Ludger Grote

Association between blood pressure reduction with antihypertensive treatment and sleep apnea activity

This study investigated whether a drug therapy-induced reduction in nocturnal blood pressure (BP) was associated with decreased sleep apnea activity. Two polysomnographies from 54 hospitalized male hypertensive, obstructive sleep apnea patients were analyzed in a double-blind, randomized, parallel-group trial of the angiotensin-converting enzyme inhibitor cilazapril (C), 2.5 mg once daily, or placebo (P). Blood pressure was measured by means of an intra-arterial catheter. Compared with P, C lowered mean arterial BP during non-rapid eye movement (NREM) (-8.3 +/- 10.7 mm Hg, P = .05) and REM sleep (-8.6 +/- 10.1 mm Hg, P = .02). Respiratory disturbance index (-8.6 +/- 3.2 events/h of sleep (n/h), P = .01) and apnea index (AI) (-6.6 +/- 3.0 n/h, P = .04) during NREM sleep were lowered by C and, to a lesser extent, by P (-5.9 +/- 3.2 n/h, P = .07 and -5.0 +/- 3.6 n/h, P = .18, respectively). The effect on AI and hypopnea index (HI) during REM sleep was not significant for C (-5.9 +/- 3.4 and 0.1 +/- 2.0, NS, respectively) and P (-2.6 +/- 3.9 and 1.6 +/- 2.0, NS, respectively). There was a significant linear correlation between the change in REM systolic BP and the change in REM AI (r = 0.28, P = .04); the mean BP change correlated negatively with the change in HI (-0.28, P = .04). During NREM sleep there was no significant correlation between changes in BP and the treatment effects on sleep apnea activity. Blood pressure reduction after short-term antihypertensive treatment did not affect sleep disordered breathing during NREM sleep. Reduced BP was associated with a weak reduction of AI and a slight increase of HI during REM sleep. It appears that elevated BP contributes only marginally to sleep apnea severity in hypertensive patients with obstructive sleep apnea.

Does short‐term treatment with modafinil affect blood pressure in patients with obstructive sleep apnea?

To investigate the effects of modafinil, a central nonamphetamine awakening substance, on blood pressure and heart rate in hypersomnolent patients with obstructive sleep apnea.

Intrathoracic pressure changes and cardiovascular effects induced by nCPAP and nBiPAP in sleep apnoea patients

SUMMARY  The effect of nasal continuous positive airway pressure (nCPAP) and nasal bi‐level positive airway pressure (nBiPAP) on intrathoracic pressure and haemodynamics during wakefulness was studied in a group of nine patients with severe sleep apnoea. No patient took cardiovascular medication.

Cardiovascular effects of mibefradil in hypertensive patients with obstructive sleep apnea

AbstractObjective: Hypertension is often seen in obstructive sleep apnea (OSA) and is characterized by increased sympathetic activity, depressed baroreflex and accentuated vascular responsiveness. The objective of this study was to investigate the effects of the new T-selective calcium channel blocker mibefradil on invasively measured blood pressure (BP) and heart rate in hypertensive patients with OSA. Methods: The present study was a double-blind, randomized and placebo-controlled before and after trial in two parallel groups. Fifty-three men aged 23–69 years with systemic hypertension and OSA were recruited from the Outpatient Department of the Marburg University Sleep Laboratory and hospitalized for 10 days. Mibefradil (50 mg) or placebo were given orally in the morning for 8 days. The main outcome measure was the mean arterial (radial) BP monitored continuously during nocturnal sleep and during standardized daytime physical and psychological performance testing. Results: Mibefradil lowered mean arterial BP and heart rate with (SD) during the entire measurement period compared with placebo: −7.25 (9.59) vs −2.11 (8.43) mmHg (P = 0.039) and −4.83 (5.94) vs −1.34 (4.13) bpm (P = 0.022), respectively. Both effects were observed during nocturnal sleep and performance testing, including graded exercise. Adverse events did not differ compared with placebo. Conclusion: Mibefradil is an effective but well-tolerated antihypertensive that also lowers heart rate over 24 h in OSA, in conditions known to increase BP.

Nocturnal Hypertension and Cardiovascular Risk: Consequences for Diagnosis and Treatment

General use of ambulatory noninvasive 24-h blood pressure monitoring in many patients has shown that new criteria for arterial hypertension are useful. A classification of circadian blood pressure in “dippers” and “nondippers” (no physiologic drop of blood pressure) needs to be specified. An altered circadian blood pressure profile, like that in nondippers, was used as a diagnostic criterion for secondary hypertension. Recent epidemiologic studies in patients with essential hypertension have shown that nondippers are at higher risk for cardiovascular complications such as myocardial infarction and cerebrovascular insult. The studies also revealed that sleep-related breathing disorders (SRBD) are characterized by increased cardiovascular risk. Increases in blood pressure caused by SRBD could be documented, with the highest amount occurring during REM sleep. A study performed in a general practice showed a high incidence (40/112) of nondippers in a group of snoring middle-aged men with obesity and daytime fatigue. This indicates diagnostic and therapeutic consequences for the control of 24-h blood pressure, including nocturnal breathing pattern and daytime symptoms due to SRBD. The goal of antihypertensive drug therapy is to reduce blood pressure significantly during the day and during the night in different stages of wakefulness and sleep. A new protocol was designed to investigate blood pressure over 24 h under a standardized load, including nocturnal hypertension. The angiotensin-converting enzyme (ACE) inhibitor cilazapril was used in this test procedure and showed a significant and clinically relevant mean blood pressure reduction of 10.0 mm Hg (versus placebo 4.3 mm Hg) over 24 h.

Effect of Angiotensin Converting Enzyme inhibition [Cilazapril] on blood pressure recording in hypertensive obstructive sleep apneic patients

We investigated the efficacy of an Angiotensin Converting Enzyme [ACE] inhibitor on daytime and night-time blood pressure in 55 male hypertensive patients with moderately severe to severe obstructive sleep apnea. We resolved to determine if treatment oriented towards the reduction of hypertension would be successful, despite persistent repetitive hypoxemia and sleep-disordered breathing. The study was a randomized, double-blind, single daily dose, placebo-controlled protocol, with 8 days drug intake (placebo or 2.5 mg Cilazapril) and monitoring on the final day of drug administration. Subjects underwent continuous 24-h arterial blood pressure monitoring during baseline and treatment conditions. Polysomnography was performed at night during the 24-h arterial monitoring period. Cilazapril (2.5 mg) lowered systolic, diastolic and mean blood pressure, despite persistence of repetitive obstructive apneas during sleep and the associated repetitive hypoxemia. The lowering of blood pressure occurred without a significant change in heart rate, and was noted during nocturnal sleep, performance testing and graded exercise.

[Sleep apnea--treatment improves hypertension].

ZusammenfassungDie obstruktive Schlafapnoe und die arterielle Hypertonie sind sehr häufige, aber leider auch oft nicht erkannte Erkrankungen. Der ursächliche Zusammenhang von Schlafapnoe und Hypertonie ist gesichert. Wahrscheinlich ist die undiagnostizierte Schlafapnoe die häufigste Ursache der früher so genannten „essentiellen“ Hypertonie. Besonders wichtig erscheint daher die Identifikation dieser Patienten. Bei allen Hypertonikern sollten nach Schnarchen, Atemstillständen und Tagesmüdigkeit gefragt werden, der Halsumfang gemessen und ggf. eine ambulante Messung der nächtlichen Atmung (kardiorespiratorische Polygraphie) erfolgen. Insbesondere sollten alle Patienten mit schwer einstellbarer Hypertonie oder fehlender Nachtabsenkung in der 24-h-Blutdruckmessung auf ein obstruktives Schlafapnoesyndrom gescreent werden. Umgekehrt sollten alle Patienten mit Schlafapnoe gezielt auf eine arterielle Hypertonie untersucht werden. Da bei diesen Patienten auch nur eine nächtliche arterielle Hypertonie vorliegen kann, reichen Einzelmessungen am Tage nicht aus, um einen Bluthochdruck sicher auszuschließen.Die CPAP-Therapie („continuous positive airway pressure“) kann den Blutdruck bei hypertensiven Schlafapnoepatienten effektiv senken. Dies gilt besonders für Patienten mit obstruktiver Schlafapnoe und therapierefraktärer Hypertonie. Für nächtliche, durch Schlafapnoe induzierte Blutdruckspitzen scheint die CPAP-Therapie die zurzeit am besten dokumentierte Therapieform zu sein.AbstractObstructive sleep apnea and arterial hypertension are frequent diseases, but they are also often overlooked. There is a causal relationship of sleep apnea and hypertension. Undiagnosed sleep apnea is probably the most important reason for “essential” hypertension. It is important to identify these patients. All hypertensive patients should be asked for snoring, breathing arrest and daytime sleepiness, neck circumference should be measured, and an ambulant sleep apnea monitoring should be performed, if necessary. Especially patients with refractory hypertension or non-dippers should be screened for sleep apnea and patients with sleep apnea should be examined for arterial hypertension.Continuous positive airway pressure (CPAP) can effectively lower blood pressure in the hypertensive sleep apnea patient. This is especially true for the obstructive sleep apnea patient with refractory hypertension. CPAP therapy is probably the best therapy for sleep apnea-induced nocturnal blood pressure rises.

Twenty-four-hour blood pressure control : effect of cilazapril on continuous arterial blood pressure during sleep, and physical and mental load in patients with arterial hypertension and sleep apnea

Summary To assess the effectiveness of cilazapril in regulating blood pressure (BP) in patients with sleep-related breathing disorders, 23 male patients (mean age, 50 years; mean body mass index, 32.7 kg/m2) with a mean apnea/hypopnea index of 49.7 and arterial hypertension (163/104 mm Hg) participated in a placebo-controlled, randomized, double-blind study. They received either cilazapril, 2.5 mg/day (n = 12) or placebo (n = 11). The effects of treatment were studied under different conditions of sleep and physical and mental load before and after 8 days of treatment. Measurements by night included cardiorespiratory polysomnography, inductive plethysmography. pulse oximetry and nasal air flow, electroencephalography, (EEG), electrooculography and electromyography, (ECG), and blood pressure (BP). Measurements by day (ECG, heart rate, and BP) were performed at rest and under physical and mental load. Systolic, diastolic, and mean BP (5 min at night; 1 s during the day), heart rate, apnea and hypopnea index, EEG data, and test reaction times were compared in both groups. The systolic and diastolic BP of patients receiving cilazapril was lower compared to baseline for all physical and mental loads. Mean BP reductions over all standardized loads was greater with cilazapril than placebo (-10 vs. −4.3 mm Hg, p < 0.05). These results show that BP is influenced similarly by mental and physical loads, and that behavior [i.e., awake state and non-rapid eye movement and rapid eye movement (NREM and REM) sleep determines BP regulation. Cilazapril is effective in reducing BP in all situations, especially during REM sleep hypertension.

Changes in upper airway resistance during progressive normocapnic hypoxia in patients with obstructive sleep apnoea syndrome

SUMMARY  The responses of the upper airway to progressive normocapnic hypoxia were studied in 6 healthy men and in 6 patients with obstructive sleep apnoea syndrome (OSAS). The upper airway resistance was calculated by the ratio of the laryngeal pressure (measured using a catheter introduced into oesophagus) to the inspiratory flow. Additionally, genioglossal EMG activity (GG‐EMG) was measured and analysed. The changes of all variables were analysed individually for each subject. The OSAS patients showed reduced ventilatory response, GG‐reactivity and changes in upper airway resistance during progressive hypoxia. It is concluded that impaired reactivity to hypoxic activation (probably due to the process of adaptation of carotid chemoreceptors to nocturnal hypoxia), might reduce the defence abilities of OSAS patients against episodes of obturation in upper airway and obstructive apnoea events.

Schlafapnoe – Behandlung verbessert Hypertonie@@@Sleep Apnea – Treatment Improves Hypertension

ZusammenfassungDie obstruktive Schlafapnoe und die arterielle Hypertonie sind sehr häufige, aber leider auch oft nicht erkannte Erkrankungen. Der ursächliche Zusammenhang von Schlafapnoe und Hypertonie ist gesichert. Wahrscheinlich ist die undiagnostizierte Schlafapnoe die häufigste Ursache der früher so genannten „essentiellen“ Hypertonie. Besonders wichtig erscheint daher die Identifikation dieser Patienten. Bei allen Hypertonikern sollten nach Schnarchen, Atemstillständen und Tagesmüdigkeit gefragt werden, der Halsumfang gemessen und ggf. eine ambulante Messung der nächtlichen Atmung (kardiorespiratorische Polygraphie) erfolgen. Insbesondere sollten alle Patienten mit schwer einstellbarer Hypertonie oder fehlender Nachtabsenkung in der 24-h-Blutdruckmessung auf ein obstruktives Schlafapnoesyndrom gescreent werden. Umgekehrt sollten alle Patienten mit Schlafapnoe gezielt auf eine arterielle Hypertonie untersucht werden. Da bei diesen Patienten auch nur eine nächtliche arterielle Hypertonie vorliegen kann, reichen Einzelmessungen am Tage nicht aus, um einen Bluthochdruck sicher auszuschließen.Die CPAP-Therapie („continuous positive airway pressure“) kann den Blutdruck bei hypertensiven Schlafapnoepatienten effektiv senken. Dies gilt besonders für Patienten mit obstruktiver Schlafapnoe und therapierefraktärer Hypertonie. Für nächtliche, durch Schlafapnoe induzierte Blutdruckspitzen scheint die CPAP-Therapie die zurzeit am besten dokumentierte Therapieform zu sein.AbstractObstructive sleep apnea and arterial hypertension are frequent diseases, but they are also often overlooked. There is a causal relationship of sleep apnea and hypertension. Undiagnosed sleep apnea is probably the most important reason for “essential” hypertension. It is important to identify these patients. All hypertensive patients should be asked for snoring, breathing arrest and daytime sleepiness, neck circumference should be measured, and an ambulant sleep apnea monitoring should be performed, if necessary. Especially patients with refractory hypertension or non-dippers should be screened for sleep apnea and patients with sleep apnea should be examined for arterial hypertension.Continuous positive airway pressure (CPAP) can effectively lower blood pressure in the hypertensive sleep apnea patient. This is especially true for the obstructive sleep apnea patient with refractory hypertension. CPAP therapy is probably the best therapy for sleep apnea-induced nocturnal blood pressure rises.