TY - JOUR
T1 - Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality
T2 - The Framingham Offspring Cohort
AU - McBurney, Michael I.
AU - Tintle, Nathan L.
AU - Vasan, Ramachandran S.
AU - Sala-Vila, Aleix
AU - Harris, William S.
N1 - Funding Information:
This work was supported in part by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS) through an International Life Sciences Institute North America Lipid Committee grant. IAFNS is a nonprofit science organization that pools funding from industry collaborators and advances science through the in-kind and financial contributions from public and private sector participants. The Framingham Heart Study (FHS) acknowledges the support of contracts N01-HC-25195, HHSN26820150000II, and 75N92019D00031 from the National Heart, Lung, and Blood Institute.
Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
KW - all-cause mortality
KW - behenic acid
KW - fatty acids
KW - lipids
KW - myristic acid
KW - omega-3 index
KW - palmitoleic acid
KW - risk factors
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U2 - 10.1093/ajcn/nqab195
DO - 10.1093/ajcn/nqab195
M3 - Article
C2 - 34134132
AN - SCOPUS:85118096217
SN - 0002-9165
VL - 114
SP - 1447
EP - 1454
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 4
ER -