Clinical Investigations Markers of Myocardial Ischemia in Patients With Coronary Artery Disease and Obstructive Sleep Apnea: Effect of Continuous Positive Airway Pressure Therapy
Address for correspondence: Claudius Teupe, MD Department of Medicine, Center of Sleep Medicine Sachsenhausen Hospital–Teaching Hospital of Goethe University Frankfurt Schulstrasse 31 60594 Frankfurt, Germany [email protected]
Misa Valo, MD; Annette Wons, MD; Albert Moeller, MD; Claudius Teupe, MD Department of Medicine, Center of Sleep Medicine, Sachsenhausen Hospital, Frankfurt, Germany
Background: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular complications. OSA and coronary artery disease (CAD) share the same risk factors and coexist in many patients. In previous studies, repeated nocturnal cardiac ischemic events in OSA patients with CAD have been reported. Hypothesis: We hypothesized that OSA may precipitate myocardial ischemia, evidenced by ST-segment depression and elevated N-terminal brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TropT) levels in patients with severe OSA and concomitant CAD. We also aimed to evaluate if the effects could be reversed by continuous positive airway pressure (CPAP) therapy. Methods: Twenty-one patients with severe OSA (apnea-hypopnea index >15/h, nadir oxygen desaturation ≤80%), and coexisting CAD underwent in-hospital polysomnography at baseline and under CPAP. Blood samples for hs-TropT and NT-proBNP measurements were drawn prior and immediately after sleep. ST-segment depression was measured at the time of maximum oxygen desaturation during sleep. Results: CPAP significantly decreased elevated NT-proBNP levels from 475 ± 654 pg/mL before sleep to 353 ± 573 pg/mL after sleep and attenuated ST-segment depression during sleep. hs-TropT was not elevated and did not differ after nocturnal oxygen desaturation at baseline and after CPAP. Conclusions: CPAP significantly reduced NT-proBNP in patients suffering from severe OSA and coexisting CAD. Repeated nocturnal myocardial ischemia did not cause myocyte necrosis evidenced by elevated hs-TropT or ST-segment depression.
Introduction Obstructive sleep apnea (OSA) is linked up with an increased risk of morbidity and mortality, with a predominance of cardiovascular deaths.1,2 OSA is characterized by intermittent hypoxia during sleep and is associated with elevated sympathetic activity, cardiovascular variability, and intrathoracic pressure fluctuations.3 OSA results in hemodynamic changes with an increase in preload and afterload.4 Atrial fibrillation, coronary artery disease, congestive heart failure, and arterial hypertension are clinical manifestations and more common in patients with OSA.5,6 Stress imposed on the myocardium by repeated severe hypoxemia during sleep and an increased oxygen demand by sympathetic overstimulation in OSA may result in subclinical myocardial injury.7 Cardiac troponin T is an important biomarker in myocardial injury and predictor of clinical outcome.8,9 Cardiac myocytes also constitute the
The authors have no funding, financial relationships, or conflicts of interest to disclose.
462
Clin. Cardiol. 38, 8, 462–468 (2015) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22419 © 2015 Wiley Periodicals, Inc.
major source of cardiac neurohormone brain natriuretic peptide (NT-proBNP). It is secreted by ventricular myocytes after myocardial hypoxemia and in response to volume expansion and pressure load.10,11 NT-proBNP production is strongly upregulated in cardiac failure and locally in the area surrounding a myocardial infarction.12 The standard treatment for moderate and severe OSA is nasal continuous positive airway pressure (CPAP).13 It was hypothesized that OSA may precipitate myocardial ischemia, evidenced by ST-segment depression and elevated NT-proBNP and high-sensitivity troponin T (hs-TropT) levels in patients with severe OSA and concomitant coronary artery disease (CAD). We also aimed to evaluate if the effects could be reversed by CPAP therapy.
Methods The prospective study was conducted between February 2012 and September 2013. The study was approved by the ethics committee of the State Medical Council of Hessen, Germany (approval number FF 6/2912). Informed consent was obtained from each patient. Received: January 2, 2015 Accepted with revision: March 28, 2015
Figure 1. Study flow diagram. Abbreviations: AHI, apnea-hypopnea index; CAD, coronary artery disease; CPAP, continuous positive airway pressure; hs-TropT, high-sensitivity troponin T; NT-proBNP, N-terminal brain natriuretic peptide; OSA, obstructive sleep apnea.
Study Population Eighty patients were screened for the presence of severe OSA with an apnea-hypopnea index (AHI) >15/h and oxygen desaturation ≤80% during apnea. Although there are no generally accepted classifications for severity of oxygen desaturation, reductions to 18 years, severe OSA with AHI >15/h, oxygen desaturation ≤80%, and proven history of CAD. Exclusion criteria were moderate and severe heart failure (left ventricular ejection fraction [LVEF] 4%. AHI was calculated as the average number of apneas and hypopneas per hour of sleep. An AHI ≥15/h was defined as severe OSA. Measurement of hs-TropT and NT-proBNP Quantitative measurement of hs-TropT was done with an immunoassay for the in vitro quantitative determination of cardiac troponin T in human serum and plasma (Cobas e 411 Roche Troponin T hs STAT; Roche Diagnostics, Indianapolis, IN), with a lower limit of normal
Address for correspondence: Claudius Teupe, MD Department of Medicine, Center of Sleep Medicine Sachsenhausen Hospital–Teaching Hospital of Goethe University Frankfurt Schulstrasse 31 60594 Frankfurt, Germany [email protected]
Misa Valo, MD; Annette Wons, MD; Albert Moeller, MD; Claudius Teupe, MD Department of Medicine, Center of Sleep Medicine, Sachsenhausen Hospital, Frankfurt, Germany
Background: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular complications. OSA and coronary artery disease (CAD) share the same risk factors and coexist in many patients. In previous studies, repeated nocturnal cardiac ischemic events in OSA patients with CAD have been reported. Hypothesis: We hypothesized that OSA may precipitate myocardial ischemia, evidenced by ST-segment depression and elevated N-terminal brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TropT) levels in patients with severe OSA and concomitant CAD. We also aimed to evaluate if the effects could be reversed by continuous positive airway pressure (CPAP) therapy. Methods: Twenty-one patients with severe OSA (apnea-hypopnea index >15/h, nadir oxygen desaturation ≤80%), and coexisting CAD underwent in-hospital polysomnography at baseline and under CPAP. Blood samples for hs-TropT and NT-proBNP measurements were drawn prior and immediately after sleep. ST-segment depression was measured at the time of maximum oxygen desaturation during sleep. Results: CPAP significantly decreased elevated NT-proBNP levels from 475 ± 654 pg/mL before sleep to 353 ± 573 pg/mL after sleep and attenuated ST-segment depression during sleep. hs-TropT was not elevated and did not differ after nocturnal oxygen desaturation at baseline and after CPAP. Conclusions: CPAP significantly reduced NT-proBNP in patients suffering from severe OSA and coexisting CAD. Repeated nocturnal myocardial ischemia did not cause myocyte necrosis evidenced by elevated hs-TropT or ST-segment depression.
Introduction Obstructive sleep apnea (OSA) is linked up with an increased risk of morbidity and mortality, with a predominance of cardiovascular deaths.1,2 OSA is characterized by intermittent hypoxia during sleep and is associated with elevated sympathetic activity, cardiovascular variability, and intrathoracic pressure fluctuations.3 OSA results in hemodynamic changes with an increase in preload and afterload.4 Atrial fibrillation, coronary artery disease, congestive heart failure, and arterial hypertension are clinical manifestations and more common in patients with OSA.5,6 Stress imposed on the myocardium by repeated severe hypoxemia during sleep and an increased oxygen demand by sympathetic overstimulation in OSA may result in subclinical myocardial injury.7 Cardiac troponin T is an important biomarker in myocardial injury and predictor of clinical outcome.8,9 Cardiac myocytes also constitute the
The authors have no funding, financial relationships, or conflicts of interest to disclose.
462
Clin. Cardiol. 38, 8, 462–468 (2015) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22419 © 2015 Wiley Periodicals, Inc.
major source of cardiac neurohormone brain natriuretic peptide (NT-proBNP). It is secreted by ventricular myocytes after myocardial hypoxemia and in response to volume expansion and pressure load.10,11 NT-proBNP production is strongly upregulated in cardiac failure and locally in the area surrounding a myocardial infarction.12 The standard treatment for moderate and severe OSA is nasal continuous positive airway pressure (CPAP).13 It was hypothesized that OSA may precipitate myocardial ischemia, evidenced by ST-segment depression and elevated NT-proBNP and high-sensitivity troponin T (hs-TropT) levels in patients with severe OSA and concomitant coronary artery disease (CAD). We also aimed to evaluate if the effects could be reversed by CPAP therapy.
Methods The prospective study was conducted between February 2012 and September 2013. The study was approved by the ethics committee of the State Medical Council of Hessen, Germany (approval number FF 6/2912). Informed consent was obtained from each patient. Received: January 2, 2015 Accepted with revision: March 28, 2015
Figure 1. Study flow diagram. Abbreviations: AHI, apnea-hypopnea index; CAD, coronary artery disease; CPAP, continuous positive airway pressure; hs-TropT, high-sensitivity troponin T; NT-proBNP, N-terminal brain natriuretic peptide; OSA, obstructive sleep apnea.
Study Population Eighty patients were screened for the presence of severe OSA with an apnea-hypopnea index (AHI) >15/h and oxygen desaturation ≤80% during apnea. Although there are no generally accepted classifications for severity of oxygen desaturation, reductions to 18 years, severe OSA with AHI >15/h, oxygen desaturation ≤80%, and proven history of CAD. Exclusion criteria were moderate and severe heart failure (left ventricular ejection fraction [LVEF] 4%. AHI was calculated as the average number of apneas and hypopneas per hour of sleep. An AHI ≥15/h was defined as severe OSA. Measurement of hs-TropT and NT-proBNP Quantitative measurement of hs-TropT was done with an immunoassay for the in vitro quantitative determination of cardiac troponin T in human serum and plasma (Cobas e 411 Roche Troponin T hs STAT; Roche Diagnostics, Indianapolis, IN), with a lower limit of normal
