Background-Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea (OSA). We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA. The effects of continuous positive airway pressure (CPAP) therapy on endothelial function and repair capacity were assessed. Methods and Results-Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied. Proteins that regulate basal endothelial nitric oxide (NO) production (endothelial NO synthase [eNOS] and phosphorylated eNOS) and inflammation (cyclooxygenase-2 and inducible NOS) and markers of oxidative stress (nitrotyrosine) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy. Vascular reactivity was measured by flow-mediated dilation. Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity. Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59% and 94%, respectively, in patients with OSA compared with control subjects. Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects, whereas inducible NOS expression was 56% greater. Expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine, cyclooxygenase-2, and inducible NOS significantly decreased in patients who adhered to CPAP Ն4 hours daily. Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects, and both significantly increased in patients who adhered to CPAP Ն4 hours daily. Conclusions-OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity. Effective CPAP therapy is associated with the reversal of these alterations.

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BackgroundThe combination of early transmitral inflow velocity and mitral annular tissue Doppler imaging (E/Em ratio) is widely applied to noninvasively estimate left ventricular (LV) filling pressures. However E/Em ratio has a significant gray zone and its accuracy in patients with heart failure is debated. Left atrial (LA) deformation analysis by speckle tracking echocardiography (STE) was recently proposed as an alternative approach to estimate LV filling pressures. This study aimed at exploring the correlation of LA longitudinal function by STE and Doppler measurements with direct measurements of LV filling pressures in patients with heart failure.MethodsA total of 36 patients with advanced systolic heart failure (ejection fraction ≤35%), undergoing right heart catheterization, were studied. Simultaneously to pulmonary capillary wedge pressure (PCWP) determination, peak atrial longitudinal strain (PALS) and mean E/Em ratio were measured in all subjects by two independent operators. PALS values were obtained by averaging all segments (global PALS), and by separately averaging segments measured in the 4-chamber and 2-chamber views.ResultsNot significant correlation was found between mean E/Em ratio and PCWP (R = 0.15). A close negative correlation between global PALS and the PCWP was found (R = -0.81, p < 0.0001). Furthermore, global PALS demonstrated the highest diagnostic accuracy (AUC of 0.93) and excellent sensitivity and specificity of 100% and 93%, respectively, to predict elevated filling pressure using a cutoff value less than 15.1%. Bland-Altman analysis confirmed this close agreement between PCWP estimated by global PALS and invasive PCWP (mean bias 0.1 ± 8.0 mmHg).ConclusionIn a group of patients with advanced systolic heart failure, E/Em ratio correlated poorly with invasively obtained LV filling pressures. However, LA longitudinal deformation analysis by STE correlated well with PCWP, providing a better estimation of LV filling pressures in this particular clinical setting.

Chronic obstructive pulmonary disease (COPD) and heart failure (CHF) are common conditions. The prevalence of COPD ranges from 20% to 30% in patients with CHF. The diagnosis of CHF can remain unsuspected in patients with COPD, because shortness of breath is attributed to COPD. Measurement of plasma B-type natriuretic peptide (BNP) levels helps to uncover unsuspected CHF in patients with COPD and clinical deterioration. Noninvasive assessment of cardiac function may be preferable to BNP to uncover unsuspected left ventricular (LV) systolic dysfunction in patients with stable COPD. Patients with COPD or CHF develop skeletal muscle alterations that are strikingly similar. Functional intolerance correlates with severity of skeletal muscle alterations but not with severity of pulmonary or cardiac impairment in COPD and CHF, respectively. Improvement of pulmonary or cardiac function does not translate into relief of functional intolerance in patients with COPD or CHF unless skeletal muscle alterations concomitantly regress. The mechanisms responsible for skeletal muscle alterations are incompletely understood in COPD and in CHF. Disuse and low-level systemic inflammation leading to protein synthesis/degradation imbalance are likely to contribute. The presence of COPD impacts on the treatment of CHF, as COPD is still viewed as a contraindication to beta-blockade. Therefore, COPD often deprives patients with CHF due to LV systolic dysfunction of the most beneficial pharmacologic intervention. A large body of data indicates that patients with COPD tolerate well selective beta-blockade that should not be denied to CHF patients with concomitant COPD.