Background: Biomarkers predicting the presence and severity of coronary artery disease (CAD) in patients with suspected CAD and previous history of cardiovascular events (CVE) are unclear.
Methods: The ANOX study is a multicenter, prospective cohort study to determine the predictive value of possible novel biomarkers related to angiogenesis or oxidative stress for major adverse cardiovascular events among patients undergoing elective angiography. Between January 1, 2010 and November 1, 2013, a total of 2,513 patients were enrolled. After excluding 93 patients who were subsequently found ineligible or withdrew consent, and 1,321 patients with no previous history of CVE, the baseline data of 1,099 patients (68% with CAD, 43% with multi-vessel disease [MVD]) were analyzed. Blood samples were collected from the arterial catheter sheath at the beginning of coronary angiography. The presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were assessed using the Gensini score. Serum levels of vascular endothelial growth factor (VEGF), VEGF-C, soluble VEGF receptor-2 (sVEGFR-2), and two oxidatively modified LDLs (the α1-antitrypsin/LDL complex and serum-amyloid-A/LDL complex [SAA-LDL]), as well as N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin-I, and high-sensitivity C-reactive protein (hsCRP), were measured. We performed stepwise regression analyses including data on age, sex, systolic blood pressure (SBP), LDL-C, HDL-C, presence of diabetes (DM), history of smoking habit, and these biomarkers.
Results: The presence of CAD was significantly correlated with age (OR, 1.2 per 10 year; 95% CI, 1.1–1.4), sex (OR, 1.9 for men; 95% CI, 1.4–2.5), SBP (OR, 1.08 per 10 mmHg; 95% CI, 1.006–1.17), DM (OR, 2.3; 95% CI, 1.8–3.0), sVEGFR-2 (OR, 1.3 per 1-SD increase; 95% CI, 1.1–1.5), and natural log-transformed SAA-LDL (Ln-SAA-LDL) (OR, 1.20 per 1-SD increase; 95% CI, 1.05–1.39). The presence of MVD was also significantly correlated with age (OR, 1.2 per 10 year; 95% CI, 1.1–1.4), sex (OR, 1.9 for men; 95% CI, 1.4–2.5), DM (OR, 1.8; 95% CI, 1.4–2.3), and Ln-SAA-LDL (OR, 1.15 per 1-SD increase; 95% CI, 1.02–1.30), as well as Ln-NT-proBNP (OR, 1.4 per 1-SD increase; 95% CI, 1.2–1.6). After excluding 101 patients with normal coronary (Gensini score, 0) to attain normal distribution, independent determinants of Ln-Gensini score were age, sex, DM, sVEGFR-2, Ln-SAA-LDL, Ln-NT-proBNP, and Ln-hsCRP.
Conclusions: Serum levels of SAA-LDL were independently correlated with the presence and severity of CAD in patients with suspected CAD and previous history of CVE. The follow-up data of the ANOX study will provide evidence for the predictive values of these biomarkers independent of known risk factors and the severity of CAD at the baseline.