Journal of the American Society of Hypertension

From the Editor

Myron H. Weinberger — 2012-05-01

Type 2 diabetes mellitus is an increasingly frequent finding, and a major risk factor for cardiovascular morbidity and mortality. New drugs have been developed and many studies have been done with these agents. This issue of the Journal of the American Society of Hypertension begins with a timely review of the relationship between classes of antidiabetic agents and cardiovascular disease by Dr. Nancy Brown, chair of the Department of Medicine at Vanderbilt University and a renowned expert in this area. Because many hypertensive patients also are obese, have impaired carbohydrate tolerance, or frank type 2 diabetes, this information is very timely for all those who treat such patients.

Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies

Nancy J. Brown — 2012-03-21

Abstract: Hyperglycemia is associated with increased risk of cardiovascular disease. Nevertheless, results of large clinical trials suggest that tight glucose control does not reduce the risk of macrovascular cardiovascular events in type 2 diabetes mellitus and may cause harm. This may reflect the adverse consequences of increased hypoglycemia or the adverse effects of many antidiabetic agents on weight gain. The consequences of intensive therapy may also depend on the mechanism of the antidiabetic agent(s) used to achieve tight control. Metformin, an antidiabetic agent that reduces weight and activates AMP-activated protein kinase, reduces risk of cardiovascular events in overweight diabetics. In contrast, the thiazolidinedione rosiglitazone increases cardiovascular risk. Sulfonylureas may increase the risk of cardiovascular events through effects on the SUR1 of the cardiac KATP channel. Stable analogues of glucagon-like peptide-1 reduce body weight and blood pressure, and have favorable effects on ischemia following reperfusion in animal models. The dipeptidyl peptidase IV inhibitors prevent the breakdown of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, but also decrease the degradation of several vasoactive peptides. Dipeptidyl peptidase IV inhibitors have favorable effects in animal models of ischemia/reperfusion. They have been reported both to decrease and to increase blood pressure. Clinical trials will address the effect of the incretin-based agents on macrovascular cardiovascular events.

Activation of vascular p38MAPK by mechanical stretch is independent of c-Src and NADPH oxidase: influence of hypertension and angiotensin II

Tamara M. Paravicini, Augusto C. Montezano, Hiba Yusuf, Rhian M. Touyz — 2012-02-17

Abstract: Little is known about vascular MAPK regulation in response to mechanical strain. Whether mechanically-sensitive pathways are altered in hypertension is unclear. We examined effects of stretch and Ang II on activation of p38MAPK in vascular smooth muscle cells (VSMC) from WKY and SHR. The role of c-Src and redox-sensitive pathways in stretch-induced effects were examined. VSMC from mesenteric arteries were plated onto flexible silastic plates and exposed to acute or chronic cyclic stretch (10%, 1 Hz) with or without Ang II (0.1 uM). Acute stretch stimulated p38MAPK activation in WKY and SHR, independently of c-Src and reactive oxygen species (ROS), since PP2 (c-Src inhibitor) and apocynin (NADPH oxidase inhibitor), failed to alter stretch-mediated p38MAPK. Chronic stretch blunted p38MAPK phosphorylation in WKY and increased phosphorylation in SHR. Stretch, in the presence of Ang II, induced an increase in procollagen-1 expression. This was blocked by SB203580 (p38MAPK inhibitor). Accordingly, vascular p38MAPK is a mechano-sensitive MAPK, differentially regulated by acute and chronic stretch in WKY and SHR. Functionally, stretch and Ang II, amplify profibrotic responses in a p38MAPK-dependent manner, responses that are perturbed in SHR. Such molecular process may influence vascular fibrosis in hypertension and appear to be independent of c-Src and ROS.

Angiotensin II type 2 receptor-interacting protein prevents vascular senescence

2012-02-24

Abstract: Angiotensin II type 2 (AT2) receptor-interacting protein (ATIP), which interacts with the C-terminal tail of the AT2 receptor, regulates the functions of the AT2 receptor. We have reported that AT2 receptor stimulation attenuated vascular senescence. Therefore, we examined the possible negative role of ATIP in regulating vascular senescence. We generated ATIP-transgenic (Tg) mice, and cultured vascular smooth muscle cells (VSMCs). Persistent angiotensin II stimulation induced increases in SA-β-gal–positive cells and the level of a DNA damage marker, 8-OHdG in VSMC, whereas these effects of angiotensin II were attenuated in VSMC prepared from ATIP-Tg mice. Angiotensin II treatment also upregulated the expression of methyl methanesulfonate-sensitive 2 (MMS2), a DNA repair factor, and Src homology 2 domain-containing protein-tyrosine phosphatase 1 (SHP-1) activity, whereas these effects of angiotensin II were further enhanced in ATIP-Tg VSMC. In vivo, x-ray irradiation to mice caused increases in SA-β-gal–positive area and 8-OHdG level in the thoracic aorta; however, these effects were reduced in ATIP-Tg mice, with a significant increase in MMS2 expression. These results suggest that ATIP could inhibit VSMC senescence, involving MMS2 expression and SHP-1 activity. ATIP might be a new therapeutic molecule to treat vascular aging and age-related vascular diseases.

Cardiomyocyte size estimated from noninvasive measurements of left ventricular wall thickness and chamber diameter

Richard E. Tracy — 2012-03-15

Abstract: Noninvasive measurements of left ventricular wall thickness (LVT) and left ventricular chamber diameter (LVD) allow calculation of expected left ventricular weight (LVW), but not of myocyte breadth (MyB), so that specification of left ventricular hypertrophy (LVH) is not optimal. Hypertrophied hearts, excluding coronary heart disease, and comparison specimens without hypertrophy were compiled into a series of 78 forensic autopsies, wherein LVT, LVD, and LVW were measured. MyB was measured in hematoxylin and eosin–stained paraffin sections. A series of clinical cases tabulating LVD and LVT was assembled from readily available publications. From postmortem data, a regression equation was derived to predict MyB from LVD and LVT. Applying this equation to the clinical data produced a scatter plot closely resembling that in the postmortem dataset. The equation derived here appears to provide valid predictions of cardiomyocyte sizes expected in histological measurements. The finding is the first of its kind and requires further testing for validation or rejection. This is offered as a provisional way to improve the determination of LVH using noninvasive measurements. How this improvement might enhance understanding of the mechanisms for hypertrophy is briefly explored, thus generating working hypotheses.

Left ventricular hypertrophy by electrocardiography and echocardiography in the African American Study of Kidney Disease Cohort Study

2012-02-20

Abstract: Although electrocardiographic criteria for diagnosing left ventricular hypertrophy have a low sensitivity in the general population, their test characteristics have not been evaluated in the high-prevalence group of American Americans with chronic kidney disease. The purpose of the current study was to evaluate these test characteristics among African Americans (n = 645) with hypertensive kidney disease as part of the African-American Study of Kidney Disease and Hypertension cohort. Electrocardiograms were read by 2 cardiologists at an independent core laboratory using the 2 Sokolow-Lyon criteria and the Cornell criteria. Left ventricular hypertrophy on echocardiography was defined as left ventricular mass index greater than 49.2 and greater than 46.7 g/m2.7 in men and women, respectively. Sixty-nine percent of the population had left ventricular hypertrophy on echo, whereas 34% had left ventricular hypertrophy by any of the electrocardiographic criteria. Sensitivity by individual electrocardiographic criteria was 16.5% by Sokolow-Lyon-1, 19.3% by Sokolow-Lyon-2, and 24.7% by Cornell criteria, with specificity ranging from 89% to 92%. When using any of the 3 criteria, sensitivity increased to 40.4% with a decrease in specificity to 78.0%. Consistent with findings in a general population, left ventricular hypertrophy by electrocardiography had low sensitivity and high specificity in this cohort of African Americans with hypertensive kidney disease.

Disparities in adherence to and persistence with antihypertensive regimens: an exploratory analysis from a community-based provider network

2012-05-01

Abstract: Despite the availability of effective antihypertensive therapies, adherence to and persistence with treatment is suboptimal. As such, there is a need to better understand factors associated with adherence and persistence, such as race/ethnicity. In a retrospective, exploratory analysis of 51,772 hypertensive adult subjects identified in the electronic medical record, we examined medication possession ratio and proportion of days covered as proxies for adherence and persistence, respectively. Logistic regression analyses were performed to assess the role of race/ethnicity in adherence to and persistence with antihypertensive treatments. Relative to white subjects, Asian American/Pacific Islander, black, Hispanic, and “other” subjects were significantly less likely to be adherent to and persistent with their antihypertensive regimens. Black and Hispanic subjects had the lowest odds of adherence (0.46, 95% CI: 0.43–0.49 and 0.58, 95% CI: 0.54–0.62, respectively) and persistence (0.70, 95% CI: 0.65–0.75 and 0.70, 95% CI: 0.66–0.74, respectively) relative to white subjects. Other factors significantly associated with both lower adherence and persistence included younger age and lower chronic disease score. Disparities were found with regard to adherence to and persistence with antihypertensive regimens. Future studies should address these disparities by designing interventions to improve medication-taking behavior in high-risk populations.

Home and clinic blood pressure responses in elderly individuals with systolic hypertension

2012-05-01

Abstract: Home blood pressure (BP) monitoring may enhance assessment of BP control. In this 16-week study, men and women 70 years or older with systolic BP between 150 and 200 mm Hg were randomized to receive valsartan/hydrochlorothiazide (V/HCTZ) 160/12.5 mg (n = 128), HCTZ 12.5 mg (n = 128), or V 160 mg (n = 128) for 4 weeks. Participants whose BP was 140/90 mm Hg or higher at weeks 4, 8, or 12 were uptitrated to a maximum of V/HCTZ 320/25 mg. Participants were evaluated by home BP monitoring using an automated device weekly before taking daily study medication (n = 301). Baseline BP ± SD for clinic (165.5 ± 11.8/85.1 ± 9.5 mm Hg) was approximately 3/1 mm Hg greater than home readings (162.5 ± 15.8/84.3 ± 10.2 mm Hg). Reductions in BP ± SEM at week 4 were similar for clinic (12.6 ± 1.0/4.7 ± 0.5 mm Hg) and home (10.9 ± 1.1/3.8 ± 0.5 mm Hg) readings (P = .25/P = .23; clinic versus home); differences between V/HCTZ and HCTZ or V were also similar for both home and clinic readings and results by either technique correlated significantly (P < .0001). Home BP measurements confirm that treatment initiated with V/HCTZ versus monotherapy resulted in greater antihypertensive efficacy. Home BP monitoring, if done with proper technique, provides a reliable indicator of BP control in elderly patients and may help guide drug dosing and titration.

Aliskiren-based dual- and triple-combination therapies in high-risk US minority patients with Stage 2 hypertension

2012-02-06

Abstract: Previously, we reported the efficacy of aliskiren/amlodipine in US minority adults with stage 2 hypertension, with additional blood pressure (BP) lowering from the addition of hydrochlorothiazide (HCTZ). A subgroup analysis in patients with hypertension and comorbidities of diabetes, cardiometabolic syndrome, or obesity, and in black participants is reported. This 8-week, multicenter, double-blind study included 412 self-identified minority patients with mean sitting systolic BP (msSBP) ≥160 mm Hg and <200 mm Hg). Patients were randomized to receive either combination aliskiren/amlodipine 150/5 mg or amlodipine 5 mg. Doses were forced-titrated to a maximum of aliskiren/amlodipine/HCTZ 300/10/25 mg or aliskiren/amlodipine 300/10 mg, respectively. There were 256 black (62%), 118 diabetic (29%), 284 cardiometabolic syndrome (69%), and 249 obese (60%) randomized patients. Baseline msSBP was ∼167 mm Hg across all subgroups. Least-square mean reductions in msSBP, the primary efficacy outcome, from baseline to week 8 across all subgroups, ranged from 35 to 37 mm Hg with aliskiren/amlodipine/HCTZ and 28 to 30 mm Hg with aliskiren/amlodipine (P < .01 for all between-treatment comparisons). Both regimens were well tolerated. Among high-risk patients, such as diabetics or those with cardiometabolic syndrome, combination aliskiren/amlodipine is effective in lowering BP; the addition of HCTZ provided incremental BP-lowering efficacy while maintaining tolerability. However, because our subgroups were not mutually exclusive, the generalization of our findings to the population seen in clinical practice is limited.

Nebivolol withdrawal results in blood pressure returning toward pretreatment levels, but without rebound symptoms: phase IV randomized trial

Andrew Lewin, Kenneth C. Lasseter, Fang Dong, John C. Whalen — 2012-03-16

Abstract: Rapid withdrawal of antihypertensive drugs may lead to blood pressure (BP) increase above pretreatment values or symptoms such as palpitations, chest pain, and tremor. This phase IV trial assessed the consequences of abrupt and stepwise withdrawal of nebivolol, a β1-selective blocker, in individuals with stage I-II hypertension. After a 4- to 5-week placebo washout phase and 12-week single-blind nebivolol treatment (10–40 mg/day, titrated based on BP response), participants achieving BP control (systolic BP [SBP]/diastolic BP [DBP] <140/90 mm Hg) or response (SBP decrease ≥10 mm Hg or DBP decrease ≥5 mm Hg) entered a 4-week, randomized, double-blind phase of continued nebivolol treatment (n = 102) or withdrawal to placebo (n = 105). Primary and secondary efficacy measures were changes in mean sitting DBP and SBP, respectively, analyzed using an analysis of covariance model. Safety and tolerability were also assessed. In the withdrawal phase, nebivolol and placebo groups demonstrated mean DBP increases of 1.8 and 7.7 mm Hg, respectively (P < .001), and SBP increases of 3.5 and 7.6 mm Hg (P = .011). Twenty-three (22.5%) nebivolol-treated and 18 (17.1%) placebo-treated participants experienced a treatment-emergent adverse event. No adverse events associated with β-blocker withdrawal and considered causally related to nebivolol were reported. Nebivolol withdrawal resulted in a mean BP increase near pretreatment levels and was not associated with rebound hypertension.

The present and future of the American Society of Hypertension: 2012

William B. White — 2012-05-01

The American Society of Hypertension (ASH) is entering its 28th year as I commence my term (2012–2014) as president, and it is a characteristic time to review our present status and accomplishments, as well as our future initiatives and goals for continued success as the leading US professional organization in hypertension and its related complications. After spending 27 years as a member and now fellow of the Society, several years as a member of the board of directors of ASH, and 2 years as program chair of our annual Scientific Meeting and Exposition, I feel that it is important to (1) evaluate our unique, premier scientific meeting that showcases state-of-the-art lectures and discussions in our field, (2) assess our relevance to clinical medicine through our members and our specialists' program, (3) review our role in education of physicians and other health care providers, and (4) forecast our potential to support new investigators and clinical and translational research in hypertension and related disorders.

Editorial Board

2012-05-01

Journal of the American Society of Hypertension

From the Editor

Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies

Activation of vascular p38MAPK by mechanical stretch is independent of c-Src and NADPH oxidase: influence of hypertension and angiotensin II

Angiotensin II type 2 receptor-interacting protein prevents vascular senescence

Cardiomyocyte size estimated from noninvasive measurements of left ventricular wall thickness and chamber diameter

Left ventricular hypertrophy by electrocardiography and echocardiography in the African American Study of Kidney Disease Cohort Study

Disparities in adherence to and persistence with antihypertensive regimens: an exploratory analysis from a community-based provider network

Home and clinic blood pressure responses in elderly individuals with systolic hypertension

Aliskiren-based dual- and triple-combination therapies in high-risk US minority patients with Stage 2 hypertension

Nebivolol withdrawal results in blood pressure returning toward pretreatment levels, but without rebound symptoms: phase IV randomized trial

The present and future of the American Society of Hypertension: 2012

Editorial Board

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