Increased levels of inflammatory biomarkers such as interleukin-6 (IL-6), 10 (IL-10), 1β (IL-1β), tumor necrosis factor-α (TNF-α) high-sensitivity C-reactive protein (hs-CRP) are associated with arterial stiffness in hypertension. Indeed, resistant hypertension (RHTN) leads to unfavorable prognosis attributed to poor blood pressure (BP) control and target organ damage. This study evaluated the potential impact of inflammatory biomarkers on arterial stiffness in RHTN.In this cross-sectional study, 32 RHTN, 20 mild hypertensive (HTN) and 20 normotensive (NT) patients were subjected to office BP and arterial stiffness measurements assessed by pulse wave velocity (PWV). Inflammatory biomarkers were measured in plasma samples.PWV was increased in RHTN compared with HTN and NT (p < 0.05). TNF-α levels were significantly higher in RHTN and HTN than NT patients. No differences in IL-6 levels were observed. RHTN patients had a higher frequency of subjects with increased levels of IL-10 and IL-1β compared with HTN and NT patients. Finally, IL-1β was independently associated with PWV (p < 0.001; R(2) = 0.5; β = 0.077).RHTN subjects have higher levels of inflammatory cytokines (TNF-α, IL-1β and IL-10) as well as increased arterial stiffness, and detectable IL-1β levels are associated arterial stiffness. These findings suggest that inflammation plays a possible role in the pathophysiology of RHTN.
Plasma IGF-1 was measured in 38 diabetic pregnant women (DPW) and in 12 non diabetic pregnant women (NDPW) during the 1st, 2nd and 3rd trimester of pregnancy. IGF-1 was measured in the cord blood of 24 infants of diabetic mothers (IDDM) and IGF-1 in 11 infants of non diabetic mothers (NIDDM). A progressive and significant (p < 0.0001) increase of IGF-1 values was found throughout the pregnancy both in DPW and NDPW IGF-1 (149 +/- 18 ng/ml vs 181 +/- 14 ng/ml, 184 +/- 17 ng/ml vs 232 +/- 25 ng/ml, 279 +/- 20 ng/ml vs 325 +/- 17 ng/ml). Furthermore IGF-1 decreased significantly soon after delivery in both groups of women. In type 1 diabetic pregnant women IGF-1 values were significantly lower than the controlled non diabetic patients. IGF-1 in the cord blood was significantly higher in IDDM than in NIDDM 86 +/- 7 ng/ml and 62 +/- 7 ng/ml respectively (p < 0.03). In addition, DPW plasma levels IGF-1 were positively correlated with the weight of the placenta (r = 0.233, p < 0.03) and negatively correlated with the diabetes duration (r = 0.412, p < 0.05). No correlations were found between IGF-1 cord blood concentrations and gestational age, birth weight and length, but there was a significant correlation with weight percentile (r = 0.846, p < 0.001). No correlation was found between maternal IGF-1 plasma levels and other parameters like insulin need, weight gain, metabolic control and time of delivery.
Hipertensao arterial resistente (HAR) e uma condicao clinica que inclui pacientes com HAR controlada (HARC) e HAR nao controlada (HARNC). Pacientes resistentes frequentemente apresentam alteracoes nos niveis de adipocinas e lesoes em orgaos-alvo (LOA) como rigidez arterial, hipertrofia ventricular esquerda (HVE) e microalbuminuria (MA). Resistina, leptina e adiponectina podem ter efeitos no controle da pressao arterial (PA), contudo, nao se sabe se os niveis de adipocinas e marcadores de LOA estao associados nos subgrupos de HAR. Objetivo: Avaliar a relacao entre os niveis de adipocinas e rigidez arterial, HVE e MA em ambos os subgrupos. Metodos: Foram avaliados em HARC (n=38) e HARNC (n=51) o IMC, PA de consultorio e MAPA, niveis plasmaticos de adiponectina, leptina e resistina (ELISA), velocidade de onda de pulso (VOP), MA e ecocardiograma. Resultados: Niveis de leptina e resistina estavam aumentados (30,4±16,8 ng/mL; p = 0,004 e 11,3±4,0 pg/mL; p = 0,007 respectivamente) em HARNC, enquanto os niveis de adiponectina diminuidos (4,7± 2,6 ug/mL; p < 0,001). Rigidez arterial, HVE e MA estavam aumentados (11,3±2,5 m/s; p < 0,001; 153,6±35,1 g/m2; p < 0,001; e 92,4±97,0 mg/g; p < 0,001 respectivamente) no subgrupo com HARNC. Neste subgrupo encontramos correlacao inversa entre adiponectina e VOP (r = -0,42, p < 0,01) bem como com MA (r = -0,48, p < 0,01). Houve correlacao positiva entre leptina e VOP (r = 0,37, p = 0,02) somente no subgrupo HARNC e a resistina nao se correlacionou com marcadores de LOA em ambos os subgrupos. Conclusao: Hipoadiponectinemia esta associada a presenca de maior rigidez arterial e MA somente em pacientes HARNC. Niveis elevados de leptina estao associados somente com rigidez arterial neste mesmo subgrupo. Essas adipocinas podem influenciar a resistencia a terapia anti-hipertensiva, contribuindo para a dificuldade de controle pressorico neste subgrupo
Objective: Currently it has been largely discussed the influence of inflammation in resistant hypertension (RH). The BP variation promotes increased expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukins 1 and 6. It was showed that treatment with TNF- α inhibitor improves BP and endothelial function, and reduces arterial stiffness in patients with rheumatoid arthritis. Recently, it was demonstrated that TNF- α levels are increased in RH subjects compared to normotensives. This project aims to assess whether the acute inhibition of TNF- α reduces BP levels, as well as changes hemodynamic parameters, target organ damage and inflammatory biomarkers in RH. Design and method: This crossover, double-blind study will include 12 resistant hypertensive subjects –regularly followed at the Outpatient Resistant Hypertension Clinic/UNICAMP – which will randomized assigned to (1) serum infusion followed by infliximab infusion (TNF- α inhibitor, 3 mg/kg) and (2) infliximab followed by serum, for two hours and washout of the 40-day period between both infusions. Office, central and ABPM BP, inflammatory biomarkers, cardiac hypertrophy (echocardiography), endothelial function by flow-mediated dilation, arterial stiffness by pulse wave velocity (Sphygmocor CPV system) will be determined before and after 7 days of infusion. Hemodynamic parameters will be simultaneously assessed during infusions. The plasma concentrations of TNF- α, ILs-1, -6 e -10, monocyte chemoattractant protein-1, and adiponectin will be determined by ELISA. Results: Since the inflammatory process is associated in pathophysiology of RH and the lack of BP control, and because the TNF- α is implicated in cardiovascular outcomes, we hypothesized that acute TNF- α inhibition reduces BP levels, as well as modulates hemodynamic parameters, target organ damage and biomarkers in RH subjects. Conclusions: As the effect of TNF- α inhibition has not been explored in RH, this study may offer news perspectives on disease pathogenesis and treatment, which could provide a more rational approach to subjects at high cardiovascular risk
Resistant hypertension (RH) is associated with organ damage and cardiovascular risk. Evidence suggests the involvement of matrix metalloproteinase 2 (MMP‐2) and tissue inhibitor of metalloproteinase 2 (TIMP‐2) in hypertension and in cardiovascular remodeling. The aim of this study was to assess the levels of MMP‐2 and TIMP‐2 in RH and its relation with organ damage, including arterial stiffness and cardiac hypertrophy. MMP‐2 and TIMP‐2 levels were compared among 19 patients with normotension (NT), 116 with nonresistant hypertension (HTN) and 116 patients with resistant HTN (RH). MMP‐2 levels showed no differences among NT, HTN, and RH groups, while TIMP‐2 levels were higher in RH compared with HTN and NT groups (90.0 [76.1–107.3] vs 70.1 [57.7–88.3] vs 54.7 [40.9–58.1] ng/mL, P <.01), respectively. MMP‐2/TIMP‐2 ratio was reduced in the RH group compared with the HTN and NT groups (2.7 [1.9–3.4] vs 3.3 [2.6–4.2] vs 4.9 [4.5–5.3], P <.01), respectively. No associations were found between MMP‐2 levels, TIMP‐2, and MMP‐2/TIMP‐2 ratio with cardiac hypertrophy and arterial stiffness in the RH and HTN groups. Finally, in a regression analysis, reduced MMP‐2/TIMP‐2 ratio and increased TIMP‐2 levels were independently associated with RH. The present findings provide evidence that TIMP‐2 is associated with RH and might be a possible biomarker for screening RH patients.
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