Altered cardiovascular variability in obstructive sleep apnea.

BACKGROUND Altered cardiovascular variability is a prognostic indicator for cardiovascular events. Patients with obstructive sleep apnea (OSA) are at an increased risk for cardiovascular disease. We tested the hypothesis that OSA is accompanied by alterations in cardiovascular variability, even in the absence of overt cardiovascular disease. METHODS AND RESULTS Spectral analysis of variability of muscle sympathetic nerve activity, RR interval, and blood pressure were obtained during undisturbed supine rest in 15 patients with moderate-to-severe OSA, 18 patients with mild OSA, and 16 healthy control subjects in whom sleep disordered breathing was excluded by complete overnight polysomnography. Patients with OSA were newly diagnosed, never treated for OSA, and free of any other known diseases. Patients with moderate-to-severe OSA had shorter RR intervals (793+/-27 ms) and increased sympathetic burst frequency (49+/-4 bursts/min) compared with control subjects (947+/-42 ms; 24+/-3 bursts/min; P=0.008 and P<0.001, respectively). In these patients, total variance of RR was reduced (P=0.01) and spectral analysis of RR variability showed an increase in low frequency normalized units, a decrease in high frequency normalized units, and an increase in the ratio of low to high frequency (all P<0.05). Even though blood pressure was similar to that of the control subjects, blood pressure variance in patients with moderate-to-severe OSA was more than double the variance in control subjects (P=0.01). Patients with mild OSA also had a reduction in RR variance (P=0.02) in the absence of any significant difference in absolute RR interval. For all patients with OSA, linear regression showed a positive correlation (r=0.40; P=0.02) between sleep apnea severity and blood pressure variance. CONCLUSIONS Cardiovascular variability is altered in patients with OSA. This alteration is evident even in the absence of hypertension, heart failure, or other disease states and may be linked to the severity of OSA. Abnormalities in cardiovascular variability may be implicated in the subsequent development of overt cardiovascular disease in patients with OSA.

[1]  P. Palatini,et al.  Clinical relevance of nighttime blood pressure and of daytime blood pressure variability. , 1992, Archives of internal medicine.

[2]  M. Turiel,et al.  Sympathetic predominance followed by functional denervation in the progression of chronic heart failure. , 1995, European heart journal.

[3]  S. Julius,et al.  Heart rate and the cardiovascular risk , 1997, Journal of hypertension.

[4]  P. Ponikowski,et al.  Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. , 1997, The American journal of cardiology.

[5]  E. Fallen,et al.  Power spectral analysis of heart rate variability: a noninvasive signature of cardiac autonomic function. , 1993, Critical reviews in biomedical engineering.

[6]  J. Szalai,et al.  Are history and physical examination a good screening test for sleep apnea? , 1991, Annals of internal medicine.

[7]  M Partinen,et al.  Daytime sleepiness and vascular morbidity at seven-year follow-up in obstructive sleep apnea patients. , 1990, Chest.

[8]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[9]  J Sellgren,et al.  Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. , 1993, Chest.

[10]  L. Fauchier,et al.  Heart rate variability in idiopathic dilated cardiomyopathy: characteristics and prognostic value. , 1997, Journal of the American College of Cardiology.

[11]  E. Bixler,et al.  SLEEP APNOEA IN A HYPERTENSIVE POPULATION , 1984, The Lancet.

[12]  D. Hillman,et al.  Association of sleep apnoea with myocardial infarction in men , 1990, The Lancet.

[13]  J. Kaprio,et al.  SNORING AS A RISK FACTOR FOR HYPERTENSION AND ANGINA PECTORIS , 1985, The Lancet.

[14]  J. Montani,et al.  Cardiac hypertrophy and telemetered blood pressure 6 wk after baroreceptor denervation in normotensive rats. , 1996, The American journal of physiology.

[15]  G Mancia,et al.  Prognostic value of 24-hour blood pressure variability , 1993, Journal of hypertension.

[16]  M. Partinen,et al.  Sleep apnea and mortality in an aged cohort. , 1988, American journal of public health.

[17]  S Cerutti,et al.  Sympathetic predominance in essential hypertension: a study employing spectral analysis of heart rate variability. , 1988, Journal of hypertension.

[18]  A. Mark,et al.  Microneurographic studies of the mechanisms of sympathetic nerve responses to static exercise in humans. , 1985, Circulation research.

[19]  P. Aegerter,et al.  Short-term variability of blood pressure during sleep in snorers with or without apnea. , 1996, Hypertension.

[20]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[21]  J. Miller,et al.  Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. , 1987, The American journal of cardiology.

[22]  V. Somers,et al.  Investigating the relationship between stroke and obstructive sleep apnea. , 1996, Stroke.

[23]  M Pagani,et al.  Absence of low-frequency variability of sympathetic nerve activity in severe heart failure. , 1997, Circulation.

[24]  F. Abboud,et al.  Sympathetic neural mechanisms in obstructive sleep apnea. , 1995, The Journal of clinical investigation.

[25]  A Pedotti,et al.  Blood Pressure and Heart Rate Variabilities in Normotensive and Hypertensive Human Beings , 1983, Circulation research.

[26]  A. Porta,et al.  Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. , 1994, Circulation.

[27]  M. Kryger,et al.  Mortality and apnea index in obstructive sleep apnea. Experience in 385 male patients. , 1988, Chest.

[28]  M Malik,et al.  Short- and long-term assessment of heart rate variability for risk stratification after acute myocardial infarction. , 1996, The American journal of cardiology.

[29]  G D Pinna,et al.  Abnormal awake respiratory patterns are common in chronic heart failure and may prevent evaluation of autonomic tone by measures of heart rate variability. , 1997, Circulation.

[30]  R J Cohen,et al.  Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. , 1988, The American journal of cardiology.

[31]  D. Eckberg,et al.  Important influence of respiration on human R-R interval power spectra is largely ignored. , 1993, Journal of applied physiology.

[32]  A. Xie,et al.  Obstructive sleep apnoea in patients with dilated cardiomyopathy: effects of continuous positive airway pressure , 1991, The Lancet.

[33]  R. Cohen,et al.  Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. , 1981, Science.

[34]  S. Farrow,et al.  HOW MUCH CAN THE NHS AFFORD TO SPEND TO SAVE A LIFE OR AVOID A SEVERE DISABILITY? , 1985, The Lancet.

[35]  E A Anderson,et al.  Elevated Sympathetic Nerve Activity in Borderline Hypertensive Humans Evidence From Direct Intraneural Recordings , 1989, Hypertension.

[36]  T Kobayashi,et al.  Augmented very low frequency component of heart rate variability during obstructive sleep apnea. , 1996, Sleep.

[37]  A Pedotti,et al.  Sequential spectral analysis of 24-hour blood pressure and pulse interval in humans. , 1990, Hypertension.

[38]  K M Hla,et al.  Population-based study of sleep-disordered breathing as a risk factor for hypertension. , 1997, Archives of internal medicine.

[39]  David Watts Apnea , 1997, The Lancet.

[40]  A. Porta,et al.  Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. , 1997, Circulation.

[41]  M. Turiel,et al.  Power Spectral Analysis of Heart Rate and Arterial Pressure Variabilities as a Marker of Sympatho‐Vagal Interaction in Man and Conscious Dog , 1986, Circulation research.

[42]  E. Bixler,et al.  Sleep apnea and sleep disruption in obese patients. , 1994, Archives of internal medicine.

[43]  D. Ewing,et al.  Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications. , 1980, Annals of internal medicine.