Prospective Association of Obstructive Sleep Apnea Risk Factors With Heart Failure and its Subtypes in Postmenopausal Women: The Women's Health Initiative.

STUDY OBJECTIVES The relationship between obstructive sleep apnea (OSA) and heart failure (HF) incidence in postmenopausal women has been understudied given the limited representation of women in heart failure studies. We investigated the relationship between OSA risk factors and HF and its subtypes in postmenopausal women. METHODS We performed a prospective analysis on the adjudicated HF outcomes in the Women's Health Initiative from enrollment (1993-1998) to September 30, 2016. HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) were defined as adjudicated acute HF hospitalization with EF ≥45% or <45%, respectively. We employed Cox regression to examine the association between OSA risk factors and symptoms (individually and using a summary risk score) and time to first hospitalized HF. RESULTS Of 42,362 women, 2205 (5.21%) developed all HF, 1162 (2.74%) women developed HFpEF, and 679 (1.60%) developed HFrEF. Individual OSA risk factors and symptoms, including obesity (HR=1.33, 95% CI 1.20-1.48), snoring (HR=1.30, 95% CI 1.16-1.46), and hypertension (HR=1.45, 95% CI 1.35-1.56), were positively associated with risk of HF and HFpEF but only hypertension was associated with HFrEF. When examined as a summary risk score compared to those with none of the OSA risk factors, presence of each additional factor was significantly associated with increased risk of hospitalized HF in a dose-response fashion for HFpEF (p-trend <0.001), but not HFrEF (p-trend 0.26). CONCLUSIONS OSA risk factors and symptoms were associated with HFpEF, but not HFrEF, among postmenopausal women and are largely dependent on BMI, snoring, and hypertension.

[1]  T. Young,et al.  Risk factors for obstructive sleep apnea in adults. , 2004, JAMA.

[2]  J. Manson,et al.  Risk Factors for Incident Hospitalized Heart Failure With Preserved Versus Reduced Ejection Fraction in a Multiracial Cohort of Postmenopausal Women , 2016, Circulation. Heart failure.

[3]  D. Steven,et al.  Sleep-disordered breathing in patients with cardiovascular diseases cannot be detected by ESS, STOP-BANG, and Berlin questionnaires , 2018, Clinical Research in Cardiology.

[4]  Paul A Friedman,et al.  Association of Atrial Fibrillation and Obstructive Sleep Apnea , 2004, Circulation.

[5]  I. Piña,et al.  Forecasting the Impact of Heart Failure in the United States: A Policy Statement From the American Heart Association , 2013, Circulation. Heart failure.

[6]  A. Jordan,et al.  Ventilatory response to brief arousal from non-rapid eye movement sleep is greater in men than in women. , 2003, American journal of respiratory and critical care medicine.

[7]  D. Reboussin,et al.  Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. , 2000, The New England journal of medicine.

[8]  Atul Malhotra,et al.  A prospective study of sleep duration and coronary heart disease in women. , 2003, Archives of internal medicine.

[9]  F. Chung,et al.  Alternative scoring models of STOP-bang questionnaire improve specificity to detect undiagnosed obstructive sleep apnea. , 2014, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[10]  Charles Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[11]  L. Lund,et al.  Atrial Fibrillation in Heart Failure With Preserved, Mid-Range, and Reduced Ejection Fraction. , 2017, JACC. Heart failure.

[12]  Garnet L Anderson,et al.  The Women's Health Initiative recruitment methods and results. , 2003, Annals of epidemiology.

[13]  A. Verma,et al.  Treatment of Patients With Atrial Fibrillation and Heart Failure With Reduced Ejection Fraction , 2017, Circulation.

[14]  F. Abboud,et al.  Sympathetic neural mechanisms in obstructive sleep apnea. , 1995, The Journal of clinical investigation.

[15]  K. Clark,et al.  Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community- Based Study , 2000 .

[16]  E. Bixler,et al.  Prevalence of sleep-disordered breathing in women: effects of gender. , 2001, American journal of respiratory and critical care medicine.

[17]  D. Kripke,et al.  Reliability and validity of the Women's Health Initiative Insomnia Rating Scale. , 2003, Psychological assessment.

[18]  Jennifer G. Robinson,et al.  Sleep duration, insomnia, and coronary heart disease among postmenopausal women in the Women's Health Initiative. , 2013, Journal of women's health.

[19]  Terry Young,et al.  Menopausal status and sleep-disordered breathing in the Wisconsin Sleep Cohort Study. , 2003, American journal of respiratory and critical care medicine.

[20]  J. Rossouw,et al.  The Women's Health Initiative: recruitment complete--looking back and looking forward. , 1999, Journal of women's health.

[21]  V. Somers,et al.  Obstructive Sleep Apnea and Hypertension An Update , 2022 .

[22]  T. Douglas Bradley,et al.  Obstructive Sleep Apnea: The Most Common Secondary Cause of Hypertension Associated With Resistant Hypertension , 2011, Hypertension.

[23]  C. Meisinger,et al.  Sleep duration and sleep complaints and risk of myocardial infarction in middle-aged men and women from the general population: the MONICA/KORA Augsburg cohort study. , 2007, Sleep.

[24]  K. Strohl,et al.  Using the Berlin Questionnaire To Identify Patients at Risk for the Sleep Apnea Syndrome , 1999, Annals of Internal Medicine.

[25]  Robert Gray,et al.  A Proportional Hazards Model for the Subdistribution of a Competing Risk , 1999 .

[26]  E. Erdmann,et al.  Prevalence and Predictors of Sleep-Disordered Breathing in Patients With Stable Chronic Heart Failure: The SchlaHF Registry. , 2016, JACC. Heart failure.

[27]  J. Murabito,et al.  Lifetime Risk for Developing Congestive Heart Failure: The Framingham Heart Study , 2002, Circulation.

[28]  N. Marshall,et al.  Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study. , 2008, Sleep.

[29]  A. Newman,et al.  Prospective Study of Obstructive Sleep Apnea and Incident Coronary Heart Disease and Heart Failure: The Sleep Heart Health Study , 2010, Circulation.

[30]  S Hulley,et al.  Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. , 1998, JAMA.

[31]  E. Vittinghoff,et al.  Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. , 1998, JAMA.

[32]  R. Langer,et al.  The Women's Health Initiative Observational Study: baseline characteristics of participants and reliability of baseline measures. , 2003, Annals of epidemiology.

[33]  Francisco Lopez-Jimenez,et al.  Interactions between obesity and obstructive sleep apnea: implications for treatment. , 2010, Chest.

[34]  L. Chambless,et al.  Classification of Heart Failure in the Atherosclerosis Risk in Communities (ARIC) Study: A Comparison of Diagnostic Criteria , 2012, Circulation. Heart failure.

[35]  L. Køber,et al.  Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial , 2012, BMJ : British Medical Journal.

[36]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.

[37]  K. Johnson An Update. , 1984, Journal of food protection.

[38]  Ruoxiang Jiang,et al.  A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. , 2015, JAMA internal medicine.