Serum individual nonesterified fatty acids and risk of heart failure in older adults

Authors: DJOUSSE, LUC - Harvard University; BIGGS, MARY - University Of Washington; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; IX, JOACHIM - University Of California; FITZPATRICK, ANNETTE - University Of Washington; KING, IRENA - University Of New Mexico; LEMAITRE, ROZENN - University Of Washington; MCKNIGHT, BARBARA - University Of Washington; KIZER, JORGE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MUKAMAL, KENNETH - Harvard University; SISCOVICK, DAVID - New York Academy Of Medicine

Submitted to: Cardiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/16/2020
Publication Date: 2/25/2021
Citation: Djousse, L., Biggs, M.L., Matthan, N., Ix, J.H., Fitzpatrick, A.L., King, I.B., Lemaitre, R.N., Mcknight, B., Kizer, J.R., Lichtenstein, A.H., Mukamal, K.J., Siscovick, D.S. 2021. Serum individual nonesterified fatty acids and risk of heart failure in older adults. Cardiology. 146(3):351-358. https://doi.org/10.1159/000513917.
DOI: https://doi.org/10.1159/000513917

Interpretive Summary: Heart failure, also known as congestive heart failure, is caused by the heart muscle not having the ability to pump blood throughout the body at a rate that allows for adequate nourishment of all the tissues. The condition is most common in older adults. Non-esterified fatty acids (NEFAs) comprise a form of fat that is carried in the bloodstream. There are many types of individual NEFAs. It has been observed that people with heart failure have higher concentrations of total NEFAs. Unknown is whether this includes all types of NEFAs or just some types. This is important to know because if it were just certain types they may be useful as early markers of heart failure risk, allowing for early introduction of mediating measures to prevent disease onset or progression. To this end we tested the hypothesis that some but not all individual NEFAs are associated with a higher risk of heart failure. To test this hypothesis, we measured 35 individual NEFAs in 2,139 participants of the Cardiovascular Health Study and followed them for 9.7 years. We observed that people with lower concentrations of a non-esterified short chain saturated fatty acid, pentadecanoic acid (15:0), and two long chain unsaturated fatty acids, gamma-linolenic (18:3n-6) and docosahexaenoic (22:6n-3), were at lower risk of developing heart failure. In contrast, people with a higher concentration of a non-esterified long chain saturated fatty acid stearic acid (18:0) and monounsaturated fatty acid nervonic acid (24:1n-9) were at higher risk of developing heart failure. These findings may provide new targets for heart failure diagnosis and prevention.

Technical Abstract: Background: Heart failure (HF) is highly prevalent among older adults and is associated with high costs. Although serum total nonesterified fatty acids (NEFAs) have been positively associated with HF risk, the contribution of each individual NEFA to HF risk has not been examined. Objective: The aim of this study was to examine the association of individual fasting NEFAs with HF risk in older adults. Methods: In this prospective cohort study of older adults, we measured 35 individual NEFAs in 2,140 participants of the Cardiovascular Health Study using gas chromatography. HF was ascertained using review of medical records by an endpoint committee. Results: The mean age was 77.7 +/- 4.4 years, and 38.8% were male. During a median follow-up of 9.7 (maximum 19.0) years, 655 new cases of HF occurred. In a multivariable Cox regression model controlling for demographic and anthropometric variables, field center, education, serum albumin, glomerular filtration rate, physical activity, alcohol consumption, smoking, hormone replacement therapy, unintentional weight loss, and all other measured NEFAs, we observed inverse associations (HR [95% CI] per standard deviation) of nonesterified pentadecanoic (15:0) (0.73 [0.57-0.94]), gamma-linolenic acid (GLA) (0.87 [0.75-1.00]), and docosahexaenoic acid (DHA) (0.73 [0.61-0.88]) acids with HF, and positive associations of nonesterified stearic (18:0) (1.30 [1.04-1.63]) and nervonic (24:1n-9) (1.17 [1.06-1.29]) acids with HF. Conclusion: Our data are consistent with a higher risk of HF with nonesterified stearic and nervonic acids and a lower risk with nonesterified 15:0, GLA, and DHA in older adults. If confirmed in other studies, specific NEFAs may provide new targets for HF prevention.