long aliphatic chain, which is either saturated or unsaturated. Recently, the role of FA and particularly omega-3 and -6 has emerged as cardiovascular risk factor in the literature. The aim of our study was to establish reference values for these FA and to compare them with data obtained in a population of acute myocardial infarction (AMI) patients. Materials and methods: Hundred thirty five healthy subjects (59.38 ± 27.12 yo, 75 men) were selected as reference population. We also evaluated FA in thirty three patients (55 ± 9 yo, 23 men) admitted in the Emergency Department of our Institution for AMI. The fasting whole blood was drawn in vacutainer containing EDTA. Before analysis, samples were washed and transmethylated. We performed the quantification of different FA by gas chromatography associated with flame ionization detector (GCFID). Results: We obtained results in control healthy patients to be used as reference values. In the AMI group, levels of omega-6 were significantly higher (p < 0.05) for C18:2n6 and C18:3n6 than the reference population and omega-3 values were significantly lower (p < 0.01) compared to reference value for C22:6n3. The omega-3 index was lower and the ratio omega-6/omega-3 was higher in AMI group compared to reference values. Conclusions: We have established reference value for FA and have compared these values with the results obtained in AMI population. FA determination is a new tool we are able to use and to process in our laboratory which can help the clinician to screen patients with the highest cardiovascular risks because of the implication of FA in the etiopathogeny of atherosclerosis.

Risk factors associated with plasma omega-3 fatty acid levels in patients with suspected coronary artery disease

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2016

Introduction: We sought to determine the associations between plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels and various cardiovascular risk factors and with the use of fish oil supplements (FOS). Patients and methods: Patients with suspected coronary artery disease (CAD) undergoing cardiac catheterization (n¼433) were studied. Serum fatty acid (FA) composition, the concentrations of lipids and biomarkers of oxidative stress, and dietary/lifestyle factors were measured. Results: FOS use was associated with a higher plasma EPAþDHA levels (3.77 1.5 vs. 2.67 1.1%, po 0.0001). However, there was no relationship between FOS dose (mg/day) and EPAþDHA levels in 76 patients reporting FOS use (r ¼ À0.21, p ¼ 0.07). Lower levels were inversely associated with risk factor profiles including lower ApoB100/ApoA1 ratios (po0.001). Discussion and conclusions: Higher EPA þ DHA levels characterized patients with lower CAD risk. The lack of relations between FOS dose and plasma EPAþ DHA levels likely reflects uncaptured variability in EPA þ DHA content of supplements.

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies

Circulation

BACKGROUND: Global 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. METHODS: We 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). RESULTS: In 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. CONCLUSIONS: In 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.

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies

JAMA internal medicine, 2016

The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. A global consortium of 19 studies identified by November 2014. Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. Incident total CHD, fatal CHD, and nonfatal myocard...

Omega-3 fatty acids and mortality in patients referred for coronary angiography. The Ludwigshafen Risk and Cardiovascular Health Study

Atherosclerosis, 2016

There is an ongoing debate whether omega-3-fatty acids protect from cardiovascular disease mortality. We examined the associations of erythrocyte omega-3 fatty acids with mortality in patients referred for coronary angiography. Erythrocyte omega-3 fatty acid proportions were measured at baseline in 3259 participants of the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) using the HS-Omega-3 Index method. Associations of omega-3 fatty acid proportions with mortality were investigated using Cox proportional hazards regression. During a median follow-up of 9.9 years, 975 patients (29.9%) died, 614 patients (18.8%) from cardiovascular causes. Proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were inversely associated with all-cause and cardiovascular mortality in models adjusted for conventional cardiovascular risk factors. The strongest association was observed for EPA with a hazard ratio (HR) of 0.89 (0.83-0.96) per increase of one standard deviation....

Omega-3 Fatty Acids in Adipose Tissue and Risk of Myocardial Infarction

Arteriosclerosis, Thrombosis, and Vascular Biology, 1999

Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and Israel. Cases (nϭ639) included patients with a first myocardial infarction admitted to coronary care units within 24 hours from the onset of symptoms. Controls (nϭ700) were selected to represent the populations originating the cases. Adipose tissue levels of fatty acids were determined by capillary gas chromatography. The mean (ϮSD) proportion of ␣-linolenic acid was 0.77% (Ϯ0.19) of fatty acids in cases and 0.80% (Ϯ0.19) of fatty acids in controls (Pϭ0.01). The relative risk for the highest quintile of ␣-linolenic acid compared with the lowest was 0.42 (95% confidence interval [CI] 0.22 to 0.81, P-trendϭ0.02). After adjusting for classical risk factors, the relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P-trendϭ0.38). The mean proportion of docosahexaenoic acid was 0.24% (Ϯ0.13) of fatty acids in cases and 0.25% (Ϯ0.13) of fatty acids in controls (Pϭ0.14), with no evidence of association with risk of myocardial infarction. In this large case-control study we could not detect a protective effect of docosahexaenoic acid on the risk of myocardial infarction. The protective effect of ␣-linolenic acid was attenuated after adjusting for classical risk factors (mainly smoking), but it deserves further research.

Adipose tissue fatty acids and risk of myocardial infarction—a case-control study

European Journal of Clinical Nutrition, 2000

Objectives: To study the association between content in adipose tissue of very long-chain n-3 fatty acids, trans fatty acids, linoleic acid and a-linolenic acid and risk of a ®rst myocardial infarction. Design and subjects: A case-control design among 100 patients and 98 population controls both men and postmenopausal women, age 45 ± 75 y. Adipose tissue fatty acids were determined by gas ± liquid chromatography. Intake data were obtained through interview using a validated food frequency questionnaire. Results: Dietary intake and adipose tissue content of the fatty acids studied correlated signi®cantly. Adipose tissue contents of eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3) and docosahexaenoic acid (22:6n-3) were signi®cantly lower while those of trans fatty acids, linoleic and a-linolenic acid were signi®cantly higher in patients than in controls. Age and sex adjusted odds ratios (OR) were signi®cantly reduced with increasing quintiles of very long-chain n-3 fatty acids, thus the OR in the ®fth compared to the ®rst quintile was 0.23 (95% CI 0.08 ± 0.70). After further adjustment for waist-to-hip ratio, smoking, family history of CHD and content of trans fatty acids, the OR in the highest quintile was 0.17 (95% CI 0.04 ± 0.76) and the P for trend 0.016. Age and sex adjusted OR was increased in the ®fth compared to the ®rst quintile of trans fatty acids (OR 2.81, 95% CI 1.16 ± 6.84), linoleic acid (OR 2.10, 95% CI 0.87 ± 5.07) and a-linolenic acid (OR 1.96, 95% CI 0.83 ± 4.61), and P for trend was 0.002, 0.005 and 0.020, respectively. The trends remained signi®cant after adjustment for waist-to-hip ratio, smoking, and family history of coronary heart disease. Trans fatty acids, linoleic acid and a-linolenic acid in adipose tissue were strongly correlated, indicating a common source, most likely margarine. When each of these fatty acid species were adjusted for the two others the trends were no longer signi®cant. Conclusion: Intake of very long-chain n-3 fatty acids as re¯ected in adipose tissue content is inversely associated with risk of myocardial infarction. Trans fatty acids, linoleic and a-linolenic acid were intercorrelated and associated with increased risk. It is suggested that the increased risk may be connected to trans fatty acids or to some other factor associated with margarine consumption.

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality

Circulation, 2019

Background: Global 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. Methods: We 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 ...

Effects of omega-3 fatty acids on cardiovascular risk factors and intermediate markers of cardiovascular disease

Evidence report/technology assessment (Summary), 2004

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