International Journal of Hypertension The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats with L-Arginine Tue, 30 Sep 2014 11:24:35 +0000 The purpose was to determine the role of renal nerves in mediating the effects of antihypertensive treatment with L-arginine in a renovascular hypertension model. The 2K1C (two-kidney one-clip model) hypertensive rats were submitted to bilateral surgical-pharmacological renal denervation. The animals were subdivided into six experimental groups: normotensive control rats (SHAM), 2K1C rats, 2K1C rats treated with L-arginine (2K1C + L-arg), denervated normotensive (DN) rats, denervated 2K1C (2K1C + DN) rats, and denervated 2K1C + L-arg (2K1C + DN + L-arg) rats. Arterial blood pressure, water intake, urine volume, and sodium excretion were measured. The 2K1C rats exhibited an increase in the mean arterial pressure (MAP) (from 106 ± 3 to 183 ± 5.8 mmHg, ), whereas L-arg treatment induced a reduction in the MAP (143 ± 3.4 mmHg) without lowering it to the control level. Renal nerve denervation reduced the MAP to normotensive levels in 2K1C rats with or without chronic L-arg treatment. L-arg and denervation induced increases in water intake and urine volume, and L-arg caused a significant natriuretic effect. Our results suggest that renal sympathetic activity participates in the genesis and the maintenance of the hypertension and also demonstrate that treatment with L-arg alone is incapable of normalizing the MAP and that the effect of such treatment is not additive with the effect of kidney denervation. Sonia Alves Gouvea, Renata V. Tiradentes, Cintia H. Santuzzi, Vinícius Mengal, Henrique de A. Futuro Neto, Nyam F. Silva, and Gláucia R. Abreu Copyright © 2014 Sonia Alves Gouvea et al. All rights reserved. Duration of Electrically Induced Atrial Fibrillation Is Augmented by High Voltage of Stimulus with Higher Blood Pressure in Hypertensive Rats Thu, 25 Sep 2014 11:37:18 +0000 Objective. Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats. Methods. AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20 V) or low (5 V) voltage. Results. Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus. Discussion and Conclusion. Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR. Tomomi Nagayama, Yoshitaka Hirooka, Akiko Chishaki, Masao Takemoto, Yasushi Mukai, Shujiro Inoue, Takuya Kishi, and Kenji Sunagawa Copyright © 2014 Tomomi Nagayama et al. All rights reserved. Quantifying Proteinuria in Hypertensive Disorders of Pregnancy Tue, 16 Sep 2014 00:00:00 +0000 Background. Progressive proteinuria indicates worsening of the condition in hypertensive disorders of pregnancy and hence its quantification guides clinician in decision making and treatment planning. Objective. To evaluate the efficacy of spot dipstick analysis and urinary protein-creatinine ratio (UPCR) in hypertensive disease of pregnancy for predicting 24-hour proteinuria. Subjects and Methods. A total of 102 patients qualifying inclusion criteria were evaluated with preadmission urine dipstick test and UPCR performed on spot voided sample. After admission, the entire 24-hour urine sample was collected and analysed for daily protein excretion. Dipstick estimation and UPCR were compared to the 24-hour results. Results. Seventy-eight patients (76.5%) had significant proteinuria of more than 300 mg/24 h. Dipstick method showed 59% sensitivity and 67% specificity for prediction of significant proteinuria. Area under curve for UPCR was 0.89 (95% CI: 0.83 to 0.95, ) showing 82% sensitivity and 12.5% false positive rate for cutoff value of 0.45. Higher cutoff values (1.46 and 1.83) predicted heavy proteinuria (2 g and 3 g/24 h, resp.). Conclusion. This study suggests that random urinary protein : creatine ratio is a reliable investigation compared to dipstick method to assess proteinuria in hypertensive pregnant women. However, clinical laboratories should standardize the reference values for their setup. Sapna V. Amin, Sireesha Illipilla, Shripad Hebbar, Lavanya Rai, Pratap Kumar, and Muralidhar V. Pai Copyright © 2014 Sapna V. Amin et al. All rights reserved. Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening Tue, 02 Sep 2014 10:34:24 +0000 Adaptive immune function is implicated in the pathogenesis of vascular disease. Inhibition of T-lymphocyte function has been shown to reduce hypertension, target-organ damage, and vascular stiffness. To study the role of immune inhibitory cells, CD4+CD25+Foxp3+ regulatory T cells (Tregs), on vascular stiffness, we stimulated the proliferation of Treg lymphocytes in vivo using a novel cytokine immune complex of Interleukin-2 (IL-2) and anti-IL-2 monoclonal antibody clone JES6-1 (). Three-month-old male C57BL/6J mice were treated with IL-2/ concomitantly with continuous infusion of angiotensin type 1 receptor agonist, [Val5]angiotensin II. Our results indicate that the IL-2/ complex effectively induced Treg phenotype expansion by 5-fold in the spleens with minimal effects on total CD4+ and CD8+ T-lymphocyte numbers. The IL-2/ complex inhibited angiotensin II-mediated aortic collagen remodeling and the resulting stiffening, analyzed with in vivo pulse wave velocity and effective Young’s modulus. Furthermore, the IL-2/ complex suppressed angiotensin II-mediated Th17 responses in the lymphoid organs and reduced gene expression of IL-17 as well as T cell and macrophage infiltrates in the aortic tissue. This study provides data that support the protective roles of Tregs in vascular stiffening and highlights the use of the IL-2/ complex as a new potential therapy in angiotensin II-related vascular diseases. Beenish Majeed, Supannikar Tawinwung, Lance S. Eberson, Timothy W. Secomb, Nicolas Larmonier, and Douglas F. Larson Copyright © 2014 Beenish Majeed et al. All rights reserved. The Flavin-Containing Monooxygenase 3 Gene and Essential Hypertension: The Joint Effect of Polymorphism E158K and Cigarette Smoking on Disease Susceptibility Wed, 27 Aug 2014 08:17:59 +0000 Gene encoding flavin-containing monooxygenase 3 (FMO3), a microsomal antioxidant defense enzyme, has been suggested to contribute to essential hypertension (EH). The present study was designed to investigate whether common functional polymorphism E158K (rs2266782) of the FMO3 gene is associated with EH susceptibility in a Russian population. A total of 2 995 unrelated subjects from Kursk (1 362 EH patients and 843 healthy controls) and Belgorod (357 EH patients and 422 population controls) regions of Central Russia were recruited for this study. DNA samples from all study participants were genotyped for the FMO3 gene polymorphism through PCR followed by RFLP analysis. We found that the polymorphism E158K is associated with increased risk of essential hypertension in both discovery population from Kursk region (OR 1.36 95% CI 1.09–1.69, ) and replication population from Belgorod region (OR 1.54 95% CI 1.07–1.89, ) after adjustment for gender and age using logistic regression analysis. Further analysis showed that the increased hypertension risk in carriers of genotype 158KK gene occurred in cigarette smokers, whereas nonsmoker carriers of this genotype did not show the disease risk. This is the first study reporting the association of the FMO3 gene polymorphism and the risk of essential hypertension. Olga Bushueva, Maria Solodilova, Mikhail Churnosov, Vladimir Ivanov, and Alexey Polonikov Copyright © 2014 Olga Bushueva et al. All rights reserved. Reference Values of Pulse Wave Velocity in Healthy People from an Urban and Rural Argentinean Population Sun, 24 Aug 2014 05:45:31 +0000 In medical practice the reference values of arterial stiffness came from multicenter registries obtained in Asia, USA, Australia and Europe. Pulse wave velocity (PWV) is the gold standard method for arterial stiffness quantification; however, in South America, there are few population-based studies. In this research PWV was measured in healthy asymptomatic and normotensive subjects without history of hypertension in first-degree relatives. Normal PWV and the 95% confidence intervals values were obtained in 780 subjects (39.8 ± 18.5 years) divided into 7 age groups (10–98 years). The mean PWV found was 6.84 m/s ± 1.65. PWV increases linearly with aging with a high degree of correlation (; ) with low dispersion in younger subjects. PWV progressively increases 6–8% with each decade of life; this tendency is more pronounced after 50 years. A significant increase of PWV over 50 years was demonstrated. This is the first population-based study from urban and rural people of Argentina that provides normal values of the PWV in healthy, normotensive subjects without family history of hypertension. Moreover, the age dependence of PWV values was confirmed. Alejandro Díaz, Cintia Galli, Matías Tringler, Agustín Ramírez, and Edmundo Ignacio Cabrera Fischer Copyright © 2014 Alejandro Díaz et al. All rights reserved. Hypertension and Its Associated Risk Factors in the Kingdom of Saudi Arabia, 2013: A National Survey Wed, 06 Aug 2014 09:25:57 +0000 Current data on hypertension in the Kingdom of Saudi Arabia are lacking. We conducted a national survey to inform decision-makers on the current magnitude of the epidemic. We measured systolic and diastolic blood pressure of 10,735 Saudis aged 15 years or older and interviewed them through a national multistage survey. We used multivariate logistic regressions to describe sociodemographic characteristics and risk factors of hypertensive, borderline hypertensive, and undiagnosed hypertensive Saudis. We found that 15.2% and 40.6% of Saudis were hypertensive or borderline hypertensive, respectively. Risk of hypertension increased among men, with age, obesity, diabetes, and hypercholesterolemia. 57.8% of hypertensive Saudis were undiagnosed. These were more likely to be male, older, and diagnosed with diabetes. Among participants diagnosed with hypertension, 78.9% reported taking medication for their condition. About 45% of participants on medication for hypertension had their blood pressure controlled. The prevalence of hypertension and borderline hypertension is very high in Saudi Arabia. Moreover, control of hypertension is poor. With the majority of hypertensive Saudis being unaware of their condition, a national plan is needed to increase utilization of freely available screening, preventive, and medical services. Charbel El Bcheraoui, Ziad A. Memish, Marwa Tuffaha, Farah Daoud, Margaret Robinson, Sara Jaber, Sarah Mikhitarian, Mohammad Al Saeedi, Mohammad A. AlMazroa, Ali H. Mokdad, and Abdullah A. Al Rabeeah Copyright © 2014 Charbel El Bcheraoui et al. All rights reserved. Prehypertension and Hypertension among Schoolchildren in Brazzaville, Congo Tue, 20 May 2014 12:05:52 +0000 Background. To determine the prevalence and associated factors of prehypertension (pre-HT) and hypertension (HT) in schoolchildren at Brazzaville (Congo). Methods. This cross-sectional study was conducted from March to May 2011 in five representative urban schools in Brazzaville. American Pediatric Society’s definition of pre-HT and HT was used. The measurement of blood pressure was obtained using auscultator method. Univariable and multivariable analyses were performed to establish associations between blood pressure levels and sociobiographical factors. Results. 603 children were included. The mean age was years (range 5–18 years). The prevalence of pre-HT was 20.7% (). Factors associated with pre-HT were secondary school (), private schools (), migrants (), the obese (), high socioeconomic level (), and overweight (). In logistic regression, the independent determinants of pre-HT were secondary school (), migration (), obesity (), and overweight (). The prevalence of HT was 10.1% () during the first screening and 3.3% () in second screening. The independent determinants of HT were obesity () and overweight (). Conclusion. Pre-HT and HT are emerging as a mass problem in Congolese schoolchildren with urban migration and overweight/obesity to be controlled and prevented. Bertrand Fikahem Ellenga Mbolla, Annie Rachel Okoko, Jean Robert Mabiala Babela, Gaston Ekouya Bowassa, Thierry Raoul Gombet, Suzy-Gisèle Kimbally-Kaky, and Benjamin Longo-Mbenza Copyright © 2014 Bertrand Fikahem Ellenga Mbolla et al. All rights reserved. Time-Related Alteration in Flow- (Shear Stress-) Mediated Remodeling in Resistance Arteries from Spontaneously Hypertensive Rats Thu, 08 May 2014 14:28:04 +0000 Hypertension is a major risk factor for cardiovascular disorders. As flow-mediated outward remodeling has a key role in postischemic revascularization, we investigated this remodeling in mesenteric resistance arteries of normotensive (WKY) and spontaneously hypertensive rats (SHRs) aged 3 to 9 months. Sequential ligation of mesenteric resistance arteries allowed modifying blood flow in vivo, thus exposing arteries to low, normal, or high flow. After 1, 3, 8, or 24 weeks, arteries were isolated for in vitro study. High flow (HF) induced outward hypertrophic remodeling in WKY rats after 1 week and persisted until 24 weeks without change in wall to lumen ratio. In SHRs, diameter increase was delayed, occurring only after 3 weeks. Nevertheless, it was reduced at 8 weeks and no longer significant after 24 weeks. In parallel, media cross-section area increased more with time in SHRs than in WKY rats and this was associated with increased contractility and oxidative stress with decreased NO-dependent relaxation. Low flow induced progressive inward remodeling until 24 weeks in both strains with excessive hypertrophy in SHRs. Thus, a chronic increase in flow induced transitory diameter expansion and long-lasting hypertrophy in SHRs. This could contribute to the higher susceptibility of hypertensive subjects to ischemic diseases. Odile Dumont, Gilles Kauffenstein, Anne-Laure Guihot, Nathalie C. Guérineau, Pierre Abraham, Laurent Loufrani, and Daniel Henrion Copyright © 2014 Odile Dumont et al. All rights reserved. Angiotensinogen Variants among Resistant Hypertensive Patients Mon, 24 Mar 2014 07:47:38 +0000 Natalia Ruggeri Barbaro, Vanessa Fontana, and Heitor Moreno Copyright © 2014 Natalia Ruggeri Barbaro et al. All rights reserved. Efficacy and Tolerability of Telmisartan Plus Amlodipine in Asian Patients Not Adequately Controlled on Either Monotherapy or on Low-Dose Combination Therapy Thu, 27 Feb 2014 07:55:03 +0000 Objective. To evaluate the efficacy and safety of the telmisartan plus amlodipine (T/A) single-pill combination (SPC) in Asian patients with hypertension whose blood pressure (BP) was not adequately controlled on either monotherapy or on low-dose combination therapy. Patients and Methods. Data are presented from five Boehringer Ingelheim-sponsored phase 3, double-blind, 8-week, studies: two studies in nonresponders to amlodipine (data pooled for amlodipine), two studies on nonresponders to telmisartan (pooled data), and one on nonresponders to low-dose T/A SPC. Results. After 8 weeks’ treatment, mean reductions from the reference baseline in diastolic BP (DBP; primary endpoint), systolic BP (SBP), and SBP, DBP goal, and response rates were higher with the T/A SPC than respective monotherapies. The T80/A5 SPC resulted in greater reductions in DBP and SBP, and higher DBP goal and response rate than the low-dose T40/A5 SPC. Peripheral edema incidence was low (amlodipine 0.5%, telmisartan 0.0%, and T/A SPC 0.7%). Discussion and Conclusion. In Asian patients whose BP is not adequately controlled with telmisartan or amlodipine monotherapy, T/A SPC treatment results in greater BP reduction, and higher DBP and SBP goal and response rates. The safety and tolerability of the T/A SPC are comparable to those of the respective monotherapies and consistent with those reported in previous studies. Dingliang Zhu, Pingjin Gao, Nobutaka Yagi, and Helmut Schumacher Copyright © 2014 Dingliang Zhu et al. All rights reserved. Long-Term Effect of an Aqueous Fraxinus excelsior L. Seed Extract in Spontaneously Hypertensive Rats Tue, 18 Feb 2014 13:20:16 +0000 The effect of long-term intake of different doses (20, 40, and 60 mg/kg/day) of a Fraxinus excelsior L. seed extract (FESE) on spontaneously hypertensive rats (SHR) was evaluated. Water was used as control and captopril (50 mg/kg/day) was used as positive control. Systolic blood pressure, body weight, and food and liquid intake were registered weekly in SHR. The antioxidant and vascular relaxing properties of FESE were also studied in these animals. The development of hypertension was attenuated in the groups treated with captopril or FESE. The antihypertensive effect was more accentuated in the captopril group than in the FESE groups, and it was paradoxically more accentuated in the groups treated with 20 mg/kg/day or 40 mg/kg/day of FESE than in the group treated with the highest dose of this extract. Body weight gain and food intake increased in the FESE groups. After removing the corresponding antihypertensive treatment, the arterial blood pressure and the body weight of the FESE treated animals returned to control values. In addition, FESE increased plasma antioxidant capacity and decreased plasma and liver malondialdehyde levels. Moreover, acetylcholine relaxation improved in the aorta rings from the FESE treated rats. Noemi López-Carreras, Sandra Fernández-Vallinas, Marta Miguel, and Amaya Aleixandre Copyright © 2014 Noemi López-Carreras et al. All rights reserved. Management of Hypertension in Intrapericardial Paraganglioma Thu, 13 Feb 2014 13:56:24 +0000 Functioning paraganglioma is extra-adrenal catecholamine-secreting tumours that may cause secondary hypertension. Primary intrapericardial paragangliomas are very rare and are located adjacent to the great vessels or heart, typically near the left atrium. These tumours are an exceptionally uncommon finding during the investigation of refractory hypertension. However, in recent years, intrapericardial paragangliomas have been diagnosed incidentally with increased frequency, due to the extensive use of radiologic chest imaging. The mainstay of treatment of functioning intrapericardial paraganglioma is surgical removal, which usually achieves blood pressure normalization. Due to the locations of these tumours, the surgical approach is through a median sternotomy or posterolateral thoracotomy, and manipulation-induced catecholamine release may cause paroxysmal hypertension. Typically in these patients, blood pressure fluctuates dramatically intra- and post-operatively, increasing the risk of cardiovascular complications. We review here the current modalities of perioperative fluid and hypotensive drug administration in the setting of surgery for functioning intrapericardial paraganglioma and discuss the recently proposed paradigm shift that omits preoperative preparation. Nicola Rotolo, Andrea Imperatori, Alessandro Bacuzzi, Valentina Conti, Massimo Castiglioni, and Lorenzo Dominioni Copyright © 2014 Nicola Rotolo et al. All rights reserved. The Burden of Blood-Pressure-Related Cardiovascular Mortality in Mexico Mon, 10 Feb 2014 13:45:37 +0000 This study shows that in Mexico, a country at an advanced stage in the epidemiologic transition, with the national burden of disease dominated by noncommunicable diseases, elevated blood pressure is a major clinical and public health problem. 31.7% of the Mexican individuals aged 50 and over had systolic hypertension, and 47.3% were at systolic prehypertensive levels. Also, approximately half of all cardiovascular deaths that occurred annually in the population of Mexico aged ≥50 years are attributable to above optimal levels of systolic blood pressure. We think these estimates may help order health priorities in Mexico (and other middle-income countries) at a time when the costs of medical care take a considerable share of the gross national product in most countries. Dora E. Cortés-Hernández, Krista J. Lundelin, Esteban Picazzo-Palencia, Juan J. de la Cruz, José J. Sánchez, and José R. Banegas Copyright © 2014 Dora E. Cortés-Hernández et al. All rights reserved. Sodium Intake, Dietary Knowledge, and Illness Perceptions of Controlled and Uncontrolled Rural Hypertensive Patients Tue, 04 Feb 2014 13:58:14 +0000 Introduction and Objectives. Nutritional knowledge of the patients is important in dietary adherence. This study aimed to determine the relationship between illness perceptions and nutritional knowledge with the amounts of sodium intake among rural hypertensive patients. Methods. In a cross-sectional study, 671 hypertensive patients were selected in a multistage random sampling from the rural areas of Ardabil city, Iran, in 2013. Data were collected using a questionnaire consisting of four sections and were analyzed using Pearson correlation and multiple linear regressions by SPSS-18. Results. The mean of sodium intake in the uncontrolled hypertensive patients was  mg/day and significantly greater than controlled group ( mg/day) (). Knowledge and illness perceptions could predict 47.2% of the variation in sodium intake of uncontrolled group. A significant negative relationship was found between knowledge and illness perceptions of uncontrolled hypertensive patients with dietary sodium intake (, and , , resp.). Conclusion. Considering the fact that patients’ nutritional knowledge and illness perceptions could highly predict their sodium intake, the importance of paying more attention to improve patients’ information and perceptions about hypertension is undeniable, especially among the uncontrolled hypertensive patients. Aziz Kamran, Leila Azadbakht, Gholamreza Sharifirad, Behzad Mahaki, and Afshan Sharghi Copyright © 2014 Aziz Kamran et al. All rights reserved. The Impact of Mood and Anxiety Disorders on Incident Hypertension at One Year Sun, 02 Feb 2014 11:16:31 +0000 Background. Studies assessing the association between psychological factors and hypertension have been equivocal, which may reflect limitations in the assessment of psychological factors. Purpose. To assess the relationship between mood and anxiety disorders, measured using a psychiatric interview, and 1-year incident hypertension. Methods. 197 nonhypertensive individuals undergoing exercise stress testing at baseline provided follow-up data at 1 year. Baseline assessments included a structure psychiatric interview (PRIME-MD), physician diagnosis of hypertension, and measured blood pressure. At follow-up, hypertension status was assessed via self-reported physician diagnosis. Results. Having an anxiety disorder was associated with a 4-fold increase in the risk of developing hypertension (adjusted OR = 4.14, 95% CIs = 1.18–14.56). In contrast, having a mood disorder was not associated with incident hypertension (adjusted OR = 1.21, 95% CIs = 0.24–5.86). Conclusions. There are potential mechanisms which could explain our differential mood and anxiety findings. The impact of screening and treatment of anxiety disorders on hypertension needs to be explored. Simon L. Bacon, Tavis S. Campbell, André Arsenault, and Kim L. Lavoie Copyright © 2014 Simon L. Bacon et al. All rights reserved. Beta-Blockers in the Management of Hypertension and/or Chronic Kidney Disease Thu, 30 Jan 2014 08:37:25 +0000 This minireview provides current summaries of beta-blocker use in the management of hypertension and/or chronic kidney disease. Accumulated evidence suggests that atenolol is not sufficiently effective as a primary tool to treat hypertension. The less-than-adequate effect of beta-blockers in lowering the blood pressure and on vascular protection, and the unfavorable effects of these drugs, as compared to other antihypertensive agents, on the metabolic profile have been pointed out. On the other hand, in patients with chronic kidney disease, renin-angiotensin system blockers are the drugs of first choice for achieving the goal of renal protection. Recent studies have reported that vasodilatory beta-blockers have adequate antihypertensive efficacy and less harmful effects on the metabolic profile, and also exert beneficial effects on endothelial function and renal protection. However, there is still not sufficient evidence on the beneficial effects of the new beta-blockers. Hirofumi Tomiyama and Akira Yamashina Copyright © 2014 Hirofumi Tomiyama and Akira Yamashina. All rights reserved. Lifestyle Factors in Hypertension Drug Research: Systematic Analysis of Articles in a Leading Cochrane Report Tue, 28 Jan 2014 07:55:43 +0000 Established standards for first-line hypertension management include lifestyle modification and behavior change. The degree to which and how lifestyle modification is systematically integrated into studies of first-line drug management for hypertension is of methodological and clinical relevance. This study systematically reviewed the methodology of articles from a recent Cochrane review that had been designed to inform first-line medical treatment of hypertension and was representative of high quality established clinical trials in the field. Source articles were systematically reviewed for lifestyle interventions including smoking cessation, diet, weight loss, physical activity and exercise, stress reduction, and moderate alcohol consumption. 54% of articles did not mention lifestyle modification; 46% contained nonspecific descriptions of interventions. We contend that hypertension management research trials (including drug studies) need to elucidate the benefits and risks of drug-lifestyle interaction, to support the priority of lifestyle modification, and that lifestyle modification, rather than drugs, is seen by patients and the public as a priority for health professionals. The inclusion of lifestyle modification strategies in research designs for hypertension drug trials could enhance current research, from trial efficacy to clinical outcome effectiveness, and align hypertension best practices of a range of health professionals with evidence-based knowledge translation. Dan E. Wilson, Tashina Van Vlack, Brendin P. Schievink, Eric B. Doak, Jason S. Shane, and Elizabeth Dean Copyright © 2014 Dan E. Wilson et al. All rights reserved. Participation of 5-HT and AT1 Receptors within the Rostral Ventrolateral Medulla in the Maintenance of Hypertension in the Goldblatt 1 Kidney-1 Clip Model Tue, 21 Jan 2014 11:07:20 +0000 The hypothesis that changes in neurotransmission within the rostral ventrolateral medulla (RVLM) are important to maintain the high blood pressure (BP) was tested in Goldblatt one kidney-one clip hypertension model (1K-1C). Male Wistar rats were anesthetized (urethane 1.2 g/kg, i.v.), and the effects of bilateral microinjections into the RVLM of the following drugs were measured in 1K-1C or control groups: glutamate (0.1 mol/L, 100 nL) and its antagonist kynurenic acid (0.02 mol/L, 100 nL), the angiotensin AT1 receptor antagonist candesartan (0.01 mol/L, 100 nL), and the nonselective 5-HT receptor antagonist methiothepin (0.06 mol/L, 100 nL). Experiments in 1K-1C rats were performed 6 weeks after surgery. In anesthetized rats glutamate response was larger in hypertensive than in normotensive rats (H: ; N:  mmHg). In contrast, kynurenic acid microinjection into the RVLM did not cause any change in BP in either group. The blockade of either AT1 or 5-HT receptors within the RVLM decreased BP only in 1K-1C rats. A largest depressor response was caused by 5-HT receptor blockade. The data suggest that 5-HT and AT1 receptors act tonically to drive RVLM in 1K-1C rats, and these actions within RVLM contribute to the pathogenesis of this model of hypertension. Cássia T. Bergamaschi, Nyam F. Silva, Jose G. Pires, Ruy R. Campos, and Henrique A. Futuro Neto Copyright © 2014 Cássia T. Bergamaschi et al. All rights reserved. Cardiovascular Risk Factors and Chronic Kidney Disease—FGF23: A Key Molecule in the Cardiovascular Disease Sun, 12 Jan 2014 00:00:00 +0000 Patients with chronic kidney disease (CKD) are at increased risk of mortality, mainly from cardiovascular disease. Moreover, abnormal mineral and bone metabolism, the so-called CKD-mineral and bone disorder (MBD), occurs from early stages of CKD. This CKD-MBD presents a strong cardiovascular risk for CKD patients. Discovery of fibroblast growth factor 23 (FGF23) has altered our understanding of CKD-MBD and has revealed more complex cross-talk and endocrine feedback loops between the kidney, parathyroid gland, intestines, and bone. During the past decade, reports of clinical studies have described the association between FGF23 and cardiovascular risks, left ventricular hypertrophy, and vascular calcification. Recent translational reports have described the existence of FGF23-Klotho axis in the vasculature and the causative effect of FGF23 on cardiovascular disease. These findings suggest FGF23 as a promising target for novel therapeutic approaches to improve clinical outcomes of CKD patients. Rika Jimbo and Tatsuo Shimosawa Copyright © 2014 Rika Jimbo and Tatsuo Shimosawa. All rights reserved. A Cost-Benefit and Accurate Method for Assessing Microalbuminuria: Single versus Frequent Urine Analysis Wed, 25 Dec 2013 11:37:59 +0000 Background. The purpose of this study was to answer the question whether a single testing for microalbuminuria results in a reliable conclusion leading costs saving. Methods. This current cross-sectional study included a total of 126 consecutive persons. Microalbuminuria was assessed by collection of two fasting random urine specimens on arrival to the clinic as well as one week later in the morning. Results. In overall, 17 out of 126 participants suffered from microalbuminuria that, among them, 12 subjects were also diagnosed as microalbuminuria once assessing this factor with a sensitivity of 70.6%, a specificity of 100%, a PPV of 100%, a NPV of 95.6%, and an accuracy of 96.0%. The measured sensitivity, specificity, PVV, NPV, and accuracy in hypertensive patients were 73.3%, 100%, 100%, 94.8%, and 95.5%, respectively. Also, these rates in nonhypertensive groups were 50.0%, 100%, 100%, 97.3%, and 97.4%, respectively. According to the ROC curve analysis, a single measurement of UACR had a high value for discriminating defected from normal renal function state (). Urinary albumin concentration in a single measurement had also high discriminative value for diagnosis of damaged kidney (). Conclusion. The single testing of both UACR and urine albumin level rather frequent testing leads to high diagnostic sensitivity, specificity, and accuracy as well as high predictive values in total population and also in hypertensive subgroups. Roholla Hemmati, Mojgan Gharipour, Alireza Khosravi, and Mahnaz Jozan Copyright © 2013 Roholla Hemmati et al. All rights reserved. Persistence and Progression of Masked Hypertension: A 5-Year Prospective Study Tue, 17 Dec 2013 10:46:43 +0000 Objectives. To examine masked hypertension persistence over 5 years. Methods. White-collar workers were recruited from three public organizations. Blood pressure (BP) was measured using Spacelabs 90207. Manually operated BP was defined as the mean of the first three readings taken at rest. Ambulatory BP was defined as the mean of the next readings taken every 15 minutes and recorded during working hours. BP was assessed three times over 5 years. Masked hypertension was defined as manually operated BP less than 140 and less than 90 mmHg and ambulatory BP at least 135 or at least 85 mmHg. Sustained hypertension was defined as manually operated BP at least 140 or at least 90 mmHg and ambulatory BP at least 135 or at least 85 mmHg or being treated for hypertension. Results. BP measurements were obtained from 1669 participants from whom 232 had masked hypertension at baseline. Persistence of masked hypertension was 38% and 18.5%, after 3 and 5 years, respectively. Progression to sustained hypertension was 26% and 37%, after 3 and 5 years, respectively. Conclusion. Among baseline masked hypertensives, one-third progressed to sustained hypertension and about one out of five remained masked after 5 years, potentially delaying diagnosis and treatment. Xavier Trudel, Alain Milot, and Chantal Brisson Copyright © 2013 Xavier Trudel et al. All rights reserved. Incidence of New-Onset Hypertension in Cancer Patients: A Retrospective Cohort Study Mon, 16 Dec 2013 08:36:02 +0000 This retrospective cohort study was conducted to estimate incidence rates of new-onset hypertension in adult cancer patients identified from the Varian Medical Oncology outpatient database. Incidence rates of increasing levels of hypertension severity were calculated overall and for periods of chemotherapy exposure and nonexposure. Cox models sought predictors of new-onset hypertension severity among baseline and chemotherapy exposure variables. New-onset hypertension was observed in about one-third of 25,090 patients with various cancer types. The incidence rates (IR) of severe and crisis-level hypertension, respectively, were the highest in patients with gastric (18.5 cases per 100 person-years (PY), 5.6 per 100 PY) and ovarian cancer (20.2 per 100 PY, 4.8 per 100 PY). The highest IR of moderate hypertension was observed in patients with renal cancer (46.7 per 100 PY). Across all cancers, chemotherapy exposure was associated with a 2–3.5-fold increase in risk of any degree of hypertension compared to periods of no chemotherapy; higher hypertension levels showed greater variability in relative risks by type and line of therapy but indicated an overall increase associated with chemotherapy exposure. These results help to elucidate the factors influencing HTN among cancer patients and the incidence of HTN relative to chemotherapy exposure. Kathy H. Fraeman, Beth L. Nordstrom, Weixiu Luo, Sarah H. Landis, and Sumitra Shantakumar Copyright © 2013 Kathy H. Fraeman et al. All rights reserved. Statin Improves Flow-Mediated Vasodilation in Chronic Kidney Diseases Wed, 11 Dec 2013 12:00:57 +0000 Background. Numbers of drugs are required to manage patients with chronic kidney disease (CKD). Drug adherence is relatively poor in this population. Methods. In 36 CKD patients with hypertension and dyslipidemia, who were prescribing amlodipine 5 mg and atorvastatin 10 mg daily, the influences of exchanging to a combination drug containing equivalent doses of amlodipine and atorvastatin were observed for 6 months. Results. At the baseline, flow-mediated dilation (FMD) was reduced (2.4 ± 0.3%), and proteinuria was significantly contributed to decrements of FMD (, , df (6,29), and  ). Six months later from exchanging to combination drug, total cholesterol (TC, 197 ± 5 to 183 ± 3 mg/dL,  ) and triglycerides (142 ± 14 to 129 ± 10 mg/dL, ) were decreased, but high density lipoprotein cholesterol (53 ± 3 to 56 ± 3 mg/dL, ) was increased. FMD was slightly albeit significantly improved to 2.7 ± 0.3% (). No serious adverse effects were seen by the combination drug. Subanalysis for the patients with considerable reductions of TC demonstrated that the combination drug decreased proteinuria and high sensitive CRP ( for both). Conclusion. Our data indicate that proteinuria constitutes a determinant of a reduced FMD. The present results implicate that combination drug is useful to improve adherence and suggest that atorvastatin refines endothelium function as well as lipid profiles in CKD patients. Tsuneo Takenaka, Hiroshi Takane, Tomohiro Kikuta, Yusuke Watanabe, and Hiromichi Suzuki Copyright © 2013 Tsuneo Takenaka et al. All rights reserved. Essential Hypertension: An Approach to Its Etiology and Neurogenic Pathophysiology Mon, 09 Dec 2013 14:29:14 +0000 Essential hypertension, a rise in blood pressure of undetermined cause, includes 90% of all hypertensive cases and is a highly important public health challenge that remains, however, a major modifiable cause of morbidity and mortality. This review emphasizes that, from an evolutionary point of view, we are adapted to ingest and excrete <1 g of sodium (2.5 g of salt) per day and that essential hypertension develops when the kidneys become unable to excrete the amount of sodium ingested, unless blood pressure is increased. The renal-mean arterial pressure set-point model is briefly described to explain that a shift of the pressure natriuresis relationship toward abnormally high pressure levels is a pathophysiological characteristic of essential hypertension. Evidence indicating that this anomaly in the pressure natriuresis relationship arises from a sympathetic nervous system dysfunction is briefly formulated, and the most widely accepted pathophysiologic proposal to explain the development of this sympathetic dysfunction is described, with commentaries about novel action mechanisms of some drugs currently used in essential hypertension treatment. Juan J. Bolívar Copyright © 2013 Juan J. Bolívar. All rights reserved. Clinical Implications of the Change in Glomerular Filtration Rate with Adrenergic Blockers in Patients with Morning Hypertension: The Japan Morning Surge-1 Study Sun, 01 Dec 2013 15:52:15 +0000 Background. The aim of this study was to clarify the relationship between the change in estimated glomerular filtration rate (eGFR) and urinary albumin by antihypertensive treatment. Methods. We randomized 611 treated patients with morning hypertension into either an added treatment group, for whom doxazosin was added to the current medication, or a control group, who continued their current medications. We compared the change in eGFR and urinary albumin creatinine ratio (UACR) between the groups. Results. The extent of the reduction in eGFR was significantly greater in the added treatment group than in the control group (−3.83  versus −1.08 mL/min/1.73 m2, ). In multivariable analyses, the change in eGFR was positively associated with the change in UACR in the added treatment group (, ), but not in the control group (, ). When the changes in eGFR were divided by each CKD stage, eGFR was significantly more decreased in stage 1 than in the other stages in the added treatment group (), but no differences were seen in the control group (). Conclusion. The reduction of eGFR could be seen only in the early stage of CKD, and this treatment appeared to have no negative effect on renal function. Seiichi Shibasaki, Kazuo Eguchi, Yoshio Matsui, Kazuyuki Shimada, and Kazuomi Kario Copyright © 2013 Seiichi Shibasaki et al. All rights reserved. Renal Denervation for Treating Resistant Hypertension: Current Evidence and Future Insights from a Global Perspective Wed, 27 Nov 2013 10:36:06 +0000 Adequate blood pressure control represents an important goal for all physicians due to the complications of hypertension which reduce patients' quality of life. A new interventional strategy to reduce blood pressure has been developed for patients with resistant hypertension. Catheter-based renal denervation has demonstrated excellent results in recent investigations associated with few side effects. With the growing diffusion of this technique worldwide, some medical societies have published consensus statements to guide physicians how to best apply this procedure. Questions remain to be answered such as the long-term durability of renal denervation, the efficacy in patients with other sympathetically mediated diseases, and whether renal denervation would benefit patients with stage 1 hypertension. Y. Castro Torres and Richard E. Katholi Copyright © 2013 Y. Castro Torres and Richard E. Katholi. All rights reserved. Metabolic Alterations in Different Stages of Hypertension in an Apparently Healthy Nigerian Population Mon, 25 Nov 2013 09:47:04 +0000 Metabolic syndrome (MS) amplifies hypertension (HTN) associated with increased risk of cardiovascular disease (CVD). MS components and other CVD risk measures were investigated in different stages of hypertension. 534 apparently healthy Nigerian traders aged 18–105 years were participants of a cohort study. The International Diabetes Federation (2005) and the National High Blood Pressure Education Program Coordinating Committee criteria were used for MS and HTN classifications, respectively. Anthropometric indices were obtained by standard methods. Levels of fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDLC) were determined by enzymatic methods, while low-density lipoprotein cholesterol (LDLC) was calculated. Data analysed statistically were significant at . 143 (26.8%), 197 (36.9%), and 194 (36.3%) of the traders had normotension, pre-HTN and HTN (stages 1 and 2), respectively. All indices tested except HDLC were significantly different among BP groups (). Waist to hip (WHR) and waist to height (WHT) ratios were significantly different between HTN groups (). HTN was associated with MS and female gender (). Metabolic alterations and significant HTN were observed. Treatment of the individual components of the syndrome and improvement of modifiable metabolic factors may be necessary to reduce MS and high BP. M. A. Charles-Davies, A. A. Fasanmade, J. A. Olaniyi, O. E. Oyewole, M. O. Owolabi, J. R. Adebusuyi, O. Hassan, M. T. Ajobo, M. O. Ebesunun, K. Adigun, K. S. Akinlade, U. A. Fabian, O. O. Popoola, S. K. Rahamon, W. Okunbolade, M. A. Ogunlakin, O. G. Arinola, and E. O Agbedana Copyright © 2013 M. A. Charles-Davies et al. All rights reserved. Hemodynamic Correlates of Late Systolic Flow Velocity Augmentation in the Carotid Artery Thu, 14 Nov 2013 10:13:37 +0000 Background. The contour of the common carotid artery (CCA) blood flow velocity waveform changes with age; CCA flow velocity increases during late systole, and this may contribute to cerebrovascular disease. Late systolic flow velocity augmentation can be quantified using the flow augmentation index (FAIx). We examined hemodynamic correlates of FAIx to gain insight into determinants of CCA flow patterns. Methods. CCA Doppler ultrasound and wave intensity analysis (WIA) were used to assess regional hemodynamics in 18 young healthy men (age 22 ± 1 years). Forward waves () and backward waves (negative area, NA) were measured and used to calculate the reflection index (NA/ = RIx). Additional parameters included which is a forward travelling expansion/decompression wave of myocardial origin that produces suction, CCA single-point pulse wave velocity (PWV) as a measure of arterial stiffness, and CCA pressure augmentation index (AIx). Results. Primary correlates of FAIx included , logRIx , and AIx . FAIx was not associated with CCA stiffness . Conclusions. FAIx is a complex ventricular-vascular coupling parameter that is associated with both increased expansion wave magnitude (increased suction from the left ventricle) and increased pressure from wave reflections. Kevin S. Heffernan, Wesley K. Lefferts, and Jacqueline A. Augustine Copyright © 2013 Kevin S. Heffernan et al. All rights reserved. Genetic and Adverse Health Outcome Associations with Treatment Resistant Hypertension in GenHAT Thu, 31 Oct 2013 18:47:21 +0000 Treatment resistant hypertension (TRH) is defined as uncontrolled hypertension (HTN) despite the use of ≥3 antihypertensive medication classes or controlled HTN while treated with ≥4 antihypertensive medication classes. Risk factors for TRH include increasing age, diminished kidney function, higher body mass index, diabetes, and African American (AA) race. Importantly, previous studies suggest a genetic role in TRH, although the genetics of TRH are largely understudied. With 2203 treatment resistant cases and 2354 treatment responsive controls (36% AA) from the Genetics of Hypertension Associated Treatment Study (GenHAT), we assessed the association of 78 candidate gene polymorphisms with TRH status using logistic regression. After stratifying by race and adjusting for potential confounders, there were 2 genetic variants in the AGT gene (rs699, rs5051) statistically significantly associated with TRH among white participants. The Met allele of rs699 and the G allele of rs5051 were positively associated with TRH:  (1.12–1.44), , and  (1.20–1.53), , respectively. There was no similar association among AA participants (race interaction for rs699 and for rs5051). This research contributes to our understanding of the genetic basis of TRH, and further genetic studies of TRH may help reach the goal of better clinical outcomes for hypertensive patients. Amy I. Lynch, Marguerite R. Irvin, Barry R. Davis, Charles E. Ford, John H. Eckfeldt, and Donna K. Arnett Copyright © 2013 Amy I. Lynch et al. All rights reserved.