The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: The Osteoporotic Fractures in Men Study and the Sleep Heart Health Study

Ali Azarbarzin; Scott A. Sands; Katie L. Stone; Luigi Taranto-Montemurro; Ludovico Messineo; Philip I. Terrill; Sonia Ancoli-Israel; Kristine Ensrud; Shaun Purcell; David P. White; Susan Redline; Andrew Wellman

doi:10.1093/eurheartj/ehy624

The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: The Osteoporotic Fractures in Men Study and the Sleep Heart Health Study

Ali Azarbarzin, Scott A. Sands, Katie L. Stone, Luigi Taranto-Montemurro, Ludovico Messineo, Philip I. Terrill, Sonia Ancoli-Israel, Kristine Ensrud, Shaun Purcell, David P. White, Susan Redline, Andrew Wellman

Medicine - Veteran's Administration Medical Center

Research output: Contribution to journal › Article › peer-review

259 Scopus citations

Abstract

Aims: Apnoea-hypopnoea index (AHI), the universal clinical metric of sleep apnoea severity, poorly predicts the adverse outcomes of sleep apnoea, potentially because the AHI, a frequency measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnoea by the 'hypoxic burden' would predict mortality among adults aged 40 and older. Methods and results: The samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality and all-cause mortality (only in MrOS). Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.81 [95% confidence interval (CI) 1.25-2.62] and 2.73 (95% CI 1.71-4.36), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11-3.43). Conclusion: The 'hypoxic burden', an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.

Original language	English (US)
Pages (from-to)	1149-1157a
Journal	European heart journal
Volume	40
Issue number	14
DOIs	https://doi.org/10.1093/eurheartj/ehy624
State	Published - Apr 7 2019

Bibliographical note

Funding Information:
The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 TR000128, K24-AR04884-06]. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839]. The Sleep Heart Health Study (SHHS) is supported by the National Heart, Lung, and Blood Institute through the following cooperative agreements: U01-HL53940 (University of Washington), U01-HL53941 (Boston University), U01-HL63463 (Case Western Reserve University), U01-HL53937 (Johns Hopkins University), U01-HL53938 (University of Arizona), U01-HL53916 (University of California, Davis), U01-HL53934 (University of Minnesota), U01-HL63429 (Missouri Breaks Research), and U01-HL53931 (New York University). This work was also supported by philanthropic funding from Fan Hongbing (President of OMPA Corporation, Kaifeng, China) and the National Institutes of Health (R01HL102321, R01HL128658, P01HL095491, UL1RR025758). S.A.S. and L.T.-M. were supported by American Heart Association grants (15SDG25890059 and 17POST33410436, respectively); and partially supported by NHLBI R35HL135818 (to S.R., S.A.S., A.W., and A.A.).

Funding Information:
The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 TR000128, K24-AR04884-06]. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study "Outcomes of Sleep Disorders in Older Men" [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839]. The Sleep Heart Health Study (SHHS) is supported by theNational Heart, Lung, and Blood Institute through the following cooperative agreements: U01-HL53940 (University of Washington), U01-HL53941 (Boston University), U01-HL63463 (Case Western Reserve University), U01-HL53937 (Johns Hopkins University), U01-HL53938 (University of Arizona), U01-HL53916 (University of California, Davis), U01-HL53934 (University of Minnesota), U01-HL63429 (Missouri Breaks Research), and U01-HL53931 (New York University). This work was also supported by philanthropic funding from Fan Hongbing (President of OMPA Corporation, Kaifeng, China) and the National Institutes of Health (R01HL102321, R01HL128658, P01HL095491, UL1RR025758). S.A.S. and L.T.-M. were supported by American Heart Association grants (15SDG25890059 and 17POST33410436, respectively); and partially supported by NHLBI R35HL135818 (to S.R., S.A.S., A.W., and A.A.).

Funding Information:
receives salary from Philips Respironics and is a consultant to Night Balance. A.W. works as a consultant for Somnifix, Cambridge Sound Management, Nox Medical, Bayer, Philips, and Galvani and has received grants from Philips and Somnifix. L.T.-M. and A.W. also have a financial interest in Apnimed Corp., a company developing pharmacologic therapies for sleep apnoea. Their interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies. S.A.-I. is a consultant for Eisai, Merck, Acadia, Pfizer, GSK. K.L.S. has grant funding from Merck. L.M., K.E., and S.P. declare no conflicts of interest.

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.

Keywords

Apnoea-hypopnoea index
CVD mortality
Hypoxic burden
Polysomnography
Sleep apnoea

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1093/eurheartj/ehy624

Find It

Find It at U of M Libraries

Cite this

Azarbarzin, A., Sands, S. A., Stone, K. L., Taranto-Montemurro, L., Messineo, L., Terrill, P. I., Ancoli-Israel, S., Ensrud, K., Purcell, S., White, D. P., Redline, S., & Wellman, A. (2019). The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: The Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. European heart journal, 40(14), 1149-1157a. https://doi.org/10.1093/eurheartj/ehy624

Azarbarzin, A, Sands, SA, Stone, KL, Taranto-Montemurro, L, Messineo, L, Terrill, PI, Ancoli-Israel, S, Ensrud, K, Purcell, S, White, DP, Redline, S & Wellman, A 2019, 'The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: The Osteoporotic Fractures in Men Study and the Sleep Heart Health Study', European heart journal, vol. 40, no. 14, pp. 1149-1157a. https://doi.org/10.1093/eurheartj/ehy624

@article{c06372eadf5b4b0c80b01ea7935b2a1e,

title = "The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: The Osteoporotic Fractures in Men Study and the Sleep Heart Health Study",

abstract = "Aims: Apnoea-hypopnoea index (AHI), the universal clinical metric of sleep apnoea severity, poorly predicts the adverse outcomes of sleep apnoea, potentially because the AHI, a frequency measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnoea by the 'hypoxic burden' would predict mortality among adults aged 40 and older. Methods and results: The samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality and all-cause mortality (only in MrOS). Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.81 [95% confidence interval (CI) 1.25-2.62] and 2.73 (95% CI 1.71-4.36), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11-3.43). Conclusion: The 'hypoxic burden', an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.",

keywords = "Apnoea-hypopnoea index, CVD mortality, Hypoxic burden, Polysomnography, Sleep apnoea",

author = "Ali Azarbarzin and Sands, {Scott A.} and Stone, {Katie L.} and Luigi Taranto-Montemurro and Ludovico Messineo and Terrill, {Philip I.} and Sonia Ancoli-Israel and Kristine Ensrud and Shaun Purcell and White, {David P.} and Susan Redline and Andrew Wellman",

note = "Funding Information: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 TR000128, K24-AR04884-06]. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839]. The Sleep Heart Health Study (SHHS) is supported by the National Heart, Lung, and Blood Institute through the following cooperative agreements: U01-HL53940 (University of Washington), U01-HL53941 (Boston University), U01-HL63463 (Case Western Reserve University), U01-HL53937 (Johns Hopkins University), U01-HL53938 (University of Arizona), U01-HL53916 (University of California, Davis), U01-HL53934 (University of Minnesota), U01-HL63429 (Missouri Breaks Research), and U01-HL53931 (New York University). This work was also supported by philanthropic funding from Fan Hongbing (President of OMPA Corporation, Kaifeng, China) and the National Institutes of Health (R01HL102321, R01HL128658, P01HL095491, UL1RR025758). S.A.S. and L.T.-M. were supported by American Heart Association grants (15SDG25890059 and 17POST33410436, respectively); and partially supported by NHLBI R35HL135818 (to S.R., S.A.S., A.W., and A.A.). Funding Information: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 TR000128, K24-AR04884-06]. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study {"}Outcomes of Sleep Disorders in Older Men{"} [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839]. The Sleep Heart Health Study (SHHS) is supported by theNational Heart, Lung, and Blood Institute through the following cooperative agreements: U01-HL53940 (University of Washington), U01-HL53941 (Boston University), U01-HL63463 (Case Western Reserve University), U01-HL53937 (Johns Hopkins University), U01-HL53938 (University of Arizona), U01-HL53916 (University of California, Davis), U01-HL53934 (University of Minnesota), U01-HL63429 (Missouri Breaks Research), and U01-HL53931 (New York University). This work was also supported by philanthropic funding from Fan Hongbing (President of OMPA Corporation, Kaifeng, China) and the National Institutes of Health (R01HL102321, R01HL128658, P01HL095491, UL1RR025758). S.A.S. and L.T.-M. were supported by American Heart Association grants (15SDG25890059 and 17POST33410436, respectively); and partially supported by NHLBI R35HL135818 (to S.R., S.A.S., A.W., and A.A.). Funding Information: receives salary from Philips Respironics and is a consultant to Night Balance. A.W. works as a consultant for Somnifix, Cambridge Sound Management, Nox Medical, Bayer, Philips, and Galvani and has received grants from Philips and Somnifix. L.T.-M. and A.W. also have a financial interest in Apnimed Corp., a company developing pharmacologic therapies for sleep apnoea. Their interests were reviewed and are managed by Brigham and Women{\textquoteright}s Hospital and Partners HealthCare in accordance with their conflict of interest policies. S.A.-I. is a consultant for Eisai, Merck, Acadia, Pfizer, GSK. K.L.S. has grant funding from Merck. L.M., K.E., and S.P. declare no conflicts of interest. Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2019",

month = apr,

day = "7",

doi = "10.1093/eurheartj/ehy624",

language = "English (US)",

volume = "40",

pages = "1149--1157a",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "14",

}

TY - JOUR

T1 - The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality

T2 - The Osteoporotic Fractures in Men Study and the Sleep Heart Health Study

AU - Azarbarzin, Ali

AU - Sands, Scott A.

AU - Stone, Katie L.

AU - Taranto-Montemurro, Luigi

AU - Messineo, Ludovico

AU - Terrill, Philip I.

AU - Ancoli-Israel, Sonia

AU - Ensrud, Kristine

AU - Purcell, Shaun

AU - White, David P.

AU - Redline, Susan

AU - Wellman, Andrew

N1 - Funding Information: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 TR000128, K24-AR04884-06]. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839]. The Sleep Heart Health Study (SHHS) is supported by the National Heart, Lung, and Blood Institute through the following cooperative agreements: U01-HL53940 (University of Washington), U01-HL53941 (Boston University), U01-HL63463 (Case Western Reserve University), U01-HL53937 (Johns Hopkins University), U01-HL53938 (University of Arizona), U01-HL53916 (University of California, Davis), U01-HL53934 (University of Minnesota), U01-HL63429 (Missouri Breaks Research), and U01-HL53931 (New York University). This work was also supported by philanthropic funding from Fan Hongbing (President of OMPA Corporation, Kaifeng, China) and the National Institutes of Health (R01HL102321, R01HL128658, P01HL095491, UL1RR025758). S.A.S. and L.T.-M. were supported by American Heart Association grants (15SDG25890059 and 17POST33410436, respectively); and partially supported by NHLBI R35HL135818 (to S.R., S.A.S., A.W., and A.A.). Funding Information: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 TR000128, K24-AR04884-06]. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study "Outcomes of Sleep Disorders in Older Men" [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839]. The Sleep Heart Health Study (SHHS) is supported by theNational Heart, Lung, and Blood Institute through the following cooperative agreements: U01-HL53940 (University of Washington), U01-HL53941 (Boston University), U01-HL63463 (Case Western Reserve University), U01-HL53937 (Johns Hopkins University), U01-HL53938 (University of Arizona), U01-HL53916 (University of California, Davis), U01-HL53934 (University of Minnesota), U01-HL63429 (Missouri Breaks Research), and U01-HL53931 (New York University). This work was also supported by philanthropic funding from Fan Hongbing (President of OMPA Corporation, Kaifeng, China) and the National Institutes of Health (R01HL102321, R01HL128658, P01HL095491, UL1RR025758). S.A.S. and L.T.-M. were supported by American Heart Association grants (15SDG25890059 and 17POST33410436, respectively); and partially supported by NHLBI R35HL135818 (to S.R., S.A.S., A.W., and A.A.). Funding Information: receives salary from Philips Respironics and is a consultant to Night Balance. A.W. works as a consultant for Somnifix, Cambridge Sound Management, Nox Medical, Bayer, Philips, and Galvani and has received grants from Philips and Somnifix. L.T.-M. and A.W. also have a financial interest in Apnimed Corp., a company developing pharmacologic therapies for sleep apnoea. Their interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies. S.A.-I. is a consultant for Eisai, Merck, Acadia, Pfizer, GSK. K.L.S. has grant funding from Merck. L.M., K.E., and S.P. declare no conflicts of interest. Publisher Copyright: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.

PY - 2019/4/7

Y1 - 2019/4/7

N2 - Aims: Apnoea-hypopnoea index (AHI), the universal clinical metric of sleep apnoea severity, poorly predicts the adverse outcomes of sleep apnoea, potentially because the AHI, a frequency measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnoea by the 'hypoxic burden' would predict mortality among adults aged 40 and older. Methods and results: The samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality and all-cause mortality (only in MrOS). Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.81 [95% confidence interval (CI) 1.25-2.62] and 2.73 (95% CI 1.71-4.36), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11-3.43). Conclusion: The 'hypoxic burden', an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.

AB - Aims: Apnoea-hypopnoea index (AHI), the universal clinical metric of sleep apnoea severity, poorly predicts the adverse outcomes of sleep apnoea, potentially because the AHI, a frequency measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnoea by the 'hypoxic burden' would predict mortality among adults aged 40 and older. Methods and results: The samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality and all-cause mortality (only in MrOS). Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.81 [95% confidence interval (CI) 1.25-2.62] and 2.73 (95% CI 1.71-4.36), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11-3.43). Conclusion: The 'hypoxic burden', an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.

KW - Apnoea-hypopnoea index

KW - CVD mortality

KW - Hypoxic burden

KW - Polysomnography

KW - Sleep apnoea

UR - http://www.scopus.com/inward/record.url?scp=85061317896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061317896&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehy624

DO - 10.1093/eurheartj/ehy624

M3 - Article

C2 - 30376054

AN - SCOPUS:85061317896

SN - 0195-668X

VL - 40

SP - 1149-1157a

JO - European Heart Journal

JF - European Heart Journal

IS - 14

ER -

The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: The Osteoporotic Fractures in Men Study and the Sleep Heart Health Study

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this