ASSOCIATION OF SUBCLINICAL INFLAMMATION MARKERS WITH PRIMARY HYPERTENSION IN CHILDREN - A SYSTEMATIC REVIEW WITH META-ANALYSIS

Abstract

Objective: Primary hypertension (PH) is a growing threat to children's health. The pathogenesis of this phenomenon is not fully known, and subclinical inflammation and activation of the immune system are potential explanations. This systematic review and meta-analysis aimed to systematically determine whether there is an association between low–grade inflammation markers and PH in children. Design and method: The MEDLINE, EMBASE, and Cochrane databases were searched up to March 2023, with no language restrictions, for cohort, cross-sectional, and case-control studies; additional references were obtained from reviewed articles. The included studies needed to investigate an association between any inflammation markers and PH defined by the authors. Participants of the study were children (<18 years old) with PH and healthy controls. The main outcome measured was the concentration of any subclinical inflammation markers in children with PH and in healthy controls. This meta-analysis included 12 studies published between 2005 and 2022, enrolling 1220 patients (689 with PH and 531 healthy controls). The data were analyzed using Review Manager. Pooled mean difference (MD) with 95% confidence interval (95% CI) was used to assess the differences in inflammation markers levels. All analyses were based on the random-effect model. The risk of bias was assessed using the Newcastle-Ottawa Scale. Results: There was a significant difference between hypertensive and control groups in high-sensitivity C-reactive protein (hsRCP) concentration (MD: 0.07 95%CI [0.04,0.09]), intercellular adhesion molecule 1 (ICAM-1) (MD: 85.28 95%CI: [50.57-119.99]), vascular cell adhesion molecule 1 (VCAM-1) (MD: 259.78 95%CI: [22.65-496.91]), neutrophil count (MD: 0.80 95%CI [0.53-1.07]), monocyte count (MD: 0.07 95%CI: [0.02-0.12]), and neutrophil-to-lymphocyte ratio (NLR) (MD: 0.49 95%CI: [0.32-0.65]). There was no difference in terms of interleukin 6 (IL-6), lymphocyte count, platelet count, mean platelet volume (MPV), as well as in platelet-to-lymphocyte (PLR) and monocyte-to-lymphocyte (MLR) ratios. Conclusions: Some easily accessible markers of low-grade inflammation might be used as an additional tool for diagnosis and screening for hypertension in pediatric patients. These promising results should be validated in large and well-conducted studies.