Current Smoking Determines the Levels of Circulating MPO and MMP-9 in Adults with Coronary Artery Disease and Obstructive Sleep Apnea

Author:

Özkan Esra12ORCID,Celik Yeliz123,Yucel-Lindberg Tülay4ORCID,Peker Yüksel25678ORCID

Affiliation:

1. Graduate School of Health Sciences, Koc University, Istanbul 34450, Turkey

2. Research Center for Translational Medicine [KUTTAM], School of Medicine, Koc University, Istanbul 34450, Turkey

3. Columbia University Irving Medical Center, New York, NY 10032, USA

4. Division of Pediatric Dentistry, Department of Dental Medicine, Karolinska Institute, 141 86 Huddinge, Sweden

5. Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Göteborg, Sweden

6. Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital & Harvard Medical School, Boston, MA 02115, USA

7. Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA

8. Department of Clinical Sciences, Respiratory Medicine and Allergology, Faculty of Medicine, Lund University, 220 02 Lund, Sweden

Abstract

(1) Background: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which a rupture of atherosclerotic plaques and oxidative stress play a role in the initiation and progression of the disorder. Circulating levels of myeloperoxidase (MPO), as an oxidative stress marker, as well as matrix metalloproteinase-9 (MMP-9), as a destabilizer of plaques, are known to be elevated in patients with CAD and are associated with worse prognosis. Some studies have suggested that OSA is associated with MPO and MMP-9, but the effect of OSA on these biomarkers in cardiac cohorts is unknown. (2) Aims: We addressed the determinants of high MPO and MMP-9 in a CAD cohort with concomitant OSA. (3) Materials and Methods: The current study was a secondary analysis of the RICCADSA trial that was conducted in Sweden between 2005 and 2013. A total of 502 revascularized CAD patients with OSA (apnea–hypopnea index [AHI] ≥ 15 events/h; n = 391) or no-OSA (AHI < 5 events/h; n = 101), based on a home sleep apnea test, and who had blood samples at baseline were included in the analysis. The patients were dichotomized into a high or low MPO and MMP-9 groups, based on the median cut-off values. (4) Results: The mean age of the participants was 63.9 (±8.6), and 84% of the study cohort were men. Median values of MPO and MMP-9 levels were 116 ng/mL and 269 ng/mL, respectively. In different multivariate linear and logistic regression models, neither OSA nor OSA severity in terms of AHI and oxygenation indices were associated with the high MPO and MMP-9 levels. Current smoking was significantly associated with both high MPO (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06–2.84; p = 0.030) and high MMP-9 levels (OR 2.41, 95% CI 1.44–4.03; p < 0.001), respectively. Other significant determinants were revealed as beta blocker use (OR 1.81, 95% CI 1.04–3.16; p = 0.036) for high MPO as well as male sex (OR 2.07, 95% CI 1.23–3.50; p = 0.006) and calcium antagonist use (OR 1.91, 95% CI 1.18–3.09; p = 0.008) for high MMP-9 levels. (5) Conclusions: Current smoking, but not OSA, was significantly associated with high MPO and MMP-9 levels in this revascularized CAD cohort. Smoking status should be seriously taken into consideration while evaluating the effects of OSA and its treatment on long-term adverse cardiovascular outcomes in adults with CAD.

Funder

Swedish Research Council

Swedish Heart-Lung Foundation

“Agreement concerning research and education of doctors” of Västra Götalandsregionen

Research fund at Skaraborg Hospital

Skaraborg Research and Development Council

Heart Foundation of Kärnsjukhuset

ResMed Foundation

ResMed Ltd.

Publisher

MDPI AG

Subject

General Medicine

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