Red Blood Cell Fatty Acids Could Serve as Predictors to All-Cause Mortality

by | Sep 13, 2021 | 2021, Cardiovascular Health, Omega - 3

Written by Chrystal Moulton, Staff Writer. Four red blood cell fatty acids were found to serve as predictors of all-cause mortality.

cardiovascular health - sliderCardiovascular disease is a leading cause of death worldwide 1. Simple behavioral changes could reduce the likelihood of developing cardiovascular disease [CVD] such as exercise, healthy diet, reduced alcohol and tobacco use. The Framingham heart study provided 8 baseline standard risk factors for CVD. These include smoking, age, sex, diabetes status, systolic blood pressure, hypertension, total cholesterol, and HDL cholesterol 2. Other biomarkers such as fatty acids have been associated with reduced risk of CVD 3,4. However, few have been able to determine the full risk profile related to fatty acids. One such study attempted to define the risk fingerprint for fatty acids using a cross sectional design with approximately 1,350 participants 5. Although this research identified 10 fatty acids as possible risk factors related to CVD, the data could not be easily applied to clinical use due to its design 5,6. In the current trial, researchers used participants with red blood cell fatty acid (RBC FA) measurements from the Framingham Offspring Cohort study to observe clinical events during a 11-year follow-up period 7. The primary outcome was to determine if red blood cell fatty acid (RBC FA) measurements could compare to standard risk factors as predictors of risk for all-cause mortality.

From the Framingham Offspring Cohort study 8, 3021 participants who attended the 8th examination cycle were eligible for this study. Patients were excluded if RBC FA measurements were missing or if they had prevalent CVD. In the end, 2240 participants were eligible for this investigation. Fasting blood samples were taken from each participant and were used to quantify the sum of EPA and DHA also referred to as the omega-3 index (O3I) and 25 RBC FAs. Hazard ratios were calculated on a per quintile of fatty acids basis. Mortality was related to quintiles of fatty acids in the primary analysis. Various models were also constructed to compare standard risk factors with RBC FAs as a risk for all-cause mortality during the 11-year follow up period.

At the end of follow up, 384 participants died. 57% of participants were women and 43% men. The average age was 65 years old. When comparing fatty acid against standard risks factors in predictive models for all-cause mortality, four fatty acids stood out among the 26 fatty acids metrics used in this analysis. These four fatty acids include 14:0, 16:1n-7, 22:0, and the omega-3 index (03I) [HR range = 0.84- 1.23, P<0.05]. When these four fatty acids where input to the predictive model together with the standard risk factors, those 4 fatty acid metrics remained a consistent predictive factor along with two standard risk factors: current smoking (HR= 1.81, P<0.05) and prevalent diabetes (HR= 1.63, P<0.05). Thus, smoking, diabetes, 4 fatty acids metrics (14:0, 16:1n-7, 22:0, and the omega-3 index [03I]) along with age and sex [i.e.: FA+Sm+D] served as a predictive model for all-cause mortality. Researchers evaluated the concordance of the predictive model fatty acid + smoking + diabetes compared with the standard risk factors model. Concordance data showed that the fatty acid + smoking + diabetes model had a significantly better concordance than the standard risk factors model even after adjusting for age and sex [C= 0.790 versus C= 0.777, P= 0.01]. Researchers also conducted a theoretical analysis of one quintile change in percentage of the four selected fatty acid metrics compared with smoking and prevalent diabetes on the risk of death during 11-year follow-up. This analysis showed that one quintile increases in fatty acids 22:0, 14:0, or O3I was associated with a 0.79y, 1.41y, or 1.18 y increase in lifespan, respectively. For RBC FA 16:1n-7, one quintile reduction was associated with an estimated 1.66 years increase in life expectancy.

Overall, concentrations of fatty acids 22:0, 14:0, the omega-3 index, and 16:1n-7 are as effective in predicting all-cause mortality as the standard risk factors found in the Framingham Heart study. The best predictive model included the aforementioned four fatty acid metrics along with smoking and diabetes status with regard to total mortality. Further analysis will be needed to verify the findings of this investigation.

Source: McBurney, Michael I., Nathan L. Tintle, Ramachandran S. Vasan, Aleix Sala-Vila, and William S. Harris. “Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality: the Framingham Offspring Cohort.” The American Journal of Clinical Nutrition (2021).

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. All rights reserved. 

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Posted September 13, 2021.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

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