Geriatric OSA: Should We Treat It?

Transcription

1 Geriatric OSA: Should We Treat It? Eric J. Kezirian, MD, MPH Director, Division of Sleep Surgery Otolaryngology Head and Neck Surgery University of California, San Francisco Sleepsurgery.ucsf.edu

2 Disclosures The following personal financial relationships with commercial interests relevant to this presentation existed during the past 24 months: Consultant Consultant Consultant Consultant/ Advisory Board Apneon Medtronic Pavad Medical Apnex Medical

3 Overview Background, including definitions OSA Consequences and Treatment Outcomes Sleep Architecture Behavioral Cognitive Health-Related Issues in Treatment Selection SDB in Context of Other Sleep Disturbances

4 Definitions Older adults: adults over the age of 60 Clinical disease Disease with signs/symptoms Treat disease if improve signs/symptoms Subclinical disease Disease without signs or symptoms Treat disease if prevent development of signs/symptoms

5 Subclinical Disease Many diseases are diagnosed in subclinical stage, esp in elderly (defined by criteria developed for young and middle-aged adults) Thyroid dysfunction, HTN, hypercholesterolemia Treatment recommendations very controversial and limited by lack of high-quality evidence General sentiment: treat on case-by-case basis (often based on presence of signs/symptoms or comorbidity)

6 Definitions OSA Sleep disordered breathing (SDB), abnormal breathing patterns during sleep (severity quantified by AHI) Symptoms: functional or health-related

7 Prevalence in Middle-Aged Adults OSA: 2% F, 4% M with AHI 15 and symptoms SDB: 4% F, 9% M with AHI 15 Source: Table 4, Young et al. NEJM 1993

8 Prevalence of SDB in Older Adults Cohort studies with wide age ranges Bixler AJRCCM 1998, 2001: prevalence of SDB increases with age from years and then stable Duran AJRCCM 2001: SDB (AHI 15) higher among age years compared to years (49 vs. 7% F, 57 vs. 14% M) Tishler JAMA 2003: age a major SDB risk factor (older vs. middle-aged) Pavlova SLEEP 2008: AHI 15 in >50% of 65+ years vs. 5% of < 50 years

9 Prevalence of SDB in Older Adults Sleep Heart Health Study: 5615 participants Prevalence of AHI 15 increases with age up to 60 Source: Figure 1, Young Arch Int Med 2002

10 SDB: Potential Mechanisms Aging process: changes in muscle tone, fat deposition Increase in Pcrit and pharyngeal resistance with age Eikermann Chest 2007 BMI: may be very important but perhaps less so than in younger populations Changes in AHI associated with BMI but

11 Obesity Has a Less Prominent Role As Risk Factor for SDB In Elderly (Young T, et al, Arch Intern Med 162:893, 2002) Odds ratio for AHI>15 events/hour with BMI increment of 5.3 kg/m 2

12 SDB: Potential Mechanisms Hormonal: prevalence of SDB among post-menopausal F similar to M Sleep disturbances (other): common Neurologic: reflexes and upper airway patency repetitive barotrauma model Medical comorbidities

13 Why does prevalence rise with age? Age-dependent Pathogenesis directly stems from aging SDB in older adults similar to middle-aged Age-related Pathogenesis occurs only during specific age period SDB in older adults a distinct disorder from that in young and middle-aged

14 Why does prevalence not continue to rise with age? Incidence low: age not associated with new cases Mortality rate high (age-dependent): deaths = incidence SDB in elderly is distinct, age-related Elderly with SDB are resistant to adverse effects? Protective mechanisms from repeated hypoxemia over time (Lavie and Lavie Med Hypotheses 2006) High prevalence, low mortality in older adults

15 Why Does Mortality from SDB Decline with Age? (Lavie L & Lavie P, Med Hypotheses 66:1069, 2006) Propose a hypothesis SDB leads to ischemic preconditioning SDB upregulation of Hypoxia-inducible factor- 1α (HIF1α) and downstream genes that promote ischemia-mediated angiogenesis SDB VEGF (vascular endothelial growth factor) coronary collateral vessels Could SDB in older adults be good for you if it does not kill you first?

16 How could one possibly advocate not treating OSA/SDB in older adults? SDB not associated with adverse consequences SDB in elderly a different phenomenon than in young and middle-aged (age-related) Survivor effect (elderly OSA who survive are resistant to adverse effects) Clinical vs. subclinical disease Even if OSA/SDB associated with adverse consequences, treatment unable to reverse or prevent development of sequellae

17 Treatment Outcomes My focus: studies including only older adults or reporting results for subgroup of older adults Studies reporting data only in aggregate not sufficient, even if they include older adults Respiratory events and sleep architecture Behavioral Cognitive Health-related

18 Respiratory Events and Sleep Architecture SDB and other sleep disturbances common in older adults CPAP efficacious in reducing respiratory events and oxygenation in SDB --effectiveness limited by compliance Effect on other aspects of sleep architecture in older adults unknown Effects of other treatments are unknown

19 Behavioral Many studies include older adults in evaluating CPAP outcomes, but few are limited to older adults or report outcomes specifically for older adults Objective sleepiness (MWT, MSLT) In studies including older adults, no improvement with CPAP, although some improvement with most severe symptoms Subjective sleepiness: lower ESS in Alzheimer s No data report CPAP or other treatment outcomes for quality of life

20 Cognitive AHI associated with impaired performance on MMSE in older adults Cohen-Zion J Psychosom Res 2004 AHI (mild-mod SDB) not associated with cognitive function in non-demented Boland J Sleep Res 2002 AHI associated with impaired cognition (verbal recall, constructional abilities) Compliant (>6 hours) CPAP use improves attention, psychomotor speed, non-verbal recall, executive functioning in older adults Aloia J Psychosom Res 2003

21 Health-Related Little research on treatment outcomes specifically in older adults (or reported for older in studies including wider age range)

22 In Sleep Heart Health Study Association Between SDB and Hypertension is Greater in <65 years of Age (Nieto FS, et al, JAMA 283:1829, 2000) Age (years) Number of Subjects Demographics OR Fully Adjusted OR (95% CI) < ( ) (NS) ( ) OR = AHI 30 compared to reference (AHI<1.5) Demographics OR = adjusted for age, gender, ethnicity Fully adjusted OR = adjusted for age, gender, ethnicity, BMI, neck circumference, waist-to-hip, alcohol, cigarette smoking

23 Untreated Severe SDB Is Associated with Increased Mortality All Ages (Wisconsin Sleep Cohort Study; Young T, et al, Sleep 31:1071, 2008)

24 Severe SDB (AHI>30) Is Not Associated with Increased Mortality Between 60 and 80 Years of Age (Lavie P, et al, Eur Respir J 25:514, 2005) **p<0.01 # p<0.007

25 Mortality: Lavie et al. J Sleep Res 2007 Research question: Among men with SDB, is untreated AHI associated with mortality? Methods: case-control study Most detailed longitudinal study 331 men with SDB (AHI > 10) diagnosed from who died prior to 9/2001 Controls matched: age, dx date, BMI, AHI Logistic regression: odds of death Predictor: AHI Adjustment: medical comorbidities

26 Mortality: Lavie et al. J Sleep Res 2007 Overall Risk factors: COPD, CHF, DM Interaction between AHI and BMI/COPD Age < 62 years (median age in sample pop) Risk factors (for mortality): COPD and DM Interaction between AHI and BMI Age 62 years Risk factors: COPD, CHF, and DM Discussion: SDB may contribute to risk factors, but it does not appear to be an independent risk factor for older adults

27 CPAP and Palate Surgery Effectiveness: Mortality Marti et al., Eur Resp J 2002 Research Questions: Is OSA associated with increased mortality? Does treatment of OSA reduce mortality? Cohort study (n=444) Baseline AHI 55 ± 27 Treatments: none (98), dietary changes/weight loss (134), CPAP (124), UPPP (88)

28 OSA Treatment Effectiveness: Mortality (Marti 2002) Untreated OSA associated with increased mortality; less so for age >60 yrs

29 OSA Treatment Effectiveness: Mortality (Marti 2002) Untreated OSA (but not treated OSA) associated with increased mortality

30 OSA Treatment Effectiveness: Mortality (Marti 2002) All OSA treatments are associated with lower mortality Diet/weight loss CPAP UPPP Adjusted for confounders Adjustment for AHI, HTN: no change in results

31 Mortality: Treatment Marti Eur Resp J 2002 Excluded untreated patients diagnosed after 1988 (when CPAP available) who refused treatment Problem: groups very different Untreated: diagnosed before 1988 and did not undergo UPPP or achieve 10% weight loss with dietary changes Treated: accepted CPAP (for diagnosis after 1988), UPPP, or successful weight loss

32 Mortality: Treatment Is OSA treatment associated with lower mortality? Weaver et al. Am Ger Soc Ann Mtg 2005 Patient age 60+ years; 98% male All VAMCs FY OSA code on inpatient or outpatient treatment 53,469 untreated 11,000 treated (surgery or CPAP) Outcome: death before 2002

33 Treatment Associated with Lower Mortality p, y py Logrank test, p < TREATED UNTREATED Years From Diagnosis

34 Surgery Associated with Lower Mortality than CPAP p, y py Logrank test, p < SURGERY CPAP Years From Diagnosis

35 Adjusted Hazard Ratios Better Survival Treated vs. Untreated 0.74 Worse Mortality Surgery vs. CPAP 0.62 Female vs. Male Diagnosis Year White vs. non-white Age Comorbidity Adjusted* Hazard Ratio *Adjusted for age, gender, diagnosis year, comorbidity

36 Mortality Similar for Middle-Aged and Geriatric 0.96 Middle-Aged vs. Geriatric: Untreated Middle-Aged: Treated v Untreated Geriatric: Treated v Untreated Adjusted* Hazard Ratio (*Adjusted for Age, Gender, Race, Comorbidity, and Diagnosis Year)

37 Mortality and Treatment: Weaver E Studies Mortality higher in untreated vs. treated OSA Surgery is associated with lower mortality than (receiving) CPAP Strengths Generalizable (multiple hospitals, providers) Huge samples Adjustment for multiple variables (best to be expected for a study of this size) Limitations No data: BMI, SDB severity (AHI), CPAP compliance (hard to compare effectiveness of CPAP vs. surgery) Possible healthy user effect (as in Marti 2002)

38 Healthy User Effect aka healthy adherer effect (medications) Form of selection bias Can occur when patients not randomly assigned to treatments (or no treatment) Subjects who enroll in studies (or receive treatment in observational studies) tend to be healthier and more concerned about their health than non-enrollees (or untreated)? More important in older adults

39 Healthy User Effect: Simpson BMJ 2006 Objective: examine association between medication adherence and mortality (in adults of all ages) Meta-analysis of 21 studies, including 8 with placebo group (n=19,633) Medical therapy for: drug therapy after recent MI HIV infection primary prevention of heart disease also NIDDM, heart failure, immune suppression after heart transplant, hyperlipidemia

40 Healthy User Effect: Simpson BMJ 2006 Compared to low adherence: Adherence to beneficial medication lower odds of mortality: 0.56 (0.50, 0.63) Adherence to placebo medication lower odds of mortality: 0.56 (0.43, 0.74) Adherence to harmful medication higher odds of mortality: 2.90 (1.04, 8.11) Placebo might be the best option, given the uncertainty about whether medication beneficial or harmful

41 Healthy User Effect: Medications Multiple observational studies showed association between taking medication and benefits, while RCTs showed no benefits or harm Vitamin E Selenium Beta carotene Estrogen replacement therapy in postmenopausal women

42 Healthy User Effect in Older Adults: Influenza Vaccine Influenza vaccine in older adults has demonstrated wide range of benefits in observational studies, including a 50% reduction in all-cause mortality Findings do not agree with experience No interventional trials suggest vaccination benefit No change (? increase) in influenza mortality/admissions with increases in vaccination among older adults Mortality reduction in off-season times of year when few/no vaccines Adjustment for functional status and health attenuate benefits seen in observational studies that have these data

43 Healthy User Effect: Influenza Vaccine Eurich AJRCCM 2008 Prospective cohort study Data collection for all adults admitted to Capital Health (Edmonton) with community-acquired pneumonia Vaccine recipients matched to control group on propensity to receive flu vacccine Vaccine: 51% reduction in mortality Vaccine: >50% reduction in ICU admission

44 No benefit of vaccine after adjustment for smoking, functional status and socioeconomic status

45 Issues in Treatment Selection Behavioral CPAP Surgery Oral Appliances

46 Behavioral Treatments Weight loss Non-supine sleep position Avoidance of alcohol and other sedatives Older adults have frequent use of hypnotics, esp benzodiazepines No studies demonstrating benefits in older adults, although weight gain associated with worsening of AHI Ancoli-Israel Sleep Med 2001

47 CPAP Compliance Appears similar to that of young and middle-aged Younger age better compliance (among older adults) Pelletier-Fleury Sleep Med 2001 Russo-Magno JAGS 2001 Limited evidence Factors associated with increased compliance Patient education only at 12 weeks (Aloia Sleep Breath 2001) Factors associated with worse compliance Current smoking and nocturia, but not living alone (Russo-Magno JAGS 2001) Living alone (Lewis SLEEP 2004)

48 Surgery Outcomes: UPPP ASDA Literature Review of OSA Surgery Sher SLEEP 1996 No effect of age on UPPP outcomes Not detailed analysis Unclear how many older adults

49 Surgery Outcomes: UPPP Stevenson Laryngoscope patients (10 age 60+) with UPPP ± T ± nasal surgery Outcome: change in apnea index --favorable outcome = AI reduction 30 Likelihood of favorable outcome decreased with age (p = 0.05), with only 10% (1/10) in adults aged 60+ years Caveat: do not report preop sleep study data (esp baseline AI would need to be 30 for favorable outcome)

50 Surgery Outcomes: Multilevel Surgery Yin Oto-HNS males; AHI > 40 Age years (44±10) UPPP (?T), genioglossus advancement, hyoid suspension (to mandible) Outcome: meaningful reduction in AHI --reduction of 50% to <20 (67%, 12/18)

51 Surgery Outcomes: Multilevel Surgery Nonresponders older than responders

52 Surgery Outcomes: Multilevel Surgery Age and increased BMI associated with increased likelihood of being non-responder, although not limited to older adults

53 Surgery Risks UPPP risks studied most thoroughly Case series from individual institutions (N = ) References: Esclamado et al. Laryngoscope 1989; Haavisto and Suonpaa Clin Otolaryngol 1994; Mickelson and Hakim Oto HNS 1998 Cohort from all VAMCs from (N = 3130) Kezirian, Weaver et al. Laryngoscope 2004 Serious perioperative complications: 1.6% (total) Respiratory (including reintubation) 1.1% 30-day mortality: 0.2%

54 Surgery Risk Factors Kezirian, Weaver et al. Archives Oto-HNS 2006 Age not an independent risk factor Risk factors Medical comorbidity Body mass index (obesity) Severity of OSA (AHI) Multilevel surgery If perform surgery on more older adults (including those with other risk factors), may be performing surgery in higher-risk population

55 Oral Appliances No studies have been performed in older adults or with data reported specifically for older adults With poorer dental health and denture use, older adults may not be candidates

56 Context: Other Sleep Disturbances in Older Adults Ohayon SLEEP 2004; Redline Arch Int Med 2004 Increase in arousal index Decrease in sleep efficiency Decline in N3 (slow wave) and REM sleep --may be more pronounced in men Wide range of medical comorbidities is associated with sleep disturbances Association between SDB and other sleep disturbances

57 Context: Importance of Sleep Time Many studies show an association between SDB and daytime sleepiness in older adults However, sleep disturbances (including decreased sleep time) are common in elderly Two multi-center studies of communitydwelling older women and men Unique: both PSG and actigraphy (sleep time)

58 Kezirian et al. SLEEP 2007 Study of Osteoporotic Fractures Cross-sectional analysis 461 women Age 83 ± 3 years (very old) 38% AHI 15 ESS AHI TST AHI independently associated with ESS No association after adjustment for sleep time No association with sleep symptoms or QOL PSQI FOSQ Adjusted for age, AA race, BMI, self-reported health status, anxiety, depression sx

59 Kezirian et al. SLEEP 2009 Study of Osteoporotic Fractures in Men Cross-sectional analysis 2849 men Age 76 ± 6 years 43% AHI 15 ESS PSQI AHI TST AHI independently associated with ESS, but no association after adjustment for sleep time No association between AHI and sleep symptoms or QOL FOSQ TST associated with outcomes Adjusted for age, AA race, BMI, self-reported health status, anxiety, depression sx

60 Context: Importance of Sleep Time Behavioral consequences of SDB in older adults an unresolved question: studies cross-sectional, not longitudinal Cross-sectional analyses in young and middle-aged also show no association between AHI and behavioral measures Weaver Arch Oto-HNS 2004; Weaver Oto-HNS 2005 SOF/MrOS cohorts: correlation between AHI and TST weak (-0.15) SDB and TST appear to be distinct Should include objective TST in assessment of behavioral (? and other) outcomes in older adults

61 Conclusions No convincing evidence that treatment of OSA in older adults reverses or prevents development of adverse sequellae Clinical disease treat Subclinical disease not treat? Interventional studies small Observational studies may be limited by healthy user effect that could be particularly strong in older adults Need studies of SDB and SDB treatment in older adults, including reporting of subgroup of older adults in larger studies

62 Conclusions Limited evidence on treatment suggests Sleepiness:? Alzheimer s Disease only Cognitive: Yes (one study) Health-related: associated with decreased mortality but beware healthy user effect

63 Conclusions Treatment of OSA in older adults is challenging Little data on CPAP compliance and measures to improve compliance Very little data on surgery No data on behavioral measures or oral appliances Examining benefits of treatment in older adults may be more complex than in young and middle-aged --functional status --sleep disturbances, including sleep time