Background Hypertension is the most prevalent and leading risk factor for stroke. SPRINT (The Systolic Blood Pressure Intervention Trial) assessed the effects on cardiovascular event risk of intensive compared with standard systolic blood pressure reduction. In this secondary analysis of SPRINT data, we investigated how low on-treatment diastolic blood pressure ( DBP ) influenced risk for stroke events. Methods and Results For this analysis, we used SPRINT _ POP (Primary Outcome Paper) Research Materials from the National Heart, Lung and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center. Data for 8944 SPRINT participants were analyzed from the period after target blood pressure was achieved until the end of the trial. Overall, there were 110 stroke events, including 49 from the intensive-treatment arm and 61 in the standard-treatment group. In participants with DBP <70 mm Hg, stroke risk was higher than with DBP ≥70 mm Hg (hazard ratio, 1.467; 95% CI 1.009-2.133; P=0.0445). Univariable Cox proportional hazard risk analysis showed that in the whole group, age and cardiovascular and chronic renal diseases were stroke risk factors. These risk factors were related to lower DBP and higher pulse pressure, however, not to study arm. Multivariable Cox proportional hazard analysis revealed that only age, history of cardiovascular disease, current smoking status and on-treatment systolic blood pressure were significantly related to stroke risk. Conclusions Low on-treatment DBP is not related to the risk for the first stroke, in contrast to older age, the history of cardiovascular disease, current smoking status, and on-treatment systolic blood pressure. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 01206062.
Kario et al showed that the discrepancies in BP measurements using watch-type blood pressure monitor (WBPM) and ambulatory blood pressure monitor (ABPM) are clinically accepted.1 Their conclusion is based on small differences between the mean values of multiple readings obtained with both devices. However, a comparison of two methods should take into account the variability in differences between measured parameters. In their study, standard deviation (SD) for the difference in SBP was 12.8 mm Hg at the office settings and 17.0 mm Hg for out-of-office readings. Assuming a normal distribution, 31.8% of WBPM readings were higher or lower by 12.8 or 17.0 mm Hg than ABPM, respectively, depending on the setting of BP measurements. Moreover, the authors reported that 41.3% (office settings) and 52.8% (out-of-office) of SBP WBPM values were higher or lower by 10 mm Hg as compared with ABPM values. These findings question the potential clinical applications of WBPM. A Bland-Altman plot is a commonly accepted method used when analyzing two different methods. It visualizes the range that includes 95% of differences between the two methods and enables comparison with an a priori defined range, for example, ±10 mm Hg.2 The potential use of WBPM will be better evaluated using the Bland-Altman plot, which is considered a methodological gold standard.3
Erythrocytosis (i.e., elevation in red cell mass) frequently develops after renal transplantation and is associated with increased risk of thromboembolic incidents and hypertension. Because it has been reported that enalapril may induce anemia in renal allograft recipients, we have undertaken a prospective study to estimate the efficacy and safety of enalapril therapy for erythrocytosis and to establish the mechanism by which enalapril reduces red cell mass. Seventeen (12 male and 5 female) long-term renal allograft recipients with increased hematocrit value (> 55% for male and > 50% for female) and elevated red cell mass as determined with 51Cr-labeled autologous erythrocytes were treated with enalapril. After 3 months of therapy, enalapril was withdrawn and patients were observed in order to differentiate spontaneous remission of erythrocytosis from effects of enalapril therapy. After 3 months of the treatment, mean hematocrit decreased from 51.1% (range 47–56%) to 42.9% (range 37–51%; P<0.01). Red cell mass significantly decreased during this period (from 46.7 ml/kg, range 32.5–60.7 ml/kg, to 32.9 ml/kg, range 20.1–60.1 ml/kg; P<0.01). Serum erythropoietin levels also changed from 12.2 mlU/ml (range 1.0–33.0 mlU/ml) at baseline to 5.4 mlU/ml (range 0.7–24.2 mlU/ml; P<0.05). During the following 3 months without enalapril treatment, an increase in hematocrit was noted, reaching 51.7% (range 46–58%; P<0.05). No serious side effects of enalapril were observed during the study, but there was a need to reduce other hypotensive drugs in some patients. Serum creatinine did not change significantly during enalapril therapy (1.49 mg/dl, range 0.9–2.3 mg/dl, and 1.55 mg/dl, range 1.0–2.3 mg/dl; before and after 3 months of therapy, respectively). Our study proves that enalapril can be safely and effectively used to treat posttransplant erythrocytosis. The effect of enalapril on red cell mass results from reducing erythropoietin production.
PTEN phosphatase acts as a tumor suppressor by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. It is unclear which downstream components of this pathway are necessary for oncogenic transformation. In this report we show that transformed cells of PTEN +/− mice have elevated levels of phosphorylated Akt and activated p70/S6 kinase associated with an increase in proliferation. Pharmacological inactivation of mTOR/RAFT/FRAP reduced neoplastic proliferation, tumor size, and p70/S6 kinase activity, but did not affect the status of Akt. These data suggest that p70/S6K and possibly other targets of mTOR contribute significantly to tumor development and that inhibition of these proteins may be therapeutic for cancer patients with deranged PI3K signaling.
