Heart disease and stroke are leading causes of death and disability. High blood pressure (BP) is a major risk factor for both.
The 2017 guidelines regarding “Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure” (JNC 7) were recently published, which is an update incorporating new information from studies regarding BP-related risk of cardiovascular disease (CVD) and strategies to improve HTN (HTN) treatment and control.
Screening for secondary causes of HTN is necessary for new-onset or uncontrolled HTN in adults, including drug-resistant HTN. Screening includes testing for obstructive sleep apnea, which is highly prevalent in this population.
Obstructive sleep apnea is a common chronic condition characterized by recurrent collapse of upper airways during sleep, inducing intermittent episodes of apnea/hypopnea, hypoxemia, and sleep disruption (Pedrosa RP, et al. Chest. 2013;144:1487).
It is estimated to affect 17% of US adults but is overwhelmingly underrecognized and untreated (JAMA. 2012;307:2169). The prevalence is higher in men than women. The major risk factors for OSA are obesity, male sex, and advancing age. Since these conditions oftentimes predispose to and are concomitant with HTN, it can be challenging to determine the independent effects of OSA on the development of HTN.
The relationship between obstructive sleep apnea (OSA) and HTN has been a point of interest for decades, with untreated OSA being associated with an increased risk for developing new-onset HTN (JAMA. 2012;307:2169).
There have been several landmark trials that have sought to determine the extent of a causal relationship between OSAS and HTN. Sleep Heart Health Study (Sleep. 2006;29;1009) was one such study, which was limited by the inability to prove that OSA preceded the onset of HTN.
Wisconsin Sleep Cohort (N Engl J Med. 2000;342:1378) was another landmark prospective longitudinal study that implicates OSA as a possible causal factor in HTN. The notable limitation of the study was the presence of HTN after initial assessment was found to be dependent upon the severity of OSA at baseline.
While these two cohort studies found an association between OSA and HTN, the Vitoria Sleep Cohort out of Spain (Am J Respir Crit Care Med. 2011;184:1299), the third and most recent longitudinal cohort study, looked at younger and thinner patients than the SHHS and the Wisconsin Sleep Cohort, failed to show a significant association between OSA and incident HTN. Methodologic differences may help to explain the disparity in results.
NREM sleep has normal circadian variation of BP, causing “dipping” of both systolic and diastolic BP at night due to decreased sympathetic and increased parasympathetic activity. REM sleep has predominant sympathetic activity and transient nocturnal BP surges.
OSA results in hypoxemia, which causes nocturnal catecholamine surges, resulting in nocturnal increase in heart rate and BP that is most prominent during post-apneic hyperventilation.
Reduced nocturnal BP (nondipping) or even higher nocturnal BP than daytime BP is an undoubted risk factor for hypertensive patients due to the end-organ damage and subsequent cardiovascular events. With sleep apnea, sleep quality is decreased due to frequent arousal from sleep (Hypertension. 2006;47:833).
Sleep duration of less than or equal to 5 hours per night was shown to significantly increase risk for HTN in patients less than or equal to 60 years of age, even after controlling for obesity and diabetes.
Sleep Heart Health Study suggests that sleep duration above or below a median of 7 to 8 hours per night is associated with a higher prevalence of HTN (Sleep. 2006;29:1009). Thus, improving duration and quality of sleep in sleep apnea patients may help decrease the risk of developing HTN.
Key question: Will treatment of OSA appreciably alter BP?
Continuous positive airway pressure (CPAP) is an efficacious treatment of choice for OSA. Interventional trials, though limited by issues related to compliance, have shown CPAP to acutely reduce sympathetic drive and BP during sleep. However, this improvement in BP control is not entirely consistent in all patients with the data being less clear-cut regarding nighttime CPAP therapy and impact on daytime BP.
A randomized controlled trial from Barbe et al suggests that normotensive subjects with severe OSA but without demonstrable daytime sleepiness are immune to the BP-reducing effects of CPAP (Ann Intern Med. 2001;134:1015); those who were objectively sleepy had a more robust response to the BP lowering effects of CPAP with better cardiovascular outcomes among patients who were adherent to CPAP therapy (≥4 hours per night).
Sleep Apnea Cardiovascular Endpoints (SAVE) study looked at CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea (N Engl J Med. 2016;375:919). CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood, but the risk of serious cardiovascular events was not lower among patients who received treatment with CPAP in addition to usual care compared with usual care alone. This study was not powered to provide definitive answers regarding the effects of CPAP on secondary cardiovascular end points, and the use of PAP was less than 4 hours.
A recent systematic review and meta-analysis looked at “Association of Positive Airway Pressure with Cardiovascular Events and Death in Adults with Sleep Apnea” (JAMA. 2017;318(2):156). No significant associations between PAP treatment and a range of cardiovascular events were noted in this meta-analysis.
It is possible that the limited adherence to therapy in many trials was insufficient to drive protection, along with short follow-up duration of most trials that may have given insufficient time for PAP to have affected vascular outcomes.
In a cross-over study of valsartan and CPAP, combining drug treatment with CPAP appeared to have a more synergistic effect in reducing BP than either agent alone (Am J Respir Crit Care Med. 2010;182:954).
The beneficial effect of CPAP remains an open question. Considering the multifactorial pathophysiology of OSA-associated HTN, proven therapies, such as BP lowering, lipid lowering, and antiplatelet therapy, along with PAP therapy, should be utilized. This combination strategy is likely to be more effective in improving both nocturnal and daytime BP control in OSA.