Journal of the American Society of Hypertension

From the Editor

Myron H. Weinberger — 2009-11-01

With this issue, Volume 3 of JASH comes to a close. As indicated elsewhere in this issue, our success would not have been possible with the dedication and expertise of our reviewers who are listed and to whom thanks and gratitude is expressed for their efforts and commitment.

The complex interaction between overweight, hypertension, and sympathetic overactivity

Carlos Feldstein, Stevo Julius — 2009-11-01

Abstract: There is ample evidence in the epidemiological and clinical literature that hypertension and overweight are closely and causally interrelated. Sympathetic nervous system (SNS) overactivity has been well documented in both hypertension and overweight, but it is not clear whether this is a coincidental finding or whether the association reflects a mechanistic role of SNS in these two interrelated clinical conditions. Whereas in this review we focus on the evidence for a primary role of SNS in the development of hypertension and overweight, it is clear that the process can be initiated from other starting points such as primary overeating or sleep apnea. After overweight evolves, hormones secreted by fat cells further accelerate SNS overactivity, weight gain, and blood pressure increase. The main thesis of this article is that regardless of where the process started, the same clinical picture of hypertension, overweight, and SNS overactivity will emerge. There is good evidence that in genetically prone individuals, prolonged SNS stimulation elicits a down regulation of beta-adrenergic receptors. This in turn decreases the ability to dissipate calories and diminishes the beta-adrenoceptor–mediated vasodilatation. We hypothesize that beta-adrenoceptor downregulation is the linchpin in the association of SNS with overweight and hypertension.

Exercise hypertension: an adverse prognosis?

Ryan G. Smith, Stanley A. Rubin, Myrvin H. Ellestad — 2009-11-01

Abstract: We sought to clarify the prognostic importance of an “exaggerated” or “hypertensive” systolic blood pressure response to exercise during an exercise test. Studies evaluating the prognosis for cardiovascular events and cardiovascular mortality in those with hypertension during exercise testing were systematically reviewed. Fourteen studies were identified. Six studies were of healthy volunteers or hypertensives. Eight studies were in subjects with known or suspected heart disease. Without established heart disease, exercise hypertension predicted cardiovascular events and cardiovascular death. However, two of the six studies included a multivariate analysis; both demonstrated no independent association. Studies in subjects with known or suspected heart disease demonstrated that exercise hypertension predicted fewer cardiac events and lesser mortality or, after multivariate adjustment, no associated risk. In a healthy population, a higher exercise blood pressure may indicate hypertension or prehypertension, instead of normal vascular function, and an associated long-term adverse prognosis. In a population with a high burden of heart disease, the highest risk subjects with the most extensive cardiac disease may not be capable of generating pressure or workload to allow the manifestation of exercise systolic hypertension. By comparison, therefore, those with exercise hypertension have a better prognosis.

O-GlcNAcylation: a novel post-translational mechanism to alter vascular cellular signaling in health and disease: focus on hypertension

2009-11-01

Abstract: O-Linked attachment of β-N-acetyl-glucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic posttranslational modification that plays a key role in signal transduction pathways. Preliminary data show that O-GlcNAcylation may represent a key regulatory mechanism in the vasculature, modulating contractile and relaxant responses. Proteins with an important role in vascular function, such as endothelial nitric oxide synthase, sarcoplasmic reticulum Ca2+-ATPase, protein kinase C, mitogen-activated protein kinases, and proteins involved in cytoskeleton regulation and microtubule assembly are targets for O-GlcNAcylation, indicating that this posttranslational modification may play an important role in vascular reactivity. Here, we will focus on a few specific pathways that contribute to vascular function and cardiovascular disease–associated vascular dysfunction, and the implications of their modification by O-GlcNAc. New chemical tools have been developed to detect and study O-GlcNAcylation, including inhibitors of O-GlcNAc enzymes, chemoenzymatic tagging methods, and quantitative proteomics strategies; these will also be briefly addressed. An exciting challenge in the future will be to better understand the cellular dynamics of this posttranslational modification, as well as the signaling pathways and mechanisms by which O-GlcNAc is regulated on specific proteins in the vasculature in health and disease.

Diagnostic accuracy of flow-mediated dilatation and intima-media thickness for the presence of significant coronary artery disease

Iana Simova, Tsvetana Katova, Stefan Denchev — 2009-11-01

Abstract: Our purpose was to determine and compare the diagnostic accuracy of flow-mediated dilatation (FMD) and intima-media thickness (IMT). Included were 543 patients. FMD was performed in 543 patients, IMT in 233, and coronary arteriography (CAG) in 442. Analyzing ROC (receiver operating characteristic) curves, FMD ≤5.64% showed 89% sensitivity, 62% specificity, 65% positive predictive value (PPV), and 88% negative predictive value (NPV) for the presence of angiographically significant coronary artery disease (CAD). IMT ≥0.788 mm had 71% sensitivity, 62% specificity, PPV 60%, and NPV 73% for the presence of advanced coronary atherosclerosis. FMD >8% or IMT <0.614 mm distinguished a group of patients with a low probability of advanced CAD (95% sensitivity for both and 91% and 81% NPV for FMD and IMT, respectively), whereas FMD ≤0% or IMT ≥1.09 mm indicated a high probability for significant coronary stenosis (specificity 95% and NPV 71 and 67%, respectively). FMD and IMT have a clinically applicable diagnostic accuracy for the presence of angiographically significant CAD with a better performance for FMD. FMD and IMT values help us define zones with high and low probability for the presence of advanced coronary atherosclerosis.

An evaluation of the efficacy of olmesartan medoxomil in Black patients with hypertension

Thomas D. Giles, Suzanne Oparil, Antonia Wang, Robert Dubiel — 2009-11-01

Abstract: Blacks appear to have a more modest blood pressure (BP) response to angiotensin receptor blocker (ARB) monotherapy than non-Blacks. This post-hoc analysis compared the BP-lowering efficacy of olmesartan medoxomil (OM), losartan potassium (LOS), and valsartan (VAL) in Black versus non-Black participants in a randomized, forced-titration study. Patients were randomized to OM 20, LOS 50, and VAL 80mg/day or placebo for 4 weeks and uptitrated to 40, 100, and 320mg/day doses, respectively, by study end. The primary end point was the mean change from baseline in diastolic BP (DBP) at week 8. All treatments produced significant reductions in mean DBP and systolic BP (SBP) in Blacks (n=150; P < .001). BP <140/90mm Hg was achieved in 35.0%, 15.6%, 29.7%, and 5.0% of Blacks receiving OM, LOS, VAL, and placebo, respectively, and in 41.0%, 21.1%, 28.8%, and 14.5% of non-Blacks receiving OM, LOS, VAL, and placebo, respectively, after 8 weeks. BP-lowering efficacy of the three agents was similar at 3 months. OM had the greatest early efficacy, with numerically greater mean reductions in DBP and SBP, and a higher proportion of Black and non-Black patients achieving goal BP of 140/90mm Hg at week 8.

Costs associated with cardiovascular events in patients with hypertension in US managed care settings

2009-11-01

Abstract: Study quantified incremental cost of cardiovascular (CV) events in 6 high-risk and compelling indication subgroups: post-myocardial infarction (MI), diabetes, diabetic nephropathy, elderly, chronic kidney disease, and prior stroke. Based on claims data from privately insured individuals with 2+ hypertension (HTN) diagnoses in 2004–2006, we estimated regression-adjusted per-member-per-month healthcare costs after CVE. Costs were compared between patients with and without a CV events, and before and after CV events in each subgroup. The following CVevents were studied: acute MI, acute coronary syndrome, angina, ventricular arrhythmia, atrial arrhythmia, heart failure, coronary artery disease, left ventricular hypertrophy, stroke, and sinus tachycardia. Of 1,598,890 HTN patients, 510,118 had ≥1 CV event. Compared with controls, healthcare costs among patients with events were significantly greater across all cost components (inpatient, outpatient, and prescription drug). Acute MI and congestive heart failure generally had the largest incremental total healthcare costs. First-quarter post-event costs were attributable to inpatient costs. CV events are costly sequelae of hypertension in high-risk and CI subgroups.

White coat hypertension in children: not rare and not benign?

Mieczyslaw Litwin, Anna Niemirska, Marcel Ruzicka, Janusz Feber — 2009-11-01

Abstract: The clinical significance of white coat hypertension (WCH) remains uncertain. We aimed to evaluate the target organ damage (TOD) in children with essential hypertension (HTN) and WCH. We retrospectively analyzed the body mass index (BMI) and ambulatory blood pressure monitoring (ABPM) in 183 untreated children aged 5 to 19 years who were referred for assessment of hypertension and had secondary hypertension ruled out. Left ventricular mass index (LVMi) and carotid intima media thickness (CIMT) were analyzed in a subset of 106 children. WCH was found in 54/183 children (29.5%) who had normal mean arterial pressure (MAP), MAP load, and MAP day/night ratio. However, the mean±SD LVMi (g/m2.7) was identical in HTN and WCH patients (38.2±10.9 vs. 37.0±11.3, P=.59); it exceeded the 95th percentile in 40% HTN and 36% WCH patients (NS). The mean CIMT was significantly higher compared with normal, but not different between HTN and WCH; it exceeded the 95th percentile in 26% HTN and 29% WCH patients. WCH was found in up to 30% of children referred for HTN. Patients with WCH have TOD comparable to that found in HTN patients despite similar BMI, significantly lower average BP and BP load and a well-preserved BP dipping pattern.

Thanks to Our Reviewers

2009-11-01

Author Index

2009-11-01

Subject Index

2009-11-01