sRAGE and early signs of cardiac target organ damage in mild hypertensives.

BACKGROUND: Soluble Receptor for Advanced Glycation End Products (sRAGE) may be considered a marker inversely related to inflammation and its participation has been established in patients with advanced atherosclerotic vascular diseases. However, it is still unknown whether sRAGE reduction could be early metabolic change in the first stage of hypertension and initial hypertension-associated cardiac damage. We sought to determine the sRAGE values in otherwise healthy, untreated and recently diagnosed mild hypertensives and evaluate their association with blood pressure (BP) values, metabolic parameters, and with subclinical initial signs of cardiac target organ damage (TOD). METHODS: sRAGE were measured in 100 hypertensive and 100 normotensive subjects matched for age, gender and body mass index (BMI), submitted to a clinic visit and both ambulatory BP monitoring and echocardiography to determine the presence of initial cardiac TOD (presence of signs of left ventricular hypertrophy: left ventricular mass indexed for height2.7 (LVMi) > 48 g/m2.7 for men and > 44 g/m2.7 for women and/or increased left atrial volume 4-chamber indexed for body surface area (LAVi) > 34 ml/m2). RESULTS: sRAGE levels were similar between hypertensive and normotensive subjects and were not significantly correlated with office and 24-h BPs values. However, when subgrouping the hypertensive patients in Hyp-TOD and Hyp-withoutTOD, sRAGE was found to be different among the three groups (p = 0.030), being lower in the Hyp-TOD group than the values of both Hyp-withoutTOD (p = 0.038) and normotensives (p = 0.038). In hypertensive patients sRAGE was negatively related with both LVMi (r = - 0.239, p = 0.034) and LAVi (r = - 0.315, p = 0.005) and was independently related to cardiac TOD also in multivariable analysis. CONCLUSIONS: In this population of mild hypertensives, low circulating sRAGE may be a very early marker of initial TOD, suggesting the possible participation of oxidative stress in initial cardiac changes in human hypertension.

Inflammation in acute heart failure.

Acute heart failure (AHF) represents a common clinical scenario that requires prompt evaluation and therapy and that is characterized by a high risk of mortality or subsequent rehospitalizations. The pathophysiology leading to AHF decompensation is still not fully understood. Significant activation of inflammatory pathways has been identified in patients with AHF, particularly in its most severe forms, and it has been hypothesized that systemic inflammation has a role in AHF pathogenesis. Several inflammatory mediators and cytokines, such as high sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-6, interleukin-1, soluble suppression of tumorigenicity 2 and galectin-3, have been shown to play a role in the pathogenesis, development and worsening of this condition with an independent prediction of adverse outcomes. This manuscript reviews the prevalence and prognostic value of systemic inflammation in AHF, as well as the potential role of anti-inflammatory therapies, focusing on available evidence from clinical trials and ongoing studies.

High-dose dexamethasone treatment for COVID-19 severe acute respiratory distress syndrome: a retrospective study.

Low-dose dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). We retrospectively analyzed the efficacy of high-dose dexamethasone in patients with COVID-19-related ARDS and evaluated factors affecting the composite outcome (death or invasive mechanical ventilation). From March 4th to April 1st 2020, 98 patients with COVID-19 pneumonia were included. Those who after at least 7 days from symptom onset presented a worsening of the respiratory function or of inflammatory biomarkers were started on intravenous high-dose dexamethasone (20 mg daily for 5 days, followed by 10 mg daily for 5 days). Most patients were males (62%) with a mean age of 69 years. Hypertension and cardiovascular disease (CVD) were prevalent. Following dexamethasone treatment, a significant improvement in PaO2/FiO2 (277.41 [178.5-374.8] mmHg vs. 146.75 [93.62-231.16] mmHg, p < 0.001), PaO2 (88.15 [76.62-112.0] mmHg vs. 65.65 [57.07-81.22] mmHg, p < 0.001), and SpO2 (96 [95-98]% vs. 94 [90-96]%, p < 0.001) was observed. A concomitant decrease in C-reactive protein and ferritin levels was found (132.25 [82.27-186.5] mg/L vs. 7.3 [3.3-24.2] mg/L and 1169 [665-2056] ng/mL vs. 874.0 [569.5-1434] ng/mL, respectively; p < 0.001 for both vs. baseline). CVD was found to increase the risk of the composite outcome (RR 7.64, 95% CI 1.24-47.06, p = 0.028). In hospitalized patients with COVID-19-related ARDS, high-dose dexamethasone rapidly improves the clinical status and decreases inflammatory biomarkers. CVD was found to increase the risk of the composite outcome. These data support the importance of randomized clinical trials with high-dose dexamethasone in COVID-19 patients.

Right ventricular remodelling in mild hypertensive patients: role of left ventricular morpho-functional parameters.

Previous studies suggested that hypertensive patients with left ventricular (LV) hypertrophy display right ventricular (RV) remodelling. Few data are available about RV remodelling in naive hypertensives without severe cardiac organ damage. Our aim was to evaluate the relationship between RV and LV morpho-functional parameters in never-treated patients with grade 1 hypertension and whether central blood pressure (CBP), inflammatory and metabolic parameters are potentially associated with RV remodelling. 150 never-treated subjects without evidence of diabetes or other cardiovascular diseases were enrolled in our study. We recruited 100 patients with mild hypertension (twenty-four hours blood pressure (24 h BP) ≥ 130/80 mmHg) and 50 normotensive subjects matched for gender, age and body mass index. To estimate the LV/RV parameters, we performed echography as well as arterial tonometry to assess pulse wave analysis/velocity (PWA/PWV). We found 24 h BP, CBP and PWV were higher in hypertensive patients than in normotensives. In addition, LV mass index was higher in hypertensives, and greater RV free wall thickness was observed (5.3 ± 1.4 vs 4.6 ± 1.2 mm, P = 0.02). RV thickness correlated with interventricular septum (IVS), systolic CBP and RV E' (r = 0.50, P = 0.0001, r = 0.30, P = 0.003, r = -0.24, P = 0.015); linear regression analysis showed a correlation with only IVS (ß = 0.39, P = 0.001). RV E' was correlated with IVS, LV E' and systolic CBP (r = -0.35, P = 0.0001, r = 0.25, P = 0.012, r = -0.24, P = 0.019); the correlation with IVS and LV E' (ß = -0.310, P = 0.001; ß = 0.27, P = 0.004) was confirmed by linear regression analysis. Our study shows RV remodelling is mostly correlated with IVS thickness, supporting the ventricular interdependence hypothesis.