Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality: the Framingham Offspring Cohort.
Level 3 - non-randomized controlled study
Prospective observational cohort study evaluating a prognostic risk prediction model over 11 years of follow-up.
PubMed 34134132 · doi:10.1093/ajcn/nqab195
What was done
Framingham Offspring Cohort participants without baseline cardiovascular disease who had erythrocyte (RBC) fatty acid (FA) measurements (n = 2240) were followed for 11 years. Investigators evaluated the association of 8 standard cardiovascular risk factors and 28 RBC FA metrics with all-cause mortality using a forward stepwise selection approach and 10-fold cross-validation in age- and sex-adjusted models.
What was found
Four of 28 FA metrics (14:0, 16:1n-7, 22:0, and the omega-3 index [20:5n-3 + 22:6n-3]) were selected in ≥5 discovery models. An age- and sex-adjusted model with these 4 FA metrics predicted all-cause mortality with a C-statistic of 0.778 (95% CI: 0.759, 0.797), performing similarly to a model with the 6 standard risk factors (C-statistic: 0.777; 95% CI: 0.753, 0.802). Combining the 4 FA metrics with smoking and diabetes increased the C-statistic to 0.790 (95% CI: 0.770, 0.811), which was significantly higher than the FA model alone (P < 0.01) and the smoking plus diabetes model alone (C-statistic: 0.766; 95% CI: 0.739, 0.794; P < 0.001).
Why it matters
A multi-marker RBC fatty acid profile predicts 11-year all-cause mortality as effectively as standard clinical risk factors in older adults, highlighting the systemic prognostic value of membrane lipid profiles.
Limits
The findings derive from a single community cohort of older adults (mean age in mid-60s) without external validation in diverse populations. The observational design cannot establish causality or determine whether modifying red blood cell fatty acid levels reduces mortality.
Cited by
- supports Smokers with a high omega-3 index have the same life expectancy as non-smokers with a low omega-3 index.
- partial An omega-3 index in the 8% range is associated with a 5-year increased life expectancy.
- context A high omega-3 index is associated with a 5-year increased life expectancy and a 90% reduction in sudden cardiac death.
- context Individuals with a high omega-3 index have a five-year increased life expectancy compared to those with a low omega-3 index.