Obstructive sleep apnea (OSA) is associated with adverse cardiovascular outcomes, including myocardial infarction and stroke. Atherosclerosis is a key mechanism for these cardiovascular events. ...Recent cross-sectional studies showed the presence of early signs of atherosclerosis in patients with OSA who were free of comorbidities.
To determine the impact of treatment with continuous positive airway pressure (CPAP) on atherosclerosis.
We randomly assigned 24 patients with severe OSA (age, 46 +/- 6 yr) who were free of comorbidities to receive no treatment (control, n = 12) or CPAP (n = 12) for 4 months. Carotid intima-media thickness, arterial stiffness (evaluated by pulse-wave velocity), carotid diameter, 24-hour blood pressure monitoring, C-reactive protein, and catecholamines were determined at baseline and after 4 months.
At baseline, all measurements were similar in both groups and did not change in the control group after 4 months. In contrast, a significant decrease occurred in carotid intima-media thickness (707 +/- 105 vs. 645 +/- 95 microm, P = 0.04), pulse-wave velocity (10.4 +/- 1.0 vs. 9.3 +/- 0.9 m/s, P < 0.001), C-reactive protein (3.7 +/- 1.8 vs. 2.0 +/- 1.2 mg/L, P = 0.001), and catecholamines (365 +/- 125 vs. 205 +/- 51 ng/ml, P < 0.001) after 4 months of CPAP. Carotid diameter did not change significantly. Regarding the whole group, changes in carotid intima-media thickness were correlated with changes in catecholamines (r = 0.41, P < 0.05). Changes in pulse-wave velocity were correlated with changes in C-reactive protein (r = 0.58, P < 0.01) and catecholamines (r = 0.54, P < 0.01).
The treatment of OSA significantly improves early signs of atherosclerosis, supporting the concept that OSA is an independent risk factor for atherosclerosis. Clinical trial registered with www.clinicaltrials.gov (NCT 00400543).
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sleep deprivation is common in Western societies and is associated with increased cardiovascular morbidity and mortality in epidemiological studies. However, the effects of partial sleep deprivation ...on the cardiovascular system are poorly understood. In the present study, we evaluated 13 healthy male volunteers (age: 31 ± 2 yr) monitoring sleep diary and wrist actigraphy during their daily routine for 12 nights. The subjects were randomized and crossover to 5 nights of control sleep (>7 h) or 5 nights of partial sleep deprivation (<5 h), interposed by 2 nights of unrestricted sleep. At the end of control and partial sleep deprivation periods, heart rate variability (HRV), blood pressure variability (BPV), serum norepinephrine, and venous endothelial function (dorsal hand vein technique) were measured at rest in a supine position. The subjects slept 8.0 ± 0.5 and 4.5 ± 0.3 h during control and partial sleep deprivation periods, respectively (P < 0.01). Compared with control, sleep deprivation caused significant increase in sympathetic activity as evidenced by increase in percent low-frequency (50 ± 15 vs. 59 ± 8) and a decrease in percent high-frequency (50 ± 10 vs. 41 ± 8) components of HRV, increase in low-frequency band of BPV, and increase in serum norepinephrine (119 ± 46 vs. 162 ± 58 ng/ml), as well as a reduction in maximum endothelial dependent venodilatation (100 ± 22 vs. 41 ± 20%; P < 0.05 for all comparisons). In conclusion, 5 nights of partial sleep deprivation is sufficient to cause significant increase in sympathetic activity and venous endothelial dysfunction. These results may help to explain the association between short sleep and increased cardiovascular risk in epidemiological studies.
Early Signs of Atherosclerosis in Obstructive Sleep Apnea Drager, Luciano F; Bortolotto, Luiz A; Lorenzi, Maria Cecilia ...
American journal of respiratory and critical care medicine,
09/2005, Letnik:
172, Številka:
5
Journal Article
Recenzirano
Obstructive sleep apnea (OSA) is associated with several cardiovascular diseases. However, the mechanisms are not completely understood. Recent studies have shown that OSA is associated with multiple ...markers of endothelial damage. We hypothesized that OSA affects functional and structural properties of large arteries, contributing to atherosclerosis progression.
Twelve healthy volunteers, 15 patients with mild to moderate OSA, and 15 with severe OSA matched for age, sex, and body mass index were studied by using (1) full standard overnight polysomnography; (2) carotid-femoral pulse wave velocity with a noninvasive automatic device; and (3) a high-definition echo-tracking device to measure intima-media thickness, diameter, and distensibility. All participants were free of hypertension, diabetes, and smoking, and were not on any medications. Patients with OSA were naive to treatment.
Significant differences existed between control subjects and patients with mild to moderate and severe OSA (apnea-hypopnea index, 3.1 +/- 0.3, 16.2 +/- 1.7, and 55.7 +/- 5.9 events/hour, respectively) in pulse wave velocity (8.7 +/- 0.2, 9.2 +/- 0.2, and 10.3 +/- 0.2 m/second; p < 0.0001), intima-media thickness (604.4 +/- 25.2, 580.2 +/- 29.0, and 722.2 +/- 35.2 microm; p = 0.004), and carotid diameter (6,607.8 +/- 126.7, 7,152.3 +/- 114.4, and 7,539.9 +/- 161.2 microm; p < 0.0001). Multivariate analyses showed that the apnea-hypopnea index correlated independently with pulse wave velocity and intima-media thickness variability (r = 0.61, p < 0.0001, and r = 0.44, p = 0.004, respectively), whereas minimal oxygen saturation correlated with the carotid diameter (r = -0.60, p < 0.0001).
Middle-aged patients with OSA who are free of overt cardiovascular diseases have early signs of atherosclerosis. All vascular abnormalities correlated significantly with the severity of the OSA, which further supports the hypothesis that OSA plays an independent role in atherosclerosis progression.
Obstructive sleep apnea (OSA) is a secondary cause of hypertension and independently associated with target-organ damage in hypertensive patients. However, OSA remains largely underdiagnosed and ...undertreated. The aim of the present study was to evaluate the characteristics and clinical predictors of OSA in a consecutive series of patients followed up in a hypertension unit. A total of 99 patients (age 46 ± 11 years, body mass index 28.8 kg/m2 , range 25.1 to 32.9) underwent polysomnography. The clinical parameters included age, gender, obesity, daytime sleepiness, snoring, Berlin Questionnaire, resistant hypertension, and metabolic syndrome. Of the 99 patients, 55 (56%) had OSA (apnea-hypopnea index >5 events/hour). Patients with OSA were older and more obese, had greater levels of blood pressure, and presented with more diabetes, dyslipidemia, resistant hypertension, and metabolic syndrome than the patients without OSA. Of the patients with OSA, 51% had no excessive daytime sleepiness. The Berlin Questionnaire and patient age revealed a high sensitivity (0.93 and 0.91, respectively) but low specificity (0.59 and 0.48, respectively), and obesity and resistant hypertension revealed a low sensitivity (0.58 and 0.44, respectively) but high specificity (0.75 and 0.91, respectively) for OSA. Metabolic syndrome was associated with high sensitivity and specificity for OSA (0.86 and 0.85, respectively). Multiple regression analysis showed that age of 40 to 70 years (odds ratio 1.09, 95% confidence interval 1.03 to 1.16), a high risk of OSA on the Berlin Questionnaire (odds ratio 8.36, 95% confidence interval 1.67 to 41.85), and metabolic syndrome (odds ratio 19.04, 95% confidence interval 5.25 to 69.03) were independent variables associated with OSA. In conclusion, more important than the typical clinical features that characterize OSA, including snoring and excessive daytime sleepiness, the presence of the metabolic syndrome is as an important marker of OSA among patients with hypertension.
1 School of Physical Education and Sport, University of São Paulo; 2 Heart Institute (InCor), School of Medicine, University of São Paulo; and 3 Department of Medicine, Division of Nephrology, ...Federal University of São Paulo, São Paulo, Brazil
Submitted 7 May 2007
; accepted in final form 30 October 2007
Exercise training (ET) is a coadjuvant therapy in preventive cardiology. It delays cardiac dysfunction and exercise intolerance in heart failure (HF); however, the molecular mechanisms underlying its cardioprotection are poorly understood. We tested the hypothesis that ET would prevent Ca 2+ handling abnormalities and ventricular dysfunction in sympathetic hyperactivity-induced HF mice. A cohort of male wild-type (WT) and congenic 2A / 2C -adrenoceptor knockout ( 2A / 2C ARKO) mice with C57BL6/J genetic background (3–5 mo of age) were randomly assigned into untrained and exercise-trained groups. ET consisted of 8-wk swimming session, 60 min, 5 days/wk. Fractional shortening (FS) was assessed by two-dimensional guided M-mode echocardiography. The protein expression of ryanodine receptor (RyR), phospho-Ser 2809 -RyR, sarcoplasmic reticulum Ca 2+ ATPase (SERCA2), Na + /Ca 2+ exchanger (NCX), phospholamban (PLN), phospho-Ser 16 -PLN, and phospho-Thr 17 -PLN were analyzed by Western blotting. At 3 mo of age, no significant difference in FS and exercise tolerance was observed between WT and 2A / 2C ARKO mice. At 5 mo, when cardiac dysfunction is associated with lung edema and increased plasma norepinephrine levels, 2A / 2C ARKO mice presented reduced FS paralleled by decreased SERCA2 (26%) and NCX (34%). Conversely, 2A / 2C ARKO mice displayed increased phospho-Ser 16 -PLN (76%) and phospho-Ser 2809 -RyR (49%). ET in 2A / 2C ARKO mice prevented exercise intolerance, ventricular dysfunction, and decreased plasma norepinephrine. ET significantly increased the expression of SERCA2 (58%) and phospho-Ser 16 -PLN (30%) while it restored the expression of phospho-Ser 2809 -RyR to WT levels. Collectively, we provide evidence that improved net balance of Ca 2+ handling proteins paralleled by a decreased sympathetic activity on ET are, at least in part, compensatory mechanisms against deteriorating ventricular function in HF.
calcium handling proteins; ventricular function; plasma norepinephrine levels; cardiomyopathy; exercise conditioning
Address for reprint requests and other correspondence: P. C. Brum, Escola de Educação Física e Esporte da Universidade de São Paulo, Departamento de Biodinâmica do Movimento do Corpo Humano Av. Professor Mello Moraes, 65 Butantã, São Paulo 05508-900, Brazil (e-mail: pcbrum{at}usp.br )
Obstructive sleep apnea (OSA) has emerged as an independent risk factor for atherosclerosis. However, OSA is frequently associated with several risk factors for atherosclerosis, including ...hypertension (HTN). The impact of OSA and HTN alone compared with the association of both conditions on carotid atherosclerosis is not understood. We studied 94 middle-aged participants free of smoking and diabetes mellitus who were divided into 4 groupscontrols (n=22), OSA (n=25), HTN (n=20), and OSA+HTN (n=27). All of the participants underwent polysomnography and carotid measurements of intima-media thickness, diameter, and distensibility with an echo-tracking device. Compared with controls, intima-media thickness and carotid diameter were similarly higher in OSA (713±117 and 7117±805 μm), and HTN groups (713±182 and 7191±818 μm), with a further significant increase in OSA+HTN patients (837±181 and 7927±821 μm, respectively; P<0.01). Carotid distensibility was significantly lower in HTN (P<0.05) and OSA+HTN subjects (P<0.001) compared with controls. In the OSA+HTN group, carotid distensibility was significantly lower than in the OSA group and controls (P<0.05 for each comparison). Multivariate analysis showed that intima-media thickness was positively related to systolic blood pressure and apnea-hypopnea index. Apnea-hypopnea index was the only factor related to carotid diameter. Age and systolic blood pressure were independently related to carotid distensibility. In conclusion, the association of OSA and HTN has additive effects on markers of carotid atherosclerosis. Because early markers of carotid atherosclerosis predict future cardiovascular events, including not only stroke but also myocardial infarction, these findings may help to explain the increased risk of cardiovascular disease in patients with OSA.
Recognition and treatment of secondary causes of hypertension among patients with resistant hypertension may help to control blood pressure and reduce cardiovascular risk. However, there are no ...studies systematically evaluating secondary causes of hypertension according to the Seventh Joint National Committee. Consecutive patients with resistant hypertension were investigated for known causes of hypertension irrespective of symptoms and signs, including aortic coarctation, Cushing syndrome, obstructive sleep apnea, drugs, pheochromocytoma, primary aldosteronism, renal parenchymal disease, renovascular hypertension, and thyroid disorders. Among 125 patients (age52±1 years, 43% males, systolic and diastolic blood pressure176±31 and 107±19 mm Hg, respectively), obstructive sleep apnea (apnea-hypopnea index>15 events per hour) was the most common condition associated with resistant hypertension (64.0%), followed by primary aldosteronism (5.6%), renal artery stenosis (2.4%), renal parenchymal disease (1.6%), oral contraceptives (1.6%), and thyroid disorders (0.8%). In 34.4%, no secondary cause of hypertension was identified (primary hypertension). Two concomitant secondary causes of hypertension were found in 6.4% of patients. Age >50 years (odds ratio5.2 95% CI1.9–14.2; P<0.01), neck circumference ≥41 cm for women and ≥43 cm for men (odds ratio4.7 95% CI1.3–16.9; P=0.02), and presence of snoring (odds ratio3.7 95% CI1.3–11; P=0.02) were predictors of obstructive sleep apnea. In conclusion, obstructive sleep apnea appears to be the most common condition associated with resistant hypertension. Age >50 years, large neck circumference measurement, and snoring are good predictors of obstructive sleep apnea in this population.
Obstructive sleep apnea (OSA) and hypertension are independently associated with increased stiffness of large arteries that may contribute to left ventricular (LV) remodeling. We sought to ...investigate the impact of OSA, hypertension, and their association with arterial stiffness and heart structure.
We studied 60 middle-aged subjects classified into four groups according to the absence or presence of severe OSA with and without hypertension. All participants were free of other comorbidities. The groups were matched for age, sex, and body mass index.
Full polysomnography, pulse-wave velocity (PWV), and transthoracic echocardiography were performed in all participants. Compared with normotensive subjects without OSA, PWV, left atrial diameter, interventricular septal thickness, LV posterior wall thickness, LV mass index, and percentage of LV hypertrophy had similar increases in normotensive OSA and patients with hypertension and no OSA (p < 0.05 for all comparisons), with a significant further increase in PWV, LV mass index, and percentage of LV hypertrophy in subjects with OSA and hypertension. Multivariate regression analysis showed that PWV was associated with systolic BP (p < 0.001) and apnea-hypopnea index (p = 0.002). The only independent variable associated with LV mass index was PWV (p < 0.0001).
Severe OSA and hypertension are associated with arterial stiffness and heart structure abnormalities of similar magnitude, with additive effects when both conditions coexist. Increased large arterial stiffness contributes to ventricular afterload and may help to explain heart remodeling in both OSA and hypertension.
The effects of exercise training on baroreflex control of sympathetic nerve activity in human hypertension are unknown. We hypothesized that exercise training would improve baroreflex control of ...muscle sympathetic nerve activity (MSNA) and heart rate (HR) in patients with hypertension and that exercise training would reduce MSNA and blood pressure (BP) in hypertensive patients. Twenty never-treated hypertensive patients were randomly divided into 2 groupsexercise-trained (n=11; age46±2 years) and untrained (n=9; age42±2 years) patients. An age-matched normotensive exercise-trained group (n=12; age42±2 years) was also studied. Baroreflex control of MSNA (microneurography) and HR (ECG) was assessed by stepwise intravenous infusions of phenylephrine and sodium nitroprusside and analyzed by linear regression. BP was monitored on a beat-to-beat basis. Exercise training consisted of three 60-minute exercise sessions per week for 4 months. Under baseline conditions (before training), BP and MSNA were similar between hypertensive groups but significantly increased when compared with the normotensive group. Baroreflex control of MSNA and HR was similar between hypertensive groups but significantly decreased when compared with the normotensive group. In hypertensive patients, exercise training significantly reduced BP (P<0.01) and MSNA (P<0.01) levels and significantly increased baroreflex control of MSNA and HR during increases (P<0.01 and P<0.03, respectively) and decreases (P<0.01 and P<0.03, respectively) in BP. The baseline (preintervention) difference in baroreflex sensitivity between hypertensive patients and normotensive individuals was no longer observed after exercise training. No significant changes were found in untrained hypertensive patients. In conclusion, exercise training restores the baroreflex control of MSNA and HR in hypertensive patients. In addition, exercise training normalizes MSNA and decreases BP levels in these patients.
PDF
