CXC Chemokine Ligand 16 as a Prognostic Marker in Patients with Intermediate Coronary Artery Lesions: A 2-Year Follow-Up Study

Abstract

There is no reliable way to identify the high-risk patients with intermediate coronary artery lesions (diameter stenosis 20%-70%) in early stage. Soluble CXC chemokine ligand 16 (CXCL16) is a newly discovered chemokine that can mediate inflammatory responses. It is released by proteolytic cleavage of its membrane-bound form, named scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) that can promote the uptake of oxidized low-density lipoprotein cholesterol by macrophages. We have hypothesized that CXCL16 is an indicator of the prognosis of intermediate coronary artery lesions, and thus assessed the association between plasma CXCL16 concentrations and the 2-year prognosis in 616 patients with intermediate coronary artery lesions. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, revascularization and angina pectoris requiring re-hospitalization. During the median follow-up time of 24 months, 69 events occurred. The plasma concentrations of CXCL16 (median 7712.88 pg/ml vs. 6792.43 pg/ml, P = 0.014) and high-sensitivity C-reactive protein (hs-CRP) (median 2.82 mg/L vs. 1.68 mg/L, P < 0.001) were higher in patients with events than patients without events. Cox hazard proportion analysis showed patients in upper CXCL16 quartile were more likely to suffer from adverse outcome than patients in lower quartile (RR = 1.271, P = 0.029, 95% CI: 1.025-1.577) after adjusting for sex, age, smoking, hypertension, diabetes, fat, dyslipidemia, hs-CRP, and medication use. In conclusion, plasma level of CXCL16 is an independent predictor of the prognosis of the patients with intermediate coronary lesions. Elevated plasma CXCL16 is associated with higher risk for these patients.

C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes

“…The predictive value of CXCL16 has also been studied in stable CAD, showing an association with a composite of all-cause death, non-fatal MI, revascularization and hospitalization for angina pectoris during 24 months of follow-up. 25 CXCL16 has furthermore been found to predict the risk of MI in healthy volunteers. 26 Accordingly, CXCL16 may be a new predictor of adverse outcome across the whole spectrum of CAD.…”

“…[15][16][17][18][19][20] Several previous studies have found higher serum levels of CXCL16 in ACS versus stable CAD and controls. 17,[21][22][23] There are, however, only a few prospective studies investigating the use of CXCL16 as a risk marker in CAD 6,[24][25][26][27] , and only one of these included patients from an ACS population 6,24 .…”

Scavenger Receptors in Myocardial Infarction and Ischemia/Reperfusion Injury: The Potential for Disease Evaluation and Therapy

“…After 2 years of follow‐up, the upper plasma sCXCL16 quartile was also independently associated with adverse outcomes (including all‐cause death, MI, and revascularization) in these patients. 65 Based on these studies, circulating sCXCL16 may have strong promising potential as a clinical biomarker for predicting MI occurrence and for the diagnosis and prognosis of MI (Table 2 ).…”

Platelet SR-PSOX/CXCL16–CXCR6 Axis Influences Thrombotic Propensity and Prognosis in Coronary Artery Disease

“…Serum sCXCL16 level influenced by pro-inflammatory hs-CRP is also suggested as a peripheral diagnostic biomarker for diabetic patients with coronary artery disease (CAD) [ 20 ]. Increased serum sCXCL16 levels, as a strong independent indicator of long-term mortality [ 20 , 21 ], are prognostically unfavorable in ACS patients and patients with intermediate coronary lesions [ 21 ]. Recently, in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome), serum sCXCL16 levels were shown to be independently associated with cardiovascular death and morbidity in ACS patients [ 22 ].…”