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SLEEP AND CARDIOVASCULAR DISEASE

Volume 2 � Number 4 � December 2007

Contents

Foreword xi

Teofilo Lee-Chiong, Jr.

Preface xiii

Shahrokh Javaheri

Cardiovascular Implications of Poor Sleep 529

Michael H. Bonnet and Donna L. Arand

Poor sleep can have many connotations, and an examination of cardiovascularrelationships must be done with reference to the various definitions of poor sleep. Themost common connotation of poor sleep is insomnia. Sleep may be less than optimalfor a number of additional reasons, however, including lack of opportunity,fragmentation, or stress not producing traditional insomnia. This article discusses eachof these types of poor sleep. This article does not discuss the relationship of medicaldisorders that produce insomnia to cardiovascular disease.

Pathophysiologic Mechanisms of Cardiovascular Disease in ObstructiveSleep Apnea 539

Walter T. McNicholas and Shahrokh Javaheri

The mechanisms underlying cardiovascular disease in patients with obstructive sleepapnea are still poorly understood. The pathogenesis is likely to be a multifactorialprocess involving a diverse range of mechanisms, including sympathetic nervous systemoveractivity, selective activation of inflammatory pathways, endothelial dysfunction,and metabolic dysregulation, the latter particularly involving insulin resistance anddisordered lipid metabolism. This sleep breathing disorder is thought to contribute to,or be a cause of systemic hypertension, atherosclerosis, coronary artery disease, heartfailure, atrial fibrillation, and stroke.

Systemic and Pulmonary Arterial Hypertension in Obstructive Sleep Apnea 549

Heinrich F. Becker and Shahrokh Javaheri

Obstructive sleep apnea (OSA) is an independent risk factor for systemic and pulmonaryarterial hypertension. Sympathetic activation, caused by recurrent hypoxemia, is themost important pathomechanism for systemic hypertension, which is probably the

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most important link concerning the markedly increased mortality and morbidity inuntreated OSA patients. Effective continuous positive airway pressure (CPAP) treatmentsubstantially reduces blood pressure in hypertensive OSA patients. Similarly, recurrenthypoxemia causing pulmonary arteriolar vasoconstriction mediates development ofpulmonary hypertension. Limited data suggest that use of CPAP improves pulmonaryarterial hypertension.

Obstructive Sleep Apnea and Coronary Artery Disease 559

Jan Hedner, Karl A. Franklin, and Yuksel Peker

Obstructive apneas during sleep lead to a sequence of events that independently, or inconcert with other recognized risk factors, appear to induce harmful effects on vascularstructure and function. Although the epidemiologic support for a causal relationshipbetween obstructive sleep apnea (OSA) and coronary artery disease (CAD) is rapidlyincreasing, data is still not fully conclusive. In general, the relationship is stronger inclinical cohorts, compared with in the general population, suggesting that comorbidOSA may provide an additive or synergistic risk factor for development of CAD in obese,hypertensive, smoking, or hyperlipidemic subjects. Recognition of the adverse impact ofOSA on vascular disease may open a perspective of new primary and secondaryprevention models for CAD, involving identification and elimination of the sleep andbreathing disorder.

Obstructive Sleep Apnea and Left Ventricular Systolic and Diastolic Dysfunction 565

Francisco Garcıa-Rıo and Miguel A. Arias

There are some epidemiologic data that potentially implicate obstructive sleep apneasyndrome as a cause of left ventricular systolic and diastolic dysfunction. The mainpathophysiologic mechanisms involved are the sympathetic overactivity, the alterationsin left ventricular preload and afterload, and the effects of hypoxemia. This articleconsiders the clinical implications of this relationship and reviews the available data onthe efficacy of continuous positive airway pressure in patients with obstructive sleepapnea syndrome and left ventricular dysfunction.

Obstructive Sleep Apnea and Arrhythmias 575

Suraj Kapa, Shahrokh Javaheri, and Virend K. Somers

There is a relationship between arrhythmias and sleep apnea, most notably during sleep.A common rhythm disturbance is nocturnal bradyarrhythmias that occur in associationwith apneic episodes; however, because of long-term autonomic, functional, andstructural cardiac changes, in addition to decreased ischemic threshold, patients withsleep apnea may potentially be at higher risk for developing atrial fibrillation andventricular arrhythmias. These complications of untreated sleep apnea may conceivablybe implicated in nocturnal sudden cardiac death.

Sleep Apnea and Stroke: A Risk Factor or an Association? 583

Henry Yaggi and Vahid Mohsenin

This article explores the relationship between obstructive sleep apnea syndrome andstroke by critically reviewing the current literature. First, epidemiologic studies areanalyzed with respect to issues regarding the strength of the association, and the

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consistency of the association using different study designs and different populations.Next, the biologic plausibility of the relationship is explored by reviewing studies thatexamine the pathophysiology of sleep apnea and stroke. Subsequently, studies exploringthe therapeutic impact of obstructive sleep apnea syndrome on stroke andcardiovascular risk are reviewed. Finally, public health implications are discussed.

Mortality in Obstructive Sleep Apnea 593

Jose M. Marin and Santiago J. Carrizo

Many recent prospective, long-term, controlled studies suggest that in untreated patientswith sleep apnea, the risk of death from all-causes and particularly cardiovascular causesis increased. There is a relation between the severity of this disease and cardiovascularrisk, but the effective treatment with nasal continuous positive airway pressuresignificantly reduces the mortality associated with this medical condition. This articleexamines the growing evidence that links obstructive sleep apnea with cardiovascularoutcomes and specifically with an excess of mortality.

Obstructive Sleep Apnea in Pregnancy 603

Fotis Kapsimalis and Meir Kryger

During pregnancy several physical and hormonal alterations may affect normal sleepand the respiratory system and predispose pregnant women to the development ofsleep-disordered breathing (SDB) or worsen pre-existing obstructive sleep apneasyndrome (OSAS). SDB has been associated with several complications of pregnancyaffecting maternal and fetal health. Clinicians should evaluate more closely obesepregnant women and those who develop hypertension. Early recognition and treatmentof SDB may improve the outcome of pregnancy but the indications for treatment ofOSAS need to be investigated. The diagnosis of OSAS in pregnancy requires a high indexof suspicion and prevention of suspected SDB should be incorporated in themanagement of pregnancy.

Prevalence and Impact of Central Sleep Apnea in Heart Failure 615

PatrickLevy, Jean-Louis Pepin, Renaud Tamisier, Yannick Neuder,Jean-Philippe Baguet, and Shahrokh Javaheri

Sleep apnea is commonly found in patients with systolic heart failure, and recent studiesstrongly suggest that the prevalence of central sleep apnea remains high, in spite of theuse of contemporary treatment of heart failure, including beta-blockers. Furthermore, ithas been shown that central sleep apnea may contribute to mortality of heart failurepatients. However, the impact of therapy for sleep apnea on survival of heart failurepatients needs to be further determined.

Mechanisms of Sleep Apnea and Periodic Breathing in Systolic Heart Failure 623

Shahrokh Javaheri and J.A. Dempsey

Periodic breathing and central sleep apnea are common in patients with systolic heartfailure. The mechanisms of central sleep apnea are complex. Recent studies havedemonstrated that those patients with systolic heart failure who have increased CO2

chemosensitivity below and above eupnea are prone to develop central apnea duringsleep. Obstructive sleep apnea also occurs frequently in patients with heart failure,

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particularly in those with obesity who presumably have alterations in the mechanicalproperties of the upper airway. This article reviews the mechanisms of central sleepapnea, obstructive sleep apnea, and periodic breathing in systolic heart failure.

Treatment of Sleep Apnea in Heart Failure 631

W. De Backer and Shahrokh Javaheri

There are no guidelines for the treatment of sleep apnea in heart failure. Central sleepapnea remains difficult to treat and well designed, long-term controlled studies areneeded to determine if any treatment prolongs survival. However, based on thepathophysiologic consequences of sleep apnea on the cardiovascular system, studiesassociating excess mortality of heart failure patients with obstructive and central sleepapnea, and limited favorable therapeutic studies, it is important to continue to identifyheart failure patients who may suffer from sleep apnea and treat them appropriately.

Index 639