lung cancer rehabilitation

Obstructive Sleep Apnea Contributes to

Poor Cardiovascular Health

Student Name

Date

Dr.

University

Sleep apnea is characterized as recurrent events of complete lack of airflow for ten seconds or longer.1 There are three forms of sleep apnea: central (CSA), obstructive (OSA), and complex or mixed sleep apnea (a combination of CSA and OSA). OSA is the most common form of sleep apnea occurring in an estimated 2% of women and 4% of men.2 There are several causes for obstruction of the air passage that leads to apnea events. With OSA the pharyngeal airway can be blocked in individuals with low muscle tone and soft tissue around the airway, most commonly due to upper body obesity, and in patients that have structural features that give rise to a narrowed airway.1 This breathing syndrome has been linked with an increased risk in the development of cardiovascular disease. OSA has been attributed to an increase in hypertension, ischemic stroke, and myocardial ischemia in patients with OSA.3 The focus of this paper is to determine some of the underlying factors associated with OSA and poor cardiovascular health and how these factors can be used to diagnostically test for cardiovascular disease attributed to OSA.

The mechanism of how OSA contributes to poor cardiac and vascular health is not well understood. An event occurring after occlusion of the air passage, known as arousal, is thought to be important in determining these underlying risk factors. Arousal has been associated with an acute increase in sympathetic activity and acutely causes surges in blood pressure and heart rate.3 This repeated event may contribute to an increased risk of developing hypertension from repeated insults from undiagnosed or untreated OSA.4 Epidemiological studies have shown that a biomarker known as lipoprotein-associated phospholipase A2 (Lp-PLA2) can be measured to predict the health of the cardiovascular system. Bekci et al. found that Lp-PLA2 levels was positively correlated with arousal, but negatively correlated with antioxidant capacity.3 These values were most highly correlated in the most severe cases of OSA with the highest arousal index.3 However, a major limitation of this study was the small number of patients and the lack of a control group without OSA. Additionally, this study focused on men, as Lp-PLA2 in women is controversial due to hormonal irregularities caused by menopause and hormone replacement therapy.5

Almendros et al. also examined the effects of arousal on cardiac health. This group used rats to establish an animal model for arousal associated with OSA. The hypothesis of this study was that untreated OSA could cause repeated acute inflammatory responses, leading to cardiac injury over the long term, and IL1- was used to assess systemic inflammation.6 OSA events correlated with early systemic and ventricular inflammation in addition to myocardial cell injury; thus, IL1- is predictive of early onset of heart disease in an animal model.6 While these results are encouraging, the next logical step is to test this hypothesis in humans.

Increased inflammation due to OSA was the focus of another study by Maruyama et al. This group measured plasma levels of platelet-derived microparticles (PDMPs) and plasminogen activator inhibitor-1 (PAI-1) to assess inflammation and coagulation, respectively, in patients with OSA. This study found that PDMP was significantly higher in patients with severe OSA than those with mild to moderate OSA. All patients had significantly higher PAI-1 levels than the control group, but there was no significant difference in the severe and mild to moderate group. To determine if these levels could be reverse by treatment, CPAP was done on a cohort of patients. The study found that PDMP but not PAI-1 was significantly decreased with CPAP treatment. These data are from 27 patients, with 7 in the control group, 7 in the OSA with no treatment group, and 7 in the OSA with CPAP treatment group; the results should be considered in the context of a small number of participants. 7

In an attempt to demonstrate the relationship between heart rate and hypertension associated with the severity of OSA, Ozeke et al. retrospectively examined 540 polysomnograms. The study found that there was a significant correlation between mean and maximal nocturnal heart rate and the severity of OSA and the presence of hypertension.8 However, one limitation to the study was that the hypertension measurements were made during an office visit and not during the recording of the polysomnogram, yet the study suggests increased heart rate could be one mechanism to explain the hypertension associated with OSA.

In an investigation by Kabir et al. cardiac and respiratory rhythms were analyzed for transient phases of phase-locking, whereby heart rate and respiratory rate coincide with different ratios. Respiratory sinus arrhythmia (RSA), in which subtle rhythmic heart rate acceleration and deceleration that oscillate close to the respiratory frequency, is a prognostic indicator of cardiac mortality. RSA is increased with exercise but decreased with OSA. Likewise, OSA decreased the phase-locking of cardiac and respiratory rhythms. However, there was no effect of phase-coupling related to age or BMI, and this test may be a good prognostic indicator for OSA contribution to poor cardiac health independent of comorbid factors. 9

While there is no definitive measurement for assessing the impact of obstructive sleep apnea on poor cardiovascular health, there are a number of studies reviewed here that have shown OSA to be deleterious to cardiovascular health.3-5,6-9 In a study by Maruyama et al., treatment with CPAP significantly reduced plasma levels of PDMP, an indicator of poor cardiac health. Adherence to treatment is a complicating factor in treating OSA, and non adherence leads to poor health outcomes.10 Therefore, in addition to measurements to assess how OSA may be contributing to cardiovascular disease, respiratory therapists should also be concerned with how to get patients to adhere to CPAP treatment to improve cardiovascular health outcomes.

References

· Wilkins RL, Stoller JK, Kacmarek RM. Egan’s Fundamentals of Respiratory Care. 9th ed. St. Louis, MO: Mosby Elsevier; 2003:500-502.

· Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230-1235.

· Bekci TT, Kayrak M, Kiyici A, et al. The association among lipoprotein-associated phospholipase A2 levels, total antioxidant capacity and arousal in male patients with OSA. Int J Med Sci. 2011;8(5):369-376.

· O'Driscoll DM, Meadows GE, Corfield DR, Simonds AK, Morrell MJ. Cardiovascular response to arousal from sleep under controlled conditions of central and peripheral chemoreceptor stimulation in humans. J Appl Physiol, 2004;96:865-870.

· Brilakis ES, Khera A, McGuire DK, et al. Influence of race and sex on lipoprotein-associated phospholipase A2 levels: observations from the Dallas Heart Study. Atherosclerosis. 2008;199(1):110-115.

· Almendros I, Farré R, Torres M, et al. Early and mid-term effects of obstructive apneas in myocardial injury and inflammation. Sleep Med. 2011 Oct 25. [Epub ahead of print]

· Maruyama K, Morishita E, Sekiya A, et al. Plasma levels of platelet-derived microparticles in patients with obstructive sleep apnea syndrome. J Atheroscler Thromb. 2011 Nov 21. [Epub ahead of print]

· Ozeke O, Güngör M, Hızel SB, et al. Influence of the severity of obstructive sleep apnea on nocturnal heart rate indices and its association with hypertension. Anadolu Kardiyol Derg. 2011;11(6):509-514.

· Kabir MM, Dimitri H, Sanders P, et al. Cardiorespiratory phase-coupling is reduced in patients with obstructive sleep apnea. PLoS One. 2010;5(5):e10602.

· Gagnadoux F, Le Vaillant M, Goupil F, et al. Influence of marital status and employment status on long-term adherence with continuous positive airway pressure in sleep apnea patients. PLoS One. 2011;6(8):e22503.