Prospective Study of Obstructive Sleep Apnea and Incident Coronary Heart Disease and Heart Failure: The Sleep Heart Health Study

Gottlieb, Daniel J.; Yenokyan, Gayane; Newman, Anne B.; O'Connor, George T.; Punjabi, Naresh M.; Quan, Stuart F.; Redline, Susan; Resnick, Helaine E.; Tong, Elisa K.; Diener-West, Marie; Shahar, Eyal

doi:10.1161/circulationaha.109.901801

Cited by 1,551Obstructive Sleep Apnea ResearchSleep and related disordersApelin-related biomedical research

Prospective Study of Obstructive Sleep Apnea and Incident Coronary Heart Disease and Heart Failure: The Sleep Heart Health Study

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Gottlieb, Daniel J., Yenokyan, Gayane, Newman, Anne B., O'Connor, George T., Punjabi, Naresh M., Quan, Stuart F., Redline, Susan, Resnick, Helaine E. +3 more·2010·Circulation

DOI 10.1161/circulationaha.109.901801PMC PMC3117288

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Abstract

Background— Clinic-based observational studies in men have reported that obstructive sleep apnea is associated with an increased incidence of coronary heart disease. The objective of this study was to assess the relation of obstructive sleep apnea to incident coronary heart disease and heart failure in a general community sample of adult men and women. Methods and Results— A total of 1927 men and 2495 women ≥40 years of age and free of coronary heart disease and heart failure at the time of baseline polysomnography were followed up for a median of 8.7 years in this prospective longitudinal epidemiological study. After adjustment for multiple risk factors, obstructive sleep apnea was a significant predictor of incident coronary heart disease (myocardial infarction, revascularization procedure, or coronary heart disease death) only in men ≤70 years of age (adjusted hazard ratio 1.10 [95% confidence interval 1.00 to 1.21] per 10-unit increase in apnea-hypopnea index [AHI]) but not in older men or in women of any age. Among men 40 to 70 years old, those with AHI ≥30 were 68% more likely to develop coronary heart disease than those with AHI <5. Obstructive sleep apnea predicted incident heart failure in men but not in women (adjusted hazard ratio 1.13 [95% confidence interval 1.02 to 1.26] per 10-unit increase in AHI). Men with AHI ≥30 were 58% more likely to develop heart failure than those with AHI <5. Conclusions— Obstructive sleep apnea is associated with an increased risk of incident heart failure in community-dwelling middle-aged and older men; its association with incident coronary heart disease in this sample is equivocal.

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In a secondary SHHS analysis, after adjustment, OSA significantly predicted incident CAD events only in men aged 70 or younger (HR 1.10 per 10-unit increase in AHI).
“After adjusting for other risk factors, OSA was significantly associated and predicted incident CAD events, defined as MI, revascularization procedure, or coronary heart disease related death, however this was only observed in men aged 70 or younger (HR 1.10, 95% CI = 1.00–1.21 per 10-unit increase in AHI).”
From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [641]
The Results report the stated adjusted HR of 1.10 (95% CI 1.00–1.21) per 10-unit AHI increase among men aged 70 or younger. But the Results say the age interaction was not statistically significant, and the Discussion calls the subgroup finding only nominally significant and possibly a type 1 error. The claim overstates the evidence by presenting the association as established only in that age group. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Possible pathophysiologic mechanisms linking OSA to myocardial ischemia include sympathetic nervous system hyperactivity, hypertension, endothelial dysfunction, metabolic dysregulation, insulin resistance, and a hypercoagulable state.
“A number of possible pathophysiologic mechanisms have been implicated including sympathetic nervous system hyperactivity, hypertension, endothelial dysfunction, metabolic dysregulation, insulin resistance, and hypercoagulable state.641,655–663”
From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [641]
The Discussion (page unavailable) identifies sympathetic activation, endothelial dysfunction, insulin resistance, hypertension, hyperlipidemia, and diabetes as possible links between OSA and coronary heart disease. It does not identify a hypercoagulable state as one of those mechanisms. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Obstructive sleep apnea is associated with increased risk of incident heart failure, which is proportional to obstructive sleep apnea severity, and may be linked to major swings in intrathoracic pressure resulting in increased cardiac preload and afterload.
“OSA is associated with increased risk of incident heart failure (Gottlieb et al., 2010), which is proportional to OSA severity, and may be linked to major swings in intrathoracic pressure resulting in increased cardiac preload and afterload (Nicholl et al., 2014).”
From Obstructive sleep apnea: transition from pathophysiology to an integrative disease model (2022) · cites this paper as Gottlieb et al., 2010
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
In the same SHHS secondary analysis, severe OSA (AHI ≥30) conferred a stronger increased risk of symptomatic CAD (HR 1.68, 95% CI 1.02-2.76), again only in men aged 70 or younger.
“Severe OSA (as defined by AHI ≥ 30 events/h) conferred a stronger increased risk of developing symptomatic CAD (HR 1.68, 95% CI = 1.02–2.76) again seen only in men aged 70 or younger.641”
From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [641]
The evidence for obstructive sleep apnea as an independent risk factor for coronary artery disease is equivocal and is stronger for males than females.
“The evidence for OSA as an independent risk factor for coronary artery disease is equivocal and is stronger for males than females (Dong et al., 2013; Gottlieb et al., 2010; Hla et al., 2015).”
From Obstructive sleep apnea: transition from pathophysiology to an integrative disease model (2022) · cites this paper as Gottlieb et al., 2010

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Obstructive Sleep Apnea in Cardiovascular Disease: A Review of the Literature and Proposed Multidisciplinary Clinical Management Strategy
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Association between Obstructive Sleep Apnea and Cancer Incidence in a Large Multicenter Spanish Cohort
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Cardiovascular Mortality in Women With Obstructive Sleep Apnea With or Without Continuous Positive Airway Pressure Treatment: A Cohort Study
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CPAP versus Oxygen in Obstructive Sleep Apnea
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Phenotypes in obstructive sleep apnea: A definition, examples and evolution of approaches
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Obstructive sleep apnea and risk of cardiovascular disease and all-cause mortality: A meta-analysis of prospective cohort studies
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Cardiovascular Mortality in Obstructive Sleep Apnea in the Elderly: Role of Long-Term Continuous Positive Airway Pressure Treatment: A Prospective Observational Study
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The economic cost of inadequate sleep
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Association of Unrecognized Obstructive Sleep Apnea With Postoperative Cardiovascular Events in Patients Undergoing Major Noncardiac Surgery
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Sleep-disordered Breathing in Hispanic/Latino Individuals of Diverse Backgrounds. The Hispanic Community Health Study/Study of Latinos
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Screening for Obstructive Sleep Apnea in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force
Jonas, D. E., Amick, H. R., Feltner, C., Weber, R. P., Arvanitis, M., Stine, A., Lux, L., & Harris, R. P. (2017) · JAMA · doi:10.1001/jama.2016.19635 · Cited by 267 · see citing works
Obstructive sleep apnea, hypertension and cardiovascular diseases
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Long-term effect of weight loss on obstructive sleep apnea severity in obese patients with type 2 diabetes
Kuna, S. T., Reboussin, D. M., Borradaile, K. E., Sanders, M. H., Millman, R. P., Zammit, G., Newman, A. B., Wadden, T. A., Jakicic, J. M., Wing, R. R., et al. (2013) · Sleep · doi:10.5665/sleep.2618 · Cited by 231 · see citing works
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Recommendations for the management of patients with obstructive sleep apnoea and hypertension
Parati, G., Lombardi, C., Hedner, J., Bonsignore, M. R., Grote, L., Tkacova, R., Lévy, P., Riha, R., Bassetti, C., Narkiewicz, K., et al. (2013) · European Respiratory Journal · doi:10.1183/09031936.00226711 · Cited by 227 · see citing works
The Sleep Apnea-Specific Hypoxic Burden Predicts Incident Heart Failure
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The Relationship between Obstructive Sleep Apnea and Alzheimer’s Disease
Andrade, A. G., Bubu, O. M., Varga, A. W., & Osorio, R. S. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179936 · Cited by 216 · see citing works
Sleep Apnea and Cardiovascular Disease: An Enigmatic Risk Factor
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Bidirectional relationships of comorbidity with obstructive sleep apnoea
Gleeson, M., & McNicholas, W. T. (2022) · European Respiratory Review · doi:10.1183/16000617.0256-2021 · Cited by 203 · see citing works
Coronary Heart Disease Incidence in Sleep Disordered Breathing: The Wisconsin Sleep Cohort Study
Hla, K. M., Young, T., Hagen, E. W., Stein, J. H., Finn, L. A., Nieto, F. J., & Peppard, P. E. (2015) · Sleep · doi:10.5665/sleep.4654 · Cited by 194 · see citing works
Eight Hours of Nightly Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Improves Glucose Metabolism in Patients with Prediabetes. A Randomized Controlled Trial
Pamidi, S., Wroblewski, K., Stepien, M., Sharif-Sidi, K., Kilkus, J., Whitmore, H., & Tasali, E. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201408-1564oc · Cited by 185 · see citing works
Role of Sleep Apnea and Continuous Positive Airway Pressure Therapy in the Incidence of Stroke or Coronary Heart Disease in Women
Campos-Rodriguez, F., Martinez-Garcia, M. A., Reyes-Nuñez, N., Caballero-Martinez, I., Catalan-Serra, P., & Almeida-Gonzalez, C. V. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201311-2012oc · Cited by 183 · see citing works
Obstructive sleep apnea in pregnancy is associated with adverse maternal outcomes: a national cohort
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Sex-Specific Association of Sleep Apnea Severity With Subclinical Myocardial Injury, Ventricular Hypertrophy, and Heart Failure Risk in a Community-Dwelling Cohort: The Atherosclerosis Risk in Communities–Sleep Heart Health Study
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Association of obstructive sleep apnoea with the risk of vascular outcomes and all-cause mortality: a meta-analysis
Xie, C., Zhu, R., Tian, Y., & Wang, K. (2017) · BMJ Open · doi:10.1136/bmjopen-2016-013983 · Cited by 180 · see citing works
Relation of the Severity of Obstructive Sleep Apnea in Response to Anti-Arrhythmic Drugs in Patients With Atrial Fibrillation or Atrial Flutter
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Impact of Obstructive Sleep Apnea Syndrome on Endothelial Function, Arterial Stiffening, and Serum Inflammatory Markers: An Updated Meta‐analysis and Metaregression of 18 Studies
Wang, J., Yu, W., Gao, M., Zhang, F., Gu, C., Yu, Y., & Wei, Y. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.115.002454 · Cited by 168 · see citing works
Effect of Sleep Apnea and Continuous Positive Airway Pressure on Cardiac Structure and Recurrence of Atrial Fibrillation
Neilan, T. G., Farhad, H., Dodson, J. A., Shah, R. V., Abbasi, S. A., Bakker, J. P., Michaud, G. F., van der Geest, R., Blankstein, R., Steigner, M., et al. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000421 · Cited by 158 · see citing works
The Link Between Obstructive Sleep Apnea and Cardiovascular Disease
Bauters, F., Rietzschel, E. R., Hertegonne, K. B. C., & Chirinos, J. A. (2016) · Current Atherosclerosis Reports · doi:10.1007/s11883-015-0556-z · Cited by 153 · see citing works
Obstructive sleep apnea: transition from pathophysiology to an integrative disease model
McNicholas, W. T., & Pevernagie, D. (2022) · Journal of Sleep Research · doi:10.1111/jsr.13616 · Cited by 153 · see citing works
“OSA is associated with increased risk of incident heart failure (Gottlieb et al., 2010), which is proportional to OSA severity, and may be linked to major swings in intrathoracic pressure resulting in increased cardiac preload and afterload (Nicholl et al., 2014).”
BackgroundInfluential
Effects of weight loss on obstructive sleep apnea severity. Ten-year results of the sleep AHEAD study
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Sleep disturbances and dementia risk: a multicenter study
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Continuous Positive Airway Pressure Reduces Postprandial Lipidemia in Obstructive Sleep Apnea: A Randomized, Placebo-Controlled Crossover Trial
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Effects of Continuous Positive Airway Pressure Treatment on Clinic and Ambulatory Blood Pressures in Patients With Obstructive Sleep Apnea and Resistant Hypertension: A Randomized Controlled Trial
Muxfeldt, E. S., Margallo, V., Costa, L. M. S., Guimarães, G., Cavalcante, A. H., Azevedo, J. C. M., de Souza, F., Cardoso, C. R. L., & Salles, G. F. (2015) · Hypertension · doi:10.1161/hypertensionaha.114.04852 · Cited by 142 · see citing works
Does obstructive sleep apnea cause endothelial dysfunction? A critical review of the literature
Hoyos, C. M., Melehan, K. L., Liu, P. Y., Grunstein, R. R., & Phillips, C. L. (2015) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2014.06.003 · Cited by 142 · see citing works
Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans
Cade, B. E., Chen, H., Stilp, A. M., Gleason, K. J., Sofer, T., Ancoli-Israel, S., Arens, R., Bell, G. I., Below, J. E., Bjonnes, A. C., et al. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201512-2431oc · Cited by 134 · see citing works
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Type of Menopause, Age at Menopause, and Risk of Developing Obstructive Sleep Apnea in Postmenopausal Women
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Pulmonary Hypertension in Obstructive Sleep Apnea: Is it Clinically Significant? a Critical Analysis of the Association and Pathophysiology
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Severe Obstructive Sleep Apnea and Outcomes Following Myocardial Infarction
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Management of continuous positive airway pressure treatment compliance using telemonitoring in obstructive sleep apnoea
Turino, C., de Batlle, J., Woehrle, H., Mayoral, A., Castro-Grattoni, A. L., Gómez, S., Dalmases, M., Sánchez-de-la-Torre, M., & Barbé, F. (2017) · European Respiratory Journal · doi:10.1183/13993003.01128-2016 · Cited by 115 · see citing works
The Value of Oxygen Desaturation Index for Diagnosing Obstructive Sleep Apnea: A Systematic Review
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Randomized clinical trials of cardiovascular disease in obstructive sleep apnea: understanding and overcoming bias
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Association of sleep characteristics with atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis
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Phenotypes of comorbidity in <scp>OSAS</scp> patients: combining categorical principal component analysis with cluster analysis
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Gender differences in the prospective associations of self-reported sleep quality with biomarkers of systemic inflammation and coagulation: Findings from the Heart and Soul Study
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Clinical Prediction Models for Sleep Apnea: The Importance of Medical History over Symptoms
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Web-Based Access to Positive Airway Pressure Usage with or without an Initial Financial Incentive Improves Treatment Use in Patients with Obstructive Sleep Apnea
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Multiethnic Meta-Analysis Identifies <i>RAI1</i> as a Possible Obstructive Sleep Apnea–related Quantitative Trait Locus in Men
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Sleep-disordered Breathing and Incident Heart Failure in Older Men
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Effects of continuous positive airway pressure on coagulability in obstructive sleep apnoea: a randomised, placebo-controlled crossover study
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Effect of Continuous Positive Airway Pressure Treatment on Health-Related Quality of Life and Sleepiness in High Cardiovascular Risk Individuals With Sleep Apnea: Best Apnea Interventions for Research (BestAIR) Trial
Zhao, Y. Y., Wang, R., Gleason, K. J., Lewis, E. F., Quan, S. F., Toth, C. M., Morrical, M., Rueschman, M., Weng, J., Ware, J. H., et al. (2017) · Sleep · doi:10.1093/sleep/zsx040 · Cited by 75 · see citing works
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Association between socioeconomic status, belonging to an ethnic minority and obstructive sleep apnea: a systematic review of the literature
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Effects of moderate-to-severe obstructive sleep apnea on the clinical manifestations of plaque vulnerability and the progression of coronary atherosclerosis in patients with acute coronary syndrome
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Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans
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Habitual Sleep Duration and All-Cause Mortality in a General Community Sample
Aurora, R. N., Kim, J. S., Crainiceanu, C., O'Hearn, D., & Punjabi, N. M. (2016) · Sleep · doi:10.5665/sleep.6212 · Cited by 66 · see citing works
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Sleep apnea: a review of diagnostic sensors, algorithms, and therapies
Shokoueinejad, M., Fernandez, C., Carroll, E., Wang, F., Levin, J., Rusk, S., Glattard, N., Mulchrone, A., Zhang, X., Xie, A., et al. (2017) · Physiological Measurement · doi:10.1088/1361-6579/aa6ec6 · Cited by 64 · see citing works
Association of Sleep Apnea and Snoring With Incident Atrial Fibrillation in the Multi-Ethnic Study of Atherosclerosis
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Sleep Apnea, the Risk of Developing Heart Failure, and Potential Benefits of Continuous Positive Airway Pressure (CPAP) Therapy
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Differences in Associations between Visceral Fat Accumulation and Obstructive Sleep Apnea by Sex
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Sleep-disordered breathing and Alzheimer's disease: A nationwide cohort study
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Cost-effectiveness of continuous positive airway pressure therapy for obstructive sleep apnea: health care system and societal perspectives
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Portable Sleep Monitoring for Diagnosing Sleep Apnea in Hospitalized Patients With Heart Failure
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Poor Outcomes Among Patients With Chronic Obstructive Pulmonary Disease With Higher Risk for Undiagnosed Obstructive Sleep Apnea in the LOTT Cohort
Donovan, L. M., Feemster, L. C., Udris, E. M., Griffith, M. F., Spece, L. J., Palen, B. N., He, K., Parthasarathy, S., Strohl, K. P., Kapur, V. K., et al. (2019) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.7574 · Cited by 50 · see citing works
Sleep in the Elderly
Feinsilver, S. H., & Hernandez, A. B. (2017) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2017.06.009 · Cited by 44 · see citing works
Obstructive sleep apnoea and comorbidity – an overview of the association and impact of continuous positive airway pressure therapy
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Circulating adhesion molecules in obstructive sleep apnea and cardiovascular disease
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Resistant Hypertension and Obstructive Sleep Apnea
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Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation
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Sleep duration, snoring habits and risk of acute myocardial infarction in China population: results of the INTERHEART study
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Sequencing Analysis at 8p23 Identifies Multiple Rare Variants in DLC1 Associated with Sleep-Related Oxyhemoglobin Saturation Level
Liang, J., Cade, B. E., He, K. Y., Wang, H., Lee, J., Sofer, T., Williams, S., Li, R., Chen, H., Gottlieb, D. J., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.10.002 · Cited by 21 · see citing works
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Sleep Overnight Monitoring for Apnea in Patients Hospitalized with Heart Failure (SOMA-HF Study)
Sharma, S., Mather, P. J., Chowdhury, A., Gupta, S., Mukhtar, U., Willes, L., Whellan, D. J., Malhotra, A., & Quan, S. F. (2017) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.6768 · Cited by 31 · see citing works
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Sleep Apnea Cardiovascular Clinical Trials—Current Status and Steps Forward: The International Collaboration of Sleep Apnea Cardiovascular Trialists
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Authors: Gottlieb, D. J., Yenokyan, G., Newman, A. B., O'Connor, G. T., Punjabi, N. M., Quan, S. F., Redline, S., Resnick, H. E., Tong, E. K., Diener-West, M., & Shahar, E.
Affiliations: Boston University (US)
From the VA Boston Healthcare System (D.J.G.), Boston, Mass; Boston University School of Medicine (D.J.G., G.T.O.), Boston, Mass; Johns Hopkins University (G.Y., N.M.P., M.D.-W.), Baltimore, Md; Graduate School of Public Health (A.B.N.), University of Pittsburgh, Pittsburgh, Pa; University of Arizona (S.F.Q.), Tucson, Ariz; Harvard Medical School (S.F.Q.), Boston, Mass; Case Western Reserve University (S.R.), Cleveland, Ohio; American Association of Homes and Services for the Aging and Georgetown...
ORCID: Gottlieb, Daniel J.
Yenokyan, Gayane
Newman, Anne B.
Punjabi, Naresh M.
Quan, Stuart F.
Redline, Susan
Resnick, Helaine E.
Tong, Elisa K.
Shahar, Eyal
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2010-07-27
Volume: 122
Issue: 4
Pages: 352-360
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.109.901801
PMC: PMC3117288
OpenAlex: W2079485496
Semantic Scholar: e850fc7004657447db67a11c267d2d2fa7ce6427
Cited by: 1,551
References: 49
Citations by year: 2026: 60 · 2025: 69 · 2024: 96 · 2023: 81 · 2022: 93 · 2021: 120 · 2020: 98 · 2019: 98 · 2018: 104 · 2017: 111 · 2016: 118 · 2015: 132 · 2014: 116 · 2013: 104 · 2012: 84
FWCI: 54.36
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Strong
National Institutes of Health (5u01hl053940-05, 5u01hl053934-14)
National Heart, Lung, and Blood Institute (U01 HL 53940, U01HL53938, U01HL053941, U01HL053938, U01 HL53934, U01HL053937, U01 HL 53941, U01HL053931, U01 HL 63429, U01HL064360, U01HL053916, U01 HL53931, U01HL063463, U01HL64360, U01HL063429, U01-HL-053934, U01HL63463, U01-HL53937)
Topics: Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Health Sciences › Medicine › Pharmacology › Apelin-related biomedical research
Keywords: obstructive sleep apnea, coronary artery disease, heart failure, apnea-hypopnea index, myocardial infarction, revascularization, sex differences, middle-aged and older adults, community-dwelling adults, cardiovascular risk
MeSH terms: Adult, Aged, Coronary Disease, Female, Heart Failure, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Proportional Hazards Models, Survival Analysis, Polysomnography, Sleep Apnea, Obstructive

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Prospective Study of Obstructive Sleep Apnea and Incident Coronary Heart Disease and Heart Failure: The Sleep Heart Health Study

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