Effects of Continuous Positive Airway Pressure on Early Signs of Atherosclerosis in Obstructive Sleep Apnea

Hypertension Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 10/2007; 176(7):706-12. DOI: 10.1164/rccm.200703-500OC
Source: PubMed


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 (NCT 00400543).

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    • "Please cite this article in press as: Ali SS, et al., Systematic review on noninvasive assessment of subclinical cardiovascular disease in obstructive sleep apnea: new kid on the block!, Sleep Medicine Reviews (2014), had a high CIMT and that AHI was correlated with CIMT, r ¼ 0.71, p < 0.001. Drager et al. [27] demonstrated that the association of OSA and intima-media thickness (IMT) was independent of the presence of the metabolic syndrome (MS). They enrolled 81 consecutive patients with the MS and showed that subjects with OSA had a higher CIMT compared to subjects without OSA, 767 AE 140 microm vs. 661 AE 117 microm, p < 0.001. "
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    ABSTRACT: Patients with obstructive sleep apnea (OSA) have a high burden of cardiovascular disease (CVD) but a causal relationship between OSA and atherosclerotic CVD remains unclear. We systematically reviewed the literature analyzing the relationship. A review of the Medline database for studies noninvasively evaluating subclinical CVD in OSA was conducted. A total of fifty-two studies were included in this review. Across the studies the prevalence of atherosclerosis, as assessed by coronary artery calcification, carotid intima-media thickness, brachial artery flow mediated dilation and pulse wave velocity was higher in patients with OSA and correlated with increasing severity and duration of OSA. This study shows OSA is an independent predictor of subclinical CVD; as CVD is more likely to occur in patients with long standing and severe OSA. Further research is however necessary to identify specific OSA populations that would benefit from aggressive screening.
    Sleep Medicine Reviews 10/2014; 18(5). DOI:10.1016/j.smrv.2014.01.004 · 8.51 Impact Factor
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    • "In OSA patients, reversing early disorders in the cardiovascular system before the occurrence of major clinical events, such as myocardial infarction or stroke, may be a means of reducing cardiovascular risk. Continuous positive airway pressure (CPAP) the first line therapy for OSA has been suggested in small size randomized controlled trials (RCTs) as being able to reverse some of these subclinical alterations [17] as well as endothelial dysfunction [18]. However, CPAP acceptance is poor in some subgroups of OSA patients [19] and recent large RCTs demonstrate that CPAP alone is not enough to reduce cardiometabolic risk in OSA patients [20]. "
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    ABSTRACT: Rationale: Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. Methods: This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters. Results: 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m(2). In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (-0.29; 0.28), P = 0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: -6.34 mmHg (-12.68; -0.01), P = 0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. Conclusion: In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695.
    Mediators of Inflammation 08/2014; 2014(5):423120. DOI:10.1155/2014/423120 · 3.24 Impact Factor
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    • "According to a previous long-term study that monitored patients for 7 years, the probability of developing cardiovascular disease was significantly higher for incompletely treated OSA patients compared to that for efficiently treated OSA patients [9]. In addition, longterm CPAP therapy has been verified to effectively improve OSA patients' vascular functions and reduce their autonomic function abnormalities [10] [11] [12] [13] [14] [15] [16]. "
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    ABSTRACT: Studies regarding the effects of short-term continuous positive airway pressure (CPAP) therapy are not sufficient. A total of 35 patients with moderate to severe untreated OSA were divided into 2 groups. Group 1 comprised 22 patients who underwent polysomnography (PSG) for one night, and Group 2 comprised 13 patients who received PSG combined with CPAP therapy. To evaluate the influence of receiving CPAP therapy for one night, we measured 5 min wrist pulse signals before and after the experiment to assess heart rate variability, as well as novel short time multiscale entropy (sMSE) indicator that examines complexity in physiological signals. The results show that the participants in Group 1 exhibited significant changes in normalized low-frequency power/normalized high-frequency power (nLF/nHF) (0.72 ± 0.09 versus 1.11 ± 0.11, P = 0.006) values before and after the PSG study. By contrast, the participants in Group 2 showed no significant changes in the 3 indicators. Regarding the sMSE indicator, Group 2 patients exhibited significant increases in the sMSE. CPAP therapy administered for one night can reduce the sympathovagal imbalance in patients with moderate to severe untreated OSA and increase the complexity of the patient's physiological system, thereby reflecting their overall improved health.
    Computational and Mathematical Methods in Medicine 07/2014; 2014:652012. DOI:10.1155/2014/652012 · 0.77 Impact Factor
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