Neutrophil/Lymphocyte ratio is associated with non-calcified plaque burden in patients with coronary artery disease

Abstract

Background: Elevations in soluble markers of inflammation and changes in leukocyte subset distribution are frequently reported in patients with coronary artery disease (CAD). Lately, the neutrophil/lymphocyte ratio has emerged as a potential marker of both CAD severity and cardiovascular prognosis.

Objectives: The aim of the study was to investigate whether neutrophil/lymphocyte ratio and other immune-inflammatory markers were related to plaque burden, as assessed by coronary computed tomography angiography (CCTA), in patients with CAD.

Methods: Twenty patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and 30 patients with stable angina (SA) underwent CCTA at two occasions, immediately prior to coronary angiography and after three months. Atherosclerotic plaques were classified as calcified, mixed and non-calcified. Blood samples were drawn at both occasions. Leukocyte subsets were analyzed by white blood cell differential counts and flow cytometry. Levels of C-reactive protein (CRP) and interleukin(IL)-6 were measured in plasma. Blood analyses were also performed in 37 healthy controls.

Results: Plaque variables did not change over 3 months, total plaque burden being similar in NSTE-ACS and SA. However, non-calcified/total plaque ratio was higher in NSTE-ACS, 0.25(0.09-0.44) vs 0.11(0.00-0.25), p<0.05. At admission, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios, CD4+ T cells, CRP and IL-6 were significantly elevated, while levels of NK cells were reduced, in both patient groups as compared to controls. After 3 months, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios and CD4+ T cells remained elevated in patients. Neutrophil/lymphocyte ratios and neutrophil counts correlated significantly with numbers of non-calcified plaques and also with non-calcified/total plaque ratio (r = 0.403, p = 0.010 and r = 0.382, p = 0.024, respectively), but not with total plaque burden.

Conclusions: Among immune-inflammatory markers in NSTE-ACS and SA patients, neutrophil counts and neutrophil/lymphocyte ratios were significantly correlated with non-calcified plaques. Data suggest that these easily measured biomarkers reflect the burden of vulnerable plaques in CAD.

Figure 1. Different plaque compositions as seen by CCTA.

The different types of coronary plaque are shown in longitudinal views, with cross-sectional views at the level of the dotted line. A non-calcified plaque is shown on the left (A and B), with white arrowheads pointing at the non-calcified plaque component. A mixed plaque is shown in the middle (C and D), with a white arrowhead indicating the non-calcified plaque component and a black arrowhead indicating the calcified component. A large calcified plaque is shown on the right side (E and F), with black arrowhead indicating the calcifications.

Figure 2. Neutrophils and coronary plaques on CCTA.

Scatterplots demonstrating the associations between non-calcified/total plaque ratio on baseline CCTA and neutrophil/lymphocyte ratio and neutrophil counts at admission. Neutrophil counts are given as ×10⁹/L.