Individual non-esterified fatty acids and incident atrial fibrillation late in life

Authors: PELLEGRINI, CARA - University Of California; BUZKOVA, PETRA - University Of Washington; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; IX, JOACHIM - University Of California; SISCOVICK, DAVID - New York Academy Of Medicine; HECKBERT, SUSAN - University Of Washington; TRACY, RUSSELL - University Of Vermont; MUKAMAL, KENNETH - Beth Israel Deaconess Medical Center; DJOUSSE, LUC - Brigham & Women'S Hospital; KIZER, JORGE - University Of California

Submitted to: Heart
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2021
Publication Date: 1/22/2021
Citation: Pellegrini, C.N., Buzkova, P., Lichtenstein, A.H., Matthan, N.R., Ix, J.H., Siscovick, D.S., Heckbert, S.R., Tracy, R.P., Mukamal, K.J., Djousse, L., Kizer, J.R. 2021. Individual non-esterified fatty acids and incident atrial fibrillation late in life. Heart. 107(22):1805-1812. https://doi.org/10.1136/heartjnl-2020-317929.
DOI: https://doi.org/10.1136/heartjnl-2020-317929

Interpretive Summary: Atrial fibrillation (AF) is a condition characterized by irregular heartbeat (arrhythmia). It increases a person's risk for blood clots, stroke, heart failure and other heart-related complications. Obesity and metabolic syndrome are major risk factors for AF. Elevated levels of circulating total non-esterified fatty acids (NEFAs) have been associated with incident AF. Unknown is whether individual NEFAs are associated with incident AF. NEFA profiles were assessed in the serum of 1,872 individuals who participated in the Cardiovascular Health Study, a community-based longitudinal investigation of US adults at least 65 years of age. During an average follow-up of 11 years, 715 cases of incident AF occurred. Of the individual NEFA measured, higher serum concentration of nervonic acid was associated with higher risk of AF. Conversely, higher serum concentration of gamma-linolenic acid was associated with lower risk of AF. None of the remaining NEFAs were significantly associated with AF. These data indicate that among community-dwelling elders, serum levels of non-esterified nervonic acid were positively associated, while serum levels of non-esterified gamma-linolenic acid were inversely associated, with incident AF. If confirmed, these results could offer new strategies for AF early detection, prevention and intervention in this segment of the population at highest risk.

Technical Abstract: Objective Obesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Expansion of fat depots is associated with increased circulating total non-esterified fatty acids (NEFAs), elevated levels of which are associated with incident AF. We undertook comprehensive serum measurement of individual NEFA to identify specific associations with new-onset AF late in life. Methods The present study focused on participants with available serum and free of AF selected from the Cardiovascular Health Study, a community-based longitudinal investigation of older US adults. Thirty-five individual NEFAs were measured by gas chromatography. Cox regression was used to evaluate the association of individual NEFAs with incident AF. Results The study sample included 1872 participants (age 77.7+/-4.4). During median follow-up of 11.3 years, 715 cases of incident AF occurred. After concurrent adjustment of all NEFAs and full adjustment for potential confounders, higher serum concentration of nervonic acid (24:1 n-9), a long-chain monounsaturated fatty acid, was associated with higher risk of AF (HR per SD: 1.18, 95% CI 1.08 to 1.29; p<0.001). Conversely, higher serum concentration of gamma-linolenic acid (GLA) (18:3 n-6), a polyunsaturated n-6 fatty acid, was associated with lower risk of AF (HR per SD: 0.81, 95% CI 0.71 to 0.94; p=0.004). None of the remaining NEFAs was significantly associated with AF. Conclusions Among older adults, serum levels of non-esterified nervonic acid were positively associated, while serum levels of non-esterified GLA were inversely associated, with incident AF. If confirmed, these results could offer new strategies for AF prevention and early intervention in this segment of the population at highest risk.