Association of Severe Obstructive Sleep Apnea and Elevated Blood Pressure Despite Antihypertensive Medication Use

Abstract

Rationale:We hypothesized that untreated severe obstructive sleep apnea (OSA) is associated with elevated ambulatory blood pressure (BP) in subjects with high cardiovascular disease (CVD) risk despite medical management. Methods: Data from the baseline examination of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a 4-site randomized controlled trial were analyzed. Individuals with moderate-severe OSA (apnea hypopnea index, AHI = 15-50) and cardiovascular risk were recruited from cardiology practices. Those with hypertension were included. Intensive antihypertensive regimen (IAR) was defi ned as ≥ 3 antihypertensives including a diuretic. Defi nitions were: controlled BP (BP < 130/80), uncontrolled elevated BP (BP ≥ 130/80 not on IAR) and resistant elevated BP (BP ≥ 130/80 mm Hg despite IAR). Associations of untreated severe OSA (AHI ≥ 30) and uncontrolled and resistant elevated BP were evaluated using logistic regression analyses adjusted for age, sex, race, body mass index, smoking status, diabetes, and CVD. Results: Among the 284 participants (mean age 63.1 ± 7.2 years, 23.6% with severe OSA), 61.6% had controlled BP, 28.5% had uncontrolled elevated BP, and 9.9% had resistant elevated BP. Among participants prescribed IAR, resistant elevated BP was more prevalent in those with severe compared to moderate OSA (58.3% vs. 28.6%, p = 0.01). Participants with severe OSA had a 4-fold higher adjusted odds of resistant elevated BP (OR 4.1, 95% CI: 1.7-10.2), a fi nding not reproduced in the absence of IAR use. Conclusions: Among patients with increased cardiovascular risk and moderate to severe OSA, untreated severe compared to moderate OSA was associated with elevated BP despite IAR suggesting untreated severe OSA contributes to poor BP control despite aggressive medication use. S C I E N T I F I C I N V E S T I G A T I O N SO bstructive sleep apnea (OSA) is characterized by reduction in upper airway muscle tone resulting in repetitive complete (apnea) or partial (hypopnea) upper airway closure during sleep. OSA results in increased sympathetic nervous system activation, changes in baroreceptor function, increased oxidative stress, and endothelial dysfunction, which can increase blood pressure (BP).1-4 Respiratory events during sleep result in acute and transient BP perturbations,5,6 which persist during the daytime. These pathophysiological changes explain the association between OSA and hypertension (HTN) in several large-scale epidemiological studies. 7Elevations in BP including high normal BP often progress to HTN. 8 There are several large-scale epidemiological studies citing the importance of high normal BP and cardiovascular risk. In the Framingham Heart Study, high-normal BP (defi ned as systolic blood pressure of 130-139 or diastolic blood pressure of 85-89 mm Hg) was associated with an approximate 2-fold increased risk factor-adjusted cardiovascular disease (CVD) risk.9 These fi ndings are consistent in cross-ethnic groups. For example, another large prospective study of approximate...

Resistant Hypertension and Untreated Severe Sleep Apnea: Slowly Gaining Insight

“…6 There is also the possibility that underlying mechanisms associated with resistant HTN could worsen OSA, so that the relationship could be bi-directional, such that treatment of HTN could improve OSA severity. Aldosterone excess is a common cause of resistant HTN, and 20% of our resistant HTN population has biochemical evidence of primary aldosteronism.…”

“…6 Twelve weeks of CPAP therapy may result in a mild reduction in mean 24-hour BP (3.1 mm Hg) in patients with resistant HTN and an AHI > 15/ hour, which has the potential to reduce CVD risk. 9 Mechanisms of the association between resistant HTN and OSA severity are still being elucidated and may be bi-directional.…”

“…Those with severe OSA on multiple BP medications had an odds ratio of 4.1 (95% CI, 1.7-10.2) for having elevated BP, a fi nding not reproduced in participants not on ≥ 3 antihypertensive medications (including a diuretic). 6 By defi nition, resistant HTN consists of patients whose HTN is uncontrolled (BP > 140/90 mm Hg) while on 3 or more medications and occurs in approximately 10% to 15% of all hypertensive patients. 7 There is a very high prevalence of OSA in patients with resistant HTN.…”

“…13 It is notable that in Walia's cohort, none of the 28 subjects with elevated BP despite an intensive BP regimen were on an aldosterone blocker. 6 This could partially explain the correlation between uncontrolled BP, despite an intensive BP regimen and OSA severity. Our laboratory has noted a correlation between plasma aldosterone levels and OSA severity in resistant HTN patients.…”

“…6 This study examined patients with established stable coronary artery disease, or patients having three or more CVD risk factors. Exclusion criteria included heart failure (EF < 30% or NYHA classifi cation > 2), poorly controlled hypertension or diabetes, prior stroke, and absence of HTN.…”