Diet associated with exercise improves baroreflex control of sympathetic nerve activity in metabolic syndrome and sleep apnea patients.

PURPOSE: We tested the hypothesis that (i) diet associated with exercise would improve arterial baroreflex (ABR) control in metabolic syndrome (MetS) patients with and without obstructive sleep apnea (OSA) and (ii) the effects of this intervention would be more pronounced in patients with OSA. METHODS: Forty-six MetS patients without (noOSA) and with OSA (apnea-hypopnea index, AHI > 15 events/h) were allocated to no treatment (control, C) or hypocaloric diet (- 500 kcal/day) associated with exercise (40 min, bicycle exercise, 3 times/week) for 4 months (treatment, T), resulting in four groups: noOSA-C (n = 10), OSA-C (n = 12), noOSA-T (n = 13), and OSA-T (n = 11). Muscle sympathetic nerve activity (MSNA), beat-to-beat BP, and spontaneous arterial baroreflex function of MSNA (ABRMSNA, gain and time delay) were assessed at study entry and end. RESULTS: No significant changes occurred in C groups. In contrast, treatment in both patients with and without OSA led to a significant decrease in weight (P < 0.05) and the number of MetS factors (P = 0.03). AHI declined only in the OSA-T group (31 ± 5 to 17 ± 4 events/h, P < 0.05). Systolic BP decreased in both treatment groups, and diastolic BP decreased significantly only in the noOSA-T group. Treatment decreased MSNA in both groups. Compared with baseline, ABRMSNA gain increased in both OSA-T (13 ± 1 vs. 24 ± 2 a.u./mmHg, P = 0.01) and noOSA-T (27 ± 3 vs. 37 ± 3 a.u./mmHg, P = 0.03) groups. The time delay of ABRMSNA was reduced only in the OSA-T group (4.1 ± 0.2 s vs. 2.8 ± 0.3 s, P = 0.04). CONCLUSIONS: Diet associated with exercise improves baroreflex control of sympathetic nerve activity and MetS components in patients with MetS regardless of OSA.

Predictors of Obstructive Sleep Apnea in Consecutive Patients with Metabolic Syndrome.

BACKGROUND: Recent evidence suggests that obstructive sleep apnea (OSA) is common in patients with metabolic syndrome (MetS) and may contribute to metabolic deregulation, inflammation, and atherosclerosis in these patients. In clinical practice, however, OSA is frequently underdiagnosed. We sought to investigate the clinical predictors of OSA in patients with MetS. METHODS: We studied consecutive patients newly diagnosed with MetS (Adult Treatment Panel-III). All participants underwent clinical evaluation, standard polysomnography, and laboratory measurements. We performed a logistic regression model, including the following variables: gender, age >50 years, neck and waist circumferences, hypertension, diabetes, body mass index (BMI) >30 kg/m2, high risk for OSA by Berlin questionnaire, presence of excessive daytime somnolence (Epworth Sleepiness Scale), abnormal serum glucose, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. RESULTS: We studied 197 patients (60% men; age: 49 ± 10 years; BMI: 32.9 ± 5.1 kg/m2). OSA (defined by an apnea-hypopnea index ≥15 events per hour) was diagnosed in 117 patients [59%; 95% confidence interval (CI): 52-66]. In multivariate analysis, male gender [odds ratio (OR): 3.28; 95% CI: 1.68-6.41; P < 0.01], abnormal glucose levels (OR: 3.01; 95% CI: 1.50-6.03; P < 0.01), excessive daytime sleepiness (OR: 2.38; 95% CI: 1.13-5.04; P = 0.02), and high risk for OSA by Berlin questionnaire (OR: 4.33; 95% CI: 2.06-9.11; P < 0.001) were independently associated with OSA. CONCLUSIONS: Simple clinical and metabolic characteristics may help to improve the underdiagnosis of OSA in patients with MetS.

Diet and exercise improve chemoreflex sensitivity in patients with metabolic syndrome and obstructive sleep apnea.

OBJECTIVE: Chemoreflex hypersensitity was caused by obstructive sleep apnea (OSA) in patients with metabolic syndrome (MetS). This study tested the hypothesis that hypocaloric diet and exercise training (D+ET) would improve peripheral and central chemoreflex sensitivity in patients with MetS and OSA. METHODS: Patients were assigned to: (1) D+ET (n = 16) and (2) no intervention control (C, n = 8). Minute ventilation (VE, pre-calibrated pneumotachograph) and muscle sympathetic nerve activity (MSNA, microneurography) were evaluated during peripheral chemoreflex sensitivity by inhalation of 10% O2 and 90% N2 with CO2 titrated and central chemoreflex by 7% CO2 and 93% O2 for 3 min at study entry and after 4 months. RESULTS: Peak VO2 was increased by D+ET; body weight, waist circumference, glucose levels, systolic/diastolic blood pressure, and apnea-hypopnea index (AHI) (34 ± 5.1 vs. 18 ± 3.2 events/h, P = 0.04) were reduced by D+ET. MSNA was reduced by D+ET at rest and in response to hypoxia (8.6 ± 1.2 vs. 5.4 ± 0.6 bursts/min, P = 0.02), and VE in response to hypercapnia (14.8 ± 3.9 vs. 9.1 ± 1.2 l/min, P = 0.02). No changes were found in the C group. A positive correlation was found between AHI and MSNA absolute changes (R = 0.51, P = 0.01) and body weight and AHI absolute changes (R = 0.69, P < 0.001). CONCLUSIONS: Sympathetic peripheral and ventilatory central chemoreflex sensitivity was improved by D+ET in MetS+OSA patients, which may be associated with improvement in sleep pattern.

Obstructive Sleep Apnea Impairs Postexercise Sympathovagal Balance in Patients with Metabolic Syndrome.

STUDY OBJECTIVES: The attenuation of heart rate recovery after maximal exercise (ΔHRR) is independently impaired by obstructive sleep apnea (OSA) and metabolic syndrome (MetS). Therefore, we tested the hypotheses: (1) MetS + OSA restrains ΔHRR; and (2) Sympathetic hyperactivation is involved in this impairment. DESIGN: Cross-sectional study. PARTICIPANTS: We studied 60 outpatients in whom MetS had been newly diagnosed (ATP III), divided according to apnea-hypopnea index (AHI) ≥ 15 events/h in MetS + OSA (n = 30, 49 ± 1.7 y) and AHI < 15 events/h in MetS - OSA (n = 30, 46 ± 1.4 y). Normal age-matched healthy control subjects (C) without MetS and OSA were also enrolled (n = 16, 46 ± 1.7 y). INTERVENTIONS: Polysomnography, microneurography, cardiopulmonary exercise test. MEASUREMENTS AND RESULTS: We evaluated OSA (AHI - polysomnography), muscle sympathetic nerve activity (MSNA - microneurography) and cardiac autonomic activity (LF = low frequency, HF = high frequency, LF/HF = sympathovagal balance) based on spectral analysis of heart rate (HR) variability. ΔHRR was calculated (peak HR minus HR at first, second, and fourth minute of recovery) after cardiopulmonary exercise test. MetS + OSA had higher MSNA and LF, and lower HF than MetS - OSA and C. Similar impairment occurred in MetS - OSA versus C (interaction, P < 0.01). MetS + OSA had attenuated ΔHRR at first, second, and at fourth minute than did C, and attenuated ΔHRR at fourth minute than did MetS - OSA (interaction, P < 0.001). Compared with C, MetS - OSA had attenuated ΔHRR at second and fourth min (interaction, P < 0.001). Further analysis showed association of the ΔHRR (first, second, and fourth minute) and AHI, MSNA, LF and HF components (P < 0.05 for all associations). CONCLUSIONS: The attenuation of heart rate recovery after maximal exercise is impaired to a greater degree where metabolic syndrome (MetS) is associated with moderate to severe obstructive sleep apnea (OSA) than by MetS with no or mild or no OSA. This is at least partly explained by sympathetic hyperactivity.

Obstructive sleep apnea is associated with increased chemoreflex sensitivity in patients with metabolic syndrome.

STUDY OBJECTIVES: 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. DESIGN: Prospective clinical study. PARTICIPANTS: 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). MEASUREMENTS: 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). CONCLUSION: 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.

Time delay of baroreflex control and oscillatory pattern of sympathetic activity in patients with metabolic syndrome and obstructive sleep apnea.

The incidence and strength of muscle sympathetic nerve activity (MSNA) depend on the magnitude (gain) and latency (time delay) of the arterial baroreflex control (ABR). However, the impact of metabolic syndrome (MetS) and obstructive sleep apnea (OSA) on oscillatory pattern of MSNA and time delay of the ABR of sympathetic activity is unknown. We tested the hypothesis that MetS and OSA would impair the oscillatory pattern of MSNA and the time delay of the ABR of sympathetic activity. Forty-three patients with MetS were allocated into two groups according to the presence of OSA (MetS + OSA, n = 21; and MetS - OSA, n = 22). Twelve aged-paired healthy controls (C) were also studied. OSA (apnea-hypopnea index > 15 events/h) was diagnosed by polysomnography. We recorded MSNA (microneurography), blood pressure (beat-to-beat basis), and heart rate (EKG). Oscillatory pattern of MSNA was evaluated by autoregressive spectral analysis and the ABR of MSNA (ABRMSNA, sensitivity and time delay) by bivariate autoregressive analysis. Patients with MetS + OSA had decreased oscillatory pattern of MSNA compared with MetS - OSA (P < 0.01) and C (P < 0.001). The sensitivity of the ABRMSNA was lower and the time delay was greater in MetS + OSA compared with MetS - OSA (P < 0.001 and P < 0.01, respectively) and C (P < 0.001 and P < 0.001, respectively). Patients with MetS - OSA showed decreased oscillatory pattern of MSNA compared with C (P < 0.01). The sensitivity of the ABRMSNA was lower in MetS - OSA than in C group (P < 0.001). In conclusion, MetS decreases the oscillatory pattern of MSNA and the magnitude of the ABRMSNA. OSA exacerbates these autonomic dysfunctions and further increases the time delay of the baroreflex response of MSNA.

Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.

Consequences of comorbid sleep apnea in the metabolic syndrome--implications for cardiovascular risk.

STUDY OBJECTIVES: Metabolic syndrome (MetSyn) increases overall cardiovascular risk. MetSyn is also strongly associated with obstructive sleep apnea (OSA), and these 2 conditions share similar comorbidities. Whether OSA increases cardiovascular risk in patients with the MetSyn has not been investigated. We examined how the presence of OSA in patients with MetSyn affected hemodynamic and autonomic variables associated with poor cardiovascular outcome. DESIGN: Prospective clinical study. PARTICIPANTS: We studied 36 patients with MetSyn (ATP-III) divided into 2 groups matched for age and sex: (1) MetSyn+OSA (n = 18) and (2) MetSyn-OSA (n = 18). MEASUREMENTS: OSA was defined by an apnea-hypopnea index (AHI) > 15 events/hour by polysomnography. We recorded muscle sympathetic nerve activity (MSNA - microneurography), heart rate (HR), and blood pressure (BP - Finapres). Baroreflex sensitivity (BRS) was analyzed by spontaneous BP and HR fluctuations. RESULTS: MSNA (34 +/- 2 vs 28 +/- 1 bursts/min, P = 0.02) and mean BP (111 +/- 3 vs. 99 +/- 2 mm Hg, P = 0.003) were higher in patients with MetSyn+OSA versus patients with MetSyn-OSA. Patients with MetSyn+OSA had lower spontaneous BRS for increases (7.6 +/- 0.6 vs 12.2 +/- 1.2 msec/mm Hg, P = 0.003) and decreases (7.2 +/- 0.6 vs 11.9 +/- 1.6 msec/mm Hg, P = 0.01) in BP. MSNAwas correlated with AHI (r = 0.48; P = 0.009) and minimum nocturnal oxygen saturation (r = -0.38, P = 0.04). CONCLUSION: Patients with MetSyn and comorbid OSA have higher BP, higher sympathetic drive, and diminished BRS, compared with patients with MetSyn without OSA. These adverse cardiovascular and autonomic consequences of OSA may be associated with poorer outcomes in these patients. Moreover, increased BP and sympathetic drive in patients with MetSyn+OSA may be linked, in part, to impairment of baroreflex gain.

The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome.

BACKGROUND: Obstructive Sleep Apnea (OSA) is tightly linked to some components of Metabolic Syndrome (MetS). However, most of the evidence evaluated individual components of the MetS or patients with a diagnosis of OSA that were referred for sleep studies due to sleep complaints. Therefore, it is not clear whether OSA exacerbates the metabolic abnormalities in a representative sample of patients with MetS. METHODOLOGY/PRINCIPAL FINDINGS: We studied 152 consecutive patients (age 48+/-9 years, body mass index 32.3+/-3.4 Kg/m2) newly diagnosed with MetS (Adult Treatment Panel III). All participants underwent standard polysomnography irrespective of sleep complaints, and laboratory measurements (glucose, lipid profile, uric acid and C-reactive protein). The prevalence of OSA (apnea-hypopnea index>or=15 events per hour of sleep) was 60.5%. Patients with OSA exhibited significantly higher levels of blood pressure, glucose, triglycerides, cholesterol, LDL, cholesterol/HDL ratio, triglycerides/HDL ratio, uric acid and C-reactive protein than patients without OSA. OSA was independently associated with 2 MetS criteria: triglycerides: OR: 3.26 (1.47-7.21) and glucose: OR: 2.31 (1.12-4.80). OSA was also independently associated with increased cholesterol/HDL ratio: OR: 2.38 (1.08-5.24), uric acid: OR: 4.19 (1.70-10.35) and C-reactive protein: OR: 6.10 (2.64-14.11). Indices of sleep apnea severity, apnea-hypopnea index and minimum oxygen saturation, were independently associated with increased levels of triglycerides, glucose as well as cholesterol/HDL ratio, uric acid and C-reactive protein. Excessive daytime sleepiness had no effect on the metabolic and inflammatory parameters. CONCLUSIONS/SIGNIFICANCE: Unrecognized OSA is common in consecutive patients with MetS. OSA may contribute to metabolic dysregulation and systemic inflammation in patients with MetS, regardless of symptoms of daytime sleepiness.

The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome.

OBJECTIVE: Metabolic syndrome (MS) is associated with subclinical atherosclerosis, but the relative role of obstructive sleep apnoea (OSA) is largely unknown. The main objective of this study is to determine the impact of OSA on markers of atherosclerosis in patients with MS. METHODS: Eighty-one consecutive patients with MS according to the Adult Treatment Panel III underwent a clinical evaluation, polysomnography, laboratory and vascular measurements of carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV) and carotid diameter (CD) in a blind fashion. OSA was defined as an apnoea-hypopnoea index (AHI) > or =15 events/hour. Multiple linear regression was performed to determine the variables that were independently associated with the vascular parameters. RESULTS: Fifty-one patients (63%) had OSA. No significant differences existed in age, sex, MS criteria, and cholesterol levels between patients with (MS+OSA) and without OSA (MS-OSA). Compared with MS-OSA patients, MS+OSA patients had higher levels of IMT (661+/-117 vs. 767+/-140 microm), PWV (9.6+/-1.0 vs. 10.6+/-1.6m/s), and CD (6705+/-744 vs. 7811+/-862 microm) (P<0.001 for each comparison). Among patients with MS+OSA, all vascular parameters were similar in patients with and without daytime sleepiness. The independent parameters associated with IMT, PWV, and CD were AHI, abdominal circumference, and systolic blood pressure (R(2)=0.42); AHI and systolic blood pressure (R(2)=0.38); and AHI, age, abdominal circumference and systolic blood pressure (R(2)=0.45), respectively. The R(2) of AHI for IMT, PWV and CD was 0.12, 0.10 and 0.20, respectively. CONCLUSIONS: OSA is very common and has an incremental role in atherosclerotic burden in consecutive patients with MS.