title: Obstructive sleep apnea is associated with increased chemoreflex sensitivity in patients with metabolic syndrome.
abstract: OBJECTIVE
  Obstructive sleep apnea (OSA) is often observed in patients with metabolic syndrome (MetS). In addition, the association of MetS and OSA substantially increases sympathetic nerve activity. However, the mechanisms involved in sympathetic hyperactivation in patients with MetS + OSA remain to be clarified. We tested the hypothesis that chemoreflex sensitivity is heightened in patients with MetS and OSA.
  
  
  METHODS
  Prospective clinical study.
  
  
  METHODS
  Forty-six patients in whom MetS was newly diagnosed (ATP-III) were allocated into: (1) MetS + OSA (n = 24, 48 ± 1.8 yr); and (2) MetS - OSA (n = 22, 44 ± 1.7 yr). Eleven normal control subjects were also studied (C, 47 ± 2.3 yr).
  
  
  METHODS
  OSA was defined as an apnea-hypopnea index ≥ 15 events/hr (polysomnography). Muscle sympathetic nerve activity (MSNA) was measured by microneurography technique. Peripheral chemoreflex sensitivity was assessed by inhalation of 10% oxygen and 90% nitrogen (carbon dioxide titrated), and central chemoreflex sensitivity by 7% carbon dioxide and 93% oxygen.
  
  
  RESULTS
  Physical characteristics and MetS measures were similar between MetS + OSA and MetS - OSA. MSNA was higher in MetS + OSA patients compared with MetS - OSA and C (33 ± 1.3 versus 28 ± 1.2 and 18 ± 2.2 bursts/min, P < 0.05). Isocapnic hypoxia caused a greater increase in MSNA in MetS + OSA than MetS - OSA and C (P = 0.03). MSNA in response to hyperoxic hypercapnia was greater in MetS + OSA compared with C (P = 0.005). Further analysis showed a significant association between baseline MSNA and peripheral (P < 0.01) and central (P < 0.01) chemoreflex sensitivity. Min ventilation in response to hyperoxic hypercapnia was greater in MetS + OSA compared with C (P = 0.001).
  
  
  CONCLUSIONS
  OSA increases sympathetic peripheral and central chemoreflex response in patients with MetS, which seems to explain, at least in part, the increase in sympathetic nerve activity in these patients. In addition, OSA increases ventilatory central chemoreflex response in patients with MetS.
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil. ivani.trombetta@incor.usp.br
authors.forename: Ivani C
authors.initials: IC
authors.lastname: Trombetta
authors.forename: Cristiane
authors.initials: C
authors.lastname: Maki-Nunes
authors.forename: Edgar
authors.initials: E
authors.lastname: Toschi-Dias
authors.forename: Maria-Janieire N N
authors.initials: MJ
authors.lastname: Alves
authors.forename: Maria Urbana P B
authors.initials: MU
authors.lastname: Rondon
authors.forename: Felipe X
authors.initials: FX
authors.lastname: Cepeda
authors.forename: Luciano F
authors.initials: LF
authors.lastname: Drager
authors.forename: Ana Maria F W
authors.initials: AM
authors.lastname: Braga
authors.forename: Geraldo
authors.initials: G
authors.lastname: Lorenzi-Filho
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Negrao
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002245:Carbon Dioxide / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism; D008875:Middle Aged; D009584:Nitrogen / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D017286:Polysomnography / Q000379:methods; D011446:Prospective Studies; D012123:Pulmonary Ventilation; D012018:Reflex; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D002245:Carbon Dioxide; D009584:Nitrogen; D010100:Oxygen