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Individual non-esterified fatty acids and incident atrial fibrillation late in life
  1. Cara N Pellegrini1,2,
  2. Petra Buzkova3,
  3. Alice H Lichtenstein4,
  4. Nirupa R Matthan4,
  5. Joachim H Ix5,
  6. David S Siscovick6,
  7. Susan R Heckbert7,
  8. Russell P Tracy8,
  9. Kenneth J Mukamal9,
  10. Luc Djoussé10,
  11. Jorge R Kizer1,2
  1. 1 Medical Service, San Francisco VA Medical Center, San Francisco, California, USA
  2. 2 Medicine, University of California San Francisco, San Francisco, California, USA
  3. 3 Biostatics, University of Washington, Seattle, Washington, USA
  4. 4 Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, Massachusetts, USA
  5. 5 Medicine, University of California San Diego, La Jolla, California, USA
  6. 6 Medicine and Epidemiology, New York Academy of Medicine, New York, New York, USA
  7. 7 Epidemiology, University of Washington, Seattle, Washington, USA
  8. 8 Pathology and Biochemistry, University of Vermont, Burlington, Vermont, USA
  9. 9 Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  10. 10 Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Cara N Pellegrini, San Francisco VA Medical Center, San Francisco, California, USA; cara.pellegrini{at}


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.

  • atrial fibrillation
  • epidemiology
  • metabolic syndrome

Data availability statement

Data are available upon reasonable request. Cardiovascular Health Study data are available upon request (

Statistics from

Data availability statement

Data are available upon reasonable request. Cardiovascular Health Study data are available upon request (

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  • Correction notice This article has been corrected since it first published. The provenance and peer review statement has been included.

  • Contributors Planning for this research was conducted by CP, AHL, JHI, DSS, RPT, KJM, LD and JRK. The project was conducted by CP, PB, AHL, NM, KJM, LD and JRK. All authors were involved in reporting the work. CP serves as guarantor.

  • Funding This research was supported by R01 AG053325 from the National Institute on Aging; by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083 and N01HC85086, and by grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging. JRK was supported by K24 HL135413 from the NHLBI. A full list of principal CHS investigators and institutions can be found at

  • Competing interests JRK discloses stock ownership in Bristol-Myers Squibb, Johnson & Johnson, Medtronic, Merck and Pfizer.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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