35489538
Prevalence and risk factors of masked hypertension identified by multiple self-blood pressure measurement.
To the Editor:

With great interest we read the article by O'Brien,1 comprehensively reviewing implementation of out-of-office blood pressure (BP) measurement, ie, ambulatory BP measurement and self-BP measurement (SBPM), for more precise evaluation and management of hypertension. Clearly, ambulatory BP measurement provides a greater amount of BP information and, thus, can be more sensitive than SBPM. However, ambulatory BP measurement is more expensive and may cause discomfort, interfering with subjects’ normal activity, which limit its routine use.2 Here, we introduce our investigation of the diurnal BP pattern and its determining factors by implementing a multiple SBPM strategy.

A total of 5009 hypertension patients in 500 primary care clinics in Korea, whose recent BP during the last 2 visits was stable without change in medication, were enrolled. This study was performed by multicenter, prospective, observational design. To minimize possible confounding factors and to compare the differential effect of various classes of antihypertensive agents, 2 strategies were used. First, enrolled patients were …
4624766
FOXO1 impairs whereas statin protects endothelial function in diabetes through reciprocal regulation of Kruppel-like factor 2.
AIMS
Krüppel-like factor 2 (KLF2) is implicated as a key molecule maintaining endothelial function. This study was designed to evaluate the reciprocal regulation of KLF2 by the forkhead transcription factor FOXO1, and the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin, in hyperglycaemic conditions.


METHODS AND RESULTS
Exposure of human umbilical vein endothelial cells to 30 mM glucose activated FOXO1 and suppressed KLF2. These effects were reversed by FOXO1 small interfering RNA. Adenoviral transfection of constitutively active FOXO1 suppressed KLF2 expression. Interestingly, atorvastatin inhibited FOXO1 by increasing phosphorylation and also by inhibiting nuclear localization and replenished KLF2 in high-glucose conditions. This effect of atorvastatin was attenuated by mevalonate. Chromatin immunoprecipitation analysis demonstrated that glucose increased whereas atorvastatin decreased FOXO1 binding to the promoter region of the KLF2 gene. In the vessels of Otsuka Long-Evans Tokushima Fatty rats, animal models of type 2 diabetes, FOXO1 was activated and KLF2 was suppressed, and this was reversed by atorvastatin treatment. The arteries from Otsuka Long-Evans Tokushima Fatty rats showed impairment of endothelium-dependent vasodilatation, and both atorvastatin and KLF2 gene therapies restored it.


CONCLUSIONS
Suppression of KLF2 by FOXO1 may be a plausible mechanism of diabetic endothelial dysfunction. High-glucose-induced, FOXO1-mediated KLF2 suppression was reversed by atorvastatin, suggesting that intensive statin treatment could be a therapeutic option in diabetic vascular dysfunction.
11700956
Cardio–renal protection with aliskiren, a direct renin inhibitor, in the ASPIRE HIGHER program
Aliskiren is the first in a new class of orally effective direct renin inhibitors. Initial results of clinical efficacy studies have demonstrated at least equivalent or superior blood pressure-lowering efficacy when compared with existing drugs, and a favorable side-effect profile either as monotherapy or as a component of combination therapy. This report aims to introduce and provide a critical appraisal of the initial results of the ASPIRE HIGHER program, evaluating the potential cardio–renal protective effects of aliskiren.
43136894
Acute oliguric renal failure associated with angiotensin II receptor antagonists.
24763110
Clinic blood pressure responses to two amlodipine salt formulations, adipate and besylate, in adult Korean patients with mild to moderate hypertension: a multicenter, randomized, double-blind, parallel-group, 8-week comparison.
BACKGROUND
The commercially available formulation of amlodipine is conjugated with besylate salt to increase water solubility. Recently, a new amlodipine salt formulation has been developed in which the free base of amlodipine is conjugated with a chemically different salt, adipate.


OBJECTIVE
The goal of this study was to compare the antihypertensive effect and tolerability of amlodipine adipate with those of amlodipine besylate in patients with mild to moderate hypertension.


METHODS
This was a multicenter, randomized, doubleblind, parallel-group study in which patients received 8 weeks of treatment with either amlodipine adipate or amlodipine besylate. The primary efficacy variable was noninferiority of the difference in mean changes from baseline in trough diastolic blood pressure (DBP) after 8 weeks of treatment. Secondary efficacy variables included mean changes in DBP, systolic blood pressure (SBP), and response rate (defined as the proportion of patients whose DBP was <90 mm Hg or whose DBP had decreased from baseline by > or =10 mm Hg). The incidence of adverse events (AEs) was also assessed.


RESULTS
Two hundred eleven patients were randomly assigned to receive amlodipine adipate (n = 106) or amlodipine besylate (n = 105). Study patients were primarily female (54.5%), with a mean (SD) age of 52.2 (9.6) years and a mean body weight of 67.1 (10.2) kg; there were no between-group differences in demographic profiles. After 4 weeks of randomized treatment, 58 (27.5%) patients (29 [27.4%] amlodipine adipate, 29 [27.6%] amlodipine besylate) had not achieved a mean DBP <90 mm Hg, and their dose was doubled. Mean DBP changes at 8 weeks were -15.2 (7.3) mm Hg in the amlodipine adipate group and -14.2 (7.4) mm Hg in the amlodipine besylate group (P = NS). Because the 95% CI for the difference in mean DBP changes between groups (-0.53 to 2.55) was within the prespecified lower limit (-4 mm Hg), amlodipine adipate was considered noninferior to amlodipine besylate. Mean SBP changes were -24.9 (12.1) mm Hg in the amlodipine adipate group and -22.0 (14.7) mm Hg in the amlodipine besylate group (P = NS). The response rates were 92.0% for amlodipine adipate and 95.4% for amlodipine besylate (P = NS). The overall incidence of clinical AEs was 20.8% in the amlodipine adipate group and 25.7% in the amlodipine besylate group (P = NS). Drug-related clinical AEs occurred in 5.7% and 12.4% of patients in the respective treatment groups (P = NS). Serum uric acid levels decreased significantly from base-line in both groups (P < 0.001).


CONCLUSIONS
Eight weeks of treatment with amlodipine adipate produced significant reductions from baseline in blood pressure in these patients with mild to moderate hypertension. The efficacy of amlodipine adipate was not inferior to that of amlodipine besylate. Tolerability was comparable between the 2 treatment groups.
25406915
Forkhead factor, FOXO3a, induces apoptosis of endothelial cells through activation of matrix metalloproteinases.
BACKGROUND
The forkhead factor, FOXO3a, is known to induce apoptosis in endothelial cells (ECs). However, its effects on extracellular matrices (ECM), which are important in EC survival, remained unknown. Here, we evaluated the role of FOXO3a on EC-ECM interaction.


METHODS AND RESULTS
Constitutively active FOXO3a was transduced to human umbilical vein endothelial cells by adenoviral vector (Ad-TM-FOXO3a). Ad-TM-FOXO3a transfection led to dehiscence of ECs from fibronectin-coated plates, resulting in anoikis, which was significantly reversed by matrix metalloproteinase (MMP) inhibitor, GM6001. FOXO3a increased the expression of MMP-3 (stromelysin-1) but decreased the expression of tissue inhibitors of metalloproteinases-1 (TIMP-1), which was associated with increased MMP enzymatic activity in zymography. Pathophysiologic conditions such as serum starvation or heat shock also induced activation of endogenous FOXO3a, leading to activation of MMP-3 and apoptosis, which was reversed by GM6001. Delivery of Ad-TM-FOXO3a to the intraluminal surface in vivo led to EC denudation, disrupted vascular integrity, and impaired endothelium-dependent vasorelaxation.


CONCLUSIONS
Activation of MMPs and possible ECM disruption represent novel mechanisms of FOXO3a-mediated apoptosis in ECs.
22916251
Wide spread of Tn2006 in an AbaR4-type resistance island among carbapenem-resistant Acinetobacter baumannii clinical isolates in Taiwan.
Carbapenem resistance in Acinetobacter baumannii is a global problem. The purpose of this study was to elucidate current resistance mechanisms of imipenem-resistant A. baumannii (IRAB) in Taiwan and their correlation with patient outcomes. Acinetobacter baumannii clinical isolates from two teaching hospitals in Taiwan were collected in 2009 and were examined by Etest for determination of the minimum inhibitory concentrations (MICs) of imipenem, ceftazidime and ceftriaxone. Primers specific for carbapenemase genes and upstream regions were designed for PCR amplification. Bacterial isolates were genotyped by pulsed-field gel electrophoresis (PFGE). Clinical presentations of patients were analysed retrospectively. Upstream insertion sequence ISAba1 was found in 34 isolates that carried bla(OXA-23), including 28 with transposon Tn2006 (ISAba1-bla(OXA-23)-ISAba1) in an AbaR4-type resistance island and 6 with Tn2008 (ISAba1-bla(OXA-23)), as well as in 8 isolates carrying ISAba1-bla(OXA-51-like). All of these isolates expressed full resistance to imipenem (MIC>32 mg/L). Forty-one different PFGE genotypes were found among 62 isolates. Tn2006 was found in 19 genotypes (46.3%), which is more common than ISAba1-bla(OXA-51-like) (12.2%) (P=0.001). Prior use of carbapenems or extended-spectrum cephalosporins for ≥5 days was the only independent risk factor significantly associated with IRAB infection (odds ratio=361.175). Higher mortality was significantly associated with infection caused by IRAB and ISAba1-bla(OXA-23)-carrying strains compared with infection caused by imipenem-susceptible A. baumannii and ISAba1-bla(OXA-51-like)-carrying strains (P=0.009 and 0.027, respectively). Tn2006 is currently the most common imipenem resistance determinant, which showed a higher ability to spread among A. baumannii and was associated with a higher mortality in IRAB-infected patients.
5720770
Surgical anatomy of the middle turbinate.
Clinicians have encountered many variations of the middle turbinate. Previous descriptions of the middle turbinate were only focused on its size and shape and lacked surgical implications associated with endoscopic sinus surgery. Therefore, the aim of this study was to examine the surgical anatomy of the middle turbinate in hemisected cadaveric heads. The middle turbinates from 101 hemisections of adult Korean cadaveric heads were measured using digital calipers and a protractor. The middle turbinates were then classified according to their shape. The mean distance between the anterior attachment of the middle turbinate and the anterior attachment of the superior turbinate was 18.5 mm. The posterior end of the middle turbinate extended more posteriorly than that of the inferior turbinate in 40% of the cases, while in 26.3% of the cases, the posterior end of the inferior turbinate extended more posteriorly than that of the middle turbinate. The middle turbinate was classified into three types according to the shape of its anterior border. In type 1, the anterior border of the middle turbinate ran directly posteroinferiorly from its attachment to the conchal plate, and was observed in 45.3% of the cases. In type 2, the anterior border of the middle turbinate initially coursed inferiorly from the conchal plate and then turned in a posteroinferior direction. This type was observed in 44.2% of the cases. Type 3 involved 10.5% of the cases where the anterior border bulged anteriorly before it coursed posteroinferiorly. The information provided in this report should assist surgeons when performing partial middle turbinectomies.
20475080
Differential association of socio-economic status with gender- and age-defined suicidal ideation among adult and elderly individuals in South Korea
South Korea has the highest suicide rate among countries in the Organisation for Economic Co-operation and Development (OECD), with a rising trend that contrasts with the trend in most other OECD countries. This study assessed differential associations of socio-demographic factors with suicidal ideation in South Korea. We used five waves of data from the 2010 Korea National Health and Nutrition Examination Survey. Study subjects included 5803 men and women aged >25 years. We analysed weighted percentages with consideration of the complex survey sample design and unequal weights. Surveylogistic regressions were applied. Protective effects against suicidal ideation were found for higher household income, higher educational attainment, and being married. Functional limitations and depressive symptoms were risk factors for suicidal ideation. However, these significant factors may exert different effects on vulnerability for suicidal ideation among different genders and age groups. Thus, household income was mainly protective for women and subjects aged 25-44 years, and educational attainment was protective for individuals aged >65 years. Our findings suggest the need for extended social protection policies for the less privileged population and special strategies for different groups.
25288603
Lung adenocarcinoma as a solitary pulmonary nodule: prognostic determinants of CT, PET, and histopathologic findings.
We aimed to retrospectively compare CT, PET, and histopathologic (the extent of bronchioloalveolar carcinoma [BAC] components) findings of solitary pulmonary nodular (SPN) adenocarcinomas of the lung to determine their value as prognostic determinants. We reviewed CT and PET characteristics of tumors and pathologic specimens from 65 consecutive patients who underwent surgical resection for SPN adenocarcinomas. Nodule size and TDR (tumor shadow disappearance rate) were assessed from CT scans, and maximum standardized uptake value (SUVmax) of tumors was measured at PET. On pathologic examination, BAC, non-BAC, and central fibrous scar ratios were quantified. Prognosis was evaluated by noting disease recurrence during a minimum 12-month follow-up period after curative resection. The interrelationships between TDR, SUVmax, BAC, and non-BAC ratio were studied, and relationships between recurrence and various variables were analyzed. The median follow-up time was 33 months, and seven patients (11%) developed disease recurrence after surgical resection. TDR at CT and SUVmax at PET correlated well with pathologic BAC and non-BAC ratios. Between subgroups with and without recurrence, there were significant differences in SUVmax and BAC and non-BAC ratios. Based on univariate survival analyses, pathologic BAC and non-BAC ratios were risk factors significantly related to recurrence, but only high non-BAC ratio remained as an independent factor associated with recurrence in the multivariate analysis (hazard ratio [HR]=0.956, P=0.013). Among the factors examined, pathologic non-BAC ratio is the only independent risk factor for poor prognosis in patients with SPN adenocarcinomas.
5927667
Risk of suicidal ideation in diabetes varies by diabetes regimen, diabetes duration, and HbA1c level.
OBJECTIVE
To investigate patient subgroups based on the clinical characteristics of diabetes to evaluate risk factors for suicidal ideation using a large population-based sample in South Korea.


METHODS
Data from the Fifth Korea National Health and Nutrition Examination Survey, a cross-sectional, nationally representative survey, were analyzed. The participants were 9159 subjects aged ≥40years. We defined patients with diabetes based on self-reported physician-diagnosed diabetes. We evaluated clinical risk factors for suicidal ideation according to diabetes regimen, diabetes duration, and glycated hemoglobin (HbA1c) level compared with no diabetes. Given the complex sample design and unequal weights, we analyzed weighted percentages and used survey logistic regression.


RESULTS
Diabetes per se was not associated with suicidal ideation. However, suicidal ideation was significantly more prevalent among patients who had injected insulin, had a duration of diabetes ≥5years and had HbA1c levels ≥6.5 compared with those without diabetes. Depressive symptoms were the most prominent predictor of suicidal ideation.


CONCLUSIONS
Insulin therapy, diabetes of long duration, and unsatisfactory glycemic control were identified as risk factors for suicidal ideation; thus, patients with these characteristics warrant special attention. Our findings suggest the need to integrate efforts to manage emotional distress into diabetes care.