Association of sleep apnea with outcomes in peripheral artery disease: Insights from the PORTRAIT study

Abstract

Background: Sleep apnea is a predictor of adverse cardiovascular outcome in many cardiovascular diseases but whether it is associated with worse health status outcomes or mortality in peripheral artery disease (PAD) is unknown.

Methods: PORTRAIT is an international (US, Netherlands, Australia) prospective PAD registry that consecutively enrolled patients who presented with new-onset or recent exacerbations of PAD symptoms to any of 16 vascular specialty clinics. Health status was assessed upon presentation and at 12 months with the disease-specific Peripheral Artery Questionnaire (PAQ). Higher PAQ scores indicate better health status. A sequentially-adjusted hierarchical linear regression model examined the association between sleep apnea and 1-year PAQ symptoms, quality of life, and summary scores. Five-year survival curves by comorbid sleep apnea status for US patients were compared using the log-rank test.

Results: The mean age of the 1204 PORTRAIT participants was 67.6 ± 9.4 years with 37.5% women and 8.3% (n = 100) having sleep apnea. Patients with sleep apnea were more likely to be from the US, more sedentary, and to have diabetes, obesity, coronary disease, more depressive symptoms and a history of prior peripheral interventions. Paradoxically, they also had higher ankle-brachial indices, but lower PAQ Summary scores at presentation and 12 months (41.2 ± 22.0 vs. 49. 9± 21.6 and 58.6 ± 27.9 vs. 71.3 ± 24.9, respectively, p = <0.05). The association between sleep apnea and 1-year health status persisted after multivariable adjustment, but there were no differences in all-cause mortality over 5 years (28.0% vs. 23.4%, p = 0.76).

Conclusion: In patients presenting with PAD, comorbid sleep apnea is independently associated with worse health status over time. Future studies should test whether better treatment of sleep apnea can improve the health status of patients with PAD.

Clinical trial registration: NCT01419080.

Conflict of interest statement

Dr. Smolderen is supported by an unrestricted research grant from Merck, Boston Scientific, Abbott Vascular and Terumo, and she is a consultant for Optum Labs. Dr. Spertus provides consultative services to Amgen, Merck, AstraZeneca, Novartis, Bayer, Janssen and United Healthcare. He has an equity interest in Health Outcomes Sciences and serves on the Board of Blue Cross Blue Shield of Kansas City. He owns the copyright to the Peripheral Artery Questionnaire, the Seattle Angina Questionnaire and the Kansas City Cardiomyopathy Questionnaire. Dr. Mena-Hurtado is a consultant for Bard, Cook, Medtronic, Abbott, Boston Scientific and Cardinal Health. Other authors report no disclosure.

Figures

Fig 1. Twelve month mean differences for the association between sleep apnea and PAQ health status scores (PAQ symptoms, quality of life, and summary scores).

The models were sequentially adjusted for (1) patient demographics (age, sex, race and country), (2) socioeconomic variables (education status, insurance, work for pay and avoiding care due to cost), (3) PAD disease severity characteristics (ABI value, functional limitation, duration of symptoms and unilateral disease), (4) cardiovascular risk factors/comorbidities (obesity, hypertension, coronary artery disease, chronic heart failure, musculoskeletal variables (back pain and osteoarthritis) and chronic lung disease, (5) psychological variables (PHQ-8 scores), and finally, (6) adjustment for baseline health status. Abbreviations: PAQ: Peripheral Artery Questionnaire; PAD: Peripheral Artery Disease; CI: Confidence Interval.

Fig 2. Kaplan Meier 5-year survival curves by sleep apnea status.

The curves were compared by the log-rank test.