Inflammation and Fibrosis in Sleep-Disordered Breathing after Acute Myocardial Infarction

Abstract

Background: After acute myocardial infarction (AMI), inflammatory processes promote tissue remodeling at the infarct site. Procollagen III amino-terminal propeptide (PIIINP) is a circulating biomarker of type III collagen synthesis that has been shown to be associated with changes in left ventricular ejection fraction (LVEF) and predicts the occurrence of heart failure after AMI. We hypothesize that sleep-disordered breathing (SDB) promotes inflammation and myocardial fibrosis, leading to reduced myocardial salvage. Therefore, in patients with first-time AMI successfully treated with percutaneous coronary intervention (PCI), we aimed to investigate whether circulating levels of high-sensitivity C-reactive protein (hs-CRP) and PIIINP are elevated in patients with SDB compared to patients without SDB.

Methods and results: This cross-sectional analysis included a total of 88 eligible patients with first AMI and PCI pooled from two prospective studies and stratified according to the apnea-hypopnea index (AHI, with SDB: AHI ≥ 15 h^-1). We analyzed circulating levels of hs-CRP and PIIINP 3-5 days after PCI. Patients with SDB had significantly higher levels of hs-CRP (18.3 mg/L [95% CI, 8.0-42.6] vs. 5.8 mg/L [95% CI, 4.2-19.8], p = 0.002) and PIIINP (0.49 U/mL [95% CI, 0.40-0.60] vs. 0.33 U/mL [95% CI, 0.28-0.43], p < 0.001). In a multivariable linear regression model accounting for important clinical confounders, SDB significantly predicted circulating levels of hs-CRP (p = 0.028). Similarly, only SDB was independently associated with PIIINP (p < 0.001). Only obstructive but not central AHI correlated with circulating levels of hs-CRP (p = 0.012) and PIIINP (p = 0.006) levels.

Conclusions: The presence of obstructive SDB after AMI was independently associated with increased circulating levels of hs-CRP and PIIINP. Our results emphasize the important role of SDB as a common comorbidity and indicate increased inflammation and myocardial fibrosis in these patients.

Keywords: acute myocardial infarction; inflammation; myocardial fibrosis; procollagen III type aminoterminal propeptide; sleep-disordered breathing.

Figure 1

Flow diagram of patients included in the study. AHI: apnea–hypopnea index; CMR: cardiac magnetic resonance imaging; PG: polygraphy; PIIINP: procollagen III type aminoterminal propeptide; SDB: sleep-disordered breathing; TEAM-ASV I: Treatment of Sleep Apnea Early After Myocardial Infarction With Adaptive Servo-Ventilation Trial I.

Figure 2

Histogram of (A) high-sensitivity C-reactive protein (hs-CRP) and (B) procollagen III type aminoterminal propeptide (PIIINP).

Figure 3

Circulating levels of high-sensitivity C-reactive protein (hs-CRP) and procollagen III type aminoterminal propeptide (PIIINP) according to the presence of sleep disorder breathing (SDB). (A) hs-CRP (18.3 mg/L [95% CI, 8.0–42.6] vs. 5.8 mg/L [95% CI, 4.2–19.8], p = 0.002) and (B) PIIINP (0.49 U/mL [95% CI, 0.40–0.60] vs. 0.33 U/mL [95% CI, 0.28–0.43], p < 0.001).

Figure 4

Scatter plot demonstrating the significant relations between high-sensitivity C-reactive protein (hs-CRP) and procollagen III type aminoterminal propeptide (PIIINP) with apnea–hypopnea index (AHI). (A) hs-CRP (r_s = 0.340, 95% CI 0.145 to 0.538, p = 0.002) and (B) PIIINP (r_s = 0.435, 95% CI 0.105 to 0.494, p < 0.001). r_s = Spearman correlation coefficient; CI: confidence interval.

Figure 5

Scatter plot demonstrating the significant relations between high-sensitivity C-reactive protein (hs-CRP) and (A) obstructive apnea–hypopnea index (oAHI) (r_s = 0.277, 95% CI 0.058 to 0.470, p = 0.012), but not (B) central apnea–hypopnea index (cAHI) (r_s = 0.160, 95% CI −0.062 to 0.366, p = 0.155). r_s = Spearman correlation coefficient; CI: confidence interval.

Figure 6

Scatter plot demonstrating the significant relations between procollagen III type aminoterminal propeptide (PIIINP) and (A) obstructive apnea–hypopnea index (oAHI) (r_s = 0.292, 95% CI 0.082 to 0.477, p = 0.006), but not (B) central apnea–hypopnea index (cAHI) (r_s = 0.097, 95% CI −0.116 to 0.302, p = 0.369). r_s = Spearman correlation coefficient; CI: confidence interval.