Agosto de 2010

Masked Hypertension Defined by Ambulatory Blood Pressure Monitoring Is Associated With an Increased Serum Glucose Level and Urinary Albumin-Creatinine Ratio
Joji Ishikawa, MD, PhD;1,2 Satoshi Hoshide, MD;1 Kazuo Eguchi, MD, PhD;1 Joseph E. Schwartz, PhD;2 Thomas G. Pickering, MD, DPhil;2* Kazuyuki Shimada, MD, PhD;1 Kazuomi Kario, MD, PhD1
The authors evaluated the relationship of hypertensive target organ damage to masked hypertension assessed by ambulatory blood pressure (BP) and home blood pressure (HBP) monitoring in 129 participants without taking antihypertensive medication. Masked hypertension was defined as office BP _140 ⁄ 90 mm Hg and 24-hour ambulatory BP _130 ⁄ 80 mm Hg. The masked hypertensive participants defined by 24-hour ambulatory BP (n=13) had a higher serum glucose level (126 vs 96 mg⁄ dL, P=.001) and urinary albumin-creatinine ratio (38.0 vs 7.5 mg⁄ gCr, P<.001) than the normotensive participants (n=74); however, these relationships were not observed when the authors defined groups using HBP (_135 ⁄ 85 mm Hg). Masked hypertension by both 24-hour ambulatory BP and HBP had a higher urinary albumin-creatinine ratio than normotension by both 24-hour ambulatory BP and HBP (62.1 vs 7.4 mg⁄ gCr, P=.001), and than masked hypertension by HBP alone (9.3 mg⁄ gCr, P=.009). Masked hypertension defined by 24-hour ambulatory BP is associated with an increased serum glucose level and urinary albumin-creatinine ratio, but these relationships are not observed in masked hypertension defined by HBP. J Clin Hypertens (Greenwich). 2010;12:578–587.

Predictors of Hypertension Control in a Diverse General Cardiology Practice
Adam D. DeVore, MD;1 Matthew Sorrentino, MD;2 Morton F. Arnsdorf, MD;2 R. Parker Ward, MD;2 George L. Bakris, MD;3 Ron Blankstein, MD1,4
Factors influencing hypertension (HTN) control in the United States are not well understood. The authors utilized a newly designed survey instrument to interview patients presenting to a diverse, general cardiology practice at a tertiary care center in order to identify factors associated with HTN control. The study was completed in 154 participants, and 121 (78.6%) had HTN. Of those, 111 (91.7%) had awareness of HTN, and 72 (59.5%) had HTN control, defined as <140 ⁄ 90 mm Hg. In a multivariate analysis, race ⁄ ethnicity was not associated with HTN control, but private insurance (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.25–9.28), nonsmoker status (OR 4.36, CI 1.22–15.51), and number of medications used (OR 1.32, CI 1.12– 1.56) were associated with HTN control. Correct recognition of systolic blood pressure goal and knowledge of one’s current state of HTN control were also associated with control. In conclusion, in a general cardiology practice where patients had a high degree of healthcare access, race ⁄ ethnicity was not associated with HTN control, while type of insurance, nonsmoker status, and increased number of medications used were associated. In addition, 2 novel predictors of HTN control, recognition of systolic blood pressure goal and knowledge of HTN control, were identified that can be utilized in creating new HTN treatment interventions. J Clin Hypertens (Greenwich). 2010; 12:570–577

Antihypertensive drug development: current challenges and future opportunities
Peter U. Feig, MDa,*, Sophie Roy, PhDb, and Robert J. Cody, MDc aCardiovascular Clinical Research, Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Rahway, New Jersey; bCardiovascular Basic Research, Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Rahway, New Jersey; and cGlobal Scientific Affairs, Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Rahway, New Jersey
Abstract : The growing rate of obesity and diabetes, and an aging population has led to increased demand for new antihypertensive compounds. This review highlights the challenges and opportunities associated with each phase of drug discovery and development of novel antihypertensive agents. Discovery and development starts with identification of a protein hypothesized to be linked to hypertension. Using the information gathered during this early stage, several potential candidates are often synthesized and moved on through preclinical evaluations, eventually leading to selection of one or more compounds for testing in humans. The compounds then enter preclinical safety studies in laboratory animal species and subsequently are tested in tiered clinical studies. As the compounds enter clinical testing, there is an exponential increase in the investment of resources to demonstrate that a new compound is a viable and worthy therapeutic agent for hypertension. The review provides some forecasting of issues that are likely to impact drug development of novel antihypertensives in the future. J Am Soc Hypertens 2010;4(4):163–173

Disorders of Orthostatic Blood Pressure Response Are Associated With Cardiovascular Disease and Target Organ Damage in Hypertensive Patients
Xiao-Han Fan1, Yibo Wang2, Kai Sun2, Weili Zhang2, Hu Wang2, Haiying Wu1, Huimin Zhang1,Xianliang Zhou1 and Rutai Hui1,2
Background The prevalence and clinical significance of orthostatic hypertension (OHT) remain largely undetermined in hypertensive patients. This study investigated the association of OHT and orthostatic hypotension (OH) with cardiovascular disease (CVD) and target organ damage (TOD) in hypertensive patients. Met hods A cross-sectional study was conducted in 4,711 hypertensives and 826 normotensives, aged 40–75 years. OHT was defined as an increase in systolic blood pressure (SBP) of ≥20 mm Hg, and OH was defined as either a reduction in SBP of at least 20 mm Hg or a reduction in diastolic BP (DBP) of at least 10 mm Hg during the first 3 min after standing. Results Hypertension was only independently associated with a risk of OHT. After controlling for age, sex, and other confounders, OH was associated with peripheral artery disease (PAD) (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.15–1.89, P < 0.01), left ventricular hypertrophy (LVH) (OR 1.48, 95% CI 1.12–1.93, P < 0.001), coronary artery disease (CAD) (OR 1.71, 95% CI 1.12–2.61, P < 0.01), and stroke (OR 1.72, 95% CI 1.19–2.34, P < 0.01), but OHT was only associated with PAD (OR 1.36, 95% CI 1.05–1.81, P < 0.05) and stroke (OR 1.76, 95% CI 1.27–2.26, P < 0.01). The adjusted OR for PAD, predicted by the quintiles of the orthostatic SBP changes, showed a J-shaped relationship in untreated hypertensive patients, as was also the casefor LVH in hypertensive women. Conclusions OH is associated with CV risk; the associations of OHT with TOD and stroke in hypertensive patients still need to be confirmed in prospective studies. Keywords: blood pressure; hypertension; hypotension; orthostatic hypertension; target organ damage Am J Hypertens 2010; 23:829-837 © 2010 American Journal of Hypertension, Ltd.

intensive glycemic control and cardiovascular disease: an update
Aparna Brown, L. Raymond Reynolds and Dennis Bruemmer
abstract | Cardiovascular complications constitute the major cause of morbidity and mortality in patients with diabetes. The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) provided consistent evidence that intensive glycemic control prevents the development and progression of microvascular complications in patients with type 1 or type 2 diabetes. However, whether intensive glucose lowering also prevents macrovascular disease and major cardiovascular events remains unclear. Extended follow‑up of participants in these studies demonstrated that intensive glycemic control reduced the long‑term incidence of myocardial infarction and death from cardiovascular disease. By contrast, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, and Veterans Affairs Diabetes Trial (VADT) results suggested that intensive glycemic control to near normoglycemia had either no, or potentially even a detrimental, effect on cardiovascular outcomes. This article discusses the effects of intensive glycemic control on cardiovascular disease, and examines key differences in the design of these trials that might have contributed to their disparate findings. Recommendations from the current joint ADA, AHA, and ACCF position statement on intensive glycemic control and prevention of cardiovascular disease are highlighted.


Risk Reduction After Regression of Echocardiographic Left Ventricular Hypertrophy in Hypertension: A Meta-Analysis
Sante D. Pierdomenico1,2 and Franco Cuccurullo1,2
Background The prognostic relevance of echocardiographic left ventricular hypertrophy (LVH) regression in hypertension is uncertain. The aim of this study was to perform an updated meta-analysis about the impact of LVH regression on the occurrence of cardiovascular events in hypertensive patients. Met hods We searched for studies on echocardiographic LVH regression and prognosis in hypertension that compared patients with or without LVH regression or groups including subjects with or without LVH regression and reported adjusted hazard ratio (HR) for calculating the overall effect size. Results Five studies were identified (3,149 patients, mean age range 48–66 years, 58% men). Follow-up echocardiography was performed after a mean period ranging from 1 to 5 years. Entire follow-up duration ranged from 3 to 9 years. Globally, 333 cardiovascular events occurred. Three whole studies and subgroups of two others were included in the meta-analysis, comprising 2,449 patients, 1,900 (78%) with baseline LVH and 969 (51%) with LVH regression, who experienced 304 events. The overall adjusted HR of total cardiovascular events was 0.54, 95% confidence interval (CI) 0.35–0.84, P = 0.007, for LVH regression/persistent normal left ventricular (LV) mass vs. LVH persistence/LVH development. Heterogeneity was found between studies. Higher baseline prevalence of comorbid conditions and Japanese ethnicity seemed to be associated with lower benefit from LVH regression. Conclusions This meta-analysis indicates that regression of echocardiographic LVH in hypertension, even after adjustment for various confounders, is associated with reduction of cardiovascular events. However, future studies are needed to evaluate whether LVH regression is of benefit for all hypertensive patients and ethnic groups. Keywords: blood pressure; hypertension; left ventricular hypertrophy; prognosis; regression Am J Hypertens 2010; 23:876-881 © 2010 American Journal of Hypertension, Ltd.


Serum Uric Acid Is Associated With New-Onset Diabetes in Hypertensive Patients With Left Ventricular Hypertrophy: The LIFE Study
Benedicte P. Wiik1,2, Anne C.K. Larstorp1,2, Aud Høieggen1,2, Sverre E. Kjeldsen1–3, Michael Hecht Olsen4,Hans Ibsen5, Lars Lindholm6, Björn Dahlöf7, Richard B. Devereux8, Peter M. Okin8 and Kristian Wachtell9
Background It is unclear whether serum uric acid (SUA) is associated with development of new-onset diabetes (NOD) in patients with hypertension and left ventricular hypertrophy (LVH). The aim of the present investigation was to test the hypothesis that SUA predicts development of NOD in these patients. Methods In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, a double-masked, parallel-group design, 9,193 patients with hypertension and electrocardiographic LVH were randomized to losartan- or atenolol-based antihypertensive treatment and followed for a mean of 4.9 years. At baseline, 7,489 patients with available SUA measurements did not have diabetes mellitus and were thus at risk of its development during the study. We used Cox regression analyses to investigate whether SUA predicted development of NOD. Results NOD developed in 522 of 7,489 patients. The association between baseline SUA and development of NOD was significant (hazard ratio (HR) 1.29 per s.d. (1.3 mg/dl), 95% confidence interval (CI) 1.18–1.42, P < 0.001) after adjustment for treatment with losartan vs. atenolol, baseline serum glucose, urinary albumin/creatinine ratio, estimated glomerular filtration rate and Framingham risk score, time-varying systolic and diastolic blood pressure, and time-varying LVH by Cornell voltage-duration product and Sokolow–Lyon voltage. In parallel analyses, baseline quartiles of SUA were significantly associated with increasing NOD (HR 1.28, 95% CI 1.18–1.40, P < 0.001). Time-varying SUA was also associated with NOD (HR 1.10 per s.d. [1.3 mg/dl], 95% CI 1.02–1.19, P = 0.015). Conclusion Our analysis suggests that SUA is an independent risk marker for NOD in hypertensive patients with LVH. Keywords: blood pressure; hypertension; left ventricular hypertrophy;new-onset diabetes; serum uric acid Am J Hypertens 2010; 23:845-851 © 2010 American Journal of Hypertension, Ltd.

Target Blood Pressure for Treatment of Isolated Systolic Hypertension in the Elderly
Valsartan in Elderly Isolated Systolic Hypertension Study
Toshio Ogihara, Takao Saruta, Hiromi Rakugi, Hiroaki Matsuoka, Kazuaki Shimamoto,
Kazuyuki Shimada, Yutaka Imai, Kenjiro Kikuchi, Sadayoshi Ito, Tanenao Eto, Genjiro Kimura,
Tsutomu Imaizumi, Shuichi Takishita, Hirotsugu Ueshima, for the Valsartan in Elderly Isolated
Systolic Hypertension Study Group
Abstract—In this prospective, randomized, open-label, blinded end point study, we aimed to establish whether strict blood pressure control (_140 mm Hg) is superior to moderate blood pressure control (_140 mm Hg to _150 mm Hg) in reducing cardiovascular mortality and morbidity in elderly patients with isolated systolic hypertension. We divided 3260 patients aged 70 to 84 years with isolated systolic hypertension (sitting blood pressure 160 to 199 mm Hg) into 2 groups, according to strict or moderate blood pressure treatment. A composite of cardiovascular events was evaluated for _2 years. The strict control (1545 patients) and moderate control (1534 patients) groups were well matched (mean age: 76.1 years; mean blood pressure: 169.5/81.5 mm Hg). Median follow-up was 3.07 years. At 3 years, blood pressure reached 136.6/74.8 mm Hg and 142.0/76.5 mm Hg, respectively. The blood pressure difference between the 2 groups was 5.4/1.7 mm Hg. The overall rate of the primary composite end point was 10.6 per 1000 patient-years in the strict control group and 12.0 per 1000 patient-years in the moderate control group (hazard ratio: 0.89; [95% CI: 0.60 to 1.34]; P_0.38). In summary, blood pressure targets of _140 mm Hg are safely achievable in relatively healthy patients _70 years of age with isolated systolic hypertension, although our trial was underpowered to definitively determine whether strict control was superior to less stringent blood pressure targets. (Hypertension. 2010;56:196-202.)

Progression of Normotensive Adolescents to Hypertensive Adults. A Study of 26.980 Teenagers
Amir Tirosh, Arnon Afek, Assaf Rudich, Ruth Percik, Barak Gordon, Nir Ayalon, Estela Derazne, Dorit Tzur, Daphna Gershnabel, Ehud Grossman, Avraham Karasik, Ari Shamiss, Iris Shai
Abstract—Although prehypertension at adolescence is accepted to indicate increased future risk of hypertension, large-scale/long follow-up studies are required to better understand how adolescent blood pressure (BP) tracks into young adulthood. We studied 23 191 male and 3789 female adolescents from the Metabolic Lifestyle and Nutrition Assessment in Young Adults cohort (mean age: 17.4 years) with BP _140/90 mm Hg at enrollment or categorized by current criteria for pediatric BP and body mass index (BMI) values. Participants were prospectively followed up with repeated BP measurements between ages 25 and 42 years and retrospectively between ages 17 and 25 years for the incidence of hypertension. We identified 3810 new cases of hypertension between ages 17 and 42 years. In survival analyses, the cumulative risk of hypertension between ages 17 and 42 years was 3 to 4 times higher in men than in women. Using Cox regression models adjusted for age, BMI, and stratified by baseline BP, the hazard ratio of hypertension increased gradually across BP groups within the normotensive range at age 17 years, without a discernible threshold effect, reaching a hazard ratio of 2.50 (95% CI: 1.75 to 3.57) for boys and 2.31 (95% CI: 0.71 to 7.60) for girls in the group with BP at 130 to 139/85 to 89 mm Hg. BMI at age 17 years was strongly associated with future risk of hypertension even when adjusted to BP at age 17 years, particularly in boys. Yet, BMI at age 30 years attenuated this association, more evidently in girls. In conclusion, BP at adolescence, even in the low-normotensive range, linearly predicts progression to hypertension in young adulthood. This progression and the apparent interaction between BP at age 17 years and BMI at adolescence and at adulthood are sex dependent. (Hypertension. 2010;56:203-209.)

Reference Values of Pulse Wave Velocity in Healthy Children and Teenagers
George S. Reusz, Orsolya Cseprekal, Mohamed Temmar, E´ va Kis, Abdelghani Bachir Cherif,
Abddelhalim Thaleb, Andrea Fekete, Attila J. Szabo´, Athanase Benetos, Paolo Salvi
Abstract—Carotid-femoral pulse wave velocity is an established method for characterizing aortic stiffness, an individual predictor of cardiovascular mortality in adults. Normal pulse wave velocity values for the pediatric population derived from a large data collection have yet to be available. The aim of this study was to create a reference database and to characterize the factors determining pulse wave velocity in children and teenagers. Carotid-femoral pulse wave velocity was measured by applanation tonometry. Reference tables from pulse wave velocities obtained in 1008 healthy subjects (aged between 6 and 20 years; 495 males) were generated using a maximum-likelihood curve-fitting technique for calculating SD scores in accordance with the skewed distribution of the raw data. Effects of sex, age, height, weight, blood pressure, and heart rate on pulse wave velocity were assessed. Sex-specific reference tables and curves for age and height are presented. Pulse wave velocity correlated positively (P_0.001) with age, height, weight, and blood pressure while correlating negatively with heart rate. After multiple regression analysis, age, height, and blood pressure remained major predictors of pulse wave velocity. This study, involving _1000 children, is the first to provide reference values for pulse wave velocity in children and teenagers, thereby constituting a suitable tool for longitudinal clinical studies assessing subgroups of children who are at long-term risk of cardiovascular disease. (Hypertension. 2010;56: 217-224.).
 

Voltar