Apneic Sleep,Insufficient Sleep

and Hypertension
[Meghna P. Mansukhani, Naima Covassin,
Virend K. Somers]

Dr Femi A.M.
07/10/2023 1

Registrar, Cardiology unit, UCH IBADAN

 OUTLINES:

 INTRODUCTION
 NORMAL SLEEP AND BLOOD PRESSURE(BP)
 SLEEP-RELATED BREATHING DISORDERS AND HYPERTENSION(HTN)
 MECHANISMS LINKING SLEEP APNEA AND HTN
 OBSTRUCTIVE SLEEP APNOEA(OSA) AND SYSTEMIC HTN
 INSUFFICIENT SLEEP, INSOMNIA, AND HTN
 CONCLUSIONS
 REFERENCES

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 INTRODUCTION
 OSA is the most common sleep-related breathing disorder, characterized by
repeated complete or partial upper airway inspiratory closure in sleep.

 OSA is associated with multiple adverse cardiovascular consequences,

including systemic HTN(the strongest association), pulmonary
hypertension, atrial fibrillation, heart failure, and stroke.

 Like OSA, Short sleep duration has been strongly associated with HTN by
recent studies via some shared mechanisms such as sympathetic activation.

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INTRODUCTION

 The article describes the normal physiology of BP in sleep and the literature
examining elevated BP in subjects with sleep-related breathing disorders
and insufficient sleep.

 The article also emphasizes on potential mechanisms underlying the

relationship between disrupted sleep and HTN and the impact of their
treatment on BP.

 The review is limited to studies of adult subjects.

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 NORMAL SLEEP AND BP

 Neural circulatory control of BP during sleep is stage dependent.

 Nonrapid Eye Movement(NREM) Sleep:

 Decrease in central respiratory drive results in a fall in minute ventilation
leading to a rise in blood CO2 levels.

 There is concomitant rise in parasympathetic tone with a decrease in

sympathetic activity.

 These changes progressively increase from lighter to deeper stages of

NREM(N1 through N3); BP, HR, CO and PVR all decrease in NREM stages and
are reasons why BP normally shows a dipping pattern at night.
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NORMAL SLEEP AND BP

 Rapid Eye Movement(REM) Sleep:

 Reduction in respiratory muscles tone(except diaphragm) with Simultaneous
decrease in sensitivity of the central chemoreceptors occur.

 Hence, ventilation decreases to levels even lower than that seen during NREM
sleep, and Paco2 levels start to rise.

 Neuronal surges during REM result in fluctuation in BP and HR similar to the

levels seen during wakefulness.

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NORMAL SLEEP AND BP

 WAKEFULNESS:
 Sudden increases in minute ventilation, HR, and BP are noted during arousals
and awakening.

 A rise in sympathetic activity and decline in parasympathetic tone leads to

rise in BP and HR during arousals and awakenings significantly exceeding
baseline wakefulness levels.

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SLEEP-RELATED BREATHING DISORDERS AND HTN

 OSA, the most common sleep-related breathing disorder, affects up to 24% of

men and 9% of women between 30 and 60 years of age in the general US adult
population.

 some other cohorts showed higher prevalence rates(eg, 50% of men and 23%
of women in a population-based study in Switzerland).

 The severity of OSA determines changes in BP during sleep in affected

patients

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 MECHANISMS LINKING SLEEP APNEA AND HTN

 Chemoreflexes:
 Recurrent episodes of sleep apnea lead to enhanced chemoreflex-mediated sympathetic
activation, result in increase in CO and sudden rise in BP that can be attenuated by CPAP.

 These sudden increases in BP may be responsible for the nondipping pattern of BP seen
in subjects with untreated OSA.

 Animal/human studies have demonstrated an increase in BP with repeated upper airway

closure and intermittent hypoxia, with hypercapnia and apnea as concomitant
mediators.

 Additionally, in subjects with OSA, repeated arousals from sleep especially in those with
persistent daytime sleepiness may contribute to persistent sympathetic overactivity and
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to the development of HTN over time
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MECHANISMS LINKING SLEEP APNEA AND
HTN
 Baroreflex:
 Blunted baroreceptor sensitivity in OSA subjects impairs acute autonomic
response to disordered breathing.

 long term repeated increases in BP may result in resetting of the

baroreceptors to a higher baseline BP level, contributing further to a
permissive sympathetic activation and BP elevation.

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MECHANISMS LINKING SLEEP APNEA AND HTN

 Central Control:
 An increase in the central neural response to chronic intermittent hypoxia
may contribute to the exaggerated acute sympathetic activity in OSA.

 There may also be a feedback loop wherein increased levels of serum

catecholamines stimulate central sympathetic nuclei, leading to further
increases in sympathetic tone

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MECHANISMS LINKING SLEEP APNEA AND HTN

 Cardiovascular Variability:
 Autonomic dysfunction in OSA subjects results in increased variability in BP;
impaired HR regulation and heightened vasomotor tone leads to hypertension.

 Vascular Mechanisms:
 Nighttime increases in endothelin release, endothelial cell dysfunction, and
apoptosis are seen in OSA, reversible with CPAP.

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MECHANISMS LINKING SLEEP APNEA AND HTN
 Renin-Angiotensin-Aldosterone System:
 Sympathetic activation results in the release of renin in the kidney, which leads to
increased production of Angiotensin II.

 This in turn increases sympathetic tone by acting through central and peripheral
mechanisms and can lead to the development of hypertension.

 Plasma aldosterone concentration and 24-hour urine aldosterone levels were found
to positively correlate with the apnea-hypopnea index in studies.

 Angiotensin production in response to hypoxemia may be increase tissue edema,

increasing upper airway obstruction and worsening OSA severity.

 A recent randomized proof-of-concept study of renal denervation in subjects with

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OSA and resistant HTN showed a reduction in OSA severity index suggesting a
potential interaction between renal sympathetics and OSA severity
MECHANISMS LINKING SLEEP APNEA AND HTN

 Aortic Stiffness:
 A marker of adverse cardiovascular outcomes, including HTN, has been associated with
OSA and sleep deprivation, and may play a role in the development of HTN.

 Hypothalamus-Pituitary-Adrenal Axis:
 Activation leads to an increase in vasopressin-induced increased BP. Sleep deprivation
are associated with higher serum cortisol levels that can also increase BP.

 Other Factors:
 Increased Oxidative stress, inflammation, disordered breathing events and impairment
of exercise tolerance may be a contributory factor to hypertension or other adverse
cardiovascular outcomes in subjects with OSA and must be further studied.
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OBSTRUCTIVE SLEEP APNOEA(OSA) AND SYSTEMIC
HTN

 OSA is seen in about 50% of those with HTN; 50% with HTN have comorbid OSA
which may be partially explained by shared risk factors eg obesity.

 Large epidemiological studies have shown OSA to be independently associated

with prevalent and incident HTN. OSA increases the risk of baseline and
future hypertension ≤12 years later in a dose-response manner.

 REM-related OSA has also been shown to be significantly associated with HTN
after accounting for confounders

 There has been strong association between HTN and OSA severity in those
with excessive daytime sleepiness(they have more severe nocturnal
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desaturation and higher diastolic BP)
OBSTRUCTIVE SLEEP APNOEA(OSA)
AND SYSTEMIC HTN
 OSA and Nondipping Pattern of BP:
 Nondipping of BP is a -ve prognostic indicator associated with increased
cardiovascular morbidity, LVH and microalbuminuria; contribute to the
adverse cardiovascular outcomes seen in subjects with OSA.

 Prevalence is high in OSA, between 50% and 80%.

 Nondipping BP causes in OSA subject appears to be age-related; severity of

respiratory abnormalities in younger individuals, whereas the severity of sleep
disturbance in older individuals.

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OBSTRUCTIVE SLEEP APNOEA(OSA)
AND SYSTEMIC HTN
 OSA and Resistant HTN:
 OSA is a common cause of resistant HTN and refractory HTN seen in approx.
70% of those with resistant HTN. The JNC 7 listed OSA as one of the
secondary causes of HTN.

 Studies revealed OSA subjects with cardiovascular disease, those with

untreated severe OSA had 4-fold higher odds of having resistant HTN.

 In Blacks, there is high prevalence of undiagnosed OSA and a >3-fold increase

in risk of having resistant HTN.

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OBSTRUCTIVE SLEEP APNOEA(OSA)
AND SYSTEMIC HTN
 Effects of Treatment of Sleep Apnea on Hypertension:
 CPAP has been shown to decrease sympathetic activity and BP in sleep
especially in those with severe OSA and coexisting DM.

 Reduction in BP is maximal in those with the longest hours of CPAP usage .

Fixed CPAP appears better than auto-titrating devices .

 There are synergistic effects between CPAP treatment and antihypertensive

medications and weight loss on decreasing BP in subjects with OSA compared
with either intervention alone.

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OBSTRUCTIVE SLEEP APNOEA(OSA)
AND SYSTEMIC HTN
 Effects of Treatment of Sleep Apnea on Hypertension:
 Recent meta-analyses have shown a reduction of 5 to 7 mm Hg in systolic BP
and 3 to 6 mm Hg in diastolic BP with the use of CPAP in subjects with OSA and
resistant HTN.

 Furthermore, a higher proportion of subjects with resistant HTN demonstrate a

dipping BP pattern after treatment with CPAP.

 The recent SAVE trial (Sleep Apnea Cardiovascular Endpoints) did not show a
beneficial effect of CPAP on major adverse cardiovascular events in subjects
with existing cardiovascular disease.

 Renal denervation has recently emerged as a potential therapeutic option for

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resistant HTN in patients with comorbid OSA

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INSUFFICIENT SLEEP, INSOMNIA, AND HTN
 Inadequate Sleep Duration:
 <2/3 of US adults sleep habitually >7 hours, a persisting state of sleep debt is thus
afflicting roughly one-third of Americans.

 Chronic sleep deficiency is an independent contributor to morbidity and mortality;

there are substantial linkage between short sleep and risk of HTN.

 While excessive sleep duration may be similarly harmful, the impact of long sleep
for future HTN is generally weaker.

 Studies have shown that associations between short sleep and elevated BP features
a demographic pattern, with greater vulnerability seen in women; younger and
middle-aged; blacks individuals
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INSUFFICIENT SLEEP, INSOMNIA, AND HTN

 Insomnia:
 The most frequent sleep disturbance; Sporadic insomnia symptoms are reported by
about 30% of the general population, and 6% to 10% for chronic insomnia disorder.

 Prevalence of HTN was found to be higher in those with insomnia than in those
without insomnia (14.9%–43.1% versus 12.8%–18.7%).

 Vgontzas et al found that odds ratios for HTN were 5-fold higher in insomniacs
sleeping <5Hrs than in normal sleepers.

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INSUFFICIENT SLEEP, INSOMNIA, AND HTN

 Insomnia:
 Mechanisms mediating HTN risk in insomnia include: abnormal neural circulatory
control; attenuated baroreflex sensitivity; increased sympathetic neural
cardiovascular reactivity to stress and enhanced hypothalamus-pituitary-
adrenal axis activity.

 This pattern of derangement supports state of physiological hyperarousal

responsible for BP elevation in insomnia.

 Insomnia has been implicated in progression of renal dysfunction; effective

treatment of insomnia may attenuate or reverse renal impairment, improving BP
control.
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INSUFFICIENT SLEEP, INSOMNIA, AND
HTN
 Shift Work:
 Shift workers experience a mismatch between behavioral rhythms, such as
rest/activity, sleep/wake, and fasting/feeding cycles, and biological
rhythms.

 Such misalignments may raise susceptibility to new-onset HTN and

progression toward more severe stages.

 Relative to day workers, those working alternative shifts have been found to
be more likely to have high BP and exhibit aberrant 24-hour BP pattern and
dampened dipping during sleep.
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INSUFFICIENT SLEEP, INSOMNIA, AND
HTN
 Shift Work:
 Sympathetic cardiac predominance, increased inflammation, sleep
deficiency, augmented insulin and glucose levels are possible mechanisms.

 Timed exposure to bright light, exogenous melatonin supplementation,

assigning habitual early risers(larks) to the early morning shift and habitual
late sleepers(owls) to the late night shift are areas of remediation strategies.

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 CONCLUSIONS
 Fluctuations in autonomic activity occur during stages of normal physiologic sleep; alterations in
these events from disrupted sleep has been strongly linked with HTN.

 Sleep disorders like OSA and insomnia have strong associations with HTN.

 OSA is associated with BP in a dose-response fashion, and treatment of OSA results modest reduction
in 24-hour BP in those with HTN.

 OSA is associated with nondipping of BP at night and is one of the most common causes of resistant
HTN; treatment of OSA may reverse nondipping and facilitate BP control in resistant HTN.

 CPAP treatment of OSA lower BP especially in those with excessive daytime sleepiness.
Normalization of sleep times and optimization of sleep quality may yield significant benefits

 The widespread prevalence of insufficient sleep and insomnia, along with their consequences in
terms of heightened hypertension risk, justifies the urgency of developing
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preemptive and corrective public health interventions.

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