cardiovascular-agents and Sleep-Apnea-Syndromes

Acute heart failure (AHF) is a complex, heterogeneous, clinical syndrome with high morbidity and mortality, incurring significant health care costs. Patients transition from home to the emergency department, the hospital, and home again and require decisions surrounding diagnosis, treatment, and prognosis at each step of the way. The purpose of this review is to examine the epidemiology, etiology, and classifications of AHF and specifically focus on practical information relevant to the clinician. We examine the mechanisms of decompensation relevant to clinical presentations-including precipitating factors, neuroendocrine interactions, and inflammation-along with how consideration of these factors may help select therapies for an individual patient. The prevalence and significance of end-organ manifestations such as renal, gastrointestinal, respiratory, and neurologic manifestations are discussed. We also highlight how the development of renal dysfunction relates to the choice of a variety of diuretics that may be useful in specific circumstances and review guideline-directed medical therapy. We discuss the practical use (and pitfalls) of a variety of evidence-based clinical scoring criteria available to risk stratify patients with AHF. Finally, evidence-based management of AHF is discussed, including both pharmacologic and nonpharmacologic therapies, including the lack of evidence for using old and new vasodilators and the recent evidence regarding initiation of newer therapies in hospital. Overall, we suggest that clinicians consider implementing the newer data in AHF and subject existing practice patterns and treatments to the same rigour as new therapies.

Topics: Acute Disease; Algorithms; Cardiac Rehabilitation; Cardiovascular Agents; Cognitive Dysfunction; Diagnostic Techniques, Cardiovascular; Diuretics; Evidence-Based Medicine; Gastrointestinal Diseases; Heart Failure; Humans; Inflammation; Kidney Diseases; Noninvasive Ventilation; Renin-Angiotensin System; Severity of Illness Index; Sleep Apnea Syndromes; Sympathetic Nervous System

Nasal continuous positive airway pressure (CPAP) is generally recommended for the treatment of obstructive sleep apnoea. CPAP lowers the cardiovascular morbidity and mortality associated with severe obstructive sleep apnoea. At least 50% of patients presenting with chronic heart failure (HF) have sleep apnoea; a subset of these patients may have obstructive sleep apnoea and may derive a survival benefit from CPAP. However, this population is also prone to developing central sleep apnoea, Cheyne-Stokes respiration or both (CSA/CSR), for which CPAP lowers the apnoea-hypopnoea index only partially and for which the overall effect of CPAP on survival remains to be determined, particularly as it has been observed to increase the mortality rate in subsets of patients. Other treatments may prove effective in patients with chronic HF and CSA/CSR, although none, thus far, has been found to confer a survival benefit. New ventilatory modes include bi-level positive airway pressure and automated adaptive servoventilation, the latter being most effective against CSA/CSR. Measures that can alleviate CSA/CSR indirectly include beta-adrenergic blockers and renin-angiotensin-aldosterone system inhibitors, nocturnal supplemental oxygen and cardiac resynchronization therapy (CRT). The effects of theophylline, acetazolamide and nocturnal CO(2) have also been studied. The second part of this review describes the applications and effects of therapies that are available for sleep apnoea in patients with chronic HF.

Topics: Cardiac Pacing, Artificial; Cardiovascular Agents; Chronic Disease; Continuous Positive Airway Pressure; Heart Failure; Humans; Oxygen Inhalation Therapy; Respiration, Artificial; Respiratory Mechanics; Sleep Apnea Syndromes; Treatment Outcome

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

There is a fascinating and exceedingly important area of medicine that most of us have not been exposed to at any level of our medical training. This relatively new area is termed chronobiology; that is, how time-related events shape our daily biologic responses and apply to any aspect of medicine with regard to altering pathophysiology and treatment response. For example, normally occurring circadian (daily cycles, approximately 24 hours) events, such as nadirs in epinephrine and cortisol levels that occur in the body around 10 PM to 4 AM and elevated histamine and other mediator levels that occur between midnight and 4 AM, play a major role in the worsening of asthma during the night. In fact, this nocturnal exacerbation occurs in the majority of asthmatic patients. Because all biologic functions, including those of cells, organs, and the entire body, have circadian, ultradian (less than 22 hours), or infradian (greater than 26 hours) rhythms, understanding the pathophysiology and treatment of disease needs to be viewed with these changes in mind. Biologic rhythms are ingrained, and although they can be changed over time by changing the wake-sleep cycle, these alterations occur over days. However, sleep itself can adversely affect the pathophysiology of disease. The non-light/dark influence of biologic rhythms was first described in 1729 by the French astronomer Jean-Jacques de Mairan. Previously, it was presumed that the small red flowers of the plant Kalanchoe bloss feldiuna opened in the day because of the sunlight and closed at night because of the darkness. When de Mairan placed the plant in total darkness, the opening and closing of the flowers still occurred on its intrinsic circadian basis. It is intriguing to think about how the time of day governs the pathophysiology of disease. On awakening in the morning, heart rate and blood pressure briskly increase, as do platelet aggregability and other clotting factors. This can be linked to the acrophase (peak event) of heart attacks. During the afternoon we hit our best mental and physical performance, which explains why most of us state that "I am not a morning person." Even the tolerance for alcohol varies over the 24-hour cycle, with best tolerance around 5 pm (i.e. "Doctor, I only have a couple of highballs before dinner"). Thus, all biologic functions, from those of the cell, the tissue, the organs, and the entire body, run on a cycle of altering activity and function.(ABSTRACT TRUNCATED AT 400 W

Topics: Arthritis; Autonomic Nervous System Diseases; Cardiovascular Agents; Cardiovascular Diseases; Chronobiology Phenomena; Circadian Rhythm; Endocrine System Diseases; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Hypersensitivity; Kidney Diseases; Male; Nervous System Diseases; Neuromuscular Diseases; Phototherapy; Respiratory Physiological Phenomena; Respiratory Tract Diseases; Sleep; Sleep Apnea Syndromes

Topics: Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Continuous Positive Airway Pressure; Hemodynamics; Humans; Risk Factors; Sleep Apnea Syndromes; Sympathetic Nervous System; Treatment Failure; Ventricular Outflow Obstruction

Our previous work showed a diminished cerebral blood flow (CBF) response to changes in Pa(CO(2)) in congestive heart failure patients with central sleep apnea compared with those without apnea. Since the regulation of CBF serves to minimize oscillations in H(+) and Pco(2) at the site of the central chemoreceptors, it may play an important role in maintaining breathing stability. We hypothesized that an attenuated cerebrovascular reactivity to changes in Pa(CO(2)) would narrow the difference between the eupneic Pa(CO(2)) and the apneic threshold Pa(CO(2)) (DeltaPa(CO(2))), known as the CO(2) reserve, thereby making the subjects more susceptible to apnea. Accordingly, in seven normal subjects, we used indomethacin (Indo; 100 mg by mouth) sufficient to reduce the CBF response to CO(2) by approximately 25% below control. The CO(2) reserve was estimated during non-rapid eye movement (NREM) sleep. The apnea threshold was determined, both with and without Indo, in NREM sleep, in a random order using a ventilator in pressure support mode to gradually reduce Pa(CO(2)) until apnea occurred. results: Indo significantly reduced the CO(2) reserve required to produce apnea from 6.3 +/- 0.5 to 4.4 +/- 0.7 mmHg (P = 0.01) and increased the slope of the ventilation decrease in response to hypocapnic inhibition below eupnea (control vs. Indo: 1.06 +/- 0.10 vs. 1.61 +/- 0.27 l x min(-1) x mmHg(-1), P < 0.05). We conclude that reductions in the normal cerebral vascular response to hypocapnia will increase the susceptibility to apneas and breathing instability during sleep.

Topics: Adolescent; Adult; Blood Flow Velocity; Brain; Carbon Dioxide; Cardiovascular Agents; Cerebrovascular Circulation; Female; Humans; Hypercapnia; Indomethacin; Male; Pulmonary Ventilation; Sleep Apnea Syndromes; Young Adult

A study was undertaken in patients with undiagnosed sleep apnoea/hypopnoea syndrome (OSAS) to document the use of prescribed medications, especially those used in cardiovascular diseases, in the year before the OSAS diagnosis was confirmed.. A total of 549 patients with OSAS (401 men of mean age 47.2 years, mean body mass index (BMI) 35.5 kg/m(2), mean apnoea/hypopnoea index (AHI) 47.2 and148 women of mean age 50.2 years, BMI 39.6 kg/m(2), AHI 32.6) were each matched to one general population control by age, sex, geographical location, and family physician. Medication use was evaluated for patients and controls using a database containing information about all prescriptions completed in the province of Manitoba, Canada.. In the year before OSAS was diagnosed, prescribed medication costs were $155.91 (Canadian dollars) (95% CI $91.34 to $220.49) greater for cases than for controls. Cases were dispensed 3.3 (95% CI 1.5 to 5.2) more prescriptions, were on 1.2 (95% CI 0.8 to 1.6) more medications, and were supplied with 157.4 (95% CI 95.9 to 218.8) more daily doses of medication. The odds ratio of OSAS cases being on a prescribed medication was 1.88 relative to controls (95% CI 1.38 to 2.54, p<0.0001). In the same year 36.6% of cases and 19.7% of controls were using medications for cardiovascular disease (OR 2.82, 95% CI 2.05 to 3.89, p<0.0001), consuming 79.4 (95% CI 48.9 to 109.8) more daily doses of medication, having been dispensed 1.7 (95% CI 1.0 to 2.4) more prescriptions, and at a $75.26 (95% CI $44.03 to $106.50) greater cost. The odds ratio of patients with OSAS being on medications indicated for the treatment of systemic hypertension was 2.71 (95% CI 1.96 to 3.77) relative to controls; however, such medications might also be prescribed for other indications such as angina pectoris and congestive heart failure, and for the secondary prevention of myocardial infarction. The use of medications indicated for the treatment of systemic hypertension was predicted significantly by age (odds ratio (OR) 1.10 per year), BMI (OR 1.05 per unit), and AHI (OR 1.01 per unit).. In the year before OSAS was diagnosed, patients with OSAS were heavy users of medications, particularly those used to treat cardiovascular diseases.

Topics: Body Mass Index; Cardiovascular Agents; Drug Costs; Electrocardiography; Electromyography; Female; Humans; Male; Middle Aged; Odds Ratio; Polysomnography; Sleep Apnea Syndromes