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Study with the experts
Interactive Course on
Sleep Medicine
Antwerp, Belgium
November 10-12, 2005
ERS School Courses 2005
Thank you for viewing this document.We would like to remind you that this material is the
property of the author. It is provided to you by the
ERS for your personal use only, as submitted by the
author.
2005 by the author
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Cardiovascular morbidity in OSA
Dr Justin Pepperell
Centre for Respiratory Medicine
Churchill Hospital Site
Oxford Radcliffe HospitalOxford OX3 7LJ, United Kingdom
Aims of the presentationAt the end of the presentation you should be able to:
1. List some of the mechanisms of cardiovascular disease in OSA2. Appreciate the confounding factors in studies in this area3. Discuss the evidence for cardiovascular disease in OSA4. Discuss the evidence for CVD risk reduction in OSA
5. Decide in the clinic who and how to treat to reduce cardiovascular risk
Study design and confounding factorsBecause of the intimate relationship between cardiovascular risk factors such as obesity, hypertension
and sleep apnoea, it is difficult to adequately control for these in epidemiological studies.
Cardiovascular risk factors are themselves associated in general population samples and tend to cluster
in unhealthy individuals. Sleep apnoea subjects are typical of this, with high prevalences of obesity,
smoking, alcohol use, insulin resistance and reduced exercise. All of these should be controlled for, in
clinical studies.
An example of this for cardiovascular disease is the frequent prescription of antihypertensive and other
cardiac medications in this group of subjects. If we assume for example that sleep apnoea causes
hypertension, and that severe disease is more likely to do so, and then relatively more subjects with
severe disease will be receiving antihypertensives. As the antihypertensives lower blood pressure, thesubjects with more severe disease, and on antihypertensives, may have their raised BP masked. If we
then attempt to correlate sleep apnoea severity with blood pressure, the relationship will be weakened,
and this will affect both cross sectional and longitudinal studies. The same problem may arise with a
number of other cardiac active drugs and cardiovascular risk factors, e.g. lipid lowering agents.
Measurement errors
Regression to the mean and regression dilution biasRegression to the mean may be illustrated by a theoretical study investigating whether drug x lowers
blood pressure. The study design selects subjects for inclusion based on the criteria that their blood
pressure is higher than 140/90 on the day of assessment. We know that blood pressure is variable day
to day and this one off measurement does not reflect usual levels. As we have selected subjects above140/90 we will have included a number of subjects who happen to have been at the upper end of their
own individual normal range on the day of assessment. When we next measure these subjects blood
pressures it is statistically probable that their blood pressure will be lower and that this is independent
of any intervention given (such as drug x). Any trial with this design must therefore have an
appropriate control group with the same inclusion criteria to be able to correct or account for this
phenomenon.
Regression dilution bias may also be influenced by office blood pressure variability. Figure 1
illustrates the increased measurement variability at the extremes of blood pressure, the usual pattern
for variables prone to regression dilution bias. If we consider studies of office blood pressure
measurement and morbidity, there is a close linear relationship between blood pressure and morbidity
through the majority of the usual range of blood pressure. In the relatively few subjects with very high
blood pressure however, the relationship flattens. This suggests that very high blood pressure does notcause an increase in morbidity. What is actually happening in these studies however is that one office
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blood pressure measurement does not reflect the subjects usual blood pressure, it just happened to be
very high that day and the subjects usual blood pressure is much lower than this, as is their risk of
morbidity.
Blood pressure (mmHg)
60 80 100 120
Blood
pressurevariability
Figure1. An illustration of blood pressure variability across the normal range of blood pressure.A typical pattern for variables prone to regression dilution bias
Relevance of sleep studiesSleep studies are imprecise through high variance and this may reduce their ability to predict
cardiovascular morbidity, but do they ever actually reflect the important pathophysiological processes
through which obstructive sleep apnoea (OSA) might lead to the development of hypertension? In
epidemiological studies, AHIs as low as 10, appear to be associated with hypertension. However, it is
hard to believe that just these 10 events per hour really cause hypertension. What is perhaps more
likely is that the these subjects have associated more subtle pathophysiological changes, such as
increased inspiratory effort due to upper airway resistance, that may be present for a greater proportion
of the sleeping hours1
and which are more likely to be the trigger which raises blood pressure. AHIwould then be acting as an indirect marker of the real pathophysiological cause. It is also likely that
there are interactions between several parallel pathophysiological processes and a patients genotype,
which produce the end result of hypertension.
Community versus Clinic Based Studies
Large prospective epidemiological studies in the normal population are well suited to investigate the
relationship between exposures and outcomes in the long term and also to estimate the public health
burden of diseases in the general population. These studies may take many years to reach a conclusion,
as outcomes may only become apparent after prolonged exposure, or interval, between risk and
disease. Where there are established risk factors for a disease, it is useful to study not only the clinical
syndrome of interest but also any likely intermediaries, which link exposure to outcome, such as OSA
to hypertension.Associations between OSA and hypertension are likely to be apparent within shorter time spans than
for overall cardiovascular morbidity but perhaps more importantly, this allows the interactions
between the exposure, the intermediate and the outcome to be fully explored. This is useful as such
interactions can bias cross sectional studies. For instance, subjects with severe OSA and hypertension
may have a higher mortality rate than predicted for a given level of BP. However, because deceased
subjects cannot be accounted for in cross sectional studies, the prevalence of severe disease may be
underestimated, relationships between OSA and hypertension are weakened, and the prognostic value
of BP would therefore be underestimated. This prevalence / incidence bias (survival bias) is best
assessed by long term prospective epidemiological studies which include all the likely interacting
factors which may affect outcome.
Many of the early studies on BP and OSA used samples from clinic populations. Whilst these identify
more subjects with moderate or severe disease, and can explore relationships across the disease
spectrum, these samples are not usually representative (of all cases) with the condition in the general
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population, and cannot be used to estimate the public health impact of the disease. Clinic based studies
however can use more intricate measures of both BP and OSA severity, and are as such more likely to
uncover the more important intermediates between the syndrome and cardiovascular risk in the longer
term. Ultimately the clinic location is perhaps best placed to address the effects of different treatments
in modifying OSA severity, symptomatic benefits and changes in BP profile, but again caution is
needed in extrapolating these results back to the general population.
Cardiovascular Consequences of Obstructive Sleep Apnoea
MortalityThere are several reports of high mortality in snorers
2and obstructive sleep apnoea subjects
3Mortality
occurs more frequently at night than should occur by chance and is likely to be due to cardiovascular
disease.4-9
. More recent reports have demonstrated high mortality in untreated OSA patients.10-
12.These studies are not randomised and the control populations cannot be considered normal,
however they provide convincing evidence of improved mortality with CPAP, and surgery in OSA.
Stroke and transient ischaemic attacks
Some authors have suggested that sleep apnoea is important as a cause of stroke 13The nocturnalincrease in ischaemic stroke incidence is likely due to the combination or sympathetic activation and a
hypercoagulable state.
OSA can lead to stroke and vice versa14
.15-18
Transient ischaemic attacks may be more common in
OSA. Since TIA is a risk factor for stroke this implies that obstructive sleep apnoea is a risk factor for-
stroke per se19
.
In subjects with stroke, obstructive sleep apnoea is associated with worse functional outcome20
,
further stroke, and mortality14
. Although there are several studies of mortality and obstructive sleep
apnoea3-9
, few of these have looked specifically at stroke deaths.
Cardiac IschaemiaEpisodes of cardiac ischaemia are precipitated by disturbances in myocardial oxygen supply and
demand. Subjects with OSA therefore have a number of triggers for myocardial ischaemia which
occur repeatedly throughout the night, with apnoea associated tachycardia, blood pressure rise and
peripheral vasoconstriction increasing cardiac work at the time of minimal oxygen saturation.
Myocardial infarction and coronary artery diseaseFrom mortality studies in obstructive sleep apnoea subjects, 4 report associations between OSA and
ischaemic heart disease incidence6;21
%7;10;22
.
OSA is more common in patients with established ischaemic heart disease23;24
,25
.
The Sleep Heart Health Study examined cross sectional associations between sleep disordered
breathing measured from polysomnography and self-reported cardiovascular disease incidence in 6424
independent members of the normal population. The authors reported increased relative odds of
cardiovascular disease across the quartiles of sleep disordered breathing. The relative odds betweenthe upper and lower court files being 1.42 (1.13-1.78) for self-reported cardiovascular disease.
Although self reported coronary heart disease prevalence alone was less strongly associated with
obstructive sleep apnoea, odds ratio between upper and lower AHI quartiles 1.27 (0.99 - 1.62)26
.
In summary OSA may precipitate cardiac ischaemia and nocturnal angina in subjects with CAD. In
addition there is some evidence that CPAP may reduce both OSA and nocturnal cardiac ischaemia in
these subjects although there is conflicting evidence as to whether OSA causes cardiac ischaemia in
the absence of coexisting CAD.
Arrhythmias
Obstructive sleep apnoea is accompanied by a characteristic cyclical Brady-tachyarrhythmia
associated closely with episodes of upper airway obstruction or increased upper airways resistance27.Bradycardia is very common following obstructive apnoeas with sinus pauses reported to occur in 5-
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10% of subjects, type II heart block in 4-8%, with prolonged sinus pauses up to 15.6 seconds
described28-31
. Some authors have suggested that cardiac arrhythmias occur more commonly below a
particular oxygen saturation threshold, and others showed that frequency of PVCs was correlated to
the duration of low oxyhaemoglobin saturation (5) demonstrated rhythm
disturbances in 16 (31%) Sinus arrhythmia was reported in 8 (14%) with marked bradycardia (heart
rate140mmHg, diastolic BP >90mmHg, or taking antihypertensive medications). Both mean systolic and
diastolic BP and the prevalence of hypertension increased significantly with increasing measures of
obstructive sleep apnoea.
The Wisconsin Sleep Cohort Study, a prospective population study of the association between
obstructive sleep apnoea and cardiovascular disease is ongoing but has reported some important data
on hypertension44
. After adjustment for confounders, the odds ratios for the presence of hypertension
at follow up for AHI 0.1-4.9 versus control (AHI 0- 0.1) was 1.42 (95% CI 1.13-1.78); AHI 5-14.9
versus control, 2.03 (95% CI 1.29-3.17); AHI > 15 versus control, 2.89 (95% CI 1.46-5.64). The
results were similar when a more conservative definition of hypertension was used (>160mmHg
systolic, >100mmHg diastolic), and for other cut points for hypertension between 130 / 85 and 180 /
110 mmHg.
Of note in all these studies is that even a mild degree of obstructive sleep apnoea, which is quiteprevalent within the general population, was associated with raised BP at baseline, and also at four
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years in the Wisconsin study. This suggestion is backed up by other population studies, which found
that self reported snoring, itself a soft marker of obstructive sleep apnoea, was associated with a higher
prevalence of hypertension at baseline and the incidence of hypertension in the longer term37;45
.
Clinic based epidemiology studies
Lavie et al, studied 2677 subjects over a 10-year period from their clinic. Excluding subjects on
antihypertensive medication, the data were explored using stepwise linear regression analysis to
identify the influence of obstructive sleep apnoea on morning BP. When corrected for age, sex and
neck circumference (the most influential marker of obesity on BP in this study), the AHI remained
significantly related to diastolic (r2
0.22) and systolic (r2
0.20) pressure, thus accounting for ~20% of
the variance in both systolic and diastolic BP. The model from this analysis predicted a rise of
0.1mmHg in systolic, and 0.04 mmHg in diastolic, pressure for each additional apnoea / hypopnoea
per hour of sleep. A subject with an AHI 60 should have a systolic pressure 6mmHg and a diastolic
pressure 4.7mmHg higher than a subject without OSA.
A further group has studied hypertension in a group of 741 men and 1000 women. The subjects were
divided into four groups on the basis of self reported snoring and apnoea / hypopnoea index. The
authors reported an independent association between both snoring and sleep apnoea, and hypertension
when corrected for age, sex, body mass index, race, alcohol and smoking. This relationship wasproportional to the severity of the sleep apnoea and decreased with advancing age.46
Case control studies
Lavie et al matched 674 subjects with AHI>10 to subjects with AHI
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Baroreflex sensitivity is reported to be depressed in non apnoeic snorers68
and subjects with
obstructive sleep apnoea69-72
. There is a loss of the normal nocturnal rise in baroreflex sensitivity in
subjects with obstructive sleep apnoea, with some groups also suggesting a reduced coupling between
respiration and cardiovascular variability73
. CPAP may improve nocturnal baroreflex sensitivity in
subjects with obstructive sleep apnoea as it does in subjects with heart failure and central apnoea74
.
Compared to a control population matched for sex and body mass index, obstructive sleep apnoea
subjects have faster heart rates with reduced overall heart rate variability and an increased component
of low frequency variation (thought to represent sympathetic modulation of heart rate)75
.Other groups
have also reported reduced heart rate variability in association with sleep apnoea76-78
with one group
reporting an increase in the very low frequency component of heart rate variability79
and another
suggesting that very low frequency power may reduce after CPAP80
.
Endothelial function
In keeping with abnormal sympathetic activation, forearm blood flow responses to infused vasoactive
agents are abnormal in subjects with sleep apnoea compared to controls81-83
, which may improve
following CPAP treatment84
. In addition they appear to have abnormal in vivo vasoconstriction
responses to hypoxic eucapnic challenge85
.
As well as high Atrial Natriuretic Peptide levels, OSA subjects also have high Renin, Angiotensin andAldosterone levels, again there is some suggestion that these may improve following CPAP86
CPAP is reported to improve cardiac function in OSA subjects87
and may reduce the incidence of
cardiovascular disease following long term use88
. Apart from its effect on BP, little is known about
other mechanisms of benefit. Although studies of CPAP in subjects with cardiac failure suggest that it
may work in part by reducing LV wall tension.
Cardiovascular risk overall
Although there is a great deal of interest in sleep disordered breathing and cardiovascular disease there
are few studies of overall cardiovascular risk in obstructive sleep apnoea. Maekawa et al mention
cardiovascular risk in their short report on ischaemic heart disease89
but the only full report is from
Keilly et al. In this study the authors allocated subjects with obstructive sleep apnoea a 10 year
cardiovascular risk based on the Framingham dataset models90-92
. They found that subjects withobstructive sleep apnoea had a high risk of future cardiovascular events from their baseline
cardiovascular risk profile independent of sleep apnoea severity. For example men had a 10 year risk
of stroke of 12.3% (95% CI 9.4 15.1) or coronary heart disease 13.9 (12.1 16.0).
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treatment on muscle sympathetic nerve activity in sleep apnea. Am.J.Respir.Crit.Care Med.
153:1333-1338.
58. Dimsdale, J. E., T. Coy, M. G. Ziegler, S. Ancoli Israel, and J. Clausen. 1995. The effect ofsleep apnea on plasma and urinary catecholamines. Sleep. 18:377-381.
59. Fletcher, E. C., J. Miller, J. W. Schaaf, and J. G. Fletcher. 1987. Urinary catecholamines
before and after tracheostomy in patients with obstructive sleep apnea and hypertension. Sleep
10:35-44.
60. Baruzzi, A., R. Riva, F. Cirignotta, M. Zucconi, M. Cappelli, and E. Lugaresi. 1991. Atrial
natriuretic peptide and catecholamines in obstructive sleep apnea syndrome. Sleep 14:83-86.
61. Tashiro, T., T. Shimizu, S. Iijima, S. Kogawa, and Y. Hishikawa. 1989. Increased urinary
noradrenaline excretion during sleep in patients with sleep apnea syndrome. Sleep Res.
18:312.
62. Peled, N., A. Greenberg, G. Pillar, O. Zinder, N. Levi, and P. Lavie. 1998. Contributions of
hypoxia and respiratory disturbance index to sympathetic activation and blood pressure in
obstructive sleep apnea syndrome.Am.J.Hypertens. 11:1284-1289.63. Hedner, J., B. Darpo, H. Ejnell, J. Carlson, and K. Caidahl. 1995. Reduction in sympathetic
activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications.
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64. Jennum, P., G. Wildschiodtz, N. J. Christensen, and T. Schwartz. 1989. Blood pressure,
catecholamines, and pancreatic polypeptide in obstructive sleep apnea with and without nasal
continuous positive airway pressure (nCPAP) treatment.Am.J.Hypertens. 2:847-852.
65. Jennum, P. 1990. Cortisol and adrenergic activity in patients suffering from obstructive sleep
apnea before and after nasal CPAP treatment. In J. Horne, editor Sleep '90 Pontenagel press,
Bochum. 426-428.
66. Marrone, O., L. Riccobono, A. Salvaggio, A. Mirabella, A. Bonanno, and M. R. Bonsignore.
1993. Catecholamines and blood pressure in obstructive sleep apnea syndrome. Chest
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67. Naughton, M. T., D. C. Benard, P. P. Liu, R. Rutherford, F. Rankin, and T. D. Bradley. 1995.
Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep
apnea.Am.J.Respir.Crit.Care Med. 152:473-479.
68. Mateika, J. H., N. B. Kavey, and G. Mitru. 1999. Spontaneous baroreflex analysis in non-
apneic snoring individuals during NREM sleep. Sleep 22:461-468.
69. Carlson, J. T., J. A. Hedner, J. Sellgren, M. Elam, and B. G. Wallin. 1996. Depressed
baroreflex sensitivity in patients with obstructive sleep apnea. Am J Respir Crit Care Med
154:1490-1496.
70. Narkiewicz, K., C. A. Pesek, M. Kato, B. G. Phillips, D. E. Davison, and V. K. Somers. 1998.
Baroreflex control of sympathetic nerve activity and heart rate in obstructive sleep apnea.
Hypertension 32:1039-1043.
71. Parati, G., M. Di Rienzo, M. R. Bonsignore, G. Insalaco, O. Marrone, P. Castiglioni, G.
Bonsignore, and G. Mancia. 1997. Autonomic cardiac regulation in obstructive sleep apnea
syndrome: evidence from spontaneous baroreflex analysis during sleep.J.Hypertens. 15:1621-
1626.
72. Resta, O., P. Guido, L. Rana, V. Procacci, F. Scarpelli, and V. Picca. 1996. Depressed
baroreceptor reflex in patients with obstructive sleep apnea (OSA). Boll.Soc.Ital.Biol.Sper.
72:247-254.73. Jo, J. A., A. Blasi, E. Valladares, R. Juarez, A. Baydur, and M. C. Khoo. 2002. Model-based
assessment of autonomic control in obstructive sleep apnea syndrome during sleep. Am J
Respir Crit Care Med.
74. Tkacova, R., H. R. Dajani, F. Rankin, F. S. Fitzgerald, J. S. Floras, and B. T. Douglas. 2000.
Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with
heart failure and obstructive sleep apnea.J Hypertens. 18:1257-1262.
75. Narkiewicz, K., N. Montano, C. Cogliati, P. J. van de Borne, M. E. Dyken, and V. K. Somers.
1998. Altered cardiovascular variability in obstructive sleep apnea. Circulation 98:1071-1077.
76. Ferini Strambi, L., M. Zucconi, A. Oldani, and S. Smirne. 1992. Heart rate variability during
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77. Bauer, T., S. Ewig, H. Schafer, E. Jelen, H. Omran, and B. Luderitz. 1996. Heart ratevariability in patients with sleep-related breathing disorders. Cardiology 87:492-496.
78. Resta, O., L. Rana, V. Procacci, P. Guido, V. Picca, and F. Scarpelli. 1998. Autonomic
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79. Hilton, M. F., M. J. Chappell, W. A. Bartlett, A. Malhotra, J. M. Beattie, and R. M. Cayton.
2001. The sleep apnoea/hypopnoea syndrome depresses waking vagal tone independent of
sympathetic activation. Eur Respir J17:6-66.
80. Roche, F., D. Duverney, Court-Fortune, V. Pichot, F. Costes, J. R. Lacour, J. A. Antoniadis, J.
M. Gaspoz, and J. C. Barthelemy. 2002. Cardiac interbeat interval increment for the
identification of obstructive sleep apnea. Pacing Clin Electrophysiol. 25:1192-1199.
81. Carlson, J. T., C. Rangemark, and J. A. Hedner. 1996. Attenuated endothelium-dependent
vascular relaxation in patients with sleep apnoea.J Hypertens. 14:5-84.82. Kato, M., P. Roberts-Thomson, B. G. Phillips, W. G. Haynes, M. Winnicki, V. Accurso, and
V. K. Somers. 2000. Impairment of endothelium-dependent vasodilation of resistance vessels
in patients with obstructive sleep apnea. Circulation 102:21-10.
83. Kraiczi, H., J. Hedner, Y. Peker, and J. Carlson. 2000. Increased vasoconstrictor sensitivity in
obstructive sleep apnea. J Appl.Physiol 89:2-8.
84. Imadojemu, V. A., K. Gleeson, S. A. Quraishi, A. R. Kunselman, L. I. Sinoway, and U. A.
Leuenberger. 2002. Impaired vasodilator responses in obstructive sleep apnea are improved
with continuous positive airway pressure therapy. Am J Respir Crit Care Med JID - 9421642
165:950-953.
85. Remsburg, S., S. H. Launois, and J. W. Weiss. 1999. Patients with obstructive sleep apnea
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86. Saarelainen, S., J. Hasan, S. Siitonen, and E. Seppala. 1996. Effect of nasal CPAP treatment
on plasma volume, aldosterone and 24-h blood pressure in obstructive sleep apnoea.
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87. Krieger, J., D. Grucker, E. Sforza, J. Chambron, and D. Kurtz. 1991. Left ventricular ejection
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88. Peker, Y., J. Hedner, A. Johansson, and M. Bende. 1997. Reduced hospitalization with
cardiovascular and pulmonary disease in obstructive sleep apnea patients on nasal CPAP
treatment. Sleep 20:645-653.
89. Maekawa, M., T. Shiomi, K. Usui, R. Sasanabe, and T. Kobayashi. 1998. Prevalence of
ischemic heart disease among patients with sleep apnea syndrome. Psychiatry Clin.Neurosci.
52:219-220.
90. Kiely, J. L. and W. T. McNicholas. 2000. Cardiovascular risk factors in patients with
obstructive sleep apnoea syndrome.Eur Respir J16:128-133.
91. Kannel, W. B., N. Brand, J. J. Skinner, T. R. Dawber, and P. M. McNamara. 1967. The
relation of adiposity to blood pressure and development of hypertension. Ann.Intern.Med.
67:48-59.
92. Kannel, W. B., A. L. Dannenberg, and D. Levy. 1987. Population implications of
electrocardiographic left ventricular hypertrophy.Am J Cardiol 60:85I-93I.
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Cardiovascular Morbidity inSleep Apnea
Just in Pepperel l
Taunton and Somerset NHSTrust, UK
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TD Bradley Ed, Marcel Dekker 2000
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Mechanisms
Renin angiotensin activation
Vascular dysfunction Sympathetic activation
Endothelial dysfunction
Oxidative stress
Inflammation Platelet activation
Gene activation apoptosis
Obesity / leptin
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Sympathetic activation
Muscle sympatheticnerve activityincreased in OSA
Plasma and urinarycatecholaminesincreased in OSA
Night-time and overall
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Flow mediated vasodilation
normals and OSA
Ip et al AJRCCM Vol
169. pp. 348-353,(2004)
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Daytime sleepiness, Obesity andinflammatory cytokines
Vgontzas AN, The Journal of Clinical Endocrinology& Metabolism Vol. 82, No. 5 1313-1316
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Platelet activation in sleep apnea
G Bokinsky, 1995;108;625-630Chest
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Study Design and Confounders
Measurement errors
Regression to the mean
Regression dilution bias
Relevance of sleep studies
Hypoxia, intrathoracic pressure and arousalCommunity versus clinic based studies
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Regression to the mean
Measurement
variability
BP
BP value high
high
low
low
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Regression to the mean
BP value highlow
number
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Regression dilution bias
CVD
risk
Blood pressure
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Evidence for CVD disease in OSA
Risk Factors for CVD
Overall CVD risk
Prevalence of CVD
Incidence of CVD
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Intermediaries of CVD in OSA;
Diabetes
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Intermediaries of CVD;
Hyperlipidaemia
High total cholesterol 46%
High triglycerides 47%
Either high 63%
n=114 mean age 52 AHI ~45
Kiely, JL,et al Eur Respir J2000;16,128-133
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Overall cardiovascular risk in OSA patients
Kiely, JL,et al Eur Respir J2000;16,128-133
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CVD in OSA BP
Prevalence hypertension higher clinic and community, IncidenceHypertension higher, BP higher than matched controls
IHD OSA common in IHD patients, IHD prevalence and incidence
higher in OSA subjects
Heart Failure More common in OSA, OSA gives worse prognosis
Stroke Snoring risk for stroke, OSA risk for TIA, OSA after stroke means
worse recovery, recurrent stroke and mortality
Mortality High in OSA and snoring, Occurs at night more commonly than
expected
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Hypertension in OSA
p for trend = 0.002
2.89 (1.46-5.64)67> 15
2.03 (1.29-3.17)1325 14.9
1.42 (1.13-1.78)5070.1 4.9
1.001870
Odds ratio of developing
hypertension (95%
CI)**
Wisconsin Sleep Cohort
Study n=
Apnoea Hypopnoea index
Events per hour
p for trend = 0.005
1.37 (1.03-1.83)373>30
1.25 (1.00-1.56)71915 29.9
1.20 (1.01-1.42)17515.0 14.9
1.07 (0.91-1.26)15981.5 4.9
1.001691< 1.5
Odds ratio of having
hypertension (95% CI)*Sleep Heart Health Study n=
Apnoea Hypopnoea index
Events per hour
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Sleep Heart Health Study Log odds ratios
of CVD for AHI
ShaharE et al , Am. J. Respir. Crit. Care Med.,Volume 163, Number 1, January 2001, 19-25
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OSA and mortality
He et al 385 male OSA (Chest 1988) 8 year cumulative mortality 37% OSA vs 4% for AHI >20
vs
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Hypertension increasesmortality
Days of Survival
0 500 1000 1500 2000 2500 3000 3500 4000
Cumulativesurvival(%)
0
10
20
30
40
50
60
70
80
90
100
without hypertension
with hypertension
Noda et al, J Clin Neuroscience, 1998, 52,79
N=148
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Evidence for reducing CVD risk in
OSA with treatment
CPAP
Intermediaries, BP, CVD, CHD, death
Obesity management
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Evidence for reducing CVD risk in
OSA with treatment
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Flow mediated vasodilation afterCPAP
Ip et al AJRCCM Vol169. pp. 348-353,(2004)
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Improved insulin sensitivity after
CPAP
AHarsch AJRCCM 2004169. pp. 156-162, (2004)
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Treatment CPAP
after treatment
Time from wake and sleep onset (hours)
Meanbloodpressure(mmHg)
85
90
95
100
105
110
115
120
wake 4 8 12 16 sleep 4 8
before treatment
Meanbloodpressure(mmHg)
85
90
95
100
105
110
115
120
Becker et al Circulation 2003 Pepperell et al, Lancet
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Change in mean BP split by median
SaO2 diprate
sleepiness
Groups split by median baseline oxygen saturation dip rate( 4% dips / hour)
33Changein24hourmeanbloodpress
ure(mmHg)
-6
-4
-2
0
2
4 p=0.4 p=0.001
Groups split by median Osler test above below 20 minutes
>20
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BMI and mortality
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Treatment Behavioural
Weight reduction
5kg~5/3mmHg
Orlistat/ sibutramine
Diet
Reduce salt 40
BMI > 35 + complications
Bariatric surgery JAMA. 2004 Oct
13;292(14):1724-37 Buchwald
22,094 patients 16-64 yrs
BMI 46.9 lost 60% ofexccess weight
Mortality .1%-1.1%
Improved Diabetes 77%
BP 62%, Lipids 70%, OSA86%
Sjostrom et al Hypertension 1998
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How to use this information in clinic
Standard CVD risks Assess and treat Obesity, Smoking, Diabetes, BP, Cholesterol
Standard OSA Treat
Asymptomatic OSA Assess CVD risk
Assess OSA severity
Investigate resistant hypertension for OSAConsider secondary causes / hyperaldosterone if compliant on CPAP
and resistant BP
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Asymptomatic
OSA Signs of secondary
causes OSA CVD
Investigations
Secondary causes
Target organ damage
Cardiovascular risk
Vascular tone
Confirm blood pressure
Sleep apnoea severity
Symptoms and AHI
riskcalculator.exe
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sleepiness
Sleepapnea
severity
Tendencyfor CPAP
trial
10 yr CVDrisk >20%
ESS 5
AHI /SaO2
diprate 10
10 yr CVD
risk
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Summary
Modify normal cardiovascular risks
Obesity, Smoking, Diabetes, BP, Cholesterol
Treat OSA to releive symptoms
Try CPAP in severe OSA if CVD risk high
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Aims
mechanisms of CVD in OSA
confounding factors in studies in thisarea
evidence for CVD in OSA
evidence for CVD risk reduction in OSA
who and how to treat in clinic to reducecardiovascular risk
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