Plasma omega-3 and saturated fatty acids are differentially related to pericardial adipose tissue volume across race/ethnicity: the Multi-ethnic Study of Atherosclerosis.

BACKGROUND: Pericardial adipose tissue (PAT) is a cardiometabolic risk factor influenced by race/ethnicity, inflammation, and metabolic dysfunction. Omega-3 fatty acids (FAs) and saturated FAs (SFAs) are known to affect these latter phenomena and may influence PAT accumulation. We aimed to determine whether plasma levels of these FAs are related to PAT volume and its rate of change over a median 3-year follow-up. METHODS: Cardiac computed tomography assessed PAT in 6785 Multi-Ethnic Study of Atherosclerosis participants. Gas chromatography flame-ionization estimated plasma phospholipid FAs. Regression analyses estimated associations of FAs with PAT volume and its rate of change with adjustments for other risk factors. Race-interactions were tested. RESULTS: In cross-section, top tertiles of omega-3 FAs and odd-chained SFAs were associated with 2.8 and 4.93 cm3 lower PAT volumes, respectively; race/ethnicity was a significant modifying variable (p < 0.002). Even-chained SFAs were associated with 3.5 cm3 greater PAT volume. With stratification by race/ethnicity, Chinese Americans in the top tertile of omega-3 FAs showed 10.5 cm3 greater PAT volume than those in the referent tertile. Black individuals in the top tertile of odd-chained SFAs showed 5.0 cm3 lower PAT compared to referents. Black and Chinese Americans in top tertiles of even-chained SFAs showed respective 3.7 and 5.9 cm3 greater PAT volumes compared to referents. Two associations were observed in prospective analyses among Caucasians; race interactions were non-significant. CONCLUSIONS: Cross-sectional and prospective findings provide inconclusive evidence as to whether plasma FAs are related to PAT in healthy individuals. Cohort studies with longer follow-up periods are warranted.

Associations of ω-3 Fatty Acids With Interstitial Lung Disease and Lung Imaging Abnormalities Among Adults.

Docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models, but human studies are lacking. We examined associations of circulating levels of DHA and other polyunsaturated fatty acids with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6,573). We examined cross-sectional associations with CT lung abnormalities in MESA (2000-2012; n = 6,541), the Framingham Heart Study (2005-2011; n = 3,917), and the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) (2002-2006; n = 1,106). Polyunsaturated fatty acid levels were determined from fasting blood samples and extracted from plasma phospholipids (MESA and AGES-Reykjavik) or red blood cell membranes (Framingham Heart Study). Higher DHA levels were associated with a lower risk of hospitalization due to ILD (per standard-deviation increment, adjusted rate ratio = 0.69, 95% confidence interval (CI): 0.48, 0.99) and a lower rate of death due to ILD (per standard-deviation increment, adjusted hazard ratio = 0.68, 95% CI: 0.47, 0.98). Higher DHA was associated with fewer interstitial lung abnormalities on computed tomography (per natural log increment, pooled adjusted odds ratio = 0.65, 95% CI: 0.46, 0.91). Higher DHA levels were associated with a lower risk of hospitalization and death due to ILD and fewer lung abnormalities on computed tomography in a meta-analysis of data from population-based cohort studies.

Circulating oleic acid levels are related to greater risks of cardiovascular events and all-cause mortality: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Limited evidence has suggested that circulating levels of the omega-9 fatty acid, oleic acid, may be related to greater risks of adverse cardiovascular outcomes. OBJECTIVE: We aimed to determine whether plasma oleic acid may be independently associated with clinical and subclinical cardiovascular disease (CVD) and all-cause mortality in a large multiethnic cohort. METHODS: Plasma fatty acids were measured by gas chromatography-flame ionization in 6568 participants of the Multi-Ethnic Study of Atherosclerosis. The presence of coronary artery calcium (CAC) and aortic valve calcification (AVC) was determined by computed tomography, and carotid plaque was assessed by ultrasound. Incident CVD was defined as myocardial infarction, fatal coronary heart disease, resuscitated cardiac arrest, stroke, or stroke death. Heart failure (HF) was adjudicated from clinical records. Relative risk regression estimated plasma oleic acid-related rate ratios for prevalent CAC, AVC, and carotid plaque. Cox regression estimated hazard ratios (HRs) for CVD, HF, and all-cause mortality over a median 13-year follow-up. RESULTS: Individuals in top quartiles of oleic acid showed greater rate ratios of CAC, AVC, and carotid plaque (all P < .001), but associations were rendered nonsignificant after adjustment for other risk factors. By contrast, those in top quartiles of plasma oleic acid showed significantly greater risks of incident HF (HR: 2.03; P < .001), CVD (HR: 1.41; P = .008), and all-cause mortality (HR: 1.55; P < .001) than those in referent quartiles independent of typical risk factors as well as plasma omega-3 fatty acid levels. CONCLUSIONS: Plasma oleic acid appears to be a risk factor for CVD events and all-cause mortality independent of typical risk factors and plasma omega-3 fatty acids. Additional studies are warranted for confirmation and to further examine whether plasma oleic acid directly contributes to, or serves as a marker of, disease pathogenesis. These findings should not be extrapolated to dietary oleic acid intake.

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

IMPORTANCE: 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. OBJECTIVE: 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. DATA SOURCES: A global consortium of 19 studies identified by November 2014. STUDY SELECTION: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS: 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. MAIN OUTCOMES AND MEASURES: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

n-3 Fatty acids attenuate the risk of diabetes associated with elevated serum nonesterified fatty acids: the multi-ethnic study of atherosclerosis.

OBJECTIVE: Chronically high nonesterified fatty acids (NEFAs) are a marker of metabolic dysfunction and likely increase risk of type 2 diabetes. By comparison, n-3 fatty acids (FAs) have been shown to have various health benefits and may protect against disease development. In 5,697 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we examined whether serum levels of NEFAs relate to risk of incident type 2 diabetes and further tested whether plasma n-3 FA levels may interact with this relation. RESEARCH DESIGN AND METHODS: NEFAs were measured in fasting serum using an enzymatic colorimetric assay and phospholipid n-3 FAs eicosapentaenoic and docosahexaenoic acids were determined in plasma through gas chromatography-flame ionization detection in 5,697 MESA participants. Cox proportional hazards regression evaluated the association between NEFA levels and incident type 2 diabetes and whether plasma n-3 FAs modified this association adjusting for age, sex, race, education, field center, smoking, and alcohol use. RESULTS: Over a mean 11.4 years of the study period, higher diabetes incidence was found across successive NEFA quartiles (Q) (hazard ratio [95% CI]): Q1, 1.0; Q2, 1.35 (1.07, 1.71); Q3, 1.58 (1.24, 2.00); and Q4, 1.86 (1.45, 2.38) (P(trend) < 0.001). A significant interaction of n-3 FAs on the relation between NEFAs and type 2 diabetes was also observed (P(interaction) = 0.03). For individuals with lower n-3 levels (<75th percentile), a higher risk of type 2 diabetes was observed across quartiles of NEFAs: Q1, 1.0; Q2, 1.41 (1.07, 1.84); Q3, 1.77 (1.35, 2.31); and Q4, 2.18 (1.65, 2.88) (P(trend) < 0.001). No significant associations were observed in those with n-3 FAs ≥ 75th percentile (P(trend) = 0.54). CONCLUSIONS: NEFAs are a marker of type 2 diabetes and may have clinical utility for detecting risk of its development. The modifying influence of n-3 FAs suggests a protective effect against disease and/or metabolic dysfunction related to NEFAs and requires further study.

APOE genotype modifies the association between plasma omega-3 fatty acids and plasma lipids in the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE: The benefits of fish oil fatty acids eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) on plasma lipid profiles have been inconsistent but may partially depend on individual Apolipoprotein E (APOE) genotypes. We aimed to determine whether APOE genotype modifies the association of lipid profile characteristics with plasma EPA and DHA levels. METHODS: APOE genotype was determined in this cross-sectional analysis of 2340 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Relative plasma phospholipid EPA and DHA levels, plasma lipids, and lipoprotein subclass particle sizes and concentrations were measured. RESULTS: Significant gene-EPA interactions were found with HDL-C, and particle concentrations of large and total HDL (p(interaction) = 0.0002, 0.006, and 0.007, respectively). The above lipid targets were positively associated with EPA in the E2 groups, whereas negative trends were observed among the E4 participants. Gene-DHA interactions were noted for small LDL particle concentrations alone (p(interaction) = 0.01), where a positive trend was found among E4 but not E2 or E3 participants. CONCLUSIONS: These results indicate a significant contribution of the APOE genotype to the EPA-lipid profile relationship; however, the results do not explain the differences in previous findings regarding LDL-C, triglycerides or total cholesterol. Future investigators examining the effects of EPA on HDL-C or lipoprotein characteristics may consider including APOE genotype in their analyses.