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).

Full-text preview

Available from:
  • Source
    • "It is conceivable that induction of TLR-2 by intermittent nocturnal hypoxemia contributes to the progression of systemic inflammation and atherosclerosis in patients with OSA. Indeed, nocturnal oxyhemoglobin desaturation in patients with OSA has been independently associated with atherosclerosis as assessed by increased carotid artery intima-media thickness [38;39] that can be reversed with continuous positive airway pressure therapy.[40] Given that exposure to intermittent hypoxia in healthy subjects, as done in the current study, can induce insulin resistance, [16] it is certainly possible that systemic induction of TLR2 may also lead to the development of insulin resistance in OSA. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent hypoxia on gene expression in humans have not been elucidated. A cross-over study was performed exposing eight healthy men to intermittent hypoxia or control conditions for five hours with peripheral blood mononuclear cell isolation before and after exposures. Total RNA was isolated followed by gene microarrays and confirmatory real time reverse transcriptase PCR. Intermittent hypoxia led to greater than two fold up-regulation of the pro-inflammatory gene toll receptor 2 (TLR2), which was not increased in the control exposure. We hypothesize that up-regulation of TLR2 by intermittent hypoxia may lead to systemic inflammation, insulin resistance and atherosclerosis in patients with obstructive sleep apnea.
    Full-text · Article · Dec 2015 · PLoS ONE
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Oct 2014 · Sleep Medicine Reviews
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Aug 2014 · Mediators of Inflammation
Show more