Biological Trace Element Research

, Volume 143, Issue 3, pp 1289–1301

Continuous Positive Airway Pressure Therapy Reduces Oxidative Stress Markers and Blood Pressure in Sleep Apnea–Hypopnea Syndrome Patients

Authors

    • Laboratorio de Investigaciones Biomédicas, Fundación IMABISHospital Clínico Universitario Virgen de la Victoria
  • Regina García-Delgado
    • Servicio de HematologíaHospital Clínico Universitario Virgen de la Victoria
  • José Alcázar-Ramírez
    • Servicio de NeumologíaHospital Clínico Universitario Virgen de la Victoria
  • Luis Fernández de Rota
    • Servicio de NeumologíaHospital Clínico Universitario Virgen de la Victoria
  • Ana Fernández-Ramos
    • Servicio de HematologíaHospital Clínico Universitario Virgen de la Victoria
  • Fernando Cardona
    • Laboratorio de Investigaciones Biomédicas, Fundación IMABISHospital Clínico Universitario Virgen de la Victoria
    • Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBER CB06/003)Instituto de Salud Carlos III
  • Francisco J. Tinahones
    • Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBER CB06/003)Instituto de Salud Carlos III
    • Servicio de Endocrinología y NutriciónHospital Clínico Universitario Virgen de la Victoria
Article

DOI: 10.1007/s12011-011-8969-1

Cite this article as:
Murri, M., García-Delgado, R., Alcázar-Ramírez, J. et al. Biol Trace Elem Res (2011) 143: 1289. doi:10.1007/s12011-011-8969-1

Abstract

Sleep apnea–hypopnea syndrome (SAHS) is characterized by recurrent episodes of hypoxia/reoxygenation, which seems to promote oxidative stress. SAHS patients experience increases in hypertension, obesity and insulin resistance (IR). The purpose was to evaluate in SAHS patients the effects of 1 month of treatment with continuous positive airway pressure (CPAP) on oxidative stress and the association between oxidative stress and insulin resistance and blood pressure (BP). Twenty-six SAHS patients requiring CPAP were enrolled. Measurements were recorded before and 1 month after treatment. Cellular oxidative stress parameters were notably decreased after CPAP. Intracellular glutathione and mitochondrial membrane potential increased significantly. Also, total antioxidant capacity and most of the plasma antioxidant activities increased significantly. Significant decreases were seen in BP. Negative correlations were observed between SAHS severity and markers of protection against oxidative stress. BP correlated with oxidative stress markers. In conclusion, we observed an obvious improvement in oxidative stress and found that it was accompanied by an evident decrease in BP with no modification in IR. Consequently, we believe that the decrease in oxidative stress after 1 month of CPAP treatment in these patients is not contributing much to IR genesis, though it could be related to the hypertension etiology.

Keywords

Continuous positive airway pressureHypertensionInsulin resistanceOxidative stressSleep apnea–hypopnea syndrome

Introduction

The sleep apnea–hypopnea syndrome (SAHS) is characterized by recurrent episodes of airflow limitation in the upper airway during sleep. These episodes induce a decrease in oxyhaemoglobin saturation and frequent micro-awakenings that lead to a restless sleep, excessive daytime sleepiness, and cardiovascular, respiratory and neuropsychiatric disorders. Consequently, SAHS has been considered an independent risk factor for hypertension [1]. However, the mechanisms underlying these disorders in SAHS patients are not completely understood.

During the phenomenon of hypoxia/reoxygenation that occurs in SAHS patients, the generation of reactive oxygen species (ROS) is increased, leading to mitochondrial dysfunction [2]. These alterations activate inflammatory transcription factors that are involved in the regulation of inflammatory cytokines and adhesion molecules. ROS production can occur via an activated inflammatory response induced by hypoxia [3], as well as by an increased sympathetic tone and elevated catecholamine production [4].

It is well known that ROS overproduction may induce oxidation and functional alterations in a variety of biological molecules. These alterations can be normalized by antioxidant systems [5], which neutralize the oxidative burst in order to maintain cell redox balance. Redox imbalance induces activation of signaling pathways, altering cell functions, and leading to a variety of diseases [6], depending on the cell and tissue types involved and the site of production of ROS.

Insulin resistance (IR) has been reported to be increased in SAHS patients [7], though the causative mechanisms are not clear. Possible reasons include various SAHS parameters [8], the degree of obesity [9], and also the presence of increased sympathetic drive. Some authors have suggested that many factors leading to IR are mediated via the generation of abnormal amounts of ROS [10].

The standard therapy for SAHS is continuous positive airway pressure (CPAP) [11]. Constant CPAP use improves quality of life and attenuates daytime sleepiness. Some authors have registered an improvement in hypertension and IR in patients with SAHS after CPAP treatment [12] while others have not [13].

In summary, SAHS seems to be associated with oxidative stress and an increased prevalence of cardiovascular and metabolic diseases, including hypertension and insulin resistance. The purpose of the present study was to evaluate in SAHS patients the effects of 1 month of treatment with CPAP on oxidative stress parameters, and the association between oxidative stress and IR or blood pressure.

Methods

Ethics Statement

The study was approved by the Ethics Committee of the Virgen de la Victoria Hospital, and all the participants provided signed consent after being fully informed of its goal and characteristics.

Study Subjects

The study included 26 men with SAHS who required nasal CPAP, according to established criteria [14]. Diabetic patients who required insulin were excluded, as were patients who failed to complete 1 month of treatment or whose weight changed by more than 1.5 kg during the study.

Sixteen healthy men, blood donors, were recruited as a control group. They had no personal or family history of cardiovascular disease, dyslipidaemia or diabetes. In these subjects, the diagnosis of SAHS was excluded by overnight polysomnography (Alice5; Respironics).

Study Design

The study design was a prospective observational study.

The subjects completed a structured interview to obtain the following data: age, medical history, and current diseases. The following data were also collected: weight, height, waist and neck circumference, body mass index, and blood pressure (BP). The subjects also completed the Epworth Sleepiness Scale (ESS) questionnaire, for the evaluation of daytime sleepiness, before and 1 month after treatment.

Methods

Polysomnography

The diagnosis of SAHS was established by overnight polysomnography (Alice5; Respironics), which included continuous recording of oronasal flow, thoracoabdominal movements, electrocardiography, submental and pretibial electromyography, electrooculography, electroencephalography, and arterial oxygen saturation. Apnea was defined as the absence of airflow for more than 10 s. Hypopnea was defined as a 50% reduction in airflow for more than 10 s that resulted in arousal or oxyhaemoglobin desaturation. The oxygen desaturation index (ODI) was defined as the number of oxygen desaturation = 4%/h. The apnea–hypopnea index (AHI) was defined as the sum of the numbers of apneas and hypopneas per hour of sleep. SAHS was defined as an AHI ≥ 10 and pathological daytime sleepiness (ESS > 10 points [14]), as defined by the Spanish Consensus Document [15] in accordance with the recommendations of the American Academy of Sleep Medicine [16]. T90 was defined as the percentage of time during which arterial oxygen saturation was less than 90%.

Measurements

The BP was measured two times with the subject seated and an interval of 5 min between measurements at 7:20 am. BP measurements were taken on the right arm, which was relaxed and supported by a table, at an angle of 45° from the trunk (ELKA aneroid manometric sphygmomanometer, Von Schlieben Co., Manheim, Germany).

Fasting venous blood samples were drawn at 7:30 am, before and 1 month after CPAP treatment. Samples were collected in vacutainers with and without ethylenediaminetetraacetic acid and placed on ice. Samples were centrifuged at 4,000 rpm for 15 min at 4°C. Plasma and serum were aliquoted and stored at −80°C until analysis.

Biochemical variables studied included glucose, uric acid, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and Hb1Ac.

The insulin was analyzed by an immunoradiometric assay (BioSource International, Camarillo, CA) in a Beckman Coulter (Fullerton, CA), showing a 0.3% crossreaction with proinsulin. The intra- and inter-assay CV was 1.9% and 6.3%, respectively. The homeostatic model assessment was used to determine IR (HOMA-IR) and beta-cell function (HOMA-beta) [17].

Serum leptin levels were measured using a human leptin enzyme-linked immunosorbent assay (ELISA) kit from Mediagnost (Reutlingen, Germany). The intra- and inter-assay coefficients of variation were 2.6% and 4.7%.

Serum adiponectin levels were measured using a human adiponectin ELISA kit from DRG diagnostics (Marburg, Germany). The intra- and inter-assay coefficients of variation were 3.4% and 7.8%.

Serum high sensitivity C-reactive protein (hs-CRP) levels were measured using a human hs-CRP ELISA kit from BLK Diagnostics (Badalona, Spain). The intra- and inter-assay coefficients of variation were 4.7% and 7.3%.

Determination of Plasma and Serum Oxidative Stress Biomarkers

Lipid peroxidation levels were measured in serum using a commercial kit (Cayman Chemical, Ann Arbor, MI).

Total antioxidant capacity (TAC) and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione s-transferase (GST), catalase, and superoxide dismutase (SOD) were measured in plasma with a commercial kit (Cayman Chemical, Ann Arbor, MI). The intra- and inter-assay coefficients of variation of TAC, GPx, GR, GST, catalase, and SOD were 3.4% and 3.0%; 5.7% and 7.2%; 3.7% and 9.3%; 4.1% and 7.9%; 3.8% and 8.9%; 3.2% and 3.7%, respectively.

Determination of White Blood Cell Oxidative Stress Biomarkers

Oxidative stress biomarkers were analyzed in white blood cells (WBCs) as total leukocytes, neutrophils, lymphocytes, and monocytes.

WBCs were isolated from patients by dextran sedimentation followed by density gradient centrifugation with Ficoll–Paque. After purification with two washing steps, 1 × 106cells/mL WBCs were analyzed on a dual-laser FACSCalibur (Becton Dickinson, Mountain View, CA). The test standardization, data acquisition and data analysis were performed using the CELL Quest software (Becton Dickinson). A forward and side scatter gate was used for the selection and analysis of the different cell subpopulations.
  1. a.

    Mitochondrial membrane potential (MMP)

     
WBCs were incubated with Rodamina-123 from Sigma-Aldrich (USA) dissolved in methanol, at a final concentration of 5 μM. After incubation at 37°C for 30 min in darkness with frequent agitation, the cells were washed and re-suspended in phosphate-buffered saline (PBS) and were analyzed on a dual-laser FACSCalibur.
  1. b.

    ROS and intracellular glutathione measurements

     

For the assessment of mitochondrial ROS generation, such as superoxide anion and hydrogen peroxide, cells were incubated with dihydroethidium × 5 mM stabilized solution in dimethyl sulphoxide (DMSO) from Molecular Probes (Eugene, OR, USA; final concentration, 4 μM) and 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate acetyl ester from Molecular Probes (Eugene, OR, USA) dissolved in DMSO at a final concentration 1 μg/μl, respectively, at 37°C for 30 min in darkness with frequent agitation. The cells were then washed and re-suspended in PBS and analyzed on a dual-laser FACSCalibur.

For detection of intracellular glutathione, WBCs were incubated with CellTracker™ Green 5-chloromethylfluorescein diacetate from Molecular Probes (Eugene, OR, USA), dissolved in DMSO at a final concentration 1 μM, for 30 min in darkness with frequent agitation. The labeled cells were washed and re-suspended in PBS and analyzed on a dual-laser FACSCalibur.

Statistical Analysis

The results are given as the mean ± standard deviation. All clinical parameters are summarized by descriptive statistics. Relationships between the results of the controls and the patients were analyzed using the Mann–Whitney U test. The Student t test for paired samples was used to compare oxidative stress and clinical parameters before and after treatment with CPAP. The Pearson’s correlation coefficient was calculated to estimate the linear correlations between variables. In all cases, the rejection level for a null hypothesis was α = 0.05 for two tails. The statistical analysis was done with SPSS (Version 15.0 for Windows; SPSS, Chicago, IL).

Results

The clinical variables of the study patients and controls are shown in Table 1.
Table 1

Distribution of clinical variables in the studied patient group

Variables

Controls (n = 16)

Patients (n = 26)

p

Age (years)

47.62 ± 7.40

52.15 ± 13.41

0.102

BMI (kg/m2)

30.56 ± 2.16

33.07 ± 5.61

0.517

Waist circumference (cm)

108.65 ± 7.13

114.65 ± 12.42

0.169

Neck circumference (cm)

42.40 ± 3.80

44.62 ± 4.31

0.102

AHI (events/h)

3.19 ± 0.73

55.41 ± 21.47

0.000

Mean SaO2 (%)

95. 75 ± 1.34

91.35 ± 3.40

0.000

ODI (desaturations/h)

2.88 ± 1.79

43.34 ± 29.06

0.000

T90 (%)

0

10.29 ± 13.08

0.000

ESS score

3.19 ± 1.22

14.07 ± 6.53

0.000

Values are presented as means ± SD

AHI apnea–hypopnea index, BMI body mass index, ESS Epworth sleepiness scale, ODI oxygen desaturation index, T90(%) percentage of time during which arterial oxygen saturation was less than 90%

Evaluation of plasma biomarkers of oxidative stress showed significant increases after CPAP treatment (p < 0.05) in TAC and catalase, SOD, GR, and GST activities (Table 2).
Table 2

Comparison of plasma oxidative stress markers

Variables

Controls (n = 16)

Patients (n = 26)

Before CPAP

After CPAP

Catalase (nmol−1 min−1 ml−1)

27.66 ± 12.11

25.22 ± 10.12

29.68 ± 10.57*

Superoxide dismutase (U/ml)

2.106 ± 0.562

1.633 ± 0.640***

1.439 ± 0.648*

Glutathione peroxidase (μmol−1 min−1 ml−1)

21.05 ± 5.09

19.59 ± 5.79

20.10 ± 6.32

Glutathione reductase (μmol−1 min−1 ml−1)

4.402 ± 1.922

3.018 ± 0.497

3.208 ± 0.559*

Glutathione transferase (μmol−1 min−1 ml−1)

2.632 ± 0.445

1.606 ± 0.534

2.105 ± 0.891**

Lipid hydroperoxide (μM)

10.37 ± 5.06

12.16 ± 3.80

11.70 ± 4.69

Total antioxidant capacity (mM)

6.237 ± 3.178

4.141 ± 1.361****

4.372 ± 1.476**

Values are presented as means ± SD. Relationships between plasma oxidative stress markers in control and in patients before CPAP were analyzed using the Mann–Whitney U test. Relationships between plasma oxidative stress markers in patients before and after CPAP were assessed using the Student’s t test

*p < 0.05; **p < 0.01, significant difference in the results found in patients between before and after treatment with CPAP; ***p < 0.05; ****p < 0.001, significant differences in the results found between controls and patients before treatment with CPAP

Analysis of oxidative stress biomarkers in WBCs showed a significant decrease after CPAP in the production of superoxide anion and hydrogen peroxide and significant increases after CPAP treatment in intracellular glutathione levels. These redox changes were accompanied by an increase in MMP (Fig. 1; Table 3).
https://static-content.springer.com/image/art%3A10.1007%2Fs12011-011-8969-1/MediaObjects/12011_2011_8969_Fig1_HTML.gif
Fig. 1

Differences between cellular oxidative stress biomarkers in total white blood cells (WBCs) before and after treatment with continuous positive airway pressure (CPAP) were analyzed on a dual-laser FACSCalibur. Green represents values before CPAP treatment; purple represents values after treatment. a Superoxide anion in total WBCs. b Hydrogen peroxide in total WBCs. c Intracellular glutathione in total WBCs. (d) Mitochondrial membrane potential of total WBCs

Table 3

Comparison of cellular oxidative stress markers

 

Controls (n = 16)

Patients (n = 26)

Before CPAP

After CPAP

Lymphocyte MMP(1)

21.99 ± 3.60

16.57 ± 4.53c

20.34 ± 4.68***

Monocyte MMP(1)

41.92 ± 7.01

32.20 ± 8.60c

39.33 ± 8.60***

Neutrophil MMP(1)

29.99 ± 6.79

27.21 ± 6.48c

23.05 ± 6.09*

Total leukocyte MMP(1)

32.25 ± 7.23

21.93 ± 6.05c

26.52 ± 7.02**

Lymphocyte hydrogen peroxide(1)

14.35 ± 3.14

20.47 ± 7.00b

15.39 ± 5.42***

Monocyte hydrogen peroxide(1)

24.87 ± 3.40

42.36 ± 16.33b

33.43 ± 15.59*

Neutrophil hydrogen peroxide(1)

21.83 ± 5.61

29.73 ± 14.23a

23.69 ± 13.22

Total leukocyte hydrogen peroxide(1)

22.07 ± 6.81

27.34 ± 11.20

21.88 ± 10.21*

Superoxide anion in lymphocytes(1)

13.15 ± 1.97

68.10 ± 39.68c

48.75 ± 30.85**

Superoxide anion in monocytes(1)

21.78 ± 3.71

139.13 ± 83.30c

105.44 ± 74.87*

Superoxide anion in neutrophils(1)

18.52 ± 2.92

91.93 ± 57.07c

70.40 ± 46.59*

Superoxide anion in total leukocytes(1)

17.93 ± 4.07

87.87 ± 51.26c

65.46 ± 41.17*

Lymphocyte intracellular glutathione(1)

173.45 ± 24.76

105.26 ± 60.23c

175.04 ± 86.66***

Monocyte intracellular glutathione(1)

478.75 ± 104.91

287.63 ± 155.00b

465.44 ± 181.26***

Neutrophil intracellular glutathione(1)

535.95 ± 90.90

252.11 ± 126.26 c

440.23 ± 163.57***

Total leukocyte intracellular glutathione(1)

343.50 ± 92.12

188.26 ± 96.34 c

306.02 ± 127.43***

Values are presented as means±SD. 1, Mean Fluorescence Intensity; MMP, mitochondrial membrane potential. Relationships between cellular oxidative stress markers in control and in patients before CPAP were analyzed using the Mann-Whitney U test. Relationships between cellular oxidative stress markers before and after CPAP were assessed Student’s t-test.

aP < 0.05; bP < 0.005; cP < 0.001: Significant differences in the results found between controls and patients before treatment with CPAP. *P < 0.05; **P < 0.01; ***P < 0.005: significant difference in the results found in patients between before and after treatment with CPAP.

Moreover, Tables 2 and 3 show differences between control group and patients. Plasma total antioxidant capacity and SOD activity, MMP and intracellular glutathione of WBC were significantly higher in the control group than in the SAHS patients. Whereas superoxide anion and hydrogen peroxide were significantly lower in the control group than in the SAHS patients.

Both SBP and DBP fell significantly after CPAP treatment. The ESS also decreased significantly after treatment. The other clinical and biological variables experienced no significant changes (Table 4).
Table 4

Distribution of biological variables in the studied patient group before and after CPAP treatment

Variables

Before CPAP

After CPAP

p

ESS

14.07 ± 6.53

9.56 ± 4.25

0.001

Systolic BP (mmHg)

150.26 ± 24.64

141.74 ± 22.99

0.014

Diastolic BP (mmHg)

91.30 ± 14.20

84.13 ±14.33

0.012

BMI (kg/m2)

33.07 ± 5.61

32.94 ± 5.29

0.783

Insulin (μUI/ml)

18.46 ± 8.09

19.11 ± 10.95

0.954

HOMA-IR

4.713 ± 2.367

4.472 ± 2.413

0.977

HOMA-IS

62.42 ± 31.77

59.90 ± 32.34

0.879

Leptin (ng/ml)

16.90 ± 10.86

18.02 ± 13.42

0.316

Adiponectin (ng/ml)

6.80 ± 2.94

6.86 ± 3.24

0.607

Triglyceride (mg/dl)

153.00 ± 130.87

164.27 ± 155.25

0.275

Cholesterol (mg/dl)

199.42 ± 45.70

195.38 ± 41.03

0.602

HDL cholesterol (mg/dl)

45.92 ± 11.51

46.38 ± 11.90

0.614

LDL cholesterol (mg/dl)

126.46 ± 35.63

123.27 ± 30.10

0.849

Values are presented as means ± SD. Relationships between biological variables before and after CPAP were assessed Student’s t test (p < 0.05)

BMI body mass index, BP blood pressure, ESS Epworth sleepiness scale

Statistically significant positive correlations were observed between plasma TAC and lymphocyte intracellular glutathione (r = 0.399; p < 0.05). Significant negative correlations were observed between GPx activity and cellular superoxide anion levels before treatment in neutrophils (r = −0.491; p < 0.02), total leukocytes (r = −0.460; p < 0.02), and monocytes (r = −0.526; p < 0.01). Also, there was a statistically significant negative correlation between plasma SOD activity and the hydrogen peroxide levels in neutrophils (r = −0.408; p < 0.05) and total leukocytes (r = −0.390; p < 0.05). Furthermore, there was a statistically significant negative correlation between plasma TAC and hydrogen peroxide levels in neutrophils (r = −0.492; p < 0.02), total leukocytes (r = −0.468; p < 0.02), and monocytes (r = −0.469; p < 0.02). After treatment with CPAP, there was a statistically significant positive correlation between plasma catalase activity and lymphocyte MMP (r = 0.398; p < 0.05).

SAHS severity, including AHI and ODI, correlated negatively with total antioxidant capacity and intracellular glutathione before treatment (Fig. 2). After CPAP, lymphocyte MMP correlated significantly with ESS (r = −0.453; p < 0.05).
https://static-content.springer.com/image/art%3A10.1007%2Fs12011-011-8969-1/MediaObjects/12011_2011_8969_Fig2_HTML.gif
Fig. 2

Correlations of sleep apnea–hypopnea syndrome severity parameters with markers of protection against oxidative stress before continuous positive airway pressure treatment were determined by Pearson’s correlation coefficient test (r). a Correlation of monocyte intracellular glutathione with apnea–hypopnea index (AHI). b Correlation of neutrophil intracellular glutathione with AHI. c Correlation of plasma total antioxidant capacity with AHI. d Correlation of plasma total antioxidant capacity with oxygen desaturation index (ODI)

Before CPAP, systolic and diastolic blood pressure correlated negatively with MMP. Also, systolic and diastolic blood pressure correlated positively with serum lipid hydroperoxide levels before CPAP (Fig. 3).
https://static-content.springer.com/image/art%3A10.1007%2Fs12011-011-8969-1/MediaObjects/12011_2011_8969_Fig3_HTML.gif
Fig. 3

Correlations of blood pressure (BP) with oxidative stress biomarkers were determined by Pearson’s correlation coefficient test (r). Correlation of lipid hydroperoxide levels with diastolic BP (a) and systolic BP (b). Correlation of total leukocyte mitochondrial membrane potential (MMP) with diastolic BP (c) and systolic BP (d). Correlation of monocyte MMP with diastolic BP (e) and systolic BP (f)

Discussion

Our results show that parameters of cellular oxidative stress were significantly lower in the control group than in the SAHS patients, while markers of protection against oxidative stress were significantly higher in the control group than in the SAHS patients. Also, we have found that parameters of oxidative stress showed a notably decrease after CPAP. Diastolic and systolic blood pressure also decreased significantly while IR did not improve significantly.

Oxidative stress is the consequence of an increase in the production of free radicals and ROS and/or a reduction in the antioxidant systems [18]. In the present study, oxidant production and antioxidant systems seem to be impaired in patients compared with the control group. After CPAP, we have found an increase in plasma levels of TAC, and catalase, SOD, GR, and GST activities. In addition, we have found an inverse correlation between plasma GPx levels and cellular ROS production. Plasma GPx is the main antioxidant enzyme in plasma and the extracellular space that redeems ROS. A deficiency of this enzyme increases extracellular oxidative stress. In hypoxic conditions, the expression of plasma GPx increases through the presence of hypoxia-inducible factor-1 [19]. Moreover, we have found a clear inverse relationship between plasma SOD and cellular ROS. Some disorders have been associated with high ROS production and reduced antioxidant activities [20]. The most significant changes in parameters of oxidative stress were found in WBCs. These parameters showed a notably decrease, whereas intracellular glutathione and MMP increased significantly. These results confirm that hypoxia normalization with CPAP treatment reduces oxidative stress. Moreover, we have found significant negative correlations between SAHS severity and markers of protection against oxidative stress, including intracellular glutathione and plasma total antioxidant capacity. In addition, ESS correlated negatively with lymphocyte MMP after CPAP. It seems that SAHS severity is contributing to impair the antioxidant system of these patients.

In our study, we have found a significant decrease in SBP and DBP after 1 month of treatment. Controversy surrounds the effect of nasal CPAP on blood pressure in SAHS patients. Some studies have found no significant changes in BP after CPAP in SAHS patients [21, 22]. Others [23] have demonstrated a significant reduction in BP in patients after CPAP. Additionally, Usui et al. [24] showed changes in both BP and sympathetic tone after 1 month of treatment. These discordant results suggest the existence of confounding factors such as IR [25]. In our study, the BP reduction was not accompanied by a decline in the IR. The benefit of CPAP treatment on BP therefore seems to be independent of IR modifications. Intermittent experimental hypoxia and clinical SAHS lead to an elevated sympathetic tone that persists throughout the day [26]. This elevation results in a high heart rate and elevated BP. Several studies have described the implication of oxidative stress in this process [27]. In accordance with this, our results show, on one hand, significant positive correlations between oxidative stress marker such as serum lipid peroxide and blood pressure, and on the other, significant negative correlations between marker of protection against oxidative stress such as MMP and blood pressure before CPAP.

The effects of CPAP on IR in SAHS patients remain unclear. While some studies show a tendency to improved insulin sensitivity or IR after CPAP [7, 12], other researchers were unable to confirm this result [13], as was also noted in our study. This disparity in results can be explained by the lack of control in anthropometric changes that occur after CPAP, because patients become more active and mass change may occur. Weight is a confounding variable in CPAP treatment and may produce changes in IR. In this study, anthropometric variables were rigorously controlled and those patients whose weight changed were excluded.

In conclusion, we observed an obvious improvement in oxidative stress and found that it was accompanied by an evident decrease in BP with no modification in IR. Consequently, we believe that the decrease in oxidative stress after 1 month of CPAP treatment in these patients is not contributing much to the genesis of IR, though it could be related to the etiology of the hypertension.

Acknowledgments

The authors thank Juan Alcaide (technician) for his technical support in developing our laboratory techniques. This work was supported in part by grants from the Andalusian Health Service (SAS PI-0326/2007) and the Spanish Ministry of Education and Science (SAF2006-12984). Murri is a recipient of a predoctoral Investigator Personal Formation grant (BES-2007-16594) from the Spanish Ministry of Education and Science, and Cardona is a recipient of CP07/0095 grant. The authors thank the Pneumology and Hematology service and the pneumology nursing staff of the Virgen de la Victoria Hospital, Málaga.

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© Springer Science+Business Media, LLC 2011