Fatima H. Sert Kuniyoshi

Day-Night Variation of Acute Myocardial Infarction in Obstructive Sleep Apnea

OBJECTIVES This study sought to evaluate the day-night variation of acute myocardial infarction (MI) in patients with obstructive sleep apnea (OSA). BACKGROUND Obstructive sleep apnea has a high prevalence and is characterized by acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of MI during the night. METHODS We prospectively studied 92 patients with MI for which the time of onset of chest pain was clearly identified. The presence of OSA was determined by overnight polysomnography. RESULTS For patients with and without OSA, we compared the frequency of MI during different intervals of the day based on the onset time of chest pain. The groups had similar prevalence of comorbidities. Myocardial infarction occurred between 12 am and 6 am in 32% of OSA patients and 7% of non-OSA patients (p = 0.01). The odds of having OSA in those patients whose MI occurred between 12 am and 6 am was 6-fold higher than in the remaining 18 h of the day (95% confidence interval: 1.3 to 27.3, p = 0.01). Of all patients having an MI between 12 am and 6 am, 91% had OSA. CONCLUSIONS The diurnal variation in the onset of MI in OSA patients is strikingly different from the diurnal variation in non-OSA patients. Patients with nocturnal onset of MI have a high likelihood of having OSA. These findings suggest that OSA may be a trigger for MI. Patients having nocturnal onset of MI should be evaluated for OSA, and future research should address the effects of OSA therapy for prevention of nocturnal cardiac events.

Obstructive sleep apnea: Implications for cardiac and vascular disease

ALONG WITH THE EPIDEMIC OF obesity, there is a growing awareness of sleep-disordered breathing as a potential and treatable risk factor for cardiovascular disease. The repetitive nocturnal hypoxemia experienced by patients with obstructive sleep apnea (OSA) is associated with activation of a number of neural, humoral, thrombotic, metabolic, and inflammatory disease mechanisms, all of which have also been implicated in the pathophysiology of cardiac and vascular disease. Activation of these mechanisms is often evident even in patients with OSA who are free of overt cardiovascular disease, suggesting that OSA may conceivably contribute to the initiation and progression of cardiovascular disease (FIGURE 1). SleepapneacanbecategorizedasOSA, in which there is preserved and increased respiratory effort despite partial or complete occlusion of the upper airway; or as central sleep apnea (CSA), in which there is absence of both respiratory efforts and airflow. The apneahypopnea index (ie, the number of apneic and hypopneic events per hour) is used as one index of the presence and severity of sleep apnea. For OSA, an apnea-hypopnea index of 5 to 15 indicates mild apnea; of 15 to 30, moderate apnea; and of greater than 30, severe apnea. Approximately 1 in 5 adults has at least mild OSA (apnea-hypopnea index, 5-15), and 1 in 15 adults has at least moderate OSA (apnea-hypopnea index, 15-30). Other measures of the severity of sleep apnea include the severity of oxygen desaturation and the level of daytime sleepiness. Obstructive sleep apnea is commonly associated with obesity and also is often present in patients with

Under-diagnosis of Sleep Apnea in Patients after Acute Myocardial Infarction

TO THE EDITOR: Obstructive sleep apnea (OSA) is highly prevalent in the general population and has been associated with arrhythmias, hypertension, stroke, and heart failure (1). Identification of OSA in cardiovascular patients is especially important as untreated OSA may be accompanied by increased cardiovascular events, and this risk may be attenuated by treatment with continuous positive airway pressure (CPAP)(2). We sought to investigate how the rates of recognition and diagnosis of obstructive sleep apnea compare to the actual prevalence of OSA in patients after myocardial infarction (MI). This study comprised two parts: a chart review of consecutive patients presenting with acute MI, and a prospective evaluation of MI patients who were recruited to undergo polysomnography. These studies were approved by the Institutional Review Board. First, we reviewed the medical records of 798 consecutive patients who were hospitalized with a diagnosis of acute MI between January and September 2007. Electronic records, including admission and dismissal notes were searched for diagnosed or suspected sleep disordered breathing, and especially for mention of OSA during the MI hospitalization. In the event of several hospital admissions for the same patient, only the first admission was used in our analysis. We further prospectively studied 74 patients who were hospitalized with acute myocardial infarction between 2004 and 2008, and were recruited to undergo attended overnight polysomnography, which is the gold standard in the diagnosis of OSA (Compumedics Siesta Wireless Sleep Recorder, Oxford Instruments, UK). All polysomnographies were performed within 6 weeks of the MI hospitalization, and scored by standard criteria (1). OSA was defined as present when the apnea hypopnea index (AHI) was >5. The diagnosis of MI was based on standard guidelines, and was made by the attending physicians who were blinded to this study. Patients were approached during their MI hospitalization, and their participation was based on their consent and availability of the study personnel and equipment. There was no systematic selection for specific demographic or patient characteristics. A review of electronic and paper records of these patients was also performed in similar fashion to that of the first part of our study. Between January and September 2007 there were 798 patients admitted to our institution with the diagnosis of acute MI. The mean age of this cohort was 69±14 years, and 512 (64%) were male. Diagnosed and suspected OSA was recorded in 97 (12%) patient records. The prospective cohort of 74 patients had a mean age of 62±13 years, and 46 (78%) were male. On review of their hospital records, 10 (14%) had documentation of diagnosed or suspected OSA. All of these patients underwent overnight polysomnography (PSG). For this group the mean AHI was 17±18 events/hour. OSA was present in 51 (69%), and severe OSA (AHI >15) in 30 (41%) patients. The main finding of this study was the low rate of documented or suspected OSA in patients hospitalized for acute MI, contrasting with the high prevalence of OSA in those in whom we conducted prospective PSG studies. This suggests a lack of awareness and recognition of OSA during treatment of acute MI. A high prevalence of OSA in the unselected general population has been well documented (1). Our results suggest that only 12 percent of patients hospitalized with acute MI had documentation of diagnosed or suspected OSA. When prospectively evaluated by overnight PSG a subgroup of patients had a much higher actual prevalence of OSA (over two thirds had at least mild OSA) but even in these patients with proven sleep apnea the possibility of OSA was documented in only 14 percent of patients. There are several limitations to our study. First, documentation in the medical record does not necessarily reflect the entire scope of medical evaluation; it is possible that in some patients OSA was suspected and they were verbally recommended to have an OSA evaluation which was not documented in the records, or this was left for a follow-up visit. Even so, it would be advantageous to arrange for screening for OSA during the hospitalization, just as we routinely initiate aspirin, beta-blocker, statin, and ACE inhibitor therapy before patient discharge. Cardiovascular disease patients with untreated severe OSA are thought to have worse cardiovascular outcomes (2,3), which may be improved with CPAP. Randomized controlled trials testing this assumption are lacking. Demonstrated beneficial effects of CPAP could lead to significant practice and guidelines changes. An absence of such clinical trials may help explain the relatively low awareness of OSA as an important consideration in the patient with MI.

Sleep Apnea and Hypertension: Interactions and Implications for Management

Obstructive sleep apnea (OSA) is highly prevalent in the United States, with an estimated 1 in 4 Americans at risk for OSA. In recent years, there has been a large body of work assessing the role of OSA as an independent risk factor for hypertension. Certain patient characteristics, such as age and the type of elevated blood pressure, may confer increased likelihood that the hypertension is secondary to underlying sleep apnea. Furthermore, early diagnosis and treatment of OSA may be beneficial in the management of hypertensive patients, particularly in those with poorly controlled hypertension. The focus of this brief review is on recent developments in the characteristics and treatment of sleep apnea-associated hypertension. Because of space limitations, only limited references are provided. The seventh report of the Joint National Committee identified OSA as an important identifiable cause of hypertension. As many as half of all patients with sleep apnea may have underlying hypertension, and many patients with hypertension, particularly resistant hypertension, may have OSA. In fact, there seems to be an interaction between OSA severity and resistance to antihypertensive medications.1 Elevated nocturnal blood pressure and reduced blood pressure “dipping” during sleep also suggest a higher likelihood of underlying sleep apnea, even in normotensive patients. Whether hypertension contributes to OSA remains unknown. OSA patients may not always exhibit elevated systolic pressures but may have a high prevalence of isolated diastolic hypertension.2–4 One study suggested that there was a significant association between the incidence of combined systolic and diastolic hypertension and the presence of sleep apnea in younger patients (<60 years of age) but not in older patients,5 and no significant association was seen between isolated systolic hypertension and sleep apnea in either age group. These studies suggest that the type of hypertension may need to be considered when …

Sleep-Disordered Breathing and Excessive Daytime Sleepiness in Patients With Atrial Fibrillation

BACKGROUND An important consequence of sleep-disordered breathing (SDB) is excessive daytime sleepiness (EDS). EDS often predicts a favorable response to treatment of SDB, although in the setting of cardiovascular disease, particularly heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is another highly prevalent condition strongly associated with SDB. We sought to assess the relationship between EDS and SDB in patients with AF. METHODS We conducted a prospective study of 151 patients referred for direct current cardioversion for AF who also underwent sleep evaluation and nocturnal polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to polysomnography and considered positive if the score was ≥ 11. The apnea-hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of ≥ 5 events/h for the diagnosis of SDB. RESULTS Among the study participants, mean age was 69.1 ± 11.7 years, mean BMI was 34.1 ± 8.4 kg/m(2), and 76% were men. The prevalence of SDB in this population was 81.4%, and 35% had EDS. The association between ESS score and AHI was low (R(2) = 0.014, P = .64). The sensitivity and specificity of the ESS for the detection of SDB in patients with AF were 32.2% and 54.5%, respectively. CONCLUSIONS Despite a high prevalence of SDB in this population with AF, most patients do not report EDS. Furthermore, EDS does not appear to correlate with severity of SDB or to accurately predict the presence of SDB. Further research is needed to determine whether EDS affects the natural history of AF or modifies the response to SDB treatment.

Muscle sympathetic nervous activity in depressed patients before and after treatment with sertraline

Background Sympathetic hyperactivity is one of the mechanisms involved in the increased cardiovascular risk associated with depression, and there is evidence that antidepressants decrease sympathetic activity. Objectives We tested the following two hypotheses: patients with major depressive disorder with high scores of depressive symptoms (HMDD) have augmented muscle sympathetic nervous system activity (MSNA) at rest and during mental stress compared with patients with major depressive disorder with low scores of depressive symptoms (LMDD) and controls; sertraline decreases MSNA in depressed patients. Methods Ten HMDD, nine LMDD and 11 body weight-matched controls were studied. MSNA was directly measured from the peroneal nerve using microneurography for 3 min at rest and 4 min during the Stroop color word test. For the LMDD and HMDD groups, the tests were repeated after treatment with sertraline (103.3 ± 40 mg). Results Resting MSNA was significantly higher in the HMDD [29.1 bursts/min (SE 2.9)] compared with LMDD [19.9 (1.6)] and controls [22.2 (2.0)] groups (P = 0.026 and 0.046, respectively). There was a significant positive correlation between resting MSNA and severity of depression. MSNA increased significantly and similarly during stress in all the studied groups. Sertraline significantly decreased resting MSNA in the LMDD group and MSNA during mental stress in LMDD and HMDD groups. Sertraline significantly decreased resting heart rate and heart rate response to mental stress in the HMDD group. Conclusion Moderate-to-severe depression is associated with increased MSNA. Sertraline treatment reduces MSNA at rest and during mental challenge in depressed patients, which may have prognostic implications in this group.

Patients With Obstructive Sleep Apnea Exhibit Impaired Endothelial Function After Myocardial Infarction

BACKGROUND Impaired brachial flow-mediated dilation (FMD) is associated with risk for subsequent cardiovascular events in patients after myocardial infarction (MI). These patients often have obstructive sleep apnea (OSA). We tested the hypothesis that patients with OSA post MI will exhibit more severe impairment in FMD. METHODS We studied 64 patients with MI admitted to our hospital. OSA was determined using polysomnography. FMD was measured using high-resolution ultrasonography, with researchers blind to the OSA diagnosis. RESULTS The mean age was 60 ± 11 years, and the mean BMI was 29 (26, 32 kg/m(2)), 84% of patients were men, 39% had moderate to severe OSA (apnea-hypopnea index [AHI] > 15), and 31% of the patients had mild OSA (5 ≤ AHI < 15). FMD was severely impaired in patients with moderate to severe OSA (0.8% ± 0.7%) as compared with patients without OSA (4.7% ± 0.8%, P = .001) and with mild OSA (3.9% ± 0.8%, P = .015). Linear regression showed that FMD was associated with log nocturnal nadir oxygen saturation (minSaO(2)) (β = 31.17, P = .0001), age (β = -0.11, P = .006). MinSaO(2) was an independent predictor of FMD after adjustment for possible confounders (β = 26.15, P = .001). CONCLUSIONS FMD is severely impaired in patients with moderate to severe OSA post MI, which may be partially related to nocturnal hypoxemia. Patients with OSA may, therefore, be at higher risk for subsequent cardiovascular events after an MI. Identifying and treating OSA may have important implications in the long-term prognosis of patients post MI. Further studies are necessary to determine if the presence of OSA would affect the long-term occurrence of cardiovascular events after an MI.

Sleep-disordered breathing, hypertension, and obesity in retired National Football League players.

To the Editor: In 1994, the Centers for Disease Control and Prevention conducted a study evaluating retired National Football League (NFL) players. Linemen were 3 times more likely than other position players to die of heart disease and had a 52% higher risk of cardiovascular death than the

Nocturnal Hypoxemia Due to Obstructive Sleep Apnea Is an Independent Predictor of Poor Prognosis After Myocardial Infarction

Background Obstructive sleep apnea (OSA) is an important risk factor for the development of cardiovascular diseases including myocardial infarction (MI). The aim of this study was to investigate the effects of OSA on prognosis after MI, and to determine which specific measures of OSA severity best predicted outcomes. Methods and Results We performed a prospective study, in which 112 patients without a prior diagnosis of sleep apnea underwent comprehensive polysomnography within a median of 7 days after MI. Patients were followed up at 6‐monthly intervals (±2 weeks) for a total of 48 months. Patients classified with central apnea (n=6) or those using continuous positive airway pressure (n=8) after polysomnography were excluded from analyses. The primary end point was major adverse cardiac events, including death from any cause, recurrent MI, unstable angina, heart failure, stroke, and significant arrhythmic events. Forty of 98 patients (41%) had OSA (apnea‐hypopnea index ≥15 events/h). OSA patients had higher major adverse cardiac event rates when compared to those without OSA (47.5% versus 24.1%; χ2=5.41, P=0.020). In a multivariate model that adjusted for clinically relevant variables including age, left ventricular ejection fraction, diabetes mellitus, oxygen desaturation index, and arousal index, significant hypoxemia, as defined by nocturnal nadir oxygen saturation ≤85%, was an independent risk factor for major adverse cardiac events (hazard ratio=6.05, P=0.004) in follow‐up 15 months after baseline. Conclusions Nocturnal hypoxemia in OSA is an important predictor of poor prognosis for patients after MI. These findings suggest that routine use of low‐cost nocturnal oximetry may be an economical and practical approach to stratify risk in post‐MI patients.

Hemodynamic reactivity to laboratory stressors in healthy subjects: influence of gender and family history of cardiovascular diseases.

Although laboratory stressor tests have been applied as a preliminary protocol in some cardiovascular studies, there is a lack of data comparing the pressor and chronotropic responses among the main stressor tests. Therefore, the aim of this study was to evaluate the variability in hemodynamic responsiveness to the main stressor tests, establish a hyperresponsiveness cutoff criterion and analyze the influence of gender and family history of cardiovascular diseases (CVDs) in healthy subjects. We examined hemodynamic responses to physical (cold pressor and handgrip tests) and mental (Stroop color-word test) stressors in 98 subjects (48 males and 50 females) without CVDs. All stressor tests resulted in increased blood pressure (BP) levels, which were lower and less dispersed in the handgrip test compared to the cold pressor test. Adopting the 75th percentile as the cutoff in our data, we classified subjects exhibiting absolute pressor changes equal to or higher than 14, 24 and 36 mmHg in systolic and 9, 13 and 24 mmHg in diastolic BP during the handgrip, Stroop and cold pressor test, respectively, as hyperresponsives. Males exhibited greater (p<0.05) increases in systolic BP in the handgrip (11% vs. 8%) and cold pressor (25% vs. 21%) tests and in diastolic BP in the handgrip (12% vs. 7%) and Stroop (22% vs. 19%) tests than females. A positive association between family history of CVDs and pressor hyperreactivity to stressor tests was observed. We propose using the 75th percentile of hemodynamic sample values as a cutoff criterion to classify individuals as pressor or chronotropic hyperreactives. We conclude that hemodynamic responsiveness to stressor tests in healthy subjects is positively influenced by male gender and family history of CVDs.