| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* From the Division of Cardiovascular Diseases (Drs. Gami, Wolk, Somers, and Ms. Svatikova), Cardiovascular Physiology Laboratory (Ms. Duenwald), Division of Pulmonary and Critical Care Medicine (Dr. Olson), Department of Laboratory Medicine and Pathology (Dr. Jaffe), Mayo Clinic and Foundation; Rochester, MN.
Correspondence to: Virend K. Somers, MD, PhD, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: somers.virend{at}mayo.edu
 |
Abstract |
|---|
 TOP Abstract IntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
Design: Prospective cohort study.
Setting: Cardiovascular physiology and sleep research laboratory.
Participants: Fifteen male volunteers with coronary artery disease (CAD) and moderate or severe OSA (apnea-hypopnea index [AHI] > 15).
Measurements and results: Polysomnography and measurement of serum cardiac troponin T before sleep, after 4 h of untreated OSA, and in the morning after 4 h of treatment with CPAP. The mean AHI for the group was 41 (SD 16), and the mean oxygen saturation nadir during sleep was 83% (SD 8%). All measurements of cardiac troponin T were < 0.010 ng/mL.
Conclusions: Despite the fact that some patients with OSA may experience nocturnal ischemia, this study shows that patients with severe OSA and coexisting CAD do not have nightly episodes of myocardial injury detectable by the current-generation cardiac troponin T assay.
Key Words: biomarker • coronary artery disease • obstructive sleep apnea • sleep-disordered breathing • troponin
|
Introduction |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
Obstructive sleep apnea (OSA) is associated with cardiovascular disease, including hypertension, congestive heart failure, arrhythmias, and coronary artery disease (CAD).56 In patients with CAD, OSA causes nocturnal angina and ST-segment depression, which are attenuated by continuous positive airway pressure (CPAP) therapy. Implicated in the development of OSA-related cardiovascular pathology are nightly hypoxic episodes, sometimes severe and numbering in the hundreds. Apnea and hypoxia also elicit surges in BP to levels as high as 240/120 mm Hg, increases in sympathetic activity,7 endothelial dysfunction,8 and systemic inflammation.9
While untreated OSA has been implicated in CAD and myocardial infarction,10 whether acute obstructive apneas elicit myocardial injury has not been studied. We studied serum cardiac troponin T levels in individuals with newly diagnosed (and previously untreated) OSA and accompanying CAD. We hypothesized that the severe nocturnal hypoxemia, sympathetic activation, and BP surges in patients with established CAD would result in myocardial injury, as evidenced by increases in serum cardiac troponin T.
|
Materials and Methods |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
Polysomnography
The presence and severity of OSA was determined by standard overnight polysomnography, including EEG, electrooculography, electromyography, oximetry, thermistor measurements of airflow, and measurements of rib cage and abdominal movements with breathing. The sleep studies followed a split-night protocol. The first half of the study was intended to quantify OSA severity, and the second half of the study consisted of a therapeutic trial of CPAP. An apnea was defined as complete cessation of airflow for at > 10 s, and hypopnea as a 
50% reduction in airflow for > 10 s associated with a > 4% decrease in oxygen saturation—each in the setting of ventilatory effort. The apnea-hypopnea index (AHI) was calculated as the total number of apneas and hypopneas per hour of sleep. An AHI > 15 defined moderate or severe OSA.
Cardiac Troponin T
Venous blood was collected on three occasions: 10 PM, 2 AM, and 6 AM. The quantitative determination of cardiac troponin T was done with the Elecsys 2010 Automated Chemiluminesence System (Roche Diagnostics; Indianapolis, IN). The assay was performed on 1 mL of serum stored at – 80°C, for which the stability of cardiac troponin T has been verified.11 The lower limit of detection for the assay is 0.010 ng/mL.
|
Results |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
|
|
Discussion |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
The hallmark of OSA is the chronic occurrence of nightly hypoxic events. It is clear that the consequences of these events are not limited to daytime sleepiness and motor vehicle accidents.12 Associations with cardiovascular diseases may pose the greatest risk to patients with OSA. The mechanisms of such associations include significant neural, endocrine, and hemodynamic abnormalities. However, the hypoxic events themselves appear to have a contributory effect to morbidity. For example, severe decreases in nocturnal oxygen saturation are associated with ventricular arrhythmogenesis.13 It is not known whether these hypoxic events are associated with the development or progression of cardiovascular disease via direct myocyte necrosis.
Previous studies have consistently noted nocturnal myocardial ischemia in patients with OSA. More than a third of OSA patients with CAD manifest ECG signs of nocturnal ischemia, predominantly during apneas and decreases in oxygen saturation > 3%.14 In another study of 51 OSA subjects with CAD, ST-segment depression during sleep and in the early morning was also evident in approximately a third of the subjects.15 Ischemia coincided with the arousal phase of obstructive apneas, and CPAP therapy attenuated the ECG abnormalities. In nine patients with nocturnal angina and OSA, Franklin and colleagues16 showed that symptoms and vectorcardiographic signs of ischemia diminished after use of nocturnal CPAP. Further studies from this group reported that nocturnal ST-segment depression occurs within 2 min of an obstructive apnea.17 Together, these studies indicate that nocturnal ischemia occurs in a substantial proportion of patients with OSA, but they do not provide evidence for or against the presence of myocardial injury. Isolated areas of myocyte necrosis during obstructive apneas would not necessarily be apparent on the ECG. Thus, studies of either chest pain or ST-segment changes would conceivably underestimate the presence of OSA-induced myocyte injury.
In our study, we measured cardiac troponin T on three occasions. Based on the kinetics of cardiac troponin release,218 our measurement before sleep would have best reflected myocardial injury from the night before, when these newly diagnosed patients experienced an entire night of untreated severe OSA. The second measurement would have captured the effects of approximately 4 h of significant obstructive apneas. The morning measurement would have best reflected myocardial injury due to the night of untreated OSA and any ameliorating effects of CPAP therapy. We did not identify any myocyte necrosis as evidenced by increases in cardiac troponin T. Our results suggest that significant myocardial injury is not evident on a nightly basis in patients with OSA. We are unaware of any prior studies that have attempted to identify myocardial ischemia or injury in patients with OSA by other diagnostic methods, such as serum biomarkers or histopathologic specimens.
Limitations
Limitations of the present study include the standard by which we assessed myocardial injury. The "gold standard" to confirm myocyte necrosis is histopathologic analysis of cardiac tissue, which clearly is outside the scope of our study. Based on European Society of Cardiology and American College of Cardiology recommendations, cardiac troponins are now the clinical measure of choice for the detection of myocardial injury.1 Cardiac troponin T exists both unbound in the cytoplasm and structurally bound to the contractile apparatus of myocytes. It is believed by most that cell death is required for its release,181920 although some have argued that elevations may occur with reversible cell injury.21 The third-generation cardiac troponin T assay is currently the most sensitive available for detection of circulating troponin T.24 In most studies, its predictive ability is similar at very low levels to that of cardiac troponin I.22 The lower limit of detection of the assay (0.010 ng/mL) is below current reference ranges used for the clinical diagnosis of myocardial infarction. We chose to use this level, which is the 99th percentile of the normal range, to maximize sensitivity while recognizing the possibility of analytic false-positive results.23 Even these minor elevations have been associated with increased morbidity and mortality in various disease processes, including acute coronary syndromes, pulmonary embolism, congestive heart failure, and renal failure.242526 Thus the identification of such elevations using the present assay might be clinically important in patients with OSA.
Future Direction
The results of the present study, although negative, do not negate the potential role of myocyte necrosis in the development of cardiovascular pathology in patients with OSA. It may be that myocardial injury occurs sporadically rather than nightly, and that the repetitive episodes cause cumulative chronic cardiovascular pathology. It is possible that the severity of hypoxemia an individual experiences at night, rather than the AHI, correlates best with myocyte necrosis. Studying patients with profound hypoxemia may identify those with cardiac troponin elevations, however the severity of OSA in our patient population is similar to that seen in prior studies that noted OSA-related ST-segment depression. Different comorbid disease states in patients with OSA, such as unstable angina, may pose greater risk of myocardial injury. However, we studied subjects with stable CAD because they were potentially susceptible to the hypoxemic and hemodynamic effects of OSA but did not have other active causes for myocyte necrosis. Any elevated cardiac troponin in our patient population would thus be a consequence of the OSA per se.
|
Conclusions |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
|
Footnotes |
|---|
Funding was provided by National Institutes of Health grants HL61560, HL65176, HL73211, and M01-RR00585; and by Mayo Clinic.
Dr. Jaffe has received research grant support and consulting fees from Roche Diagnostics, the makers of the troponin assay.
Dr. Gami is also supported by the Dr. Ralph and Marian C. Falk Medical Research Trust Fellowship for Clinical Research Training.
Received for publication September 2, 2003. Accepted for publication December 9, 2003.
|
References |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
