ABC | Volume 112, Nº4, April 2019

Original Article A Proposed Inflammatory Score of Circulating Cytokines/ Adipokines Associated with Resistant Hypertension, but Dependent on Obesity Parameters Ana Paula de Faria, 1 A lessandra Mileni Versuti Ritter, 1 Carolina Souza Gasparetti, 1, 2 Nathália Batista Corrêa, 1 Veridiana Brunelli, 1 A urélio Almeida, 1 N ayara Fraccari Pires, 1 Rodrigo Modolo, 3 Heitor Moreno Junior 4 Departamento de Farmacologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas, 1 Campinas, SP – Brazil Pontifícia Universidade Católica de Campinas (PUC-Campinas), 2 Campinas, SP – Brazil Departamento de Medicina Interna - Disciplina de Cardiologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas, 3 Campinas, SP – Brazil Departamento de Medicina Interna da Faculdade de Ciências Médicas da Universidade Estadual de Campinas, 4 Campinas, SP – Brazil Mailing Address: Ana Paula de Faria • Rua Tessália Vieira de Camargo, 126. FCM 10. Universidade Estadual de Campinas (UNICAMP). Postal Code 13093-970, Barão Geraldo, Campinas, SP – Brazil E-mail: aninha_cfaria@hotmail.com, ana.cabralfaria@gmail.com Manuscript received April 28, 2018, revised manuscript August 22, 2018, accepted September 05, 2018 DOI: 10.5935/abc.20190032 Abstract Background: There is evidence that subclinical systemic inflammation is present in resistant hypertension (RHTN). Objective: The aim of the study was to develop an integrated measure of circulating cytokines/adipokines involved in the pathophysiology of RHTN. Methods: RHTN (n = 112) and mild to moderate hypertensive (HTN) subjects (n=112) were studied in a cross-sectional design. Plasma cytokines/adipokines (TNF-alpha, interleukins [IL]-6, -8, -10, leptin and adiponectin) values were divided into tertiles, to which a score ranging from 1 (lowest tertile) to 3 (highest tertile) was assigned. The inflammatory score (IS) of each subject was the sum of each pro-inflammatory cytokine scores fromwhich anti-inflammatory cytokines (adiponectin and IL-10) scores were subtracted. The level of significance accepted was alpha = 0.05. Results: IS was higher in RHTN subjects compared with HTN subjects [4 (2-6) vs. 3 (2-5); p = 0.02, respectively]. IS positively correlated with body fat parameters, such as body mass index (r = 0.40; p < 0.001), waist circumference (r = 0.30; p < 0.001) and fat mass assessed by bioelectrical impedance analysis (r = 0.31; p < 0.001) in all hypertensive subjects. Logistic regression analyses revealed that IS was an independent predictor of RHTN (OR = 1.20; p = 0.02), independent of age, gender and race, although it did not remain significant after adjustment for body fat parameters. Conclusion: A state of subclinical inflammation defined by an IS including TNF-alpha, IL-6, IL-8, IL-10, leptin and adiponectin is associated with obese RHTN. In addition, this score correlates with obesity parameters, independently of hypertensive status. The IS may be used for the evaluation of conditions involving low-grade inflammation, such as obesity-related RHTN. Indeed, it also highlights the strong relationship between obesity and inflammatory process. (Arq Bras Cardiol. 2019; 112(4):383-389) Keywords: Hypertension/physiopathology; Obesity; Inflammation; Cytokines; Adipokines; Probability; Risk Factors Introduction Inflammation is an important pathophysiological factor underlying hypertension, obesity, and metabolic syndrome. Overweight and obese status include a higher prevalence of hypertension and maladaptive consequences including cardiorenal and metabolic disorders. Excess visceral fat is a source of cytokines, that creates an inflammatory-oxidative stress cascade contributing to insulin resistance (IR), endothelial dysfunction, vascular stiffening, and sodium retention in the kidney. 1,2 The combined presence of obesity and IR also contributes to overactivation of both sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system. 3 Ultimately, these disarrangements can lead to the occurrence of resistance to antihypertensive treatment. 4 Our research group have explored inflammatory cytokines – the anti-inflammatory adiponectin and interleukin 10 and the pro-inflammatory leptin, tumor necrosis factor-alpha (TNF- α ), and interleukins 6 (IL-6) – in resistant hypertension (RHTN) associating them to the lack of blood pressure (BP) control and vascular-renal damage. 5-7 In addition, low-grade chronic inflammation, estimated by high C-reactive protein levels, was able to predict major fatal and nonfatal cardiovascular outcomes, and cardiac remodeling in this high-risk population. 8-10 Adiponectin has an anti-inflammatory role and directly stimulates the production of nitric oxide (NO) in endothelial cells via phosphorylation of endothelial 383