Dataset Information

Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality: the Framingham Offspring Cohort.

ABSTRACT:

Background

RBC long-chain omega-3 (n-3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction.

Objectives

The objective of this study was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease (CVD) in predicting risk of all-cause mortality.

Methods

Framingham Offspring Cohort participants without prevalent CVD having RBC FA measurements and relevant baseline clinical covariates (n = 2240) were evaluated during 11 y of follow-up. A forward, stepwise approach was used to systematically evaluate the association of 8 standard risk factors (age, sex, total cholesterol, HDL cholesterol, hypertension treatment, systolic blood pressure, smoking status, and prevalent diabetes) and 28 FA metrics with all-cause mortality. A 10-fold cross-validation process was used to build and validate models adjusted for age and sex.

Results

Four of 28 FA metrics [14:0, 16:1n-7, 22:0, and omega-3 index (O3I; 20:5n-3 + 22:6n-3)] appeared in ≥5 of the discovery models as significant predictors of all-cause mortality. In age- and sex-adjusted models, a model with 4 FA metrics was at least as good at predicting all-cause mortality as a model including the remaining 6 standard risk factors (C-statistic: 0.778; 95% CI: 0.759, 0.797; compared with C-statistic: 0.777; 95% CI: 0.753, 0.802). A model with 4 FA metrics plus smoking and diabetes (FA + Sm + D) had a higher C-statistic (0.790; 95% CI: 0.770, 0.811) compared with the FA (P < 0.01) or Sm + D models alone (C-statistic: 0.766; 95% CI: 0.739, 0.794; P < 0.001). A variety of other highly correlated FAs could be substituted for 14:0, 16:1n-7, 22:0, or O3I with similar predicted outcomes.

Conclusions

In this community-based population in their mid-60s, RBC FA patterns were as predictive of risk for death during the next 11 y as standard risk factors. Replication is needed in other cohorts to validate this FA fingerprint as a predictor of all-cause mortality.

SUBMITTER: McBurney MI

PROVIDER: S-EPMC8488873 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality: the Framingham Offspring Cohort.

McBurney Michael I MI Tintle Nathan L NL Vasan Ramachandran S RS Sala-Vila Aleix A Harris William S WS

The American journal of clinical nutrition 20211001 4

<h4>Background</h4>RBC long-chain omega-3 (n-3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction.<h4>Objectives</h4>The objective of this study was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease (CVD) in predicting risk of all-cause mortality.<h4>Methods</h4>Framingham Offspring Cohort participants without prevalent CVD having RB ...[more]

PMID: 34134132

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Project description:BackgroundCognitive decline, and more specifically Alzheimer's disease, continues to increase in prevalence globally, with few, if any, adequate preventative approaches. Several tests of cognition are utilized in the diagnosis of cognitive decline that assess executive function, short- and long-term memory, cognitive flexibility, and speech and motor control. Recent studies have separately investigated the genetic component of both cognitive health, using these measures, and circulating fatty acids.ObjectivesWe aimed to examine the potential moderating effect of main species of ω-3 polyunsaturated fatty acids (PUFAs) on an individual's genetically conferred risk of cognitive decline.MethodsThe Offspring cohort from the Framingham Heart Study was cross-sectionally analyzed in this genome-wide interaction study (GWIS). Our sample included all individuals with red blood cell ω-3 PUFA, genetic, cognitive testing (via Trail Making Tests [TMTs]), and covariate data (N = 1620). We used linear mixed effects models to predict each of the 3 cognitive measures (TMT A, TMT B, and TMT D) by each ω-3 PUFA, single nucleotide polymorphism (SNP) (0, 1, or 2 minor alleles), ω-3 PUFA by SNP interaction term, and adjusting for sex, age, education, APOE ε4 genotype status, and kinship (relatedness).ResultsOur analysis identified 31 unique SNPs from 24 genes reaching an exploratory significance threshold of 1×10-5. Fourteen of the 24 genes have been previously associated with the brain/cognition, and 5 genes have been previously associated with circulating lipids. Importantly, 8 of the genes we identified, DAB1, SORCS2, SERINC5, OSBPL3, CPA6, DLG2, MUC19, and RGMA, have been associated with both cognition and circulating lipids. We identified 22 unique SNPs for which individuals with the minor alleles benefit substantially from increased ω-3 fatty acid concentrations and 9 unique SNPs for which the common homozygote benefits.ConclusionsIn this GWIS of ω-3 PUFA species on cognitive outcomes, we identified 8 unique genes with plausible biology suggesting individuals with specific polymorphisms may have greater potential to benefit from increased ω-3 PUFA intake. Additional replication in prospective settings with more diverse samples is needed.

Dataset Information

Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality: the Framingham Offspring Cohort.

Background

Objectives

Methods

Results

Conclusions

Publications

Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality: the Framingham Offspring Cohort.

Similar Datasets

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