Relationship of Blood Inflammatory Composite Markers with Cardiovascular Risk Factors and Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis

Abstract

The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been described as potential blood-derived inflammatory biomarkers in several diseases. Rheumatoid arthritis is an inflammatory disease that has been related to an increased risk of cardiovascular (CV) disease. In the present work, we analyze how these hematological composite scores of inflammation are related to classic CV risk factors and subclinical atherosclerosis in patients with RA. In this cross-sectional study that included 430 patients with RA, the NLR, MLR, PLR, and SIRI scores were calculated. Multivariable analysis was performed to examine the relationships of these composite blood scores with subclinical carotid atherosclerosis and with traditional cardiovascular factors, producing a complete profile of lipid molecules and insulin resistance or indices of beta-cell function, and a Systematic Coronary Risk Assessment (SCORE2) calculation. C-reactive protein and disease activity were significantly and positively associated with the four blood composite scores. SCORE2 was significantly associated with higher values of SIRI, NLR, and MLR, but not PLR. These relationships were maintained when SCORE 2 was considered categorical; patients in the very high CV risk category had higher values in all hematological composite scores, except PLR. In the multivariable analysis, SIRI and NLR were independently associated with higher levels of beta cell dysfunction. In conclusion, SCORE2 and the values of the hematological composite scores were positively correlated in patients with RA. In addition, there were some relationships of these scores with traditional CV risk factors, with their association with beta cell dysfunction being the most consistent.

Hematological Composite Scores in Patients with Inflammatory Bowel Disease

“…In a previous work by our group, 430 patients with rheumatoid arthritis had a SIRI value of 1.22 ± 0.81 [8]. We have estimated that we would expect to find a difference in patients with IBD of 0.1.…”

“…These are regarded as markers of inflammation because white blood cells and platelets are typically present in acute and chronic inflammatory settings, where they release cytokines, proteases, angiogenic factors, and chemokines [5]. In recent years, these scores have generated interest and have gained relevance because they have been described as relating to or predicting certain outcomes in chronic inflammatory, autoimmune [6][7][8], and cardiovascular diseases [9], as well as in cancer [10] or infections [11].…”

Association between blood cell ratios and coronary heart disease: A 10-year nationwide study (NHANES 2009–2018)

“…[ 26 ] González-Sierra M et al noted rheumatoid arthritis as a chronic inflammatory disease, in which patients with rheumatoid arthritis have increased inflammation-associated blood cell ratios (SIRI, NLR, MLR), induces an increased risk of comorbid cardiovascular system diseases. [ 27 ] Ma et al noted a negative correlation between SII and CHD incidence. Also, they found an inverted U-shaped relationship between SII and coronary heart disease risk after adjusting for the gender variable, with a significant effect, suggesting a gender-specific association between SII and coronary heart disease.…”

Association of the systemic immune-inflammation index with all-cause and cardiovascular mortality in individuals with rheumatoid arthritis

“…An escalated SII denotes not only an increased neutrophil activation and innate inflammatory response but also suggests a key role in the pathogenesis and progression of RA. The heightened systemic inflammation, as indicated by a raised SII, may further expedite atherosclerotic processes, elevating cardiovascular risk and mortality 41 . On the flip side, lymphocytes, including regulatory T cells, are integral in dampening inflammatory reactions and reinstating immune equilibrium 42 .…”