Daytime Sleepiness and Vascular Morbidity at Seven-Year Follow-up in Obstructive Sleep Apnea Patients• Markku lbrtinen, M.D.; and Christian Guilleminault, M.D.
To evaluate the morbidity associated with obstructive sleep apnea syndrome (OSAS), we undertook a seven-year followup study of 198 OSAS patients seen between 1972 and 1980. The patients had been submitted to tracheostomy (71 patients) or had received a weight-loss recommendation (127 patients). Despite a lower mean apnea index (AI) (43 VB 69) and a lower mean body mass index (BMI) (31 VB 34 kglm•) at entry, excessive daytime sleepiness (EDS) and vascular morbidity were signi&cantly higher in the conservatively treated group. The relative risk (odds ratio) of &nding EDS in the conservatively treated group, after adjustment for BMI at seven-year follow-up, was 3. 7 (95 percent con6dence interval [CI] 2.6-5.3). The relative risk
=
associated with OSAS has recently T hebeenmortality the subject of several studies that included 1-3
our report on the results of a five-year follow-up. These mortality studies had several drawbacks. All were retrospective and only one found the outcome of each case at entry, documented the cause of death, and compared the findings with the mortality rate of the age-adjusted United States population} However, these studies were the first clear indication that a mortality risk could be associated with OSAS. Some of the studies also indicated that tracheostomy was far more effective in reducing mortality risk than was weight-loss recommendation. The present short report, based on a seven-year follow-up of the same population studied for mortality, 1 assesses the health risks (ie, morbidity) associated with OSAS and evaluates the long-term outcome for adult OSAS patients who received one of two treatment options offered at Stanford between 1972 and 1980: tracheostomy or a medical approach encouraging weight loss and better sleep hygiene. We selected 1980 as the last year for data collection in our study for the following reasons: the commercial availability in 1979 of an accurate, noninvasive ear oximeter; changes in treatment options for OSAS with *From the Stanford University Sleep Disorders Clinic, Stanford, CA and Helsinki University Medical School, Helsinki, FinJand. This work was SUPll.Orted by grant AGf11772 from the National Institute of Agingi -by the Miina Sillanpaii. and Sigrid Juselius Foundations of Helsinlci, FlnJand; and US Public Health Service International Research Fellowship 1 FO S'IW03648-0l. Manuscript received January 9; revision accepted May 17.
of developing new vascular problems in the same population, estimated by Cox models, was 2.3 (95 percent CI 1.53.6). The effect of tracheostomy, independent of age, BMI, and AI at entry, was highly signi&cant. At entry, 56 percent of the population already had a vascular problem, particularly hypertension, thus emphasizing the need for earlier treatment of the sleep-related abnormal breathing. (Chat 1990; 97:27-32)
=
OSAS =obstructive sleep apnea syndrome; AI= apnea index;
BMI =body mass inclexi EDS =excessive daytime sleepiness; CI = coofidence interval; CPAP= continuous positive airway pressure
the introduction of nasal continuous positive airway pressure (CPAP) in 1981; and the development of successful naso-pharyngo-maxillo-mandibular surgical treatments in the early 1980s. METHODS
Criteria for Inclusion in the Study Before searching our clinic records to fonn two retrospective cohorts of surgically (tracheostomy) and conservatively treated patients, we established the following requirements for subjects: 1. Residence in a western state of the United States (California, Nevada, Arizona, Oregon, or Washington), to facilitate followup. 2. A previous polygraphic monitoring, with sufficient infonnation in the chart to calculate Al. (Hypopneas or partial obstruction of the upper aiJWay were not scored before availability of an accurate ear oximeter.) 3. Information on age, height, weight, cardiovascular diseases, arterial hypertension, strokes, and cardiovascular medication intake. 4. Age at least 16 years at entry, with a minimum of five years since the initial polygraphic monitoring. 5. A signed general consent fonn, giving pennission to use data for research purposes and supplying the name of a relative who might be contacted. We were able to collect data on 198 patients who met these criteria.
Definttions Arterial Hypertension: high blood pressure diagnosed by a cardiologist, with blood pressure repeatedly recorded at 165J95 mm Hg or higher. Coronary Heart DiaetJ&e: diagnosis by a cardiologist with prescribed nitroglycerin, beta blockers, or calcium antagonists; or bypass surgery. MfPCGrdiallnforction, Stroks: medical confirmation of diagnosis CHEST I 97 I 1 I JANUARY, 1890
rl
after hospitalization. Excemve Daytime Sleepiness: difficulty in driving, working, or interacting socially because of sleepiness.
Follow-up Information Search Investigators contacted the following sources in order until the necessary information was obtained: 1. Phone number on chart (minimum of three calls at short intervals during one month). 2. Current phone number. 3. Letter to address of record, asking that we be contacted. 4. ~rk phone number on chart ifauthorized to call there. 5. Relative, iflisted. 6. City directory: neighbors contacted. 7. Department of Motor Vehicles, ifauthorized by law. 8. As a last resort, the National Death Index. If a record was available, we contacted the family about the cause of death and obtained a death certificate from the appropriate vital statistics office. (At the end of the study, these certificates were disposed of per state regulations.) Eooluaffon at Entry
The clinical interview, physical evaluation, and nocturnal polygraphic recording were reviewed. The polygraphic recording always included EEG (C3/A2-C4/A1 of the 10 to 20 international electrode placement system), EOG, chin EMG, ECG-modilied v. lead, monitoring of respiration by abdominal and thoracic strain gauges, and airftow by nasal and mouth thermistors. • Questionncn~
At follow-up, a standardized questionnaire' ensured that the three investigators asked identical questions in the same order. The test
Table 1-Age, AI, and BMl in the Population Studied Variable Age,yr Mean Median Range AI Mean Median Range BMI, kglm.. At entry Mean Median Range At follow-up Mean Median Range
Total Population (n=198)
Men (n= 190)
Women (n=8)
51.3±11.3 52 18-78
51.1±11.4 52 18-78
55.8±9.1 57 41-67
52.4±30.6 54.8 5.3-130
52.0±30.8 53.5 8-130
56.0±28.9 58.4 25-87
32.8±8.0 31.0 18.7-61.8
31.9±8.0 30.7 18.7-61.8
35.1±7.6 38.4 32-44
32.1±9.2 30.6 19.4-62.1
31.1±8.6 30.1 19.4-62.1
34.9±8.1 38.1 31.1-44.3
*No statistical difference between entry and follow-up BMI was noted. took 15 to 30 minutes to administer. The questionnaire covered such topics as weight loss, health problems occurring since the initial visit, treatments received, current impairments, daytime sleepiness, snoring, intellectual functioning, current medications, specilic cardiovascular problems, and lung or kidney diseases. Ifa point was unclear, we asked permission to contact the patient's current physician.
62%
25.9% 21.1% 9.9%
HBP -
Trach (N•71)
CHD
l.i .I
CerebroVD
Conserv (N•127)
0
COPD U.S. NCHS 1984
1. Distribution of health problems seen in our two patient groups at entry, compared with those reported in the general United States population in 1984. The OSAS population contains a significantly higher percentage of subjects with hypertension, cerebrovascular disease, and coronary heart disease at entry than would be expected from the general United States population statistics. The conservatively treated patients are moderately less affected than the patients who secondarily underwent tracheostomy. For comparison, the percentage of the total OSAS population presenting with cardiovascular morbidity at entry is outlined in the text. HBP=high blood pressure; CHD=coronary heart disease; Cerebro VD =cerebrovascular disease; COPD =chronic obstructive pulmonary disease; TRACH = tracheostomized patients; CONSERV =conservatively treated patients. FIGURE
28
Daytime Slaepil- and Vascular Morblclly (Pertlnen, Gulllem/nau/1)
Outcome MeastmJ8 At seven-year follow-up, we de6ned "sleepiness morbidity" in terms of persisting and disabling daytime sleepiness that impaired work, driving, and social interaction. Any new hypertension, myocardial infarction, or stroke occurring since the initial recording was considered in our evaluation of"vascular morbidity," regardless of whether or not myocardial infarction or stroke had also occurred prior to entry. A subgroup of patients in whom these vascular conditions were absent at entry was also evaluated. Finally, we adjusted morbidity for BMI• and age.
Stati&tical Antdy.fts Descriptive statistics with means and standard deviations, and medians, were used to analyze total population and subgroups. Analysis of variance, Students t-test, and nonparametric statistics (depending on the distribution) were performed using the BMDP statistical package.• Similarly, the BMDP statistical package 1 L (life table method) was used to construct the seven-year survival curve. We used the Wilcoxon-Breslow and Mantel-Cox statistics to compare the tracheostomized and weight-loss-treated subgroups. The 95 percent CI for morbidity rates and odds ratios (relative risks) were determined as indicated by Schoenberg' and by Kahn. •
Variable
AliT CHD MI 81 EDS COPD
Death Vascular death
Tracheostomy (n = 71) Percentage
Weight Loss (n = 127) Percentage
At Entry
Follow-up
At Entry
Follow-up
62 21 14 9.8 97 22.5 0 0
59 28 15.5 11 18.3
53.5 14 4.7 5 83.5 19 0 0
61.4 23 13.4 10.2 45.6
2.8 1.4
17.3 11
*ART, arterial hypertension; MI, myocardial infarction; 81, brain infarction; CHD, coronary heart disease; COPD, chronic obstructive pulmonary disease; EDS, excessive daytime somnolence. Percentages were calculated for the total population of each subgroup, fe, if a patient died but had had a vascular accident prior to death (MI, 81), the vascular accident was considered as a follow-up "morbidity."
acceptance of the recommended surgical treatment. RESULTS
7btal Population The initially seen population included 198 patients described in Thble 1. At entry, 112 patients (56.6 percent) presented with arterial hypertension. Coronary artery disease had been diagnosed in 33 (16. 7 percent) patients (31 men, two women). Previous medical history noted myocardial infarction in 16 (8.1 percent) and stroke in 14 (7.1 percent). Chronic obstructive pulmonary disease was found in 40 cases (20 percent) and EDS in 173 (87.4 percent) patients (Fig 1).
Description of the 7Wo Subgroups The conservatively treated (weight-loss recommendation) group included 127 patients with, at entry, a mean age of 53± 11 years, a mean BMI of 31 ± 8 leW m1 , and a mean AI of 43±30.5. The surgically (tracheostomy) treated group (71 patients) had a mean age of48.8 ± 11 years (p
To evaluate the morbidity associated with obstructive sleep apnea syndrome (OSAS), we undertook a seven-year followup study of 198 OSAS patients seen between 1972 and 1980. The patients had been submitted to tracheostomy (71 patients) or had received a weight-loss recommendation (127 patients). Despite a lower mean apnea index (AI) (43 VB 69) and a lower mean body mass index (BMI) (31 VB 34 kglm•) at entry, excessive daytime sleepiness (EDS) and vascular morbidity were signi&cantly higher in the conservatively treated group. The relative risk (odds ratio) of &nding EDS in the conservatively treated group, after adjustment for BMI at seven-year follow-up, was 3. 7 (95 percent con6dence interval [CI] 2.6-5.3). The relative risk
=
associated with OSAS has recently T hebeenmortality the subject of several studies that included 1-3
our report on the results of a five-year follow-up. These mortality studies had several drawbacks. All were retrospective and only one found the outcome of each case at entry, documented the cause of death, and compared the findings with the mortality rate of the age-adjusted United States population} However, these studies were the first clear indication that a mortality risk could be associated with OSAS. Some of the studies also indicated that tracheostomy was far more effective in reducing mortality risk than was weight-loss recommendation. The present short report, based on a seven-year follow-up of the same population studied for mortality, 1 assesses the health risks (ie, morbidity) associated with OSAS and evaluates the long-term outcome for adult OSAS patients who received one of two treatment options offered at Stanford between 1972 and 1980: tracheostomy or a medical approach encouraging weight loss and better sleep hygiene. We selected 1980 as the last year for data collection in our study for the following reasons: the commercial availability in 1979 of an accurate, noninvasive ear oximeter; changes in treatment options for OSAS with *From the Stanford University Sleep Disorders Clinic, Stanford, CA and Helsinki University Medical School, Helsinki, FinJand. This work was SUPll.Orted by grant AGf11772 from the National Institute of Agingi -by the Miina Sillanpaii. and Sigrid Juselius Foundations of Helsinlci, FlnJand; and US Public Health Service International Research Fellowship 1 FO S'IW03648-0l. Manuscript received January 9; revision accepted May 17.
of developing new vascular problems in the same population, estimated by Cox models, was 2.3 (95 percent CI 1.53.6). The effect of tracheostomy, independent of age, BMI, and AI at entry, was highly signi&cant. At entry, 56 percent of the population already had a vascular problem, particularly hypertension, thus emphasizing the need for earlier treatment of the sleep-related abnormal breathing. (Chat 1990; 97:27-32)
=
OSAS =obstructive sleep apnea syndrome; AI= apnea index;
BMI =body mass inclexi EDS =excessive daytime sleepiness; CI = coofidence interval; CPAP= continuous positive airway pressure
the introduction of nasal continuous positive airway pressure (CPAP) in 1981; and the development of successful naso-pharyngo-maxillo-mandibular surgical treatments in the early 1980s. METHODS
Criteria for Inclusion in the Study Before searching our clinic records to fonn two retrospective cohorts of surgically (tracheostomy) and conservatively treated patients, we established the following requirements for subjects: 1. Residence in a western state of the United States (California, Nevada, Arizona, Oregon, or Washington), to facilitate followup. 2. A previous polygraphic monitoring, with sufficient infonnation in the chart to calculate Al. (Hypopneas or partial obstruction of the upper aiJWay were not scored before availability of an accurate ear oximeter.) 3. Information on age, height, weight, cardiovascular diseases, arterial hypertension, strokes, and cardiovascular medication intake. 4. Age at least 16 years at entry, with a minimum of five years since the initial polygraphic monitoring. 5. A signed general consent fonn, giving pennission to use data for research purposes and supplying the name of a relative who might be contacted. We were able to collect data on 198 patients who met these criteria.
Definttions Arterial Hypertension: high blood pressure diagnosed by a cardiologist, with blood pressure repeatedly recorded at 165J95 mm Hg or higher. Coronary Heart DiaetJ&e: diagnosis by a cardiologist with prescribed nitroglycerin, beta blockers, or calcium antagonists; or bypass surgery. MfPCGrdiallnforction, Stroks: medical confirmation of diagnosis CHEST I 97 I 1 I JANUARY, 1890
rl
after hospitalization. Excemve Daytime Sleepiness: difficulty in driving, working, or interacting socially because of sleepiness.
Follow-up Information Search Investigators contacted the following sources in order until the necessary information was obtained: 1. Phone number on chart (minimum of three calls at short intervals during one month). 2. Current phone number. 3. Letter to address of record, asking that we be contacted. 4. ~rk phone number on chart ifauthorized to call there. 5. Relative, iflisted. 6. City directory: neighbors contacted. 7. Department of Motor Vehicles, ifauthorized by law. 8. As a last resort, the National Death Index. If a record was available, we contacted the family about the cause of death and obtained a death certificate from the appropriate vital statistics office. (At the end of the study, these certificates were disposed of per state regulations.) Eooluaffon at Entry
The clinical interview, physical evaluation, and nocturnal polygraphic recording were reviewed. The polygraphic recording always included EEG (C3/A2-C4/A1 of the 10 to 20 international electrode placement system), EOG, chin EMG, ECG-modilied v. lead, monitoring of respiration by abdominal and thoracic strain gauges, and airftow by nasal and mouth thermistors. • Questionncn~
At follow-up, a standardized questionnaire' ensured that the three investigators asked identical questions in the same order. The test
Table 1-Age, AI, and BMl in the Population Studied Variable Age,yr Mean Median Range AI Mean Median Range BMI, kglm.. At entry Mean Median Range At follow-up Mean Median Range
Total Population (n=198)
Men (n= 190)
Women (n=8)
51.3±11.3 52 18-78
51.1±11.4 52 18-78
55.8±9.1 57 41-67
52.4±30.6 54.8 5.3-130
52.0±30.8 53.5 8-130
56.0±28.9 58.4 25-87
32.8±8.0 31.0 18.7-61.8
31.9±8.0 30.7 18.7-61.8
35.1±7.6 38.4 32-44
32.1±9.2 30.6 19.4-62.1
31.1±8.6 30.1 19.4-62.1
34.9±8.1 38.1 31.1-44.3
*No statistical difference between entry and follow-up BMI was noted. took 15 to 30 minutes to administer. The questionnaire covered such topics as weight loss, health problems occurring since the initial visit, treatments received, current impairments, daytime sleepiness, snoring, intellectual functioning, current medications, specilic cardiovascular problems, and lung or kidney diseases. Ifa point was unclear, we asked permission to contact the patient's current physician.
62%
25.9% 21.1% 9.9%
HBP -
Trach (N•71)
CHD
l.i .I
CerebroVD
Conserv (N•127)
0
COPD U.S. NCHS 1984
1. Distribution of health problems seen in our two patient groups at entry, compared with those reported in the general United States population in 1984. The OSAS population contains a significantly higher percentage of subjects with hypertension, cerebrovascular disease, and coronary heart disease at entry than would be expected from the general United States population statistics. The conservatively treated patients are moderately less affected than the patients who secondarily underwent tracheostomy. For comparison, the percentage of the total OSAS population presenting with cardiovascular morbidity at entry is outlined in the text. HBP=high blood pressure; CHD=coronary heart disease; Cerebro VD =cerebrovascular disease; COPD =chronic obstructive pulmonary disease; TRACH = tracheostomized patients; CONSERV =conservatively treated patients. FIGURE
28
Daytime Slaepil- and Vascular Morblclly (Pertlnen, Gulllem/nau/1)
Outcome MeastmJ8 At seven-year follow-up, we de6ned "sleepiness morbidity" in terms of persisting and disabling daytime sleepiness that impaired work, driving, and social interaction. Any new hypertension, myocardial infarction, or stroke occurring since the initial recording was considered in our evaluation of"vascular morbidity," regardless of whether or not myocardial infarction or stroke had also occurred prior to entry. A subgroup of patients in whom these vascular conditions were absent at entry was also evaluated. Finally, we adjusted morbidity for BMI• and age.
Stati&tical Antdy.fts Descriptive statistics with means and standard deviations, and medians, were used to analyze total population and subgroups. Analysis of variance, Students t-test, and nonparametric statistics (depending on the distribution) were performed using the BMDP statistical package.• Similarly, the BMDP statistical package 1 L (life table method) was used to construct the seven-year survival curve. We used the Wilcoxon-Breslow and Mantel-Cox statistics to compare the tracheostomized and weight-loss-treated subgroups. The 95 percent CI for morbidity rates and odds ratios (relative risks) were determined as indicated by Schoenberg' and by Kahn. •
Variable
AliT CHD MI 81 EDS COPD
Death Vascular death
Tracheostomy (n = 71) Percentage
Weight Loss (n = 127) Percentage
At Entry
Follow-up
At Entry
Follow-up
62 21 14 9.8 97 22.5 0 0
59 28 15.5 11 18.3
53.5 14 4.7 5 83.5 19 0 0
61.4 23 13.4 10.2 45.6
2.8 1.4
17.3 11
*ART, arterial hypertension; MI, myocardial infarction; 81, brain infarction; CHD, coronary heart disease; COPD, chronic obstructive pulmonary disease; EDS, excessive daytime somnolence. Percentages were calculated for the total population of each subgroup, fe, if a patient died but had had a vascular accident prior to death (MI, 81), the vascular accident was considered as a follow-up "morbidity."
acceptance of the recommended surgical treatment. RESULTS
7btal Population The initially seen population included 198 patients described in Thble 1. At entry, 112 patients (56.6 percent) presented with arterial hypertension. Coronary artery disease had been diagnosed in 33 (16. 7 percent) patients (31 men, two women). Previous medical history noted myocardial infarction in 16 (8.1 percent) and stroke in 14 (7.1 percent). Chronic obstructive pulmonary disease was found in 40 cases (20 percent) and EDS in 173 (87.4 percent) patients (Fig 1).
Description of the 7Wo Subgroups The conservatively treated (weight-loss recommendation) group included 127 patients with, at entry, a mean age of 53± 11 years, a mean BMI of 31 ± 8 leW m1 , and a mean AI of 43±30.5. The surgically (tracheostomy) treated group (71 patients) had a mean age of48.8 ± 11 years (p
