Sleep-Disordered Breathing in Healthy, Aged Persons

in Healthy, Breathing Sleep-Disordered Aged Persons* Fifth and Final Year

Follow-up

Phillips, MD,BAFCCP; David TR. Berry, PhD; and Tanja C. Lipke-Molby,

Barbara A.

The frequency of sleep-disordered breathing (SDB) events increases dramatically with age, although the clinical significance of this phenomenon is uncertain. We report herein on data from the fifth of healthy elderly which we selected, evaluated, and followed up follow-up observation ofthisa cohort issue. Baseline observations on this group of 95 normal older persons in an effort to address nocturnal polysomnograms and daytime as¬ medically screened for good healthandincluded standardvariables. At fifth-year follow-up, 42 subjects sessment of medical, sleep/wake, psychological returned for assessment. Comparison of returning vs nonreturning subjects indicated no significant differences in baseline characteristics between these groups. Division of returning subjects into moderate (apnea-hypopnea index [AHI] >5) vs low (AHI<5) SDB at baseline resulted in 10 subjects in the moderate group and 32 subjects in the low group. The two groups were comparable with re¬ older (70.4 gard to sex, weight, and education, although the moderate SDB group was significantly and SDB than the low (64.8 medical, sleep/wake, psychological data group years). Follow-up years) were contrasted for the two groups using a mixed design multivariate analysis of variance (repeat¬ ed measures factor-time-6 observations; between-subjects factor SDB level, 2 groups). There were no statistically significant effects of SDB or interactions of SDB and time across this 5-year followup. These results confirm observations from the third-year follow-up. We conclude that observation of a moderate level of SDB in an otherwise healthy older person is apparently not a significant risk across a 5-year follow-up period and therefore does not seem to warrant investigation beyond a thorough medical history and physical examination to rule out other disorders.

(CHEST 1996; 110:654-58)

Key words: elderly; pulmonary function; sleep-disordered breathing Abbreviations: AHI=apnea-hypopnea index; Scale-Revised R=Wechsler Adult Intelligence dlrg

SAS=sleep

middle-aged populations, sleep apnea syndrome (SAS) is characterized by numerous episodes of sleep-related abnormalities such as sleep-disordered sleep disturbance, and cardiac breathing (SDB),1 symptoms arrhythmias, as well as primarily daytimeand/or neusuch as hypersomnolence, psychological and hypertension. SAS can be ropsychological deficits, a life-threatening disorder.2 Although nocturnal disturbances are obviously a sine qua non for breathing SAS, the relationship between SDB and SAS is not known if there is entirely clear. For example, it is not between level of a tight dose/response relationship in subclinical of other Tn

-"*

SDB and

intensity

symptoms

*From the University of Kentucky Departments of Medicine (Dr. Phillips) and Psychology (Dr. Berry and Ms. Lipke-Molby),

Sanders-Brown Center on Aging (Drs. Phillips and Berry), and Samaritan Medical Center, Lexington, Ky. in part by a Preventive Pulmonary Academic Award Supported from the National Institutes of Health. Manuscript received January 29, 1996; revision accepted April 3.

654

apnea

syndrome; SDB=sleep-disordered breathing;

WAIS-

levels of the disorder or even in SAS. Additionally, features reported to be associated with SAS are quite variable. Although flexibility is in some ways an as a syn¬ advantagefromoftheconceptualizingof the disorder drome, standpoint research, the variability in definition of the condition is problematic and may contribute to conflicting findings in the literature. The methodologic challenges of studying SDB are exacerbated when applied to a geriatric population.3 For example, it has been shown that, in some older individuals, high levels of SDB may be associated with in a condition termed significantSAS.4 daytime symptoms well established that is now it However, geriatric in are older persons, general, significantly more likely to have levels of SDB thought to be pathologic in middle-aged persons.5 The extent to which SDB observed in the typical older person is pathologic is debated. On the one hand, old age can be vigorously rife with physical deterioration, including cardiopulClinical Investigations

monary and neurologic declines that resemble some of the abnormalities seen in younger SAS samples which could conceivably be attributed to the breathing disorder.6 However, because moderately high levels of SDB may be seen in apparently otherwise healthy older persons/ it seems implausible that SDB is the major cause of many ofthe pathologic conditions found in this population, particularly among those who are otherwise in good health. Of course, it is also possible that the abnormality thought to be associated with SDB might not have developed yet, but will appear if the individual is followed up for a sufficient period. This article addresses this question through presen¬ tation of data from a prospective study of the impact of SDB in healthy older persons. The basic question addressed by the study was: do otherwise healthy in¬ dividuals with SDB experience increased levels of ab¬

normality across a 5-year follow-up period? Materials

and

Methods

Subjects Subjects were a subset of individuals described by Phillips et al8 who explored the relationship between SDB and daytime func¬ tioning in 122 healthy individuals between 50 and 80 years of age. This study was approved by the Institutional Review Board of the University of Kentucky. As noted by Phillips et al,8 subjects were required to be in current good health, to have no history of neuro¬ logic, pulmonary, or psychiatric disorder, to have no sleep-related complaints beyond typical age-related changes, and to be taking no psychoactive or respiratory stimulant medications. Because of resource limitations, only the first 95 ofthese subjects were targeted for inclusion in the 5-year follow-up study. Of the 95 subjects ini¬ tially targeted, 13 were eliminated from follow-up because of un¬ disclosed or unsuspected illness or medication usage, chronic con¬ ditions predisposing to SDB, or inability to sleep at least 4 h in the sleep laboratory at initial observation. The remaining 82 subjects were invited to return for the follow-up study that occurred over a 5-year period. The number of subjects available at each observation fluctuated somewhat from year to year as some dropped out, some declined physically or mentally to the point of being unable to par¬ ticipate, and some died. Another source of variance was the fact that all eligible subjects were recruited for participation each year, but sometimes were absent 1 year only to return the next. Every effort was made to locate subjects who did not return for follow-up. The Kentucky Vital Statistics Department of the Cabi¬ net for Human Resources conducted a search for years 1986 through 1994, yielding 6 death certificates. Raseline Measures Materials for the baseline observation have been described pre¬ in a detailed presentation. Nocturnal apparatus included viously8 standard equipment for a diagnostic sleep study. Daytime materi¬ als have also been described and included equipment and materi¬ als necessary to assess medical, sleep/wake, and psychological status.

Follow-up Measures

Materials and equipment used in the follow-up observations were described by Phillips et al.9 Essentially, a subset of daytime proce¬ dures assessed at baseline was used for follow-up assessments.

1.Apparatus and Measures for Baseline and

Table

Yearly Follow-up*

Nocturnal PSG

MSLT15

Serial BP

measurements

H&P ECG

Pulmonary function testing Neuropsychological testing Aphasia Screening Test10

Controlled Oral Word Association10

Finger Tapping Test10 Geriatric Depression Inventory11

Judgment of Line Orientation10 MMPI12

Mini-Mental State Examination13 Sickness Impact Profile14

Stroop Test10 Symptom Checklist 90-RevisedlD

Trail-Making Test10

WAIS-R16

Wechsler Memory Scale-Russell R1' Florida Sleep Questionnaire18 Stanford Sleepiness Scale19

Baseline

Year 1-5

X X X X X X

X X X X

X X X X X X X X X X X X X X X X

X X X X X X X X X X X X X X X

Sleep Logs20 *PSG=polysomnography; MSLT=Multiple Sleep Latency Test; H&P= history and physical examinations; MMPI=Minnesota Multiphasic Personality Inventory.

Procedures.Raseline Procedures followed at baseline observation were as previously described.9 All subjects received an overnight polysomnogram that assessed their nocturnal sleep and breathing status using standard procedures. During the following day, their medical, sleep/wake, and psychological status were assessed using a variety of procedures outlined in Table l.10"19 All procedures and tests were administered and scored in accordance with directions given in the citations. Procedu res.Follow-up Subjects were invited to return for follow-up evaluations on an annual basis. They were administered a subset of procedures given at baseline. A summary of these also appears in Table 1. In brief, the neuropsychological measures used were chosen because they were sensitive to hypoxemia in past reports, possible to administer at a bedside table, and available in several forms that would be relatively insensitive to practice effects. Dependent measures included total score from the Symptom Checklist 90, to¬ tal score from the Mini-Mental State, raw scores from the Wech¬ sler Adult Intelligence Scale-Revised (WAIS-R) subtests, mean taps for dominant and nondominant hands from the Finger Tapping Test, total time for Trail-Making parts A and B, color-naming total from the Stroop Test, delayed recall score from the Weschler Memory Scale subtests, copy and delayed recall score from the Rey Figure Recall, and total words from the Controlled Oral Word As¬ sociation.

Data Analyses Two types of analyses were used. In the first, or between-group analyses, subjects were divided into moderate and low SDB groups

based on their apnea-hypopnea index (AHI), with those having an AHI of 5 or greater classified as having moderate SDB, and those having an AHI less than 5 classified as having low SDB. The secCHEST 7110/3/ SEPTEMBER, 1996

655

Table 2.Baseline Data for Subjects Followed Up for 5 Years Compared With Those Unavailable for

Follow-up*

Age at entry, yr Education, yr

Height, cm Weight, kg BMI M:F

White race No. of AHI>5(%)

Dropouts (n=40)

Long-term (n=42)

63.0+8.4 14.6±3.1 166.75±9 71.1±11.745 2.3±0.4 21:19 40 6/40 (15)

66.2±7.8 14.8±2.87 170.25±9 73.35 ±12.825 2.4+0.3 23:19 42 10/42 (23)

*BMI=body mass index, kg (cm)

Data presented with SD.

ond set of analyses was correlational in nature, with baseline AHI correlated with status at each of the five follow-up observations.

Results

Table 2 presents baseline demographic data for those subjects who completed 5 years of follow-up and for those who were unavailable for follow-up. There were no statistically significant differences between these two groups, although there was a tendency for the long-term follow-up group to be older (p<0.08) and to have a higher AHI (p<0.38). We were able to ascertain that 6 of the original 82 subjects died it is possible that others may have died out (although and thus be unknown to us). Five of these of state, "unavailable" subjects had AHI less than 5. Data from the 42 subjects who completed 5 years of of follow-up after initialinevaluation (actually 6 years are presented Table 3, grouped by level of study)Those AHI. with AHI less than 5 (n=32) were signif¬ with AHI greater than 5, but icantly younger than those no different were otherwise except for having they AHI. Five later (fifth follow-up), the years higher had 0.9 an of kg, but there subjects gained average were no significant differences in their weights or body mass indexes by AHI grouping.

Neuropsychological Testing

With few exceptions, there were no statistically sig¬ nificant differences between the two groups (AHI<5, AHI>5) at the fifth year of follow-up for the following Table 3.Demographics for 5-Year Cohort at

Entry by AHI*

AHI<5

Age, yr*

Education, yr

Weight, kg BMI

AHI* M:F

*Data presented with SD.

fp=0.013. *p=0.004.

656

(n=32)

64.8±8.1 15.0±3.0 74.025+13.23 2.4±0.4 1.0±1.2 17:15

AHI>5

(n=10)

70.4±4.8 14.2±2.3 71.775±11.97 2.3±0.3 13.6±10.4 6:4

Symptom Checklist 90 Positive Symptom Total Score, Geriatric Depression Total Symptoms Score, Mini-Mental State Score, WAIS-R Digit Symbol or Similarities Scores, Wechsler Logical Memory Devel¬ opment or Visual Memory Development, Rey Figure Recall, Finger Tapping Test using the dominant hand, or the Trail-Making Part A. Exceptions to this were an increase from baseline Wechsler Visual Memory Re¬ for the first 3 years of production Development then a decline that was not different by AHI follow-up, group; a lower Geriatric Total Depression Score for the AHI greater than 5 group that disappeared in subse¬ quent follow-up; an increase in Rey Figure Recall from both groups over time; and a statistically higher (poorer) score on Trail-Making Form B for the low

tests:

AHI group at the final year of follow-up.

Further, partial correlation coefficients controlling for age showed no significant correlation beyond that expected by chance between any of the neuropsycho¬ at logical tests and the following parameters measured baseline: AHI, self-reported snoring, number of 4% oxygen desaturations, sleep stage shifts, time spent in stage 0, or number of awakenings. No consistent pat¬ tern of differential performance between group or neuropsychological tests emerged across the study.

Cardiopulmonary Data There were no statistically significant differences between the two groups or by time for BP, for self-re¬ ported hypertension, for pulse rate, or for spirometric FVC, actual and percent pre¬ performance, including actual and dicted, FEVi, percent predicted. Persons with AHI greater than 5 were more likely to have more than 1 but fewer than 10 premature ventricular contractions noted on ECG during baseline polysomnogram, but there were no differences in abnormal on 12-lead ECG findings between the groups findings at fifth-year follow-up. Measured BP did not correlate with baseline data on sleep structure. We once again found a suggestion of an association of between measures of sleep quality and pulmonary function. The number of awakenings (events after correlated inversely with asleep onset ofat20 s stage 0) and 5. The percentage of FEVi percent years 1, 2, time spent awake correlated inversely with FEVi and FVC at baseline, and FEVi percent at years 1 and 4 of follow-up. Medical History and Physical Examination Data There were no statistically significant differences between the low AHI vs moderate AHI groups at the fifth follow-up for Cornell Medical Indices, for Sick¬ ness Impact Total, Psychological, or Physical Summary Scores, or for reporting of the following: abdominal surgery, use of prescription medicines, self-reported Clinical

Investigations

snoring (52% of sample), sinusitis, snoring status, alcohol consumption, use of antihypertensives, hospi¬ talizations, trouble with colds, pneumonia, nosebleeds, headaches, chest pains, irregular heartbeat, heart fail¬

significant illness. the Regarding sleep histories, groups did not differ significantly with regard to trouble staying awake dur¬ ing the day or difficulty falling asleep at night, com¬ plaints by others about snoring, automobile accidents, or daytime napping. Responses to these questions (in¬ cluding the questions about others complaining about snoring and daytime measures) did not correlate with measures of sleep architecture. The AHI greater than 5 group was more likely to report having had previous ear, nose, and throat sur¬ gery at the fifth-year follow-up, although this differ¬ ence was present at baseline as well.7 The two groups did not differ statistically with regard to abnormal findings on physical examination, includ¬ ing bruits, nodes, palpable thyroid, septal deviation, nasal polyps, gallops, crackles, wheezes, clubbing, or Those with AHI greater than 5 were peripheral edema. more likely to have palmar erythema. significantly

ure,

or

Discussion

While many have adopted a higher point of SDB in published reports, the "gold standard"20 and a recent landmark epidemiologic study21 still apply an AHI of greater than or equal to 5 as the definition of sleep apnea. This appears not to be applicable to the

asymptomatic healthy elderly. Two limitations ofthis study that limit application of this conclusion to the aging population at large are the relatively mild SDB of our participants and the attri¬

of our initial cohort. sample is different from a clinical population presenting to a sleep clinic or laboratory and is differ¬ ent even from the general population of Kentucky. Because of the pool of research subjects we used, our subjects were all white. Recent data22,23 suggest that a higher prevalence of clinically significant SDB might be found in a population that included African-Amer¬ icans. Our subjects were all community dwelling, which again, would predispose to a lower level of clin¬ ically significant SDB18 than found in the general tion

Our

population. In addition, we had a significant attrition rate over 6 years of study. We began with 95 carefully studied individuals and completed the study with 42. Never¬ theless, we have compared those subjects we followed up longitudinally to those who were unavailable for follow-up and did not find significant differences with intake parameters. We believe that our regard toaretheir thus findings applicable to the population we studied.

We did find that the group with a higher level of SDB was more likely to have palmar erythema. It is tempting to speculate that palmar erythema is a marker

for alcohol

SDB.24

consumption,

a

known risk factor for

We were intrigued to find again at the fifth follow-up suggestion of an association between measures of sleep quality and pulmonary function. We have reported this

and are no closer to understanding the previously, mechanism than before, although this appears to be a consistent finding. Series et al25 have demon¬ fairly strated recently that sleep fragmentation enhances upper airway collapsibility in normal subjects, both in and sleeping conditions. Sleep apnea is also working associated with COPD,26 although a cause and effect has not been well established. A recent report27 indicts for SDB; airflow obstruction smoking as aberiskthefactor marker of cigarette smoking. may simply The data that we collected about snoring are of in¬ terest. We assessed snoring in two ways: subjects were asked by a physician in each year of follow-up "Do you snore?" and were also asked on a questionnaire "Has anyone complained about your snoring?" Previous studies about sequelae of snoring have linked it to a variety ofadverse effects, ranging from hypertension to death.28"34 However, most studies that have evaluated snoring's clinical significance have been marred by several factors, including the following: (1) obesity, smoking, male sex, and aging are usually important covariants that are difficult to control for; (2) many of the studies evaluating snoring have not included poly¬ so it is difficult to tell if the data being somnography, are the effects of undipresented actually indicating most of the studies have been (3) agnosed sleep apnea; still remains difficult to (4) retrospective; sleep apnea define numerically; and (5) studies about the preva¬ lence of snoring and its sequelae often do not report the way that the snoring was measured. Our study ad¬ dresses most of those concerns. We did not find an association between self-reported snoring and impor¬ tant sequelae. We agree with Strollo and Sanders35 that simple snoring does not appear to be a risk factor and that taking a comprehensive history and performing a are probably the most appropri¬ physical examination in ate steps evaluating the significance of snoring. REFERENCES

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Clinical

Investigations