The pathophysiology of Hypertension and Obstructive Sleep Apnea

The pathophysiology of Hypertension and Obstructive Sleep Apnea

The pathophysiology of Hypertension and Obstructive Sleep Apnea

Hypertension and its epidemiology :

Hypertension is a leading preventable risk factor for Cardiovascular disease (CVD) and all-cause mortality worldwide (1,2). In 2010, a total of 1.38 billion people (31.1% of the global adult population) had hypertension, defined as systolic blood pressure (SBP) ≥ 140mmHg and or/ diastolic BP (DBP) ≥ 90 mmHg. The prevalence of hypertension is 46%, according to a report from WHO in 2021. Men are more prevalent to have hypertension (about 1 in 4), while about 1 in 5 women have hypertension.  The global mean age-standardized DBP was 78.7mHg in men and 76.7 mmHg in women (3). Higher mean SBP and DBP in both men and women were found in South Asia, sub-Saharan Africa, and Central and Eastern Europe, whereas lower mean BPs were found in high-income Western and high-income Asia-Pacific regions (3). Notably, more than half of adult hypertensive patients are undiagnosed and untreated. Even for treated patients, only 1 in 5 these patients have an effective treatment with well-controlled blood pressure.

For more information, you may also refer to the infographics provided by WHO on hypertension: https://cdn.who.int/media/docs/default-source/documents/hypertension-infographic-005-web.pdf?sfvrsn=f0973d0c_2

Social and Economic Burden of HT

The prevalence and absolute burden of hypertension are rising globally, especially in low and middle-income countries (LMICs). Awareness and proper management of hypertension are unacceptably low worldwide, especially in LMICs (4,5). A global burden of disease study estimated in 2015 around 3.5 billion adults worldwide had SBP of at least 110-115 mmHg, a level that is associated with an increased risk of ischaemic heart disease (IHD), stroke, and kidney disease. This prevalence represents a marked increase from 1990 when only 1.87 billion people had an SBP of at least 110-115mmHg (3).

Emerging guidelines for blood pressure proposed on 2017

In 2017, the American College of Cardiology / American Heart Association Task Force on Clinical Practice Guidelines redefined the classification of hypertension (6). While hypertension was commonly defined as SBP ≥ 140mmHg and or/ diastolic BP ≥ 90 mmHg over the past 30 years, new guidelines in recent years advocated the re-classification of hypertension as 130/80 mmHg and higher for all adults. With the lowering of SBP and DBP for hypertension and without stratification of age, the new guidelines provided more stringent criteria to highlight the importance to patients with the potential underlying risk of subsequent cardiovascular development. Based on previous meta-analysis findings from 48 randomized clinical trials involving 344716 participants with a mean age of 65 years, the relative reduction in the risk of developing major cardiovascular events was proportional to the magnitude of achieved reduction in blood pressure. For each 5-mmHg reduction in SBP, the risk of developing cardiovascular events dropped by 10% (7). Furthermore, lowing blood pressure was effective in preventing major cardiovascular events regardless of individuals with previous cardiovascular comorbidities (7). By lowering of SBP to <130 mmHg, compared to the traditional SBP target of <140 (130-139) mmHg, was consistently associated with a 25-30% relative risk reduction in cardiovascular events (8). However, it is worthwhile to note that the prevalence of hypertension in the US increased from 32.0% to 45.4% and 23.2% to 46.4% in the Chinese population respectively. And it is expected to surge in prevalence among LMICs and high-income countries (HICs) after the recent implementation of hypertension re-classification (5).

Blood pressure is now re-categorized in the following:

  1. Normal – less than 120/80 mmHg;
  2. Elevated: SBP between 120-129 and DBP <80;
  3. Stage 1: SBP between 130-139 / DBP between 80-89;
  4. Stage 2 : SBP≥ 140 mmHg /DBP ≥ 90 mmHg

Hypertensive crisis: SBP ≥ 180 mmHg/ DBP ≥ 120mmHg, with patients needing prompt changes in medication if there are no other indications of problems or immediate hospitalization if there are signs of organ damage.

Definition of resistant and refractory hypertension, and prevalence of OSA in hypertensive patients

As mentioned before, only a minority of patients (approximately 21%) with HT have well-controlled BP. Poorly controlled hypertension remains a strong cause of cardiovascular morbidity and mortality worldwide. It is, therefore, crucial to control blood pressure well as a small drop of 2 mmHg in DBP on a population-based may result in an overall decrease of 17% in the prevalence of hypertension, a 6% reduction in coronary heart disease risk, and 15% reduction in the risk of stroke and transient ischemic attack (9). Among these 4 in 5 patients with poor control of blood pressure, 25% of the hypertensive patients are classified as resistant HT that patients have elevated blood pressure even after the concurrent use of at least 3 classes of anti-hypertensive drugs. Among these patients with resistant HT, a minor of 5% of patients fall into refractory HT which patients have uncontrolled blood pressure despite the concurrent use of at least 5 different classes of anti-hypertensive drugs. Treatment-resistant hypertension is often associated with a greater risk of end-stage renal disease (ESRD), ischemic heart disease, heart failure, stroke, and mortality compared with non-treatment-resistant hypertension (8).

In addition, OSA and hypertension commonly coexist. About 50% of patients with OSA are hypertensive, whereas more than 50% of hypertensive patients have OSA (10–14). Among the patients with resistant HT, about 70-80% of the patients have OSA (15), and the prevalence of OSA can be as high as 90% in patients with refractory HT (16).

Hypertension and associated sleep-related disorders

Sleep-related disorders (such as insomnia and OSA) that induce increased BP would be anticipated to affect cardiovascular risks (17) significantly. While both sleep deprivation and insomnia have been associated with an increase in the incidence and prevalence of hypertension, extensive studies also demonstrated the strong correlation between the severity of OSA and the risk as well as the severity of hypertension. Cross-sectional studies of 238 adolescents without sleep apnea or severe comorbidities were conducted from Cleveland Children’s Sleep and Heart Study. In their unadjusted analysis, the odds of pre-hypertension were increased 4.5-fold in adolescents with poor sleep efficiency and 2.8-fold in those with short sleep. Adjusted analyses showed that adolescents with low sleep efficiency, with a mean of 4.0 ± 1.2 mmHg higher SBP compared to other children (p<0.001), suggest poor sleep quality is associated with pre-hypertension even in healthy subjects (18).

Ambulatory BP studies indicate that even small increases in BP, particularly night-time BP levels, are associated with a significant increase in cardiovascular morbidities and mortality. Lack or diminished nocturnal reduction of BP is a strong and independent predictor of cardiovascular risk. In fact, large prospective studies reported that ambulatory BP is superior in predicting cardiovascular mortality compared to daytime BP in clinical settings. Moreover, nocturnal BP measurement was the strongest predictor of outcome (19).

The overlapping conditions between hypertension and obstructive sleep apnea

Previous cross-sectional studies showed that moderate to severe OSA (with apnea-hypopnea index [AHI] > 15 events/h) is significantly associated with the risk of having arterial hypertension. Furthermore, a linear relationship between AHI and hypertension was observed, indicating the severity of OSA is proportionally related (dose-dependent fashion) to the increased risk of hypertension and its severity (12). Large observational longitudinal studies also showed subjects with baseline normal BP but with moderate to severe OSA had 3.2-fold increased odds of developing hypertension compared with subjects without OSA after 4 years of follow-up (20,21).  It is also interesting to note that there are several prominent and similar clinical characteristics between patients with OSA and hypertension. Obesity is one of the major indicators in patients with OSA and hypertension. Other predictors include ethnic differences, age, alcohol abuse, and smoking (22).

Effect of Continuous Positive Airway pressure (CPAP) on BP

Although the causal relationship between OSA and hypertension remains unclear, the effective OSA treatment by CPAP has shown a modest antihypertensive effect. In addition, greater beneficial effects were reported among patients with more severe OSA and high CPAP compliance. Trigger on sympathetic activation by OSA has been proposed as a potential mechanism of OSA-induced hypertension. The sympathetic activation in patients with untreated OSA can last during the daytime, and it is not limited to the sleep period. These heightened sympathetic activities may increase BP via increasing vascular resistance and cardiac output, probably triggering the renin-angiotensin-aldosterone system (23). Therefore, it is particularly important that effective OSA treatment should be administered to OSA patients to prevent aberrant activation of the sympathetic pathways (24).

How Belun can facilitate Hypertension treatment

Belun Sleep System has the capability of monitoring and analyzing SpO2, heart rate variability (HRV), photoplethysmography (PPG) waveform, and accelerometer-derived actigraphy data. It can calculate an estimated apnea-hyponea index (bAHI). It can also differentiate wakefulness from sleep and perform sleep stage analysis and give REM sleep duration and NREM sleep duration using its artificial intelligence platform. From the PPG assessment provided by Belun Healthcare Platform, objective sleep impairments data (eg. prolonged sleep latencies, reduced sleep time, fluctuations in heart rate, and heart rate variability) can be provided to clinicians with a more accurate diagnosis of the severity of OSA, monitoring the efficacy of CPAP titration treatment and sleep quality improvements. In addition, we are the only PPG device so far that could also provide parallel autonomic nervous system (ANS) activities, including sympathetic and parasympathetic activities apart from sleep data throughout the monitoring period. This may eventually help improve the blood pressure of patients with both OSA and hypertension in the hope of reducing the development of cardiovascular comorbidities.

Although polysomnography is currently the gold standard for measuring sleep quality, the test is costly, not easily available, and required skilled sleep technicians for assessment. Belun Sleep System herein serves to provide a cost-effective, readily available, automated, no-skilled technician-needed solution to clinicians and patients with OSA population-wide in the hope of reducing the subsequent incidence, prevalence of hypertension, and associated cardiovascular risks.

Partnering with Belun :

Up to now, over a hundred organizations, including HK hospital authority hospitals, medical groups, clinic groups, dentists, and elderly centers selected to use the Belun Sleep SystemBelun® Ring and Sleep App, and Belun® remoVital monitoring system. Many doctors read our medical journal papers, including: 

1) “Belun® Ring Platform: a novel home sleep apnea testing system for assessment of obstructive sleep apnea” (https://jcsm.aasm.org/doi/10.5664/jcsm.8592),

2) “Detection of obstructive sleep apnea using Belun Sleep Platform wearable with neural network based algorithm and its combined use with STOP-Bang questionnaire” (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258040),

3)Belun® Ring (Belun Sleep System BLS-100): Deep Learning-Facilitated Wearable Enables OSA Detection, Apnea Severity Categorization, and Sleep Stage Classification in Patients Suspected of OSA  (https://journals.lww.com/jhypertension/Abstract/2023/06000/The_Belun_sleep_platform_to_diagnose_obstructive.16.aspx), 

4) Correlation of Pulse Rate Variability(PRV) and Heart Rate Variability(HRV) Metrics During Sleep in Subjects Suspected of OSA (Accepted in SLEEP conference 2023, Abstract ID: 954).

If you would like to know more about how to adopt Belun’s solution in your organization or home use, please feel free to contact us to schedule a meeting by filling out the form below:

References:

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3.            NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet. 2017 Jan 7;389(10064):37–55.

4.            Chow CK, Teo KK, Rangarajan S, Islam S, Gupta R, Avezum A, et al. Prevalence, Awareness, Treatment, and Control of Hypertension in Rural and Urban Communities in High-, Middle-, and Low-Income Countries. JAMA. 2013 Sep 4;310(9):959–68.

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10.          Fletcher EC, DeBehnke RD, Lovoi MS, Gorin AB. Undiagnosed sleep apnea in patients with essential hypertension. Ann Intern Med. 1985 Aug;103(2):190–5.

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14.          Sjöström C, Lindberg E, Elmasry A, Hägg A, Svärdsudd K, Janson C. Prevalence of sleep apnoea and snoring in hypertensive men: a population based study. Thorax. 2002 Jul;57(7):602–7.

15.          Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001 Dec;19(12):2271–7.

16.          Martínez-García MA, Navarro-Soriano C, Torres G, Barbé F, Caballero-Eraso C, Lloberes P, et al. Beyond Resistant Hypertension. Hypertension. 2018 Sep;72(3):618–24.

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20.          Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000 May 11;342(19):1378–84.

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24.          Nocturnal Continuous Positive Airway Pressure Decreases Daytime Sympathetic Traffic in Obstructive Sleep Apnea | Circulation [Internet]. [cited 2022 Aug 12]. Available from: https://www.ahajournals.org/doi/10.1161/01.cir.100.23.2332