cardiovascular-agents and Sleep-Apnea--Central

Although sleep apnea is closely associated with cardiovascular disease, it remains underdiagnosed and undertreated. Obstructive sleep apnea elicits a cascade of harmful cardiovascular stimuli, and central sleep apnea is a prognostic factor for heart failure and may exert adverse effects on outcomes. The adverse effects of obstructive sleep apnea can promote the development of atherosclerosis and have also been implicated in the pathogenesis of cardiovascular disease. Sleep apnea characterized by variables of the autonomic nervous system may have a direct association with arrhythmia. Polysomnography with electroencephalography is the gold standard for assessing sleep apnea. Alternative methods of screening for OSA have recently become available. Continuous positive airway pressure for obstructive sleep apnea reduces cardiac risk and cardiovascular disease mortality. Targeting sleep apnea in the primary and/or secondary prevention of cardiovascular disease may lead to better outcomes.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Continuous Positive Airway Pressure; Electroencephalography; Heart Failure; Humans; Polysomnography; Sleep Apnea Syndromes; Sleep Apnea, Central; Treatment Outcome

To further our understanding of central sleep apnea (CSA) at high altitude during acclimatization, we tested the hypothesis that pharmacologically altering cerebral blood flow (CBF) would alter the severity of CSA at high altitude.. The study was a randomized, placebo-controlled single-blind study.. A field study at 5,050 m in Nepal.. We studied 12 normal volunteers.. Between days 5 to 10 at high altitude, CBF velocity (CBFv) was increased by intravenous (IV) acetazolamide (10 mg/kg) and reduced by oral indomethacin (100 mg).. Arterial blood gases, hypoxic and hypercapnic ventilatory responses, and CBFv and its reactivity to carbon dioxide were measured awake. Overnight polysomnography was performed. The central apnea-hypopnea index was elevated following administration of indomethacin (89.2 ± 43.7 to 112.5 ± 32.9 events/h; mean ± standard deviation; P < 0.05) and was reduced following IV acetazolamide (89.2 ± 43.7 to 47.1 ± 48.1 events/h; P < 0.001). Intravenous acetazolamide elevated CBFv at high altitude by 28% (95% confidence interval [CI]: 22-34%) but did not affect ventilatory responses. The elevation in CBFv was partly mediated via a selective rise in partial pressure of arterial carbon dioxide (PaCO2) (28 ± 4 to 31 ± 3 mm Hg) and an associated fall in pH (P < 0.01). Oral indomethacin reduced CBFv by 23% (95% CI: 16-30%), blunted CBFv reactivity, and increased the hypercapnic ventilatory response by 66% (95% CI: 30-102%) but had no effect on PaCO2 or pH.. Our findings indicate an important role for cerebral blood flow regulation in the pathophysiology of central sleep apnea at high altitude.

Topics: Acclimatization; Acetazolamide; Administration, Intravenous; Administration, Oral; Adult; Altitude; Carbon Dioxide; Cardiovascular Agents; Cerebrovascular Circulation; Female; Humans; Hypercapnia; Hypoxia; Indomethacin; Male; Middle Aged; Polysomnography; Single-Blind Method; Sleep Apnea, Central; Wakefulness; Young Adult

In the main analysis of the Canadian Continuous Positive Airway Pressure (CPAP) for Patients with Central Sleep Apnea (CSA) and Heart Failure Trial (CANPAP), CPAP had no effect on heart transplant-free survival; however, CPAP only reduced the mean apnea-hypopnea index to 19 events per hour of sleep, which remained above the trial inclusion threshold of 15. This stratified analysis of CANPAP tested the hypothesis that suppression of CSA below this threshold by CPAP would improve left ventricular ejection fraction and heart transplant-free survival.. Of the 258 heart failure patients with CSA in CANPAP, 110 of the 130 randomized to the control group and 100 of the 128 randomized to CPAP had sleep studies 3 months later. CPAP patients were divided post hoc into those whose apnea-hypopnea index was or was not reduced below 15 at this time (CPAP-CSA suppressed, n=57, and CPAP-CSA unsuppressed, n=43, respectively). Their changes in left ventricular ejection fraction and heart transplant-free survival were compared with those in the control group. Despite similar CPAP pressure and hours of use in the 2 groups, CPAP-CSA-suppressed subjects experienced a greater increase in left ventricular ejection fraction at 3 months (P=0.001) and significantly better transplant-free survival (hazard ratio [95% confidence interval] 0.371 [0.142 to 0.967], P=0.043) than control subjects, whereas the CPAP-CSA-unsuppressed group did not (for left ventricular ejection fraction, P=0.984, and for transplant-free survival, hazard ratio 1.463 [95% confidence interval 0.751 to 2.850], P=0.260).. These results suggest that in heart failure patients, CPAP might improve both left ventricular ejection fraction and heart transplant-free survival if CSA is suppressed soon after its initiation.

Topics: Aged; Cardiovascular Agents; Cheyne-Stokes Respiration; Combined Modality Therapy; Continuous Positive Airway Pressure; Exercise Tolerance; Female; Heart Failure; Heart Transplantation; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxygen; Partial Pressure; Polysomnography; Proportional Hazards Models; Severity of Illness Index; Single-Blind Method; Sleep Apnea, Central; Stroke Volume; Survival Analysis; Sympathetic Nervous System; Treatment Outcome

Patients with heart failure have high levels of central sympathetic outflow and also have a high prevalence of sleep-related breathing disorders, predominantly central sleep apnea. The options for treating central sleep apnea in heart failure are limited and include theophylline. Whether theophylline alters sympathetic activity in heart failure patients is not known.. Using a single-blinded, randomized, placebo-controlled study design, we investigated the sympathetic, hemodynamic, neurohumoral, and ventilatory effects of theophylline in patients with congestive heart failure compared with healthy control subjects closely matched for age, sex, and body mass index. Theophylline increased muscle sympathetic nerve activity and lowered transcutaneous CO2 in the control subjects but only lowered transcutaneous CO2 in the heart failure patients. Theophylline nearly doubled plasma renin concentration in both the healthy subjects (P<0.01) and the heart failure patients (P<0.02).. Our study shows that in heart failure patients, there are differential effects of theophylline: in contrast to healthy subjects, theophylline does not increase sympathetic activity in heart failure, whereas increases in plasma renin and ventilation are still evident. These novel findings may have important implications for understanding the potential harmful and beneficial effects of theophylline and related substances in heart failure patients.

Topics: Adolescent; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Cardiovascular Agents; Endothelin-1; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Renin; Respiration; Single-Blind Method; Sleep Apnea, Central; Sympathetic Nervous System; Theophylline