Skip to main content

Advertisement

Log in

Elevated Serum and Cerebrospinal Fluid Free Fatty Acid Levels Are Associated with Unfavorable Functional Outcome in Subjects with Acute Ischemic Stroke

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The aim of this study was to evaluate the prognostic value of serum and cerebrospinal fluid (CSF) free fatty acid (FFA) levels in a cohort of patients with an acute ischemic stroke (AIS). In a prospective study, FFA levels were measured using an enzyme cycling method on admission in serum and CSF of 252 consecutive patients with AIS. The prognostic value of FFA to predict the functional outcome and mortality within 90-day was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Serum and CSF levels of FFA increased with increasing severity of stroke as defined by the NIHSS score (all P < 0.001). Patients with an unfavorable outcomes and non-survivors had significantly increased FFA serum and CSF levels on admission (all P < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that serum FFA ≥0.71 mmol/L (third quarters) was an independent predictor of functional outcome (odds ratios (OR) = 4.86; 95 % confidence interval (CI) 2.26–10.48) and mortality (OR = 7.72; 95 % CI 3.01–21.48). The area under the receiver operating characteristic curve of serum FFA was 0.79 (95 % CI, 0.72–0.86) for functional outcome and 0.86 (95 % CI, 0.78–0.94) for mortality. Similarly, CSF FFA level also was an indicator for predicting of functional outcome and mortality. FFA levels in serum and CSF may serve as independent biomarkers in addition of the traditional methods for assessing the functional outcome and mortality of AIS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Ebbert JO, Jensen MD (2013) Fat depots, free fatty acids, and dyslipidemia. Nutrients 5:498–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Jump DB (2011) Fatty acid regulation of hepatic lipid metabolism. Curr Opin Clin Nutr Metab Care 14(2):115–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Stefan N, Häring HU (2013) Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans. Nat Med 19(4):394–395

    Article  CAS  PubMed  Google Scholar 

  4. Reaven G (2012) Insulin resistance and coronary heart disease in nondiabetic individuals. Arterioscler Thromb Vasc Biol 32(8):1754–1759

    Article  CAS  PubMed  Google Scholar 

  5. de Oliveira OMC, Nettleton JA, Lemaitre RN et al (2013) Biomarkers of dairy fatty acids and risk of cardiovascular disease in the multi‐ethnic study of atherosclerosis. J Am Heart Assoc 2(4):e000092

    Google Scholar 

  6. Yaemsiri S, Sen S, Tinker LF et al (2013) Serum fatty acids and incidence of ischemic stroke among postmenopausal women. Stroke 44(10):2710–2717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yamagishi K, Folsom AR, Steffen LM et al (2013) Plasma fatty acid composition and incident ischemic stroke in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Cerebrovasc Dis 36(1):38–46

    Article  CAS  PubMed  Google Scholar 

  8. Khawaja O, Maziarz M, Biggs ML et al (2014) Plasma free fatty acids and risk of stroke in the Cardiovascular Health Study. Int J Stroke 9(7):917–920

    Article  PubMed  PubMed Central  Google Scholar 

  9. Nakamura S, Takamura T, Matsuzawa-Nagata N et al (2009) Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. J Biol Chem 284(22):14809–14818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gasparovic C, Rosenberg GA, Wallace JA et al (2001) Magnetic resonance lipid signals in rat brain after experimental stroke correlate with neutral lipid accumulation. Neurosci Lett 301(2):87–90

    Article  CAS  PubMed  Google Scholar 

  11. Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke 24:35–41

    Article  PubMed  Google Scholar 

  12. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C (1991) Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 337:1521–1526

    Article  CAS  PubMed  Google Scholar 

  13. Sims JR, Gharai LR, Schaefer PW, Vangel M, Rosenthal ES (2009) ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology 72:2104–2110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsanl WG et al (1989) Measurements of acute cerebral infarction: a clinical examination scale. Stroke 20:864–870

    Article  CAS  PubMed  Google Scholar 

  15. Bonita RBR (1988) Modification of Rankin Scale: recovery of motor function after stroke. Stroke 19:1497–1500

    Article  CAS  PubMed  Google Scholar 

  16. Tso AWK, Lam TKY, Xu A et al (2011) Serum adipocyte fatty acid–binding protein associated with ischemic stroke and early death. Neurology 76(23):1968–1975

    Article  CAS  PubMed  Google Scholar 

  17. Carlsson M, Wessman Y, Almgren P et al (2000) High levels of nonesterified fatty acids are associated with increased familial risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 20(6):1588–1594

    Article  CAS  PubMed  Google Scholar 

  18. Pilz S, Scharnagl H, Tiran B et al (2006) Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease. J Clin Endocrinol Metab 91(7):2542–2547

    Article  CAS  PubMed  Google Scholar 

  19. Wei XJ, Han M, Wei GC et al (2015) Prognostic value of cerebrospinal fluid free fatty acid levels in patients with acute ischemic stroke. Front Hum Neurosci 9:402

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pilitsis JG, Coplin WM, O’Regan MH et al (2003) Measurement of free fatty acids in cerebrospinal fluid from patients with hemorrhagic and ischemic stroke. Brain Res 985(2):198–201

    Article  CAS  PubMed  Google Scholar 

  21. Choi JY, Kim JS, Kim JH et al (2014) High free fatty acid level is associated with recurrent stroke in cardioembolic stroke patients. Neurology 82(13):1142–1148

    Article  CAS  PubMed  Google Scholar 

  22. Sun GJ, Ding SC, Ling WY et al (2015) Cerebrospinal fluid free fatty acid levels are associated with stroke subtypes and severity in Chinese patients with acute ischemic stroke. World Neurosurg 84:1299–1304

    Article  PubMed  Google Scholar 

  23. Fretts AM, Mozaffarian D, Siscovick DS et al (2014) Plasma phospholipid saturated fatty acids and incident atrial fibrillation: the Cardiovascular Health Study. J Am Heart Assoc 3(3):e000889

    Article  PubMed  PubMed Central  Google Scholar 

  24. Seo WK, Kim J, Kim YH et al (2011) Elevated free fatty acid is associated with cardioembolic stroke subtype. Can J Neurol Sci 38(06):874–879

    Article  PubMed  Google Scholar 

  25. Connor WE, Hoak JC, Warner ED (1963) Massive thrombosis produced by fatty acid infusion. J Clin Invest 42:860–866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Didisheim P, Mibashan RS (1963) Activation of Hageman factor (factor XII) by long-chain saturated fatty acids. Thromb Diath Haemorrh 143:346–353

    CAS  PubMed  Google Scholar 

  27. Gupta S, Knight AG, Gupta S et al (2012) Saturated long‐chain fatty acids activate inflammatory signaling in astrocytes. J Neurochem 120(6):1060–1071

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the subject of Sichuan Province Health Department (150077), the subject of Luzhou Medical College (2013ZRQN082), and the subject of the affiliated hospital (14020). We also express our gratitude to all the patients who participated in this study and thereby made this work possible.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiao-Xia Duan.

Ethics declarations

Conflict of Interest

On behalf of all authors, the corresponding author (Duan XX) states that there is no conflict of interest.

Research Involving Human Participants

This study was approved by the Institutional Review Board of the Affiliated Hospital of Luzhou Medical College.

Informed Consent

Informed written consent was obtained from each patient, family, or legal guardian.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Duan, XX., Zhang, GP., Wang, XB. et al. Elevated Serum and Cerebrospinal Fluid Free Fatty Acid Levels Are Associated with Unfavorable Functional Outcome in Subjects with Acute Ischemic Stroke. Mol Neurobiol 54, 1677–1683 (2017). https://doi.org/10.1007/s12035-016-9756-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-016-9756-y

Keywords

Navigation