The Neutrophil-to-Lymphocyte Ratio

We read the article “Neutrophils/Lymphocytes Ratio in Patients with Cardiac Syndrome X and Its Association With Carotid Intima–Media Thickness” by Demirkol et al ¹ with great interest. They aimed to evaluate the levels of the neutrophil-to-lymphocyte (N/L) ratio in patients with cardiac syndrome X (CSX) and compare patients having coronary artery disease (CAD) with normal control participants. They found that N/L ratio is significantly higher in both the CSX and the CAD groups than that in the control group. However, there was no statistically significant difference in N/L ratio and carotid intima–media thickness (CIMT) between CSX and CAD groups. Although this study is interesting, we would like to make a minor criticism based on its methodology. Although statistical significance was defined as P < .05 and the P values of N/L ratio and CIMT were given, P values of all variables should have been given in the article.

The CSX is an angina with signs associated with decreased blood flow to heart tissue but with normal coronary arteries. There are a number of systemic microvascular abnormalities, including endothelial cell dysfunction, diffuse atherosclerosis, and systemic inflammation, which result in reduced blood flow.^2,3 Many trials have reported that atherosclerosis is essentially an inflammatory response to a variety of traditional risk factors. Therefore, new studies have focused on inflammatory markers to determine their importance in cardiovascular disease including CSX. The N/L ratio represents the balance between neutrophil and lymphocyte levels. Most of the conditions including traditional risk factors (ie, hypertension, atherogenic lipoproteins, and hyperglycemia) and many other inflammatory conditions (ie, infection, chronic renal failure) change this ratio. ⁴ They did not exclude the local or systemic infection and the previous history of infection (especially <3 months).

Glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the kidney and gives more precise information about renal function than serum creatinine level. It can be measured by modification of diet in renal disease formula and Cockcroft-Gault equation. As it is well known, renal dysfunction from stage 1 to stage 5 is an ever-increasing systemic inflammatory process, respectively, and most of the large-scale studies that investigated inflammatory markers have recommended the calculation of GFR. ⁵ However, in this study, they defined the exclusion criteria with serum creatinine level despite the insufficient determination of renal dysfunction.

In addition, in the current study, it is mentioned that they did not analyze inflammation markers such as C-reactive protein (CRP), as the role of inflammation was previously reported in those patients. However, measuring other proven inflammatory markers such as CRP might help to correct the analysis. Recently, the same group has reported that N/L ratio without other inflammatory markers may not give information to clinicians about the chronic endothelial inflammation. ⁶ So, we agree with their previous article.

In conclusion, the N/L ratio seems to be a novel marker permitting the use of inflammatory marker as indicator of atherogenesis and/or as predictor of atherosclerotic complication in complement with the traditional risk factors and other serum inflammatory markers. Therefore, further large-scale prospective clinical studies with these recommendations are needed.