Abstract MP014: Very Long Chain Saturated Fatty Acids and Diabetes Risk: Meta-Analysis of Cohort Studies in the FORCE Consortium

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Amanda Fretts ◽  
Fumiaki Imamura ◽  
Chaoyu Yu ◽  
Alexis C Frazier-Wood ◽  
Maria Lankinen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Palmitic Acid ◽  
Lower Risk ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Arachidic Acid ◽  
Saturated Fatty Acids ◽  
Diabetes Risk ◽  
Incident Diabetes ◽  
Long Chain

Background: Circulating saturated fatty acids are biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. Unlike palmitic acid (16:0), which has been extensively studied, little is known of the relationship of very long-chain saturated fatty acids (VLSFAs), with 20 carbons or more, to diabetes risk. Objective: To investigate the associations of circulating levels of VLSFA with incident diabetes. Methods: A meta-analysis was conducted within a consortium of prospective (cohort or nested case-control) studies having circulating measures of one or more VLSFAs, including arachidic acid (20:0), behenic acid (22:0) and lignoceric acid (24:0). Standardized analysis was conducted in each study using pre-specified models, exposures, outcomes, and covariates. Study-specific estimates were pooled using fixed effects meta-analysis. Results: Current findings were based on 9 participating studies, including 46,549 total participants and 13,750 incident diabetes. In multivariable-adjusted analyses, higher levels of all 3 VLSFAs were associated with lower risk of incident diabetes. Pooled RRs (95% CI) per interquintile range were 0.80 (0.71-0.90) for 20:0; 0.83 (0.76-0.91) for 22:0; and 0.70 (0.63-0.79) for 24:0, after adjustment for demographics, lifestyle factors and clinical conditions. Additional adjustments for circulating palmitic acid and triglyceride levels moved the RRs toward the null (illustrated for 24:0, in model 3 of the Figure ). Conclusions: Based on meta-analysis of results from several studies around the world, biomarker levels of VLSFA are associated with lower risk of incident diabetes, potentially mediated by effects on circulating triglycerides and 16:0.

scholarly journals Circulating Very-Long-Chain Saturated Fatty Acids Were Inversely Associated with Cardiovascular Health: A Prospective Cohort Study and Meta-Analysis

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2709
Author(s):  
Meng Liu ◽  
Luo-Shi-Yuan Zuo ◽  
Ting-Yu Sun ◽  
Yan-Yan Wu ◽  
Yu-Ping Liu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cohort Study ◽  
Cardiovascular Health ◽  
Biological Activities ◽  
Meta Analysis ◽  
Arachidic Acid ◽  
Saturated Fatty Acids ◽  
Behenic Acid ◽  
Incident Cases ◽  
Long Chain

Saturated fatty acids with different chain lengths have different biological activities, but little is known about very-long-chain saturated fatty acids (VLCSFAs). This study investigated the associations between the circulating VLCSFAs and cardiovascular health. This community-based cohort study included 2198 adults without carotid artery plaques (CAPs) at baseline. The percentage of baseline erythrocyte VLCSFA (arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)) was measured by gas chromatography. The presence of CAPs was determined at baseline and every 3 years thereafter by ultrasound examination. A meta-analysis was conducted to summarize the pooled associations between circulating VLCSFAs and the risk of cardiovascular diseases (CVDs). During a median of 7.2 years of follow-up, 573 women (35.1%) and 281 men (49.6%) were identified as CAP incident cases. VLCSFAs were inversely related with CAP risk in women (all p-trend <0.05) but not in men. Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of CAPs for the highest (vs. lowest) quartile were 0.80 (0.63–1.01) for C20:0, 0.71 (0.56–0.89) for C22:0, 0.75 (0.59–0.94) for C24:0, and 0.69 (0.55–0.87) for total VLCSFAs in women. The pooled HRs (95% CIs) of CVDs for the highest (vs. lowest) circulating VLCSFAs from seven studies including 8592 participants and 3172 CVD events were 0.67 (0.57–0.79) for C20:0, 0.66 (0.48–0.90) for C22:0, and 0.57 (0.42–0.79) for C24:0, respectively. Our findings suggested that circulating VLCSFAs were inversely associated with cardiovascular health.

scholarly journals Associations of circulating very-long-chain saturated fatty acids and incident type 2 diabetes: a pooled analysis of prospective cohort studies

2019 ◽  
Vol 109 (4) ◽  
pp. 1216-1223 ◽  
Author(s):  
Amanda M Fretts ◽  
Fumiaki Imamura ◽  
Matti Marklund ◽  
Renata Micha ◽  
Jason H Y Wu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Lower Risk ◽  
Saturated Fatty Acids ◽  
Pooled Analysis ◽  
Incident Diabetes ◽  
Incident Type ◽  
Incident Type 2 Diabetes ◽  
Long Chain

ABSTRACT Background Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed. Objective We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies. Methods Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants. Results There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides. Conclusions Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.

Abstract MP26: Biomarkers of n-6 Polyunsaturated Fatty Acids and CVD Risk: A Global Pooling Project of 19 Cohort Studies

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Matti Marklund ◽  
Tzu-An Chen ◽  
Janette de Goede ◽  
Fumiaki Imamura ◽  
Federica Laguzzi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lower Risk ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Case Control Studies ◽  
Cvd Risk ◽  
Incidence And Mortality ◽  
Tissue Biomarker ◽  
Cvd Mortality

Background: Despite cholesterol-lowering and other potential beneficial properties of dietary linoleic acid (LA; 18:2n-6), LA has been considered pro-inflammatory and is a precursor to arachidonic acid (AA; 20:4n-6), which has also been considered harmful for CVD. Thus, the role of n-6 fatty acids in CVD prevention remains debated. Objective: To investigate across harmonized global studies the relation of circulating/tissue biomarker levels of LA and AA with incidence of CVD, CHD, and stroke. Methods: We conducted a pooled analysis within a global consortium of prospective cohort or nested case-control studies having circulating or tissue biomarker measures of LA and AA. Each study ascertained CVD risk, including incident CVD, CHD, ischemic stroke (IS), and/or CVD mortality in adults with no prevalent CVD at baseline. Standardized individual-level analysis was conducted in each study using pre-specified models, exposures, outcomes, and covariates. Study-specific estimates were pooled using inverse variance-weighted fixed effects meta-analysis. Results: We evaluated 19 studies, including 6,569 total CVD events, 2,407 CVD deaths, 6,557 CHD events, and 2,237 IS events (values may not sum due to cohort-specific outcomes). In continuous (90th vs 10th percentile) multivariable-adjusted analyses, higher levels of both LA and AA were associated with lower risk of incident CVD, with modest between-compartment heterogeneity (I2=33-35%) (Figure). LA and AA were inversely associated with CVD mortality, with RRs (95% CI): LA 0.81 (0.73 - 0.90) and AA 0.90 (0.81 - 0.99). LA, but not AA, was associated with lower risk of incident CHD and IS, with RRs (95% CI) 0.94 (0.88 - 0.99) and 0.80 (0.69 - 0.92), respectively. Conclusions: Based on harmonized analysis of multiple studies on free-living populations, biomarker levels of the two major n-6 fatty acids are associated with lower risk of CVD incidence and mortality. Relevance of potential differences in compartment-specific associations requires further investigation.

scholarly journals Plasma Ceramides and Sphingomyelins in Relation to Atrial Fibrillation Risk: The Cardiovascular Health Study

2020 ◽  
Vol 9 (4) ◽  
Author(s):  
Paul N. Jensen ◽  
Amanda M. Fretts ◽  
Andrew N. Hoofnagle ◽  
Colleen M. Sitlani ◽  
Barbara McKnight ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Fatty Acids ◽  
Palmitic Acid ◽  
Cardiovascular Health ◽  
Saturated Fatty Acids ◽  
Behenic Acid ◽  
Hazard Ratio ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Long Chain

Background Ceramides exhibit multiple biological activities that may influence the pathophysiological characteristics of atrial fibrillation (AF). Whether the length of the saturated fatty acid carried by the ceramide or their sphingomyelin precursors are associated with AF risk is not known. Methods and Results Among 4206 CHS (Cardiovascular Health Study) participants (mean age, 76 years; 40% men) who were free of prevalent AF at baseline, we identified 1198 incident AF cases over a median 8.7 years of follow‐up. We examined 8 sphingolipid species: ceramide and sphingomyelin species with palmitic acid and species with very‐long‐chain saturated fatty acids: arachidic; behenic; and lignoceric. In adjusted Cox regression analyses, ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk (ie, per 2‐fold higher ceramide with behenic acid hazard ratio, 0.71; 95% CI, 0.59–0.86; sphingomyelin with behenic acid hazard ratio, 0.60; 95% CI, 0.46–0.77). In contrast, ceramides and sphingomyelins with palmitic acid were associated with increased AF risk (ceramide with palmitic acid hazard ratio, 1.31; 95% CI, 1.03–1.66; sphingomyelin with palmitic acid hazard ratio, 1.73; 95% CI, 1.18–2.55). Associations were attenuated with adjustment for NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), but did not differ significantly by age, sex, race, body mass index, or history of coronary heart disease. Conclusions Our findings suggest that several ceramide and sphingomyelin species are associated with incident AF, and that these associations differ on the basis of the fatty acid. Ceramides and sphingomyelins with palmitic acid were associated with increased AF risk, whereas ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk.

Abstract P414: Biomarkers of Very Long-chain Saturated Fatty Acids and Incident Coronary Heart Disease: Prospective Evidence From 15 Cohorts in the Fatty Acids and Outcomes Research Consortium

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Andres V Ardisson Korat ◽  
Frank Qian ◽  
Fumiaki Imamura ◽  
Nathan Tintle ◽  
Jiaying Chen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Outcomes Research ◽  
Arachidic Acid ◽  
Saturated Fatty Acids ◽  
Inverse Association ◽  
Total Plasma ◽  
Research Consortium ◽  
Long Chain

Background: Biomarker levels of very long-chain saturated fatty acids (VLCSFAs) have been found to be favorably associated with cardiovascular risk factors including lower risk of diabetes and reduced triglycerides. Few studies have examined the association between VLCSFAs and coronary heart disease (CHD). Aims: To assess the association of circulating arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with incident total, fatal, and nonfatal CHD. Methods: We used data from the Fatty Acids and Outcomes Research Consortium consisting of 15 prospective cohorts worldwide which included adults (age≥18 years) who were free of cardiovascular disease and had blood measurements of 20:0, 22:0, and 24:0 at baseline. A study protocol with standardized definitions of exposures, disease outcomes, and covariates was developed, for which each cohort conducted individual participant-level analysis. Cohort-specific associations were pooled using inverse variance-weighted meta-analysis to calculate the overall relative risk (RR) per interquintile range (difference between the 90 th and 10 th percentiles) and 95% confidence interval (CI). Results: Among 33,083 participants, 6,165 cases of total CHD were ascertained. The overall pooled RR and 95% CI were 0.96 (0.89, 1.02) for 20:0, 1.01 (0.92, 1.11) for 22:0, 0.94 (0.86, 1.02) for 24:0, and 0.96 (0.89, 1.04) for 20:0 + 22:0 + 24:0 ( Figure 1 ). However, we noted heterogeneity by lipid compartments, with significant inverse associations for higher 22:0 [0.77 (0.62, 0.96)], 24:0 [0.61 (0.49, 0.77)], and 20:0 + 22:0 + 24:0 [0.73 (0.60, 0.89)] in the total plasma/serum compartment but not in the phospholipid compartment. Similar associations were observed for fatal and nonfatal CHD and when using a random-effects model. Conclusion: Higher circulating VLCSFAs were not associated with total CHD in a global consortium of prospective studies. The finding of an inverse association with total CHD for VLCSFAs in the total plasma/serum compartment warrants further research.

scholarly journals Erythrocyte very long-chain saturated fatty Acids associated with lower risk of incident sudden cardiac arrest

2014 ◽  
Vol 91 (4) ◽  
pp. 149-153 ◽  
Author(s):  
Rozenn N. Lemaitre ◽  
Irena B. King ◽  
Kenneth Rice ◽  
Barbara McKnight ◽  
Nona Sotoodehnia ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cardiac Arrest ◽  
Lower Risk ◽  
Saturated Fatty Acids ◽  
Sudden Cardiac Arrest ◽  
Long Chain

Abstract P357: Omega-3 Fatty Acid Biomarkers and Coronary Heart Disease: a Pooling Project of 17 Cohort Studies

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Liana C Del Gobbo ◽  
Stella Aslibekyan ◽  
Pascale Barberger-Gateau ◽  
Hannia Campos ◽  
Stephanie E Chiuve ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lower Risk ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Omega 3 Fatty Acid ◽  
Chd Risk ◽  
Intermediate Chain

Background: Recent trials have raised questions about the role of seafood-derived long-chain omega-3 fatty acids for prevention of CHD; and evidence linking intermediate-chain omega-3 fatty acids to CHD remains weak. Methods: We developed a global consortium of 17 prospective (cohort or nested case-control) and retrospective studies having circulating or tissue biomarker measures of eicosapentaenoic (EPA; 20:5n-3), docosapentaenoic (DPA; 22:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and α-linolenic acid (ALA; 18:3n-3). Each study ascertained CHD risk, including total CHD, nonfatal MI, and/or fatal CHD. Associations of each omega-3 fatty acid biomarker with CHD were evaluated within each cohort using standardized models, exposures, outcomes, and covariates across studies. Omega-3 fatty acid levels were analyzed continuously (per SD) and categorically (quintiles), and study-specific estimates were centrally pooled using fixed effects meta-analysis. Results: Current findings (Oct 2013) were based on 13 of 17 participating studies, including 7105 total CHD, 4926 nonfatal MI, and 2466 fatal CHD events. In both continuous and categorical multivariable-adjusted analyses, each omega-3 biomarker was inversely associated with fatal CHD. For each 1 SD unit increment, ALA was associated with 9% lower risk [HR 0.91 (95% CI 0.84-0.99)]; EPA, with 8% lower risk [HR 0.92 (95% CI 0.85-1.00)]; DPA, with 8% lower risk [HR: 0.92 (0.87-0.98)]; and DHA, with 9% lower risk [HR: 0.91 (0.86-0.96)] (Figure). Associations with total CHD and nonfatal MI were generally weaker and non-significant, except for EPA and nonfatal MI [HR: 0.93 (0.89-0.98)] and DHA and nonfatal MI [HR: 0.95 (0.91-0.99)]. Conclusions: Based on all available studies from around the world, both long and intermediate-chain omega-3 fatty acids, measured using objective biomarkers, are associated with lower risk of fatal CHD. These findings support potential benefit of omega-3 fatty acids for reducing CHD death.

scholarly journals Plasma Ceramide Species Are Associated with Diabetes Risk in Participants of the Strong Heart Study

2019 ◽  
Vol 150 (5) ◽  
pp. 1214-1222 ◽  
Author(s):  
Amanda M Fretts ◽  
Paul N Jensen ◽  
Andrew Hoofnagle ◽  
Barbara McKnight ◽  
Barbara V Howard ◽  
...  
Keyword(s):  
American Indian ◽  
Multiple Testing ◽  
Meta Analysis ◽  
Arachidic Acid ◽  
Behenic Acid ◽  
Diabetes Risk ◽  
Incident Diabetes ◽  
Survival Models ◽  
Strong Heart Study ◽  
Heart Study

ABSTRACT Background Few studies have assessed the associations of ceramides and sphingomyelins (SMs) with diabetes in humans. Objective We assessed associations of 15 circulating ceramides and SM species with incident diabetes in 2 studies. Methods The analysis included 435 American-Indian participants from the Strong Heart Study (nested case-control design for analyses; mean age: 57 y; 34% male; median time until diabetes 4.3 y for cases) and 1902 participants from the Strong Heart Family Study (prospective design for analyses; mean age: 37 y; 39% male; median 12.5 y of follow-up). Sphingolipid species were measured using stored plasma samples by sequential LC and MS. Using logistic regression and parametric survival models within studies, and an inverse-variance-weighted meta-analysis across studies, we examined associations of 15 ceramides and SM species with incident diabetes. Results There were 446 cases of incident diabetes across the studies. Higher circulating concentrations of ceramides containing stearic acid (Cer-18), arachidic acid (Cer-20), and behenic acid (Cer-22) were each associated with a higher risk of diabetes. The RRs for incident diabetes per 1 SD of each log ceramide species (μM) were 1.22 (95% CI: 1.09, 1.37) for Cer-18, 1.18 (95% CI: 1.06, 1.31) for Cer-20, and 1.20 (95% CI: 1.08, 1.32) for Cer-22. Although the magnitude of the risk estimates for the association of ceramides containing lignoceric acid (Cer-24) with diabetes was similar to those for Cer-18, Cer-20, and Cer-22 (RR = 1.13; 95% CI: 1.01, 1.26), the association was not statistically significant after correction for multiple testing (P = 0.007). Ceramides carrying palmitic acid (Cer-16), SMs, glucosyl-ceramides, or a lactosyl-ceramide were not associated with diabetes risk. Conclusions Higher concentrations of circulating Cer-18, Cer-20, and Cer-22 were associated with a higher risk of developing diabetes in 2 studies of American-Indian adults. This trial was registered at clinicaltrials.gov as NCT00005134.

Differential effects of medium- and long-chain saturated fatty acids on blood lipid profile: a systematic review and meta-analysis

2018 ◽  
Vol 108 (4) ◽  
pp. 675-687 ◽  
Author(s):  
Nisha Panth ◽  
Kylie A Abbott ◽  
Cintia B Dias ◽  
Katie Wynne ◽  
Manohar L Garg
Keyword(s):  
Fatty Acids ◽  
Blood Lipids ◽  
Ldl Cholesterol ◽  
Meta Analysis ◽  
Saturated Fatty Acids ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Weighted Mean ◽  
Lipids And Lipoproteins ◽  
Long Chain

Abstract Background Medium-chain saturated fatty acids (MCFAs) may affect circulating lipids and lipoproteins differently than long-chain saturated fatty acids (LCSFAs), but the results from human intervention trials have been equivocal. Objective The aim of this study was to determine whether MCFAs and LCSFAs have differential impacts on blood lipids and lipoproteins. Design Five databases were searched (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus) until April 2018, and published clinical trials investigating the differential effects of dietary MCFAs and LCSFAs on blood lipids were included. Searches were limited to the English language and to studies with adults aged >18 y. Where possible, studies were pooled for meta-analysis using RevMan 5.2. The principle summary measure was the mean difference between groups calculated using the random-effects model. Results Eleven eligible crossover and 1 parallel trial were identified with a total of 299 participants [weighted mean ± SD age: 38 ± 3 y; weighted mean ± SD body mass index (kg/m2): 24 ± 2]. All studies were pooled for the meta-analysis. Diets enriched with MCFAs led to significantly higher high-density lipoprotein (HDL) cholesterol concentrations than diets enriched with LCSFAs (0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L) with no effect on triglyceride, low-density lipoprotein (LDL) cholesterol, and total cholesterol concentrations. Consumption of diets rich in MCFAs significantly increased apolipoprotein A-I (apoA-I) concentrations compared with diets rich in LCSFAs (0.08 g/L; 95% CI: 0.02, 0.14 g/L). There was no evidence of statistical heterogeneity for HDL cholesterol, apoA-I, and triglyceride concentrations; however, significant heterogeneity was observed for the total cholesterol (I2 = 49%) and LDL cholesterol analysis (I2 = 58%). Conclusion The findings of this research demonstrate a differential effect of MCFAs and LCSFAs on HDL cholesterol concentrations. Further investigations are warranted to elucidate the mechanism by which the lipid profile is altered. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42017078277.

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