Arterial stiffness is associated with oxidative stress and endothelial activation among persons with treated HIV in Zambia

Background: Cardiovascular disease (CVD) prevalence is rising among persons with HIV (PLWH) in sub-Saharan Africa. Oxidative stress and endothelial activation, resulting in reduced vascular compliance, are contributors to CVD risk. However, there is a paucity of vascular health data in this population.Objectives: To assess the relationships of oxidative stress and endothelial activation with vascular stiffness among PLWH.Method: Fifty-four PLWH on antiretroviral therapy 5 years and 57 HIV-negative controls, all aged 18–45 years, were enrolled from the University Teaching Hospital, Lusaka, Zambia. Oxidative stress was measured by nitrotyrosine, a peroxynitrite biomarker, and endothelial activation by soluble intercellular adhesion molecule-1 (sICAM-1) plasma levels. Vascular compliance was measured using carotid-radial pulse wave velocity (crPWV) and arterial stiffness index (crASI).Results: PLWH had higher sICAM-1 levels (median 345 ng/mL) compared to controls (275 ng/mL, p 0.01), as well as higher nitrotyrosine levels (297 versus 182 nM; p = 0.02). Median crPWV was similar between the groups, but PLWH had higher crASI (2.4 versus 2.2 cm/ms; p 0.05). After adjusting for age, fat mass, and blood pressure, the estimated effect of a one unit increase in nitrotyrosine on crPWV were twofold higher in the PLWH, but neither reached significance. In a model pooling all participants, there were significant differences in the relationship of nitrotyrosine with crPWV and crASI by HIV status.Conclusion: PLWH in sub-Saharan Africa had significantly greater oxidative stress and endothelial activation compared to HIV-negative individuals. These factors may contribute to increased arterial stiffness and higher CVD prevalence in this population.

Ability of dynamic preload indices to predict fluid responsiveness in a high femoral-to-radial arterial pressure gradient: a retrospective study

Background: Dynamic preload indices may predict fluid responsiveness in end-stage liver disease. However, their usefulness in patients with altered vascular compliance is uncertain. This study is the first to evaluate whether dynamic indices can reliably predict fluid responsiveness in patients undergoing liver transplantation with a high femoral-to-radial arterial pressure gradient (PG).Methods: 80 liver transplant recipients were retrospectively categorized as having a normal (n = 56) or high (n = 24, difference in systolic pressure ≥ 10 mmHg and/or mean pressure ≥ 5 mmHg) femoral-to-radial arterial PG, measured immediately after radial and femoral arterial cannulation. The ability of dynamic preload indices (stroke volume variation, pulse pressure variation [PPV], pleth variability index) to predict fluid responsiveness was assessed before the surgery. Fluid replacement of 500 ml of crystalloid solution was performed over 15 min. Fluid responsiveness was defined as ≥ 15% increase in the stroke volume index. The area under the receiver-operating characteristic curve (AUC) indicated the prediction of fluid responsiveness.Results: Fourteen patients in the normal, and eight in the high PG group were fluid responders. The AUCs for PPV in the normal, high PG groups and total patients were 0.702 (95% confidence interval [CI] 0.553–0.851, P = 0.008), 0.633 (95% CI 0.384–0.881, P = 0.295) and 0.667 (95% CI 0.537–0.798, P = 0.012), respectively. No other index predicted fluid responsiveness.Conclusion: PPV can be used as a dynamic index of fluid responsiveness in patients with end-stage liver disease but not in patients with altered vascular compliance.

Total Effective Vascular Compliance of a Global Mathematical Model for the Cardiovascular System

In this work, we determined the total effective vascular compliance of a global closed-loop model for the cardiovascular system by performing an infusion test of 500 mL of blood in four minutes. Our mathematical model includes a network of arteries and veins where blood flow is described by means of a one-dimensional nonlinear hyperbolic PDE system and zero-dimensional models for other cardiovascular compartments. Some mathematical modifications were introduced to better capture the physiology of the infusion test: (1) a physiological distribution of vascular compliance and total blood volume was implemented, (2) a nonlinear representation of venous resistances and compliances was introduced, and (3) main regulatory mechanisms triggered by the infusion test where incorporated into the model. By means of presented in silico experiment, we show that effective total vascular compliance is the result of the interaction between the assigned constant physical vascular compliance and the capacity of the cardiovascular system to adapt to new situations via regulatory mechanisms.

EXPRESS: Inspiratory flow patterns with dry powder inhalers of low and medium flow resistance in patients with pulmonary arterial hypertension

Inhalation profiles to support use of dry powder inhalers (DPIs) for drug delivery in patients with pulmonary arterial hypertension (PAH) have not been reported. We aimed to evaluate the inspiratory flow pattern associated with low and medium flow resistance DPI devices (RS01-L, RS01-M, respectively) in patients with PAH. This single-center study enrolled patients with PAH associated with connective tissue disease (aPAH,n=10) and idiopathic PAH (iPAH,n=10) to measure the following inhalation parameters: inspiratory effort (kPa), peak inspiratory flow rate (L/min), inhaled volume (L), and flow increase rate (L/s2) using the two devices. We identified a trend toward higher mPAP in the iPAH group (50±13mmHg vs. 40±11mmHg in aPAH;p=0.077). On average, peak inspiratory flow rate was higher with RS01-L vs. RS01-M (84±19.7 L/min vs. 70.4±13.2 L/min; p=0.015). In the overall group, no differences between RS01-L and RS01-M were observed for inhaled volume, inspiratory effort, or flow increase rate. Inhaled volume with RS01-L was higher in aPAH vs iPAH patients: 1.6±0.4L vs. 1.3±0.2L;p=0.042. For the RS01-L, inhaled volume correlated with forced expiratory volume in one second (r=0.460, p=0.030) and forced vital capacity (r=0.50,p=0.015). In patients with aPAH using RS01-L, both inspiratory effort and flow increase rate were highly correlated with pulmonary vascular compliance (r=0.903,p=0.0001 and r=0.906,p=0.001; respectively); while with RS01-M, inspiratory effort was highly correlated with pulmonary vascular compliance (r=0.81,p=0.001). Our data suggest that the use of RS01-L and RS01-M DPI devices allowed adequate inspiratory flow in PAH patients. The correlation between flow increase rate and pulmonary vascular compliance in aPAH deserves further investigation.

Immune activation and arterial stiffness in lean adults with HIV on antiretroviral therapy

Background: Greater T-cell activation was associated with reduced vascular compliance amongst persons living with HIV (PLWH) especially among overweight and obese individuals. There is a paucity of data regarding immune activation and arterial stiffness amongst PLWH in sub-Saharan Africa (SSA).Objective: To determine the association between immune activation and arterial stiffness in lean PLWH in SSA.Method: Forty-eight human immunodeficiency virus positive (HIV+) adults on antiretroviral therapy (ART) 5 years and 26 HIV-negative adults, all with BMI 25 kg/m2 and no history of CVD, were enrolled. The relationship of vascular compliance with circulating CD4+ and CD8+ naïve, memory, activated and senescent T cells, and serum 8-isoprostane was assessed by HIV status.Results: Increased immune activation was observed in the CD4+ and CD8+ T cells of PLWH, 16.7% vs. 8.9% and 22.0% vs. 12.4% respectively; p 0.001 (both). Furthermore, a higher proportion of senescent CD4+ T cells were associated with a lower carotid-femoral pulse wave velocity (cfPWV; p = 0.01), whilst a higher proportion of activated CD8+ T cells were associated with a lower carotid-radial pulse wave velocity (crPWV; p = 0.04), after adjustment for BMI and age. However, PLWH also had a higher median carotid-femoral augmentation index (cfAiX) (21.1% vs. 6.0%; p 0.05) in comparison to their HIV controls.Conclusion: Our population of lean PLWH had increased immune activation and higher cfAiX, a marker of arterial stiffness, compared to HIV-negative persons. The negative association between immune activation and arterial stiffness as measured by crPWV in PLHW on long-term treatment needs further elucidation.