Assessment of Inflammatory Hematological Ratios (NLR, PLR, MLR, LMR and Monocyte/HDL-Cholesterol Ratio) in Acute Myocardial Infarction and Particularities in Young Patients

Abstract

Cardiovascular disease, particularly coronary artery disease (CAD), remains a predominant cause of mortality globally. Factors such as atherosclerosis and inflammation play significant roles in the pathogenesis of CAD. The nexus between inflammation and CAD is underscored by the role of immune cells, such as neutrophils, lymphocytes, monocytes, and macrophages. These cells orchestrate the inflammatory process, a core component in the initiation and progression of atherosclerosis. The activation of these pathways and the subsequent lipid, fibrous element, and calcification accumulation can result in vessel narrowing. Hematological parameters derived from routine blood tests offer insights into the underlying inflammatory state. Recent studies have highlighted the potential of inflammatory hematological ratios, such as the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio and lymphocyte/monocyte ratio. These parameters are not only accessible and cost-effective but also mirror the degree of systemic inflammation. Several studies have indicated a correlation between these markers and the severity, prognosis, and presence of CAD. Despite the burgeoning interest in the relationship between inflammatory markers and CAD, there remains a paucity of data exploring these parameters in young patients with acute myocardial infarction. Such data could offer valuable insights into the unique pathophysiology of early-onset CAD and improve risk assessment and predictive strategies.

Keywords: acute myocardial infarction; lymphocyte/monocyte ratio; monocyte/lymphocyte ratio; neutrophil/lymphocyte ratio; platelet/lymphocyte ratio; young patients.

Figure 1

The role of monocytes, neutrophils and lymphocytes in atherosclerotic plaque formation. A, B: Activated endothelial cells produce chemoattractants and adhesion molecules that draw in monocytes. The binding of inflammatory chemoattractants by monocytes from the blood promotes their chemotaxis to the atherosclerotic endothelium; C, D: Inflammatory monocytes then move intima by adhering to the atherosclerotic endothelium; E: Once reaching the location of the lesion, monocytes differentiate into macrophages, which further contribute to inflammation. Ingesting cholesterol causes these cell types to develop into foam cells, thus contributing to the formation of atherosclerotic plaque. Although these macrophages initially help by removing these lipoproteins from the subendothelium, with time the macrophages become engorged with lipids, which leads to dysregulated lipid metabolism. These foam cells eventually experience apoptosis and necrosis, and if they are not removed effectively by M2 macrophages through efferocytosis, they will release their toxic and pro-inflammatory contents into the subendothelial space. This will further encourage cell death and inflammation, the development of the necrotic core and further increase the vulnerability of the plaque. The plaque is susceptible to rupture when the fibrous cover thins and the necrotic core expands, which might cause a thrombosis or other acute cardiovascular event. F: Endothelial cell lesions result from the breakdown of the basement membrane by neutrophilic MMP, MPO and ROS. G: Neutrophils produce chemoattractant for monocytes. H: NETs complexes trigger macrophages to release the proinflammatory cytokine. NETosis, a cell death mechanism distinct from apoptosis or necrosis, is the method by which these chromatin complexes are released from neutrophil nuclei. NETosis enables neutrophils to destroy infections more effectively by creating a mechanical barrier to “trap” germs. I: Neutrophils block the tissue factor plasminogen inhibitor, which causes thrombus to develop. J: Neutrophils that have been activated produce NETs complexes, which promote thrombus development. K: T lymphocyte responses are induced by APCs such as macrophages, DCs and B cells. There are many subsets of naive CD4+ T helper (Th) cells, and stimulatory chemicals in fact encourage T cells to express transcription factors that result in differentiation into Th phenotypes. Both pro-atherogenic and atheroprotective properties may be seen in CD4+ T cells. Th1, Th2, Th9, Th17, Th22, Treg and follicular helper T (TFH) cells may be detected in atherosclerotic lesions. By releasing IFN-γ, interleukins, TGF-β and protease, these lymphocytes promote inflammation, endothelial cell death, plaque cell apoptosis, monocytic migration, and thus the development of atherosclerotic plaques, foam cells and atherosclerotic plaque rupture. Type I NKT cells may stimulate immune cells in plaque by secreting cytokines and accelerating the development of atherosclerosis. The cytotoxic effects of CD8+ T cells, in contrast with lesion-stabilizing cells and the generation of inflammatory cytokines by CD8+ T cells, may worsen the growth and instability of lesions by escalating inflammatory reactions in plaques of atherosclerosis. L. White blood cells of the lymphocyte subtype known as B cells, or B lymphocytes, are classified into two separate groups (B1 and B2). By secreting antibodies, B cells are essential to the humoral immunity part of the adaptive immune system. B cells also present antigens, which are classified as expert APCs, and release cytokines. B lymphocytes, which aid in the development of lymphoid follicles, may contribute to atherosclerosis. At all phases of the disease’s development, IgG and IgM antibodies may be found in atherosclerotic plaques. Ox-LDL—oxidized low-density lipoprotein; TFPI—tissue factor plasminogen inhibitor; MMP—matrix metalloproteinases; MPO—myeloperoxidase; ROS—reactive oxygen species; NETs—neutrophil extracellular traps; APCs—antigen-presenting cell; DCs—dendritic cells; IFN-γ—interferon gamma; TGF-β—transforming growth factor beta; NKT—natural killer T; IgG—immunoglobulin G; IgM—immunoglobulin M. There are some potential factors that may influence the inflammatory hematological ratios.