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    Home > Active Ingredient News > Study of Nervous System > The chart summarizes the evidence from the latest consensus of SIIA: the relationship between sleep disorders, hypertension and cardiovascular disease and the diagnosis and treatment process

    The chart summarizes the evidence from the latest consensus of SIIA: the relationship between sleep disorders, hypertension and cardiovascular disease and the diagnosis and treatment process

    • Last Update: 2021-06-11
    • Source: Internet
    • Author: User
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    Hypertension is the main cause of cardiovascular disease, and timely identification and proper management of the factors affecting hypertension and its control are mandatory public health issues.

    Sleep disorders affect a variety of cardiovascular risk factors including hypertension by inducing neurohormonal changes and metabolic damage, thereby increasing the risk of cardiovascular events.

    There is evidence that qualitative and quantitative sleep disturbances are related to refractory hypertension and impaired circadian blood pressure variation.

    However, sleep disorders are often not recognized, or non-experts in the field have heterogeneity in their management.

    The Italian Society of Hypertension summarized the latest evidence linking sleep disorders with hypertension and cardiovascular disease, including the main underlying mechanisms and possible management strategies, and targeted hypertension and common sleep disorders, namely obstructive sleep apnea and Insomnia, a simplified, evidence-based diagnosis and treatment algorithm is proposed.

    Compiled and compiled by Yimaitong, please do not reprint without authorization.
    Overview Proper sleep-wake cycle obviously affects the neuroendocrine system, which is closely related to cardiovascular and internal metabolic balance.

    Therefore, qualitative and/or quantitative sleep disturbances can adversely affect the hypothalamic-pituitary-adrenal axis, glucose and lipid metabolism and the physiology of the cardiovascular system, thereby having a significant impact on the overall cardiometabolic risk.

     Specifically, a large number of observational studies and experimental evidence fully support the close connection between sleep disorders and arterial hypertension, cardiovascular disease, diabetes and/or obesity.

    Because these diseases have brought a heavy burden to the national health system and related economic losses and social impacts, adequate knowledge of sleep disorders and related solutions are essential for clinicians to participate in the prevention and treatment of cardiovascular and metabolic diseases.

     Among sleep disorders that affect blood pressure, obstructive sleep apnea (OSA) is associated with an increased risk of occasional and refractory hypertension, and night-time physiological blood pressure drops.

    Delaying falling asleep also increases the likelihood of high blood pressure.

    Secondly, sleep deprivation is a special cause of women's susceptibility to hypertension and cardiovascular disease; in addition, sleep deprivation can also change the expression of genes.

     The hypertension guidelines also emphasize the importance of studying refractory hypertension and night-time physiological blood pressure drops in reducing sleep disorders in patients.

    Therefore, when assessing patients with hypertension, it is essential to accurately collect the patient's history of sleep disorders.

    Classification of sleep disorders According to the International Classification of Sleep Disorders (ICSD), sleep disorders can be divided into the following categories: ➤Insomnia: It is defined as difficulty falling asleep or staying asleep, or a disease characterized by non-restorative sleep.

    This disease can affect subjective well-being and even cause psychological, cognitive, and physical changes during the day.
    It is the most commonly reported sleep disorder in clinical practice and the general population.

    It is often associated with other diseases, especially mental illness.

    It has been proved that the existence of insomnia can predict the onset of depression, anxiety, alcoholism or psychosis, and has the risk of suicidal ideation and behavior development.

     ➤Sleep-related breathing disorder: refers to all breathing disorders that occur during sleep, the most common being obstructive sleep apnea syndrome (OSAS).

    OSAS is caused by short but repeated breathing interruptions during sleep.

    This phenomenon can lead to the qualitative change of night rest, which can lead to symptoms such as excessive daytime sleepiness and fatigue when waking up.

     ➤Central hypersomnia disorder: It is characterized by excessive daytime sleepiness, which is a condition of primary hypersomnia, including narcolepsy-a pathological phenomenon characterized by excessive daytime sleepiness, which usually experiences repeated involuntary during the day Sleep attacks.

     ➤Circadian rhythm sleep-wake disorder: Delayed sleep phase syndrome.
    Patients tend to fall asleep between 3:00 am and 6:00 am and wake up between 12:00 pm and 3:00 pm.

     ➤ Parasomnia: It is a broad and heterogeneous sleep disorder, including abnormal and unconscious behaviors during sleep.

    It can be further divided into non-REM sleep abnormalities (such as sleepwalking and night terrors) and REM sleep abnormalities (such as REM sleep behavior disorder).

    The latter is characterized by the loss of physiological muscle paralysis during REM sleep.

    Therefore, during the episode, the patient exhibits excessive motor activity, usually in the form of sudden dream-related behaviors (such as screaming, punching and kicking).

    This disease can be accompanied by certain neurodegenerative diseases in 40% of cases, such as Parkinson's disease, multiple system atrophy and some forms of dementia.

     ➤Sleep-related dyskinesia: It is characterized by simple and repetitive movements that interfere with sleep and the onset of sleep.

    Restless Legs Syndrome (RLS) is a common disease characterized by a feeling of restlessness in the lower limbs when resting (usually at night), which affects the continuity of falling asleep and sleeping.

     The relationship between sleep disorders and cardiovascular diseases Over time, more and more evidence has begun to support the important relationship between sleep disorders and metabolic diseases and cardiovascular diseases.

    The main mechanism by which sleep disorders increase the morbidity and mortality of cardiovascular diseases is shown in Figure 1.

     Figure 1 The main mechanism that sleep disorders increase the morbidity and mortality of cardiovascular diseases.
    Sleep time and cardiovascular disease risk factors.
    Increasing data prove that there is a correlation between short sleep time and the risk of cardiovascular events (see Table 1 ), although there is a certain degree of heterogeneity in these data.

    This relationship may be related to hormone changes related to reduced sleep time (cortisol levels may rise, leptin levels may be suppressed, ghrelin levels, melatonin levels, and endocannabinoid system changes), insulin resistance, It can disrupt eating behavior (leading to overweight and obesity), thereby releasing pro-inflammatory cytokines.

    The relationship between long sleep time and the risk of cardiovascular complications does not seem to be clear.

     Table 1 The relationship between sleep time, cardiovascular risk factors and cardiovascular events.
    Note: "↑" or "↓" indicates an increase/decrease in the relative disease risk, and "=" indicates a similar risk compared with moderate sleep time. The same number of arrows indicates that there is no difference in the risk of short sleep time and long sleep time.

    "?" indicates controversial evidence.

     Abnormal sleep quality and cardiovascular risk In addition to sleep time, sleep quality disturbance may be another factor that negatively affects the cardiovascular system (Figure 1).

    Abnormal sleep quality includes frequent night awakenings caused by excessive sleep dispersion, respiratory sleep disorders (including OSA), and periodic movement of limbs (RLS) during sleep (Table 2).

     Table 2 Abnormal sleep quality and cardiovascular risk Note: "↑" and "=" indicate the strength of the association ("=": no connection; one, two, three or four "↑": indicate mild, moderate, Strong and very strong connection).

     Treatment of sleep disorders In order to better treat sleep disorders, especially when accompanied by high blood pressure or other cardiovascular risk factors, a correct sleep diagnosis should be made based on the collected medical history information, physical examination, and polysomnography.

     OSA is the first choice for the treatment of sleep disordered breathing, especially OSA, mainly based on the severity of the disease, the general characteristics of the patient, and possible comorbidities.

    The diagnostic examination and treatment options of OSA are shown in Figure 2.

    Figure 2 OSA diagnostic examination and treatment options.

    OSA: obstructive sleep apnea; BDZ: benzodiazepines; CPAP: continuous positive airway pressure; BIPAP: bilevel positive airway pressure; ASV: adaptive servo ventilation; MAD: mandibular advancement device.

     The gold standard for OSA treatment is to use continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP) devices through the patient's nasal cavity or nose and mouth.
    The choice of device depends on the patient's face shape.

    These ventilatory support devices provide positive airway pressure so that the patient can keep the airway open during sleep.

     In recent years, people have also developed a mandibular advancement device (MAD), which is worn during sleep to fix the lower jaw so that it is slightly higher than the upper jaw so that it will not block the airway during sleep.

    Treatment of insomnia The first-line treatment for insomnia is cognitive behavioral therapy, which should ideally be given before hypnotics are prescribed.

    Good sleep hygiene is an integral part of cognitive behavioral therapy.
    Regardless of the cause, it is important and is usually the only treatment needed for mild patients.

    Cognitive behavioral therapy for insomnia focuses on dealing with thoughts, worries, and behaviors that interfere with sleep.

     General guidelines recommend that the use of hypnotics should minimize abuse, misuse, and dependence.

     All hypnotics (except Ramelteamide, low-dose doxepin and Suvorexan) act on the benzodiazepine recognition site on the γ-aminobutyric acid receptor (GABA) and enhance the γ-amino group The inhibitory effect of butyric acid.

    Melatonin is registered as a 2mg sustained-release drug in Italy.
    It has specific first-line indications for insomnia patients over 55 years old, but it does not act on GABA receptors.

     Hypnotics differ mainly in elimination, half-life, and principle of action.

    Some hypnotics (such as first-generation benzodiazepines) may be more likely to induce residual sedation in the morning, especially after prolonged use and/or in the elderly, in which case they may also increase Risk of falls, confusion, and impaired cognitive abilities.

     In addition, European guidelines and Italian consensus both show that 2 mg of sustained-release melatonin is the first choice for patients with insomnia over 55 years of age, lasting up to 13 weeks.

    In addition to benzodiazepines and hypnotics, there are many other non-specific insomnia drugs used to induce and maintain sleep.

    Antihistamines such as doxorubicin and diphenhydramine can induce sleep.

    However, their efficacy is different; in addition, these drugs may cause adverse reactions such as confusion, urinary retention, and systemic anticholinergic side effects, which are very serious for the elderly.

     The effect of treatment of sleep disorders on blood pressure OSA studies have shown that treatment of OSA can significantly reduce BP, albeit not much.

    In the treatment of OSA syndrome, CPAP and MAD devices are mainly affected by blood pressure.

    A recent meta-analysis showed that the blood pressure of OSA patients receiving CPAP treatment decreased significantly, and the impact on patients with refractory hypertension and overnight blood pressure was more obvious.

     In terms of drug treatment, the most promising class of antihypertensive drugs that can reduce the severity of OSA and BP is diuretics, especially mineralocorticoid receptor antagonists, whose beneficial effects are believed to come from reducing peripheral edema and Volume overload, and reduction in volume transferred to the neck and central circulation in the supine position.

     In addition, other types of antihypertensive drugs have also shown convincing results.

    A study proved that acetazolamide combined with CPAP alone can reduce BP, vascular stiffness, and sleep-disordered breathing in patients with OSA and hypertension.

    In addition, a French study showed that OSA patients treated with valsartan had a greater reduction in BP compared with CPAP alone, regardless of day or night.

     Other sleep disorders A systematic review of the effects of non-respiratory sleep disorders and prolonged sleep on cardiometabolic risk factors included only three small-scale studies evaluating BP.

    None of these studies reported significant positive effects.

    However, a recent study using cognitive behavioral therapy to prolong the sleep of "short sleepers" and patients with prehypertension or stage 1 hypertension found that blood pressure was significantly reduced after treatment.

    However, data on the beneficial effects of treating insomnia and RLS on blood pressure are scarce and often controversial.

     Summary This guide aims to define a disease sharing approach that has a significant negative impact on cardiometabolic risk and related fatal/non-fatal events.

    In view of the current many confounding factors, further research is needed to better clarify the relationship between hypertension and sleep disorders.

     Literature Index: Italian Society of Hypertension (SIIA); SIIA Young Researchers Study Group; President of SIIA; Past President of SIIA; Italian Society of Hypertension (SIIA).
    Diagnostic and Therapeutic Approach to Sleep Disorders, High Blood Pressure and Cardiovascular Diseases: A Consensus Document by the Italian Society of Hypertension (SIIA).
    High Blood Press Cardiovasc Prev.
    2021 Mar;28(2):85-102.
    doi: 10.
    1007/s40292-021-00436-y.
    Epub 2021 Feb 25.
    PMID: 33630269 ; PMCID: PMC7952372.
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