Since noninvasive central blood pressure (BP) measuring devices are readily available, central BP has gained growing attention regarding its clinical application in the management of hypertension. The disagreement between central and peripheral BP has long been recognized. Some previous studies showed that noninvasive central BP may be better than the conventional brachial BP in association with target organ damages and long-term cardiovascular outcomes. Recent studies further suggest that the central BP strategy for confirming a diagnosis of hypertension may be more cost-effective than the conventional strategy, and guidance of hypertension management with central BP may result in less use of medications to achieve BP control. Despite the use of central BP being promising, more randomized controlled studies comparing central BP-guided therapeutic strategies with conventional care for cardiovascular events reduction are required because noninvasive central and brachial BP measures are conveniently available. In this brief review, the rationale supporting the utility of central BP in clinical practice and relating challenges are summarized.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jch.13758

Central blood pressure for the management of hypertension: Is it a practical clinical tool in current practice?

G-protein-coupled receptor kinase 4 (GRK4) gene variants, via impairment of renal dopamine receptor and enhancement of renin-angiotensin system functions, cause sodium retention and increase blood pressure. Whether GRK4 and the angiotensin type 1 receptor (AT(1)R) interact in the aorta is not known. We report that GRK4 is expressed in vascular smooth muscle cells of the aorta. Heterologous expression of the GRK4γ variant 142V in A10 cells increased AT(1)R protein expression and AT(1)R-mediated increase in intracellular calcium concentration. The increase in AT(1)R expression was related to an increase in AT(1)R mRNA expression via the NF-κB pathway. As compared with control, cells expressing GRK4γ 142V had greater NF-κB activity with more NF-κB bound to the AT(1)R promoter. The increased AT(1)R expression in cells expressing GRK4γ 142V was also associated with decreased AT(1)R degradation, which may be ascribed to lower AT(1)R phosphorylation. There was a direct interaction between GRK4γ and AT(1)R that was decreased by GRK4γ 142V. The regulation of AT(1)R expression by GRK4γ 142V in A10 cells was confirmed in GRK4γ 142V transgenic mice; AT(1)R expression was higher in the aorta of GRK4γ 142V transgenic mice than control GRK4γ wild-type mice. Angiotensin II-mediated vasoconstriction of the aorta was also higher in GRK4γ 142V than in wild-type transgenic mice. This study provides a mechanism by which GRK4, via regulation of arterial AT(1)R expression and function, participates in the pathogenesis of conduit vessel abnormalities in hypertension.

Role of GRK4 in the Regulation of Arterial AT1 Receptor in Hypertension

Introduction
Central blood pressure (BP), an important measure of cardiovascular risk, has been shown to be effectively reduced by calcium channel blockade with amlodipine (AML) plus renin–angiotensin system blockade by the angiotensin-converting enzyme inhibitor, perindopril (PER). The aim of the SEVITENSION study was to compare the central effects of PER/AML against renin–angiotensin system blockade with the angiotensin II receptor blocker olmesartan (OLM) plus AML.

/pdf/erratum-to-the-fixed-dose-combination-of-olmesartan-8o0tqzakif.pdf

Erratum to: The Fixed-Dose Combination of Olmesartan/Amlodipine Was Superior in Central Aortic Blood Pressure Reduction Compared with Perindopril/Amlodipine: A Randomized, Double-Blind Trial in Patients with Hypertension

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly used anti-hypertensive medications in a number of clinical settings. They are often used interchangeably, but we pose the provocative question as to whether they should be. We review the literature to evaluate for any differences in efficacy between the two classes in order to determine if the greater side effects associated with angiotensin-converting enzyme inhibitors are offset by any advantageous effects on outcomes to warrant their use over angiotensin receptor blockers. In many clinical scenarios, the data supports similar efficacy between ACE inhibitors and ARBs, while in a minority of others, there are murky signals from previous trials that suggest ACE inhibitors may be better. However, when reviewing the literature in its entirety, and taking into account recently published pooled analysis and head to head trials, it is reasonable to conclude that ACE inhibitors and ARBs have similar efficacy. This is in contrast to data on adverse effects, which consistently favors the use of ARBs. From the available data, it is reasonable to conclude that ACE inhibitors and ARBs have equal efficacy yet unequal adverse effects. It is in this context that we take the provocative stance that ACE inhibitors should not be used to treat hypertension.

/pdf/should-angiotensin-converting-enzyme-inhibitors-ever-be-used-1zvazhpvp2.pdf

Should Angiotensin-Converting Enzyme Inhibitors ever Be Used for the Management of Hypertension?

Despite the improvements in the management of hypertension during the last three decades, it continues to be one of the leading causes of cardiovascular morbidity and mortality worldwide. Effective and sustained reductions in blood pressure (BP) reduce the incidence of myocardial infarction, stroke, congestive heart failure and cardiovascular death. However, the proportion of patients who achieve the recommended BP goal (< 140/90 mmHg) is persistently low, worldwide. Poor adherence to therapy, complex therapeutic regimens, clinical inertia, drug-related adverse events and multiple risk factors or comorbidities contribute to the disparity between the potential and actual BP control rate. Previously we published a practical therapeutic platform for the treatment of hypertension based on clinical evidence, guidelines, best practice and clinical experience. This platform provides a personalised treatment approach and can be used to improve BP control and simplify treatment. It uses long-acting, effective and well-tolerated angiotensin receptor blocker (ARB) olmesartan, in combination with a calcium channel blocker amlodipine, and/or a thiazide diuretic hydrochlorothiazide. These drugs were selected based on the availability in most European Countries of single-pill, fixed formulations in a wide range of doses for both dual- and triple-drug combinations. The platform approach could be applied to other ARBs or angiotensin-converting enzyme inhibitors available in single-pill, fixed-dose combinations. Here, we present an update, which takes into account the results of the recently published studies and extends the applicability of the platform to common conditions that are often neglected or poorly considered in clinical practice guidelines.

/pdf/personalised-single-pill-combination-therapy-in-hypertensive-4ccgwvj8ld.pdf

Personalised Single-Pill Combination Therapy in Hypertensive Patients: An Update of a Practical Treatment Platform

Background: Angiotensin type 1 receptor blockers are recommended for first-line antihypertensive treatment. Methods: We performed a pooled-analysis of 20 post-authorization surveys of olmesartan involving 156,682 hypertensive patients. Olmesartan was used as monotherapy or in combination with other antihypertensive drugs, for example, hydrochlorothiazide. Objectives: We assessed the safety of olmesartan by monitoring adverse drug reactions (ADRs). The number of patients achieving systolic and diastolic blood pressure (BP) targets (< 140/90 mmHg in the overall population, < 130/80 mmHg in high-risk patients) or responding to treatment (BP decrease of ≥ 20/10 mmHg) was also determined. Results: In all, 43.8% of patients received olmesartan monotherapy, 29% olmesartan with hydrochlorothiazide and 27.2% olmesartan in combination with other antihypertensives. The frequency of ADRs was 0.4% and not altered by dose, age ≥ 65 years or presence of co-morbidities. About 90% of patients were responders. Blood pressu...

Safety and efficacy of olmesartan: an observational pooled-analysis of 156,682 hypertensive patients

Efficacy of Sevikar® compared to the combination of perindopril plus amlodipine on central arterial blood pressure in patients with moderate-to-severe hypertension: Rationale and design of the SEVITENSION study.

Angie Schaefer

Papers

Erratum to: The Fixed-Dose Combination of Olmesartan/Amlodipine Was Superior in Central Aortic Blood Pressure Reduction Compared with Perindopril/Amlodipine: A Randomized, Double-Blind Trial in Patients with Hypertension

Safety and efficacy of olmesartan: an observational pooled-analysis of 156,682 hypertensive patients

Efficacy of Sevikar® compared to the combination of perindopril plus amlodipine on central arterial blood pressure in patients with moderate-to-severe hypertension: Rationale and design of the SEVITENSION study.