Department of Pulmonary Medicine and Clinical Pharmacology,
Sahlgrenska University Hospital, Göteborg

SLEEP DISORDERED BREATHING AND HEMODYNAMIC FUNCTION

Disputation fredagen den 4 maj 2001 klockan 09.00. Konferensrummet, elevhemmet,
Sahlgrenska Universitetssjukhuset, Göteborg.

Sleep Disordered Breathing and Hemodynamic Function

Akademisk Avhandling

som för avläggande av medicine doktorexamen vid Göteborgs universitet kommer att offentligen försvaras i Konferensrummet, Elevhemmet, Sahlgrenska Universitetssjukhuset, Göteborg, fredagen den 4 maj 2001, kl 0900,

av

Ludger Grote
Leg läkare.

Avhandlingen baseras på följande delarbeten.

I Grote L., Ploch T., Heitmann J., Knaack L., Penzel T., Peter J.H.
Sleep related breathing disorder is an independent risk factor for systemic hypertension.
Am. J. Respir. Crit. Care Med. 1999; 160: 1875-82.

II Grote L., Hedner J., Peter J.H.
Sleep related breathing disorder is an independent risk factor for uncontrolled hypertension.
J. Hypertension 2000; 18: 679-85.

III Grote L., Hedner J., Peter JH.
The heart rate response is blunted in patients with sleep related breathing disorder.
Submitted for publication.

IV Grote L., Kraiczi H., Hedner J.
A reduced alpha- and beta2-adrenergic vascular response in patients with obstructive sleep apnea.
Am. J. Respir. Crit. Care Med., 2000; 162: 1480-87.

V Grote L., Ding Z., Kraiczi H., Hedner J.
Fingerplethysmography: a method for continuous monitoring of sympathetic vascular tone.
Submitted for publication.

Sleep Disordered Breathing and Hemodynamic Function

Ludger Grote
Department of Pulmonary Medicine and Clinical Pharmacology,
Sahlgrenska University Hospital, SE-41315 Göteborg, Sweden

This thesis addresses the association between sleep disordered breathing (SDB), in particular obstructive sleep apnea (OSA), and hemodynamic function. Hemodynamic aspects including blood pressure, heart rate, the risk of hypertension, as well as dynamic vascular function have been investigated in patients with SDB.

A cross sectional study in a sleep laboratory cohort (n=1190) demonstrated a dose-response relationship between the severity of SDB, expressed as respiratory disturbance index (RDI), and office blood pressure, heart rate, and the risk of hypertension. This association was independent of confounding factors like age, Body Mass Index (BMI), and gender. Men aged 50 years or below seemed to be more susceptible for the association between SDB and hypertension. Moreover, resting heart rate, an independent cardiovascular risk marker, was associated with SDB in a dose related manner.

The control of hypertension was assessed in a subgroup of 599 previously diagnosed hypertensive patients derived from the above mentioned cohort. RDI was increased in patients with an actual blood pressure exceeding160/95 mmHg, defined as uncontrolled hypertension. Elevated blood pressure was also associated with age and BMI. In multivariate analysis RDI and age were the only significant predictors for uncontrolled hypertension in younger patients.

Hemodynamic function during supine bicycle exercise testing was assessed in 1149 patients of the sleep laboratory cohort. Maximal load tended to decrease by every RDI unit in multivariate analysis. The systolic blood pressure response to exercise was increased in SDB patients whereas the heart rate response was reduced by SDB activity in a dose related manner.

The increase in peripheral arterial resistance after adrenergic a -receptor stimulation with norepinephrine (NE), assessed with forearm venous plethysmography, was attenuated in normotensive patients with OSA. The relative increase in resistance following NE was lower in the OSA group and negatively correlated with resting plasma NE concentration. In addition, there was a reduced vascular response to b 2-adrenoreceptor stimulation with isoproterenol. The results suggest a functional downregulation of vascular a - and b 2-receptors in normotensive patients with OSA.

A fingerplethysmographic device was designed to assess changes in digital blood flow by analysis of pulse wave amplitude (PWA). Respiration related changes in PWA were identified during wakefulness and sleep. Arousal following apneas, hypopneas, and upper airway flow restriction during sleep were associated with a markedly reduction in PWA. Fingerplethysmography was found to provide a tool for continuous non-invasive assessment of changes in a -receptor mediated vasoconstriction in the digital vascular bed and may be helpful to characterise autonomic activation during disturbed sleep.

SDB is associated with acute, intermediate and long-term hemodynamic dysfunction. The high prevalence of cardiovascular disease, such as systemic hypertension, in SDB patients provides support for consideration of SDB in diagnostic and therapeutic procedures related to cardiovascular disease.

Key words: sleep apnea, hypertension, blood pressure, vascular function, exercise, arousal

ISBN 91-628-4773-2, Göteborg 2001