Ten-year changes in ambulatory blood pressure: The prognostic value of ambulatory pulse pressure.

Blood pressure (BP) changes and risk factors associated with pulse pressure (PP) increase in elderly people have rarely been studied using ambulatory blood pressure monitoring (ABPM). The aim is to evaluate 10-year ambulatory blood pressure (ABP) changes in older hypertensives, focusing on PP and its associations with mortality. An observational study was conducted on 119 consecutive older treated hypertensives evaluated at baseline (T0) and after 10 years (T1). Treatment adherence was carefully assessed. The authors considered clinical parameters at T1 only in survivors (n = 87). Patients with controlled ABP both at T0 and T1 were considered as having sustained BP control. Change in 24-hour PP between T0 and T1 (Δ24-hour PP) was considered for the analyses. Mean age at T0: 69.4 ± 3.7 years. Females: 57.5%. Significant decrease in 24-hour, daytime, and nighttime diastolic BP (all P < .05) coupled with an increase in 24-hour, daytime, and nighttime PP (all P < .05) were observed at T1. Sustained daytime BP control was associated with lower 24-hour PP increase than nonsustained daytime BP control (+2.23 ± 9.36 vs +7.79 ± 8.64 mm Hg; P = .037). The association between sustained daytime BP control and Δ24-hour PP remained significant even after adjusting for age, sex, and 24-hour PP at T0 (ß=0.39; P = .035). Both 24-hour systolic BP and 24-hour PP at T0 predicted mortality (adjusted HR 1.07, P = .001; adjusted HR 1.25, P < .001, respectively). After ROC comparison (P = .001), 24-hour PP better predicted mortality than 24-hour systolic BP. The data confirm how ABP control affects vascular aging leading to PP increase. Both ambulatory PP and systolic BP rather than diastolic BP predict mortality in older treated hypertensives.

Oscillating glucose induces microRNA-185 and impairs an efficient antioxidant response in human endothelial cells.

BACKGROUND: Intracellular antioxidant response to high glucose is mediated by Cu/Mn-superoxide dismutases (SOD-1/SOD-2), catalase (CAT) and glutathione peroxidases (GPx), particularly glutathione peroxidase-1 (GPx-1). Although oscillating glucose can induce a more deleterious effect than high glucose on endothelial cells, the mechanism by which oscillating glucose exerts its dangerous effects is incompletely understood; however, the involvement of oxidative damage has been generally accepted. In this study we sought to determine whether oscillating glucose differentially modulates antioxidant response, and to elucidate the potential regulatory mechanisms exerted by the microRNA-185 (miR-185). METHODS: Human endothelial cells were exposed for 1 week to constant and oscillating high glucose. SOD-1, SOD-2, CAT and GPx-1, as well as two markers of oxidative stress [8-hydroxy-2'-deoxyguanosine (8-OHdG) and the phosphorylated form of H2AX (γ-H2AX)] were measured at the end of the experiment. Intracellular miR-185 was measured and loss-of function assays were performed in HUVEC. Bioinformatic tool was used to predict the link between miR-185 on 3'UTR of GPx-1 gene. Luciferase assay was performed to confirm the binding on HUVEC. RESULTS: After exposure to constant high glucose SOD-1 and GPx-1 increased, while in oscillating glucose SOD-1 increased and GPx-1 did not. SOD-2 and CAT remained unchanged under both conditions. A critical involvement of oscillating glucose-induced miR-185 in the dysregulation of endogenous GPx-1 was found. Computational analyses predict GPx-1 as miR-185's target. HUVEC cultures were used to confirm glucose's causal role on the expression of miR-185, its target mRNA and protein and finally the activation of antioxidant response. In vitro luciferase assays confirmed computational predictions targeting of miR-185 on 3'-UTR of GPx-1 mRNA. Knockdown of miR-185, using anti-miR-185 inhibitor, was accompanied by a significant upregulation of GPx-1 in oscillating glucose. 8-OHdG and γ-H2AX increased more in oscillating glucose than in constant high glucose. CONCLUSIONS: Glucose oscillations may exert more deleterious effects on the endothelium than high glucose, likely due to an impaired response of GPx-1, coupled by the upregulation of miR-185.