Proteomic profiling for prediction of recurrent cardiovascular event in patients with acute coronary syndrome and obstructive sleep apnea: A post-hoc analysis from the ISAACC study

Abstract

Background: Obstructive sleep apnea (OSA) is associated with a recurrent cardiovascular event (CVE) risk in patients with a first acute coronary syndrome (ACS). However, the pathological pathways by which OSA promotes this deleterious role are unknown. We aim to explore the proteomic profile associated with OSA that promote the recurrent CVE risk in severe OSA patients with ACS without previous cardiovascular diseases. Methods: This post-hoc analysis from the ISAACC study (NCT01335087) included 86 patients admitted for ACS. Patients underwent respiratory polygraphy for the first 24-72 h to OSA diagnosis. We analyzed of 276 cardiovascular and inflammatory related proteins in baseline fasting plasma samples using proximity expression assay technology (Olink®, Sweden). Protein levels were compared between severe OSA patients with/without recurrent CVEs during follow-up. Random forest was conducted to select relevant proteins and generate a predictive model of recurrent CVE. Results: We included 86 patients (median age: 61 years, median BMI: 29.4 kg/m2 and 86 % males) admitted for ACS with severe OSA (56 without recurrent CVE/30 with recurrent CVE). The plasma levels of 38 proteins were differentially expressed between groups. Additionally, 12 proteins had a significant association with respiratory polygraphy parameters. Three proteins discriminate with an AUC of 0.81 (95 % CI of 0.71-0.9) between severe OSA patients with and without recurrent CVE. These proteins were implicated in cell proliferation, communication and apoptosis, and regulation/response to the inflammatory and immune systems. Conclusion: In ACS patients with severe OSA, a proteomic profile was associated with recurrent CVEs. This proteomic profile was correlated with specific OSA parameters from respiratory polygraphy. Proteomic profiling may provide an new direction for patient risk stratification and clinical management.

Instituto de Salud Carlos III (ISCIII) (PI10/02763, PI10/02745, PI18/00449, PI21/ 00337) (Spain), co-funded by the European Union, IRBLleida-Fundació Dr.Pifarré, CERCA Programme/Generalitat de Catalunya (Spain), SEPAR (Spain), ResMed Ltd. (Australia), Esteve-Teijin (Spain), Oxigen Salud (Spain), Associació Lleidatana de Respiratori (ALLER) (Spain), and Sociedad Española de Sueño (SES) (Spain). AZ held a predoctoral fellowship “Ajuts 2021 de Promoció de la Recerca en Salut-9ª edició” from IRBLleida/Diputació de Lleida. JdB acknowledges receiving financial support from ISCIII (Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund (ESF), “Investing in your future”. MS has received financial support from a “Ramón y Cajal” grant (RYC2019-027831-I) from the “Ministerio de Ciencia e Innovación- Agencia Estatal de Investigación ” co-funded by the European Social Fund (ESF)/“Investing in your future”.