ABC | Volume 112, Nº4, April 2019

Original Article de Faria et al Inflammatory score and resistant hypertension Arq Bras Cardiol. 2019; 112(4):383-389 Table 2 – Medications used by subjects with mild-to-moderate hypertension (HTN) and subjects with resistant hypertension (RHTN) HTN (n = 112) RHTN (n = 112) p-value Antihypertensive drugs Number of classes 2 (2-3) 4 (4-5) < 0.001 Diuretics, n (%) 70 (63) 108 (96) 0.02 ACEIs, n (%) 20 (18) 43 (38) 0.02 ARBs, n (%) 81 (72) 61 (54) 0.01 CCBs, n (%) 53 (47) 94 (84) < 0.001 Beta-blockers, n (%) 14 (13) 79 (71) < 0.001 Central α-agonists, n (%) 01 (01) 31 (28) < 0.001 Statins, n (%) 84 (75) 60 (54) 0.001 Glucose-lowering drugs, n (%) 42 (38) 57 (51) 0.06 Antiplateletdrugs, n (%) 20 (18) 65 (58) < 0.001 ACEIs: angiotensin-converting enzyme inhibitors; ARBs: angiotensin receptor blockers; CCBs: calcium channel blockers. In addition, the HTN group was older than the RHTN group, and hence an increased IS could be attributed to age. 22 Experimental studies share similar findings of the role of inflammation on hypertension. Researchers have investigated changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab – a TNF-alpha-neutralizing agent. 23 This study revealed cardiovascular benefits of inhibiting this cytokine in SHR with the reduction of both systolic BP and cardiac remodeling. The authors suggested a vasodilation dependent-mechanism in which the infliximab effect is able to induce the NO synthesis. 23 Interestingly, a recent study 24 described a new pathway of hypertension linked to an immune-inflammatory-oxidative stress cascade. Kirabo et al. 24 demonstrated that an angiotensin II–infused mice model increased reactive oxygen species in dendritic cells releasing pro-inflammatory cytokines (IL-6, IL-1 beta, and IL-23), which in turn promoted T cell proliferation featuring a pro-inflammatory phenotype. Ultimately, these mechanisms led to hypertension, suggesting new potential targets to treat hypertension. 24 Our results revealed that the IS – already investigated in type 2 diabetes 25 – was able to address in a single measure a great variety of mechanistically aligned cytokines/adipokines, involved in the pathophysiology of RHTN. Therefore, this approach could enhance estimation of the relation between the low‑grade inflammation and high-risk populations such as the obese subjects with RHTN studied in this work. It is well recognized that obesity, characterized by chronic activation of the immune system and inflammatory pathways, is a critical factor contributing to IR and type 2 diabetes, both comorbidities quite often presented in subjects with RHTN. In this context, many studies have supported this relationship. Esposito et al. 26 found that weight loss and lifestyle changes decreased vascular inflammatory markers, such as IL-6, IL-18, and C-reactive protein, whereas adiponectin levels increased significantly in obese women. Similar effects of reducing levels of TNF-alpha were found in response to these interventions. 27 Overweight and obesity have been suggested to cause microvascular dysfunction characterized by (1) impaired insulin sensitivity, (2) SNS activation and (3) increased vascular peripheral resistance. Along with this, changes in adipokines secretion leading to increased levels of free fatty acids and inflammatory mediators have also Figure 1 – Inflammatory score calculated between subjects with mild-to-moderate hypertension (HTN) and resistant hypertension (RHTN) (3 [2-5] vs. 4 [2-6], p = 0.02, respectively). IS of each subject was the sum of each pro-inflammatory cytokine score (TNF-alpha, interleukins (IL) -6, -8, -10) from which the scores of anti-inflammatory cytokines (adiponectin and IL-10) were subtracted; *p < 0.05 vs. HTN 10 5 0 –5 HTN RHTN* Inflammatory Score 386