» Articles » PMID: 38358332

Heterogeneous Effects of Continuous Positive Airway Pressure in Non-Sleepy Obstructive Sleep Apnea on Cardiovascular Disease Outcomes: Machine Learning Analysis of the ISAACC Trial (ECSACT Study)

Abstract

Randomized controlled trials of continuous positive airway pressure (CPAP) therapy for cardiovascular disease (CVD) prevention among patients with obstructive sleep apnea (OSA) have been largely neutral. However, given that OSA is a heterogeneous disease, there may be unidentified subgroups demonstrating differential treatment effects. We sought to apply a novel data-drive approach to identify nonsleepy OSA subgroups with heterogeneous effects of CPAP on CVD outcomes within the Impact of Sleep Apnea Syndrome in the Evolution of Acute Coronary Syndrome (ISAACC) study. Participants were randomly partitioned into two datasets. One for training (70%) our machine-learning model and a second (30%) for validation of significant findings. Model-based recursive partitioning was applied to identify subgroups with heterogeneous treatment effects. Survival analysis was conducted to compare treatment (CPAP vs. usual care [UC]) outcomes within subgroups. A total of 1,224 nonsleepy OSA participants were included. Of 55 features entered into our model, only two appeared in the final model (i.e., average OSA event duration and hypercholesterolemia). Among participants at or below the model-derived average event duration threshold (19.5 s), CPAP was protective for a composite of CVD events (training hazard ratio [HR], 0.46;  = 0.002). For those with longer event duration (>19.5 s), an additional split occurred by hypercholesterolemia status. Among participants with longer event duration and hypercholesterolemia, CPAP resulted in more CVD events compared with UC (training HR, 2.24;  = 0.011). The point estimate for this harmful signal was also replicated in the testing dataset (HR, 1.83;  = 0.118). We discovered subgroups of nonsleepy OSA participants within the ISAACC study with heterogeneous effects of CPAP. Among the training dataset, those with longer OSA event duration and hypercholesterolemia had nearly 2.5 times more CVD events with CPAP compared with UC, whereas those with shorter OSA event duration had roughly half the rate of CVD events if randomized to CPAP.

Citing Articles

Exploring the Relationship Between Sleep Apnea, Myocardial Infarct Size, and Coronary Collaterals in Acute Myocardial Infarction: A Multidisciplinary Study.

Kundel V, Devarakonda K, Khan S, Suarez-Farinas M, Cohen O, Santos-Gallego C Nat Sci Sleep. 2025; 17():27-42.

PMID: 39817189 PMC: 11733186. DOI: 10.2147/NSS.S489788.


An Artificial Intelligence-Based Non-Invasive Approach for Cardiovascular Disease Risk Stratification in Obstructive Sleep Apnea Patients: A Narrative Review.

Saba L, Maindarkar M, Khanna N, Puvvula A, Faa G, Isenovic E Rev Cardiovasc Med. 2025; 25(12):463.

PMID: 39742217 PMC: 11683711. DOI: 10.31083/j.rcm2512463.


The Great Controversy of Obstructive Sleep Apnea Treatment for Cardiovascular Risk Benefit: Advancing the Science Through Expert Consensus. An Official American Thoracic Society Workshop Report.

Cohen O, Kundel V, Barbe F, Peker Y, McEvoy D, Sanchez-de-la-Torre M Ann Am Thorac Soc. 2024; .

PMID: 39513996 PMC: 11708754. DOI: 10.1513/AnnalsATS.202409-981ST.


Impacts of exercise on inflammatory markers in individuals with OSA: more questions than answers.

Kline C, Edwards B Sleep Biol Rhythms. 2024; 22(3):297-298.

PMID: 38962801 PMC: 11217253. DOI: 10.1007/s41105-024-00531-2.


Personalizing Obstructive Sleep Apnea Therapy Using Machine Learning: Insights from the ISAACC Trial.

BaHammam A Ann Am Thorac Soc. 2024; 21(7):1005-1006.

PMID: 38949604 PMC: 11284318. DOI: 10.1513/AnnalsATS.202403-308ED.


References
1.
Sanchez-de-la-Torre A, Soler X, Barbe F, Flores M, Maisel A, Malhotra A . Cardiac Troponin Values in Patients With Acute Coronary Syndrome and Sleep Apnea: A Pilot Study. Chest. 2017; 153(2):329-338. PMC: 6026229. DOI: 10.1016/j.chest.2017.06.046. View

2.
Esquinas C, Sanchez-de-la Torre M, Aldoma A, Flores M, Martinez M, Barcelo A . Rationale and methodology of the impact of continuous positive airway pressure on patients with ACS and nonsleepy OSA: the ISAACC Trial. Clin Cardiol. 2013; 36(9):495-501. PMC: 6649460. DOI: 10.1002/clc.22166. View

3.
Tang I, Turnbull C, Sen D, Craig S, Kohler M, Stradling J . Effect of CPAP on cardiovascular events in minimally symptomatic OSA: long-term follow-up of the MOSAIC randomised controlled trial. BMJ Open Respir Res. 2020; 7(1). PMC: 7490925. DOI: 10.1136/bmjresp-2020-000742. View

4.
Zapater A, Sanchez-de-la-Torre M, Benitez I, Targa A, Bertran S, Torres G . The Effect of Sleep Apnea on Cardiovascular Events in Different Acute Coronary Syndrome Phenotypes. Am J Respir Crit Care Med. 2020; 202(12):1698-1706. DOI: 10.1164/rccm.202004-1127OC. View

5.
Edwards B, Redline S, Sands S, Owens R . More Than the Sum of the Respiratory Events: Personalized Medicine Approaches for Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2019; 200(6):691-703. PMC: 6775874. DOI: 10.1164/rccm.201901-0014TR. View