Serum Levels of Adipocyte Fatty Acid–Binding Protein are Independently Associated with Left Ventricular Mass and Myocardial Performance Index in Obstructive Sleep Apnea Syndrome
Restricted accessResearch articleFirst published online October, 2012
Serum Levels of Adipocyte Fatty Acid–Binding Protein are Independently Associated with Left Ventricular Mass and Myocardial Performance Index in Obstructive Sleep Apnea Syndrome
To investigate the cross-sectional association between serum adipocyte fatty acid–binding protein (A-FABP) level and diagnosis or severity of obstructive sleep apnea syndrome (OSAS) and some echocardiographic indices related with cardiac dysfunction.
Methods
In this study, plasma A-FABP and high-sensitivity C-reactive protein concentrations were measured, and echocardiography was performed in subjects without any cardiac or pulmonary disease who were referred for evaluation of OSAS. According to the apnea-hypopnea index (AHI), subjects were classified into 3 groups: control group (AHI <5; n = 33), mild to moderate OSAS (30 > AHI ≥ 5; n = 30), and severe OSAS (AHI ≥ 30; n = 31).
Results
Levels of A-FABP were significantly different between the groups (P < 0.001). After post hoc analyses, all 3 groups were also significantly different from each other. The levels of A-FABP were significantly higher in the patients with severe OSAS (36.4 ± 13.0 ng/mL) than in the control subjects (9.3 ± 4.6 ng/mL; P < 0.0001) or in patients with mild-moderate OSAS (24.5 ± 10.5 ng/mL; P < 0.001). Patients with myocardial performance index (MPI) greater than 0.47 had higher serum A-FABP levels than those with MPI of less than 0.47 (31.8 ± 13.2 ng/mL vs 10.9 ± 6.3 ng/mL; P = 0.001). Multivariable regression analyses revealed that increased serum A-FABP concentrations were independently associated with increased left ventricular mass index (β = 0.195; P = 0.033) and increased MPI (β = 0.165; P = 0.015).
Conclusions
Increased A-FABP levels were found in the patients with OSAS, which were correlated significantly with left ventricular mass index and MPI. Further prospective studies are needed to clarify whether increased serum A-FABP level is a marker or a potential mechanism for left ventricular involvement in patients with OSAS.
SteiropoulosP, KotsianidisI, NenaE. Long-term effect of continuous positive airway pressure therapy on inflammation markers of patients with obstructive sleep apnea syndrome. Sleep. 2009; 32: 537–543.
4.
Bravo MdeL, SerperoLD, BarcelóA. Inflammatory proteins in patients with obstructive sleep apnea with and without daytime sleepiness. Sleep Breath. 2007; 11: 177–185.
5.
YokoeT, MinoguchiK, MatsuoH. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation. 2003; 107: 1129–1134.
6.
HertzelAV, BernlohrDA.The mammalian fatty acid-binding protein multigene family: molecular and genetic insights into function. Trends Endocrinol Metab. 2000; 11: 175–180.
7.
BoordJB, FazioS, LintonMF.Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis. Curr Opin Lipidol. 2002; 13: 141–147.
8.
BoordJB, MaedaK, MakowskiL. Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice. Circulation. 2004; 110: 1492–1498.
9.
XuA, WangY, XuJY. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem. 2006; 52: 405–413.
10.
XuA, TsoAW, CheungBM. Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation. 2007; 115: 1537–1543.
11.
TsoAW, XuA, ShamPC. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort. Diabetes Care. 2007; 30: 2667–2672.
12.
MakowskiL, BoordJB, MaedaK. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med. 2001; 7: 699–705.
13.
YooHJ, KimS, ParkMS. Serum adipocyte fatty acid-binding protein is associated independently with vascular inflammation: analysis with (18)F-fluorodeoxyglucose positron emission tomography. J Clin Endocrinol Metab. 2011; 963: 488–492.
14.
LamDC, XuA, LamKS. Serum adipocyte-fatty acid binding protein level is elevated in severe OSA and correlates with insulin resistance. Eur Respir J. 2009; 33: 346–351.
15.
Lamounier-ZepterV, LookC, AlvarezJ. Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease. Circ Res. 2009; 105: 326–334.
16.
XuA, VanhouttePM.Adiponectin and adipocyte fatty acid binding protein in the pathogenesis of cardiovascular disease. Am J Physiol Heart Circ Physiol. 2012; 302: H1231–H1240.
17.
MallampatiSR, GattSP, GuginoLD. A clinical sign to predict difficult tracheal intubation: a prospective study. Can Anaesth Soc J. 1985; 32: 429–434.
18.
SongMK, HaJH, RyuSH. The effect of aging and severity of sleep apnea on heart rate variability indices in obstructive sleep apnea syndrome. Psychiatry Investig. 2012; 9: 65–72.
19.
OzkanY, FiratH, SimşekB. Circulating nitric oxide (NO), asymmetric dimethylarginine (ADMA), homocysteine, and oxidative status in obstructive sleep apnea-hypopnea syndrome (OSAHS). Sleep Breath. 2008; 12: 149–154.
20.
SchillerNB, ShahPM, CrawfordM. American Society of Echocardiography Committee on standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms, Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr. 1989; 2: 358–367.
21.
ReichekN, DevereuxRB.Left ventricular hypertrophy: relationship of anatomic, echocardiographic and electrocardiographic findings. Circulation. 1981; 65: 99–108.
22.
TeiC.New non-invasive index for combined systolic and diastolic ventricular function. J Cardiol. 1995; 26: 135–136.
23.
BruchC, SchmermundA, MarinD. Tei-index in patients with mild-to-moderate congestive heart failure. Eur Heart J. 2000; 21: 1888–1895.
24.
LeungRS, BradleyTD.Sleep apnea and cardiovascular disease. Am J Respir Crit Care Med. 2001; 164: 2147–2165.
25.
PhillipsB.Sleep-disordered breathing and cardiovascular disease. Sleep Med Rev. 2005; 9: 131–140.
26.
MarinJM, CarrizoSJ, VicenteE. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005; 365: 1046–1053.
27.
GozalD, KheirandishL.Oxidant stress and inflammation in the snoring child: confluent pathways to upper airway pathogenesis and end-organ morbidity. Sleep Med Rev. 2006; 10: 83–96.
28.
ShamsuzzamanAS, GershBJ, SomersVK.Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA. 2003; 290: 1906–1914.
29.
RyanS, TaylorCT, McNicholasWT.Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation. 2005; 112: 2660–2667.
30.
UysalKT, SchejaL, WiesbrockSM. Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology. 2000; 141: 3388–3396.
31.
FuY, LuoN, Lopes-VirellaMF.Oxidized LDL induces the expression of ALBP/aP2 mRNA and protein in humanTHP-1 macrophages. J Lipid Res. 2000; 41: 2017–2023.
32.
KazemiMR, McDonaldCM, ShigenagaJK. Adipocyte fatty acid-binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists. Arterioscler Thromb Vasc Biol. 2005; 25: 1220–1224.
33.
HuiX, LiH, ZhouZ. Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH2-terminal kinases and activator protein-1. J Biol Chem. 2010; 285: 10273–10280.
34.
AcıoğluE, YiğitO, VolkanSunter A. Obesity and obstructive sleep apnea syndrome. J Otolaryngol Head Neck Surg. 2010; 39: 744–751.
35.
ShivalkarB, Van de HeyningC, KerremansM. Obstructive sleep apnea syndrome: more insights on structural and functional cardiac alterations, and the effects of treatment with continuous positive airway pressure. J Am Coll Cardiol. 2006; 47: 1433–1439.
36.
Akar BayramN, CiftciB, DurmazT. Effects of continuous positive airway pressure therapy on left ventricular function assessed by tissue Doppler imaging in patients with obstructive sleep apnoea syndrome. Eur J Echocardiogr. 2009; 10: 376–382.
37.
DursunogluD, DursunogluN, EvrengulH. Impact of obstructive sleep apnoea on left ventricular mass and global function. Eur Respir J. 2005; 26: 283–288.
38.
MakowskiL, BrittinghamKC, ReynoldsJM. The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor γ and IκB kinase activities. J Biol Chem. 2005; 280: 12888–12895.
39.
MiyoshiT, DoiM, HirohataS. Olmesartan reduces arterial stiffness and serum adipocyte fatty acid-binding protein in hypertensive patients. Heart Vessels. 2011; 26: 408–413.
ImagawaS, YamaguchiY, HiguchiM. Levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apneahypopnea syndrome. Blood. 2001; 98: 1255–1257.
42.
SchulzR, HummelC, HeinemannS. Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia. Am J Respir Crit Care Med. 2002; 165: 67–70.
43.
MatsuiH, IharaY, FujioY. Induction of IL-6 by hypoxia is mediated by NF-kB and NF-IL-6 in cardiac myocyte. Cardiovasc Res. 1999; 42: 104–112.
44.
Biron-ShentalT, SchaiffWT, RatajczakCK. Hypoxia regulates the expression of fatty acid-binding proteins in primary term human trophoblasts. Am J Obstet Gynecol. 2007; 197: 516.
