Effective Blood Pressure Reduction Research Articles

Discovery of MT-1207: A Novel, Potent Multitarget Inhibitor as a Promising Clinical Candidate for the Treatment of Hypertension.

Herein, a series of novel arylpiperazine (piperidine) derivatives were designed, synthesized, and evaluated for mechanisms of action through in vitro and in vivo studies. The most promising compound, II-13 (later named as MT-1207), is a potent α1 and 5-HT2A receptor antagonist with remarkable IC50 in the picomolar level. Importantly, in the in vivo assay, II-13 achieved an effective blood pressure (BP) reduction in the 2K2C rat model without damaging renal function. Compound II-13, with its significant advantages in terms of pharmacological effects, pharmacokinetic parameters, and a large safety window, was extensively investigated. Moreover, data also showed that compound II-13 had fewer side effects in a postural BP assay and could prevent the onset of postural hypotension. Together, these results suggested that compound II-13 is a highly potent antihypertensive drug candidate with multitarget mechanisms of action in preclinical models. Currently, MT-1207 is in phase II hypertensive clinical trials in China.

0542 The Association Between the Effective Apnea Hypopnea Index and Blood Pressure Reduction Efficacy After Treatment

0542 The Association Between the Effective Apnea Hypopnea Index and Blood Pressure Reduction Efficacy After Treatment

The association between the effective apnea-hypopnea index and blood pressure reduction efficacy following CPAP/oxygen treatment

BackgroundThe effect of sleep apnea treatment on reducing cardiovascular disease risk remains inconclusive. This study aims to assess if the effective apnea hypopnea index (eAHI), a measure of residual sleep apnea burden post-treatment, is a factor in determining blood pressure (BP) response to continuous positive airway pressure therapy. The eAHI integrates time on therapy, residual apnea, and % of sleep time untreated. MethodsA secondary analysis of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a randomized, controlled, parallel group assessment of continuous positive airway pressure (CPAP), oxygen and sleep hygiene. The Delta-AHI (▲AHI) was defined as the difference between baseline AHI and effective AHI at 12 weeks. Logistic and linear regression models estimated the predictors for nocturnal systolic BP change following sleep apnea therapy. ResultsOne hundred and sixty-nine subjects with a mean age of 62.82 ± 6.99 years were included in the final analysis. Fifty subjects had ▲AHI ≤8/hour of sleep and 119 subjects were higher. After adjustment, baseline mean nighttime systolic blood pressure (OR 1.036, 95% CI 1.015–1.058, p: 0.001) and ▲AHI ≥8/hour (OR 2.406, 95% CI 1.116–5.185, p:0.025) were independent predictors for mean nighttime systolic blood pressure change >3 mm Hg. The higher effective AHI was negatively related with BNP (β: −2.564, SE: 1.167, p: 0.029) and positively related with troponin change (β: 0.703, SE: 0.256, p: 0.007). ConclusionThe ▲AHI was an independent predictor of the blood pressure response to sleep apnea treatment. Register numberNCT01086800.

Effects of Postural Resonance on Skin Sympathetic Nerve Activity and Blood Pressure: A Pilot Study Evaluating Vascular Tone Baroreflex Stimulation Through Biofeedback.

Heart rate and vascular tension baroreflex exhibit resonance characteristics at approximately 0.1 and 0.03Hz. In this study, we aimed to induce postural resonance (PR) through rhythmic postural adjustments. To assess the viability of this technique, we investigated the acute impacts of postural resonance on blood pressure, sympathetic nerve activity, and mood. Fifteen healthy study participants, consisting of 8 males and 7 females, were selected for this self-controlled study. Skin sympathetic nerve activity was continuously monitored during both the intervention and stress test on the experimental day. After PR intervention, the diastolic blood pressure and mean arterial pressure in the PR group exhibited significant reductions compared to the CON group (P = 0.032, CON = 71.67 ± 2.348, PR = 64.08 ± 2.35; P = 0.041, CON = 75.00 ± 2.17, PR = 81.67 ± 2.17). After PR intervention both left brachial ankle pulse wave velocity and right brachial ankle pulse wave velocity exhibited a significant reduction compared to pre-intervention levels (from 1115.86 ± 150.08 to 1048.43 ± 127.40cm/s, p < 0.001; 1103.86 ± 144.35 to 1060.43 ± 121.35cm/s, p = 0.018). PR intervention also led to a significant decrease in burst frequency and duration (P = 0.049; CON = 8.96 ± 1.17, PR = 5.51 ± 1.17) and a noteworthy decrease in burst amplitude and burst threshold during the cold-pressor test (P = 0.002; P = 0.002). Additionally, VAS scores exhibited a substantial increase following PR (P = 0.035, CON = 28.4 ± 4.49, PR = 42.17 ± 4.10). PR can induce resonance effects within the cardiovascular system, resulting in the effective reduction of blood pressure, skin sympathetic nerve activity and pulse wave velocity, and decreased burst amplitude and burst threshold of the sympathetic nerve during the cold-pressor test.

Abstract P354: Leveraging Electronic Health Records For Quality Improvement Among Patients With Markedly Elevated Blood Pressure

Introduction: Electronic health records (EHR) can improve quality of care for patients with markedly elevated blood pressure (BP). This study aimed to develop EHR-based computable algorithms to identify barriers to BP control and enhance triage and patient management. Methods: We conducted a retrospective analysis using EHR data from Yale New Haven Health System (YNHHS) employees and their dependents. Patients with markedly elevated BP had ≥2 outpatient BP readings ≥160/100 mmHg within a 180-day period. We assessed 3-month follow-up visits after BP elevation, along with the proportions of patients prescribed antihypertensives, filled prescriptions, and self-reported adherence using EHR data sources. Results: The study included 46,361 adult patients, with a mean age of 45.7 (14.5) years; 65% were female, 59% were White, and 17% were Black. Among them, 1,437 (3.3%) had markedly elevated BP, and 880 (1.9%) had consecutive markedly elevated BP readings. Among patients with markedly elevated BP, 626 (43.6%) had follow-up visits with relevant specialties within 3 months after the BP elevation. Moreover, 970 (67.5%) patients had antihypertensive prescriptions, of whom 927 (95.6%) filled their prescriptions, and among those who filled prescriptions, 806 (87.2%) reported taking the medications. Black patients were more likely to receive antihypertensive prescriptions but less likely to fill them or report taking medications (Figure). Conclusion: This study demonstrates the potential of EHR data and computable algorithms to enhance patient triage, interventions, and resource allocation for effective BP reduction among YNHHS employees.

Experiencia de 20 años en el control de la hipertensión arterial en un centro de salud en España: control estricto versus no estricto

Introduction and aimsDuring clinical trials effective reduction of blood pressure (BP) leads to a reduction in the incidence of cardiovascular (CV) morbimortality. Our main aim is to ascertain whether, under actual conditions of clinical practice, BP monitoring leads to a long-term reduction in CV events. Patients and methodsThe study was performed on 164 patients with hypertension (HT) selected among patients who came to family medicine consultations because of HT. An analysis was performed between patients who presented clinical BP lower than 140/90mmHg and those that had higher levels. When patients entered the study, they were followed up until a CV event occurred or up to a maximum of 20 years, at which time follow up ended. ResultsOf the total of 164 patients, good control of BP was attained by 93 (56.7%), and 71 did not attain good control (42.2%). In the multivariate analysis, the only predictive variable for CV events was the lack of strict control of BP (HR: 2.93; 95% CI: 1.45-5.89; p=0.003), and the female sex was protective for CV events (HR: 0.37; 95% CI: 0.18-0.74; p=0.005). ConclusionsThe fundamental predictor variable of CV morbimortality in patients with HT is the lack of HT strict control; the women also had fewer CV complications.

COMPARISON OF FIRST RESULTS OF RADIOFREQUENCY RENAL DENERVATIONS WITH FIRST AND SECOND GENERATION TECHNIQUES

Objective: A form of renal denervation, when using radiofrequency technique, thermal energy destroys the nerve-fibres around the renal artery. The Symplicity FlexTM was the first such catheter, an improved new generation version of it is the Symplicity SpyralTM catheter. In the Albert Szent-Györgyi Health Center of the University of Szeged, renal denervations were performed with both devices in hypertensive patients whose blood pressure could not be reduced to the goal range with multiple antihypertensive combinations. Design and method: With the first generation catheter, only the main branch was ablated at 4-5 points per side, and with the Symplicity SpyralTM catheter, even the segmental small branches together with the main branches were ablated at a total of at least 16-18 points per side. Results: With the old method after RDN, SBP decreased by 40 mmHg and DBP by 20 mmHg. The reduction was greatest 1 month after the intervention, 45 and 35 mm Hg. But did not reach the goal values. With new method after RDN, SBP decreased by 38 mmHg and DBP by 27 mmHg. The reduction was greatest 1 month after the intervention, 49 and 37 mm Hg. With the new the SBP was already in the target range after the intervention and remained there for 6 months. In addition, the number of antihypertensives could be significantly reduced. With the old method the goal BP value could not be achieved. Vascular complications did not occur in either case of interventions. Conclusions: Our first result with the Symplicity SpyralTM catheter according to the new concepts supports the view that more accurate ablation and preferably distal ablation can lead to more effective blood pressure reduction.

PS-BPB03-1: ASSOCIATION OF ANTIHYPERTENSIVE EFFECTS OF ESAXERENONE WITH THE INTERNAL SODIUM BALANCE IN DAHL SALT-SENSITIVE HYPERTENSIVE RATS

Background: We have recently shown that the nonsteroidal mineralocorticoid receptor blocker, esaxerenone elicits effective blood pressure reduction in Dahl salt-sensitive hypertensive (DSS) rats. Here, we investigated the potential contribution of alterations in sodium homeostasis to esaxerenone-induced blood pressure reduction. Methods: In the different experimental setups, we evaluated blood pressure by the radio-telemetry system and sodium homeostasis by an approach of sodium in (food intake) and out (urinary excretion) in a low-salt diet (LSD, 0.3% NaCl), high-salt diet (HSD, 8% NaCl), HSD with 0.001 % esaxerenone (w/w), and HSD with 0.05% furosemide fed DSS rats. Results: HSD-fed DSS rats exhibited a non-dipper type hypertension, while esaxerenone treatment but not furosemide significantly reduced the BP with a dipper pattern. The cumulative urinary sodium excretion was significantly elevated from day 6 onward both in esaxerenone- and furosemide-treated rats compared to their HSD-fed counterparts in the active period where a significant increase in Na+/K+ ratio was evident for only the esaxerenone treatment group. Sodium content in the skin, skinned carcass as well as total body level tended to reduce in esaxerenone-treated rats compared to the HSD-fed matching parts, while these values were not changed in furosemide-treated rats. Consistently, sodium balance tended to be reduced in esaxerenone-treated rats during the active period. Histological evaluation revealed that esaxerenone but not furosemide treatment significantly attenuated glomerulosclerosis and tubulointerstitial fibrosis in HSD-fed DSS rats. Collectively, these findings suggest that esaxerenone-induced blood pressure reduction is associated with the body sodium homeostasis in salt-loaded DSS rats.

Enhanced Oral NO Delivery through Bioinorganic Engineering of Acid-Sensitive Prodrug into a Transformer-like DNIC@MOF Microrod.

Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe2(μ-SCH2CH2COOH)2(NO)4] (DNIC-2) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO. In simulated gastric fluid, protonation of the BDC linker in DNIC@MOF initiates its transformation into a DNIC@tMOF microrod, which consisted of DNIC-2 well dispersed and confined within the BDC-based framework. Moreover, subsequent deprotonation of the BDC-based framework in DNIC@tMOF under simulated intestinal conditions promotes the release of DNIC-2 and NO. Of importance, this discovery of transformer-like DNIC@MOF provides a parallel insight into its stepwise transformation into DNIC@tMOF in the stomach followed by subsequent conversion into molecular DNIC-2 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive DNIC-2, oral administration of DNIC@MOF results in a 2.2-fold increase in the oral bioavailability of NO to 65.7% in mice and an effective reduction of systolic blood pressure (SBP) to a ΔSBP of 60.9 ± 4.7 mmHg in spontaneously hypertensive rats for 12 h.

Abstract 13682: Remote Hypertension Management During the COVID-19 Pandemic

Introduction: During the COVID-19 pandemic, much of routine chronic disease monitoring and management via outpatient visits was deferred, revealing a disruption in care delivery. We demonstrate that an established remote care delivery program enabled delivery of uninterrupted, effective care. Methods: The team-based Digital Care Transformation (DCT) program remotely manages hypertension via monitoring home blood pressure (BP) readings that are automatically transmitted, using a team of navigators who follow expert-designed titration algorithms. We examined all patients enrolled in this program during the first six months of the health emergency in Boston (3/15- 9/15/2020) to assess outcomes at a cutoff one year into the pandemic (3/15/2021). We also assessed healthcare utilization by analyzing monthly PCP and non-PCP visits, as well as BPs measured, in the year prior to enrollment compared to the study year 3/15/2020 - 3/15/2021. Results: 651 patients were enrolled and transmitted a home baseline BP during the first week. 475 patients (73%) had sustained hypertension according to home BPs. PCP visits decreased by 50% and non-PCP visits by 40% over this period (both p&lt;0.001.) The weekly mean BP at program baseline was 145/84 + 15/9 mmHg, and at program exit was 135/79 + 15/10 mmHg (p&lt;0.001.) Assessing the 240 patients who completed all follow-up, maintenance BP was 125/73 + 7/7 mmHg (p&lt;0.001.) Control was reached with a mean 2.3 medication titrations. While in the program, patients received an average of 8.2 phone calls/month and recorded 32.4 individual BP measurements monthly. Conclusions: While in-person clinical care delivery during the COVID-19 pandemic decreased dramatically, an established remote health delivery program continued to deliver effective BP reduction and achieve clinical targets. Further study is warranted to understand the role remote care can play in hypertension management as we exit the pandemic.

Зміни гемодинаміки у разі неускладнених гіпертонічних кризів

Aim: to improve the results of treatment of uncomplicated hypertensive crises at the prehospital stage by studying the state of systemic hemodynamics, determining the balance of the autonomic nervous system, in patients with hypertension in uncomplicated hypertensive crises. A study of 206 patients with documented stage II hypertension, 75 people who had a stable course of the disease and were examined on an outpatient basis. Almost healthy 31 people the indicators of heart rate variability in the examined persons were analyzed. For diagnosis were recorded according to the standard method “Cardiolab” (KhAI-Medika, Kharkіv). Assessment of the initial vegetative status in patients with hypertension and the direction of its changes after taking antihypertensive drugs, conducted within the framework of acute drug tests, suggests the possibility of differentiated choice of drug therapy and to predict its effectiveness. Reducing blood pressure significantly reduced the % risk, as on a SCORE scale of 5.83 [3.68; 8.66] % to 3.39 [1.87; 6.65] %, (p &lt; 0.05) and Framingham Risk Score with 31.93 [22.72; 43.25] % to 21.74 [15.35; 31.43] %, (p &lt; 0.05). The provision of EMD to patients with GC was generally effective and was accompanied by a significant decrease in CAT by – 3.93 % and DBP by – 12.5 %. Effective reduction of blood pressure led to a reduction in cardiovascular risk, both on the SCORE scale and the Framingham Risk Score. Assignment of differentiated EMD to patients with HA depending on the balance of the (autonomic nervous system) ANS was effective and was accompanied by normalization of total peripheral vascular resistance.

Abstract 118: Mitochondrial Fission in Vascular Cells Mediates Hypertensive Vascular Remodeling and Inflammation

Worldwide, high blood pressure affects nearly 1/3 of adults and is the most common cause of cardiovascular disease-related deaths. While there is effective blood pressure reduction therapy, the underlying pathophysiology leading to the hypertensive end-organ damage including the mechanism of vascular remodeling remains poorly understood. Mitochondrial dysfunction has been implicated in various cardiovascular diseases. Currently, there is little understanding on mechanism and role of mitochondrial quality control in hypertension. Our data shows that activation of mitochondrial fission via a dynamin-related GTPase, Drp1, is involved in hypertensive vascular remodeling. In vivo, 8-week old male C57BL/6 mice were infused with AngII (1000ng/kg/min) for 2 weeks with or without treatment with a Drp1 inhibitor, mdivi1, (25 mg/kg ip every other day). Mdivi1 suppressed vascular hypertrophy and perivascular fibrosis induced by AngII in aorta (thickness Mean±SEM: 0.291±.012 AngII only vs. 0.275±.006 AngII + mdivi1; p=0.07) and heart (LV wall thickness Mean±SEM: 0.423±.034 AngII only vs. 0.219±.017 AngII + mdivi1; p&lt;0.01). Mdivi1 also inhibited AngII-induced left ventricular hypertrophy but not the elevated blood pressure measured continuously by telemetry. Reduced KDEL and nitro-tyrosine staining in coronary and renal arteries suggests attenuation of vascular ER stress and oxidative stress, respectively, in mdivi1 treated mice. To assess the role of acute signaling in this model C57BL/6 mice went through the same protocol for only 3 days. Several inflammatory targets (VCAM1, MMP2, HMGB1) were upregulated in aortas of AngII stimulated mice and attenuated with mdivi1 treatment. In addition, inhibition of mitochondrial fission (mdivi1) attenuated AngII-induced leukocyte adhesion at mesenteric micro-circulation assessed by intravital microscopy. In vitro , Ang-II induced inflammatory response in rat aortic endothelial cells (ECs) with THP-1 adhesion assay was attenuated by mdivi1 and an ER stress inhibitor (4-PBA). In conclusion, these data suggest that inhibition of mitochondrial fission prevents AngII-induced cardiovascular remodeling and inflammation through attenuating VSMC as well as EC signaling events.

Effective blood pressure reduction: results of the regional program “DOVERIE”

In clinical practice, quite often the practitioner faces difficulties in correcting arterial pressure in patients with arterial hypertension. Patients mostly for various reasons prefer to be treated with generic drugs, sometimes to the detriment of the effectiveness of treatment. The regional study conducted by us clearly showed the presence of additional possibilities of the original drug Prestans (Servier, France) in reducing blood pressure compared to equivalent dosages of generic fixed combinations.

Abstract 061: Mitochondrial Fission Mediates Hypertensive Vascular Remodeling and Aneurysm Development

The prevalence of hypertension is growing steadily with mortality reaching 30,221. While effective blood pressure reduction therapy exists, the underlying pathophysiology leading to vascular remodeling remains poorly understood. Hypertension is a risk factor for abdominal aortic aneurysms (AAA) which when ruptured has 80% mortality. Surgery is the only treatment due to insufficient understanding of the disease process. Mitochondrial dysfunction has been implicated in various cardiovascular diseases but the role of mitochondrial dynamics, a mechanism regulating mitochondrial homeostasis, is under-investigated in hypertension and aneurysm. Our data shows that enhancement of mitochondrial fission via a GTPase, Drp1, in vascular smooth muscle cells (VSMCs) is involved in hypertensive vascular remodeling and aneurysm. In vitro, AngII induced transient mitochondrial fission (2-4 h) and enhanced mitochondrial ROS production in rat aortic VSMCs. Mitochondrial fission, mito-ROS generation, total cell protein, cell volume and extracellular collagen increased by 100 nM AngII were all attenuated in VSMCs by pretreatment with adenovirus encoding Drp1 siRNA/control non-silencing RNA or mdivi1, a Drp1 inhibitor. In vivo, male C57BL/6 mice were infused with AngII (1000ng/kg/min) for 2 weeks (hypertensive remodeling model) +/- mdivi1 (25 mg/kg ip every other day) or infused with AngII for 4 weeks with beta-aminopropionitrile in the drinking water (AAA model) +/- mdivi1 (25 mg/kg ip 3x per week). In the 2-week AngII model, mdivi1 suppressed left ventricular hypertrophy, vascular hypertrophy and perivascular fibrosis induced by AngII in aorta, heart and kidney, independent of blood pressure. In the AAA model, mdivi1 attenuated aneurysm development (External AA diameter (mm) Mean±SEM: 2.15±0.13 vs 1.49±0.07 (, p&lt;0.01). Reduced KDEL and nitro-tyrosine staining in aorta (4w model), coronary and renal arteries (2w) in mdivi1 treated mice, suggests attenuation of ER stress and oxidative stress, respectively. These data suggest that inhibition of mitochondrial fission prevents AngII-induced cardiovascular remodeling and aneurysm development independently of hypertension via ER stress/mito-ROS mechanisms.

Clinical factors predicting blood pressure reduction after catheter-based renal denervation.

IntroductionRenal denervation (RD) can lead to a significant and sustained decrease in mean values of arterial blood pressure (BP). However, there is still a subset of patients without a significant BP drop after RD (non-responders).AimTo compare characteristics of RD responders to RD non-responders and to identify the clinical predictors of BP reduction.Material and methodsThirty-one patients with diagnosed resistant hypertension underwent RD. Three years after RD the analysis of BP reduction was performed in regard to the baseline patient characteristics.ResultsAfter 3 years’ follow-up a 10% or more reduction of systolic baseline BP was observed in 74% of patients. Ten percent or more reduction of diastolic baseline BP was observed in 71% of patients. Among responders we observed the following risk factors: hypercholesterolemia in 70%, body mass index (BMI) > 30 kg/m2 in 55%, diabetes mellitus in 35%, current smoking in 5%. Comorbidity included coronary artery disease (CAD) in 30%, cardiomyopathy in 10%, chronic obstructive pulmonary disease (COPD) in 10%, renal insufficiency in 10%, and ventricular arrhythmia in 5%. Among non-responders we observed the following risk factors: hypercholesterolemia in 38%, diabetes mellitus type 2 in 38% and BMI > 30 kg/m2 in 86%. Comorbidity included CAD in 50% and cardiomyopathy in 13% of patients.ConclusionsA 10% reduction of systolic baseline BP was observed in 74% of patients 3 years after renal denervation. Clinical factors like COPD, chronic kidney disease 3a, female sex and hypercholesterolemia increase the chances of effective reduction of BP.

Moving Beyond Office Blood Pressure to Achieve a Personalized and More Precise Hypertension Management: Which Way to Go?

Blood pressure (BP) has a well-documented, continuous relationship with cardiovascular risk,1 and hypertension has a huge impact at population level in terms of cardiovascular complications and mortality.2 On the other hand, BP reduction in hypertensive subjects is easily achievable and provides dose-dependent prognostic benefits.3 While evidence from large-scale trials represents the backbone for clinical decisions, physicians must strive to achieve a personalized approach to disease management in individual subjects, including those with hypertension and cardiovascular diseases. Indeed, current use of terms such as personalized or precision medicine refers to patients’ care guided by individual molecular characteristics combined with up-to-date diagnostic methods. Specifically, when considering hypertension management, it has been proposed that the intensity of BP lowering should be personalized according to individual cardiovascular risk profile, meaning that (1) prompt BP control should mainly be achieved in high-risk patients; and (2) achievement of lower BP levels may be beneficial in subjects at higher cardiovascular risk. Evidence is available that in high-risk individuals, absolute benefits of treatment are greatest, and pharmacological treatment is more cost-effective.4 On the other hand, when targeting high-risk hypertensive subjects, the large reduction of absolute cardiovascular risk obtained by treatment is accompanied by a considerable residual risk. The latter represents the excess of risk due to the presence of irreversible organ damage, which persists even after achieving optimal control of BP and other risk factors.5 On the contrary, an effective BP reduction by treatment obtained earlier in the clinical history of hypertension, that is in still low-risk individuals, leaves much less residual risk and, thus, offers more solid lifelong cardiovascular protection.5 This kind of reasoning supports the importance of achieving effective and early BP control also in subjects with mild–moderate BP elevations and low cardiovascular risk. Whether lower BP targets are justified …

Monotherapy and Dual Combination Therapies Based on Olmesartan: A Comprehensive Strategy to Improve Blood Pressure Control.

Olmesartan medoxomil is an antihypertensive drug of the class of angiotensin II type 1 (AT1) receptor antagonists (or blockers), characterized by tight and prolonged binding to AT1 receptor compared to other molecules within the same class. These characteristics produce effective and sustained blood pressure reductions in hypertensive patients at different cardiovascular risk profile with a good tolerability profile. After a brief description of the pharmacological characteristics of olmesartan, we will provide a thorough overview of the clinical studies that investigated its efficacy and safety in the clinical management of hypertensive patients both in monotherapy and in dual combination therapies with either thiazide diuretics or calcium channel blockers. These studies demonstrated that olmesartan-based antihypertensive strategy may indeed provide sustained BP control over the 24-h period in a wide proportion of hypertensive patients, thus contributing to a substantial progress in hypertension management. Finally, since growing evidence suggest that olmesartan may also exert potential favourable effects at vascular level, thereby antagonizing the vascular inflammatory process involved in the development and progression of atherosclerosis, the main clinical studies addressing this issue will be also discussed.

Acute Blood Pressure Management in Intracerebral Hemorrhage: Equipoise Resists an Attack.

There are 2 competing rationales for acute blood pressure (BP) management in primary intracerebral hemorrhage (ICH). A conservative approach is predicated on the possibility that cerebral blood flow is passively dependent on perfusion pressure, whereas an aggressive approach has been hypothesized to improve outcomes via a reduction in early hematoma expansion. Although the latter is a biologically plausible hypothesis, this relationship has not been consistently demonstrated in retrospective or prospective studies, likely reflecting the fact that hematoma expansion is dependent on multiple factors, in particular the time from symptom onset to diagnostic scan, and baseline volume.1 The most effective way to address this clinical equipoise is, therefore, a randomized controlled trial of the 2 different BP management strategies. In the ATACH-II trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage II), 1000 patients were randomized to a systolic BP (SBP) target of 110 to 139 mm Hg or 140 to 179 mm Hg, after the Data Safety Monitoring Board–recommended trial suspension on the basis of a futility analysis.2 Despite a robust and early difference in achieved BP between the 2 groups, the 90-day mortality and disability rate was unaffected (38.7% versus 37.7%; P =0.84). The reasons for this lack of treatment effect are not clear. There was no effect on the frequency of hematoma expansion, although the trend was in favor …

BPS 02–35 COMPARATIVE EFFICACY AND SAFETY OF THERAPY WITH LCZ696 AND NGIOTENSIN-RECEPTOR BLOCKER IN PATIENTS WITH HYPERTENSION

Objective: The treatment of resistant hypertension is challenging LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 receptor. Previous trials indicated that the dual actions of LCZ696 lead to further lowering of blood pressure (BP), compared with the angiotensin-receptor blocker. We therefore conducted a meta-analysis to evaluate the efficacy and safety of therapy with LCZ696 and ngiotensin-receptor blocker in patients with hypertension on major cardiovascular outcomes. Design and Method: RCTs were obtained from searches of PubMed, EmBase, and the Cochrane Library electronic databases until Feb. 2016. The effects of LCZ696 on systolic BP, diastolic BP and 24-h ambulatory BP or adverse events in patients were included for analysis. The quality assessment, sensitivity analyses, subgroup analyses, and publication biases were also conducted. Results: Five Randomized controlled trials (RCTs) included with 1927 patients were eligible. Relative to the ngiotensin-receptor blocker, LCZ696 treatment in patients decreased systolic BP (−2.70 mmHg, −4.61 to −0.80, p < 0.001), diastolic BP (2.97 mmHg, 95% CI −4.88 to −1.07, p < 0.001), 24-h ambulatory diastolic BP (−2.17 mmHg, 95% CI −3.28 to −1.06; p < 0.001), 24-h ambulatory systolic (BP −2.04 mmHg, −2.61 to −0.73, p < 0.001). No cases of angio-oedema were reported, only three serious adverse events occurred, of which none was judged to be related to the study drug, and no patients died. The LCZ696-based regimen was generally well-tolerated and could present a treatment option for hypertension inpatients especially in effective BP reduction. Conclusions: Compared with ARB, LCZ696 has proved to be a potent, effective antihypertensive agent, complementary and fully additive reduction of blood pressure. LCZ696 was shown to be safe and well tolerated.

Effect of Renal Sympathetic Denervation on Specific MicroRNAs as an Indicator of Reverse Remodeling Processes in Hypertensive Heart Disease.

A total of 90 consecutive patients undergoing renal sympathetic denervation (RSD) were included in this study. A significant reduction in office systolic blood pressure (SBP) of 21.1 mm Hg (P<.001) was documented 6 months after RSD. At this time point, circulating concentrations of microRNA (miR)-133a were significantly increased (sevenfold; P<.001) compared with baseline values. Correlation analysis showed a significant relationship between baseline SBP values and SBP reduction (P<.001) as well as between miR-133a baseline levels and the increase in miR-133a expression (P<.001) after the 6-month follow-up. The effect of RSD on miR-133a expression was significantly greater in patients at high risk for hypertensive heart disease. In addition to the effective blood pressure reduction in response to RSD, this study demonstrates an effect of RSD on miR reflecting cardiovascular reverse remodeling processes. Thus, these results provide information on a beneficial effect of RSD on cardiac recovery in patients at high risk for hypertensive heart disease.