Mm Hg Reduction In Blood Pressure Research Articles

Cost-effective analysis of enalapril, amlodipine, and enalapril plus amlodipine combination in newly diagnosed patients of hypertension: A pharmacoeconomic comparison of the antihypertensive efficacy of drugs

Hypertension (HTN) is a chronic condition with severe complications, so early detection and effective management are essential to prevent cardiovascular events and reduce the associated economic burden. This study aims to compare the cost-effectiveness of enalapril, amlodipine, and their combination in terms of blood pressure reduction, considering overall efficacy and economic implications. A prospective, observational cost-effectiveness analysis was conducted in 150 newly diagnosed hypertensive patients who were prescribed either enalapril (5 mg), amlodipine (5 mg), or enalapril plus amlodipine (2.5 mg each). The primary outcome was the difference in systolic and diastolic blood pressure between baseline and follow-up, as well as the evaluation of overall efficacy and cost. Based on the data, statistical analysis was carried out using ANOVA and post hoc Tukey tests for drug efficacy, and cost-effectiveness was compared using MS Excel. After 30 days, all treatments significantly reduced systolic and diastolic blood pressure (p = 0.0001). The combination therapy with a lower dose showed superior efficacy in blood pressure reduction and was most cost-effective, requiring less expense for a 1 mmHg reduction in blood pressure compared to individual drugs with a higher dose. Quality of life assessment favored low-dose combination therapy, with fewer reported adverse effects. The combinationof amlodipine and enalapril at a lower dose demonstrated superior cost-effectiveness, efficacy in blood pressure reduction, and a favorable impact on patients' quality of life compared to individual drugs at a higher dose. This suggests that combination therapy may be a preferred option in the management of hypertension, emphasizing the importance of considering both clinical and economic factors in treatment decisions.

Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior.

Brain and muscle ARNT-like 1 (BMAL1) is a core circadian clock protein and transcription factor that regulates many physiological functions, including blood pressure (BP). Male global Bmal1 knockout (KO) mice exhibit ∼10 mmHg reduction in BP, as well as a blunting of BP rhythm. The mechanisms of how BMAL1 regulates BP remains unclear. The adrenal gland synthesizes hormones, including glucocorticoids and mineralocorticoids, that influence BP rhythm. To determine the role of adrenal BMAL1 on BP regulation, adrenal-specific Bmal1 (ASCre/+ ::Bmal1) KO mice were generated using aldosterone synthase Cre recombinase to KO Bmal1 in the adrenal gland zona glomerulosa. We confirmed the localization and efficacy of the KO of BMAL1 to the zona glomerulosa. Male ASCre/+ ::Bmal1 KO mice displayed a shortened BP and activity period/circadian cycle (typically 24 h) by ∼1 h and delayed peak of BP and activity by ∼2 and 3 h, respectively, compared with littermate Cre- control mice. This difference was only evident when KO mice were in metabolic cages, which acted as a stressor, as serum corticosterone was increased in metabolic cages compared with home cages. AS Cre/+ ::Bmal1 KO mice also displayed altered diurnal variation in serum corticosterone. Furthermore, these mice have altered eating behaviors where they have a blunted night/day ratio of food intake, but no change in overall food consumed compared with controls. Overall, these data suggest that adrenal BMAL1 has a role in the regulation of BP rhythm and eating behaviors.

Effects of pharmacist interventions on cardiovascular risk factors and outcomes: An umbrella review of meta-analysis of randomized controlled trials.

To grade the evidence from published meta-analyses of randomized controlled trials (RCTs) that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes. MEDLINE, Embase, and the Cochrane Library were searched from database inception to July 2021. Meta-analyses of RCTs were eligible. Quality of evidence were assessed by GRADE approach. From 9308 publications, 149 full-text articles were evaluated for eligibility, and 24 studies with 85 unique meta-analyses that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes were selected. Overall, 71.7% (61/85) of unique meta-analyses showed significant impacts of pharmacist intervention. For the quality of evidence, 63.4% of meta-analyses had large heterogeneity (I2 > 50%) while 1.2, 16.5, 32.9 and 49.4% of meta-analyses were graded as high, moderate, low and very low quality based on GRADE approach, respectively. Among meta-analyses with moderate quality, pharmacist interventions significantly mitigated risk factors (including 6/3mmHg reduction of blood pressure, increased the rate of lipid control, glucose control and smoking cessation (pooled odds ratio, [95% confidence interval] 1.91 [1.55, 2.35], 3.11 [2.3, 4.3] and 2.3 [1.33, 3.97], respectively) and improved medication adherence (1.67 [1.38, 2.02]). Furthermore, pharmacist interventions significantly reduced all-cause mortality (0.72 [0.58, 0.89]) and improved quality of life in patients suffering from chronic heart failure. This umbrella review found convincing evidence that pharmacist intervention can provide a wide range of benefits in cardiovascular disease management, ranging from risk factor control, improvement in medication adherence and, in some settings, reduction in morbidity and mortality.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Blood Pressure Lowering and Sodium-Glucose Co-transporter 2 Inhibitors (SGLT2is): More Than Osmotic Diuresis.

This is an update of data regarding changes in blood pressure using sodium-glucose co-transporter 2 inhibitors (SGLT2i) for the treatment of diabetes. The mechanism of blood pressure lowering by SGLT2i was thought to be due to their osmotic diuretic effects. New data, however, has emerged from meta-analyses and studies of people with impaired kidney function demonstrating similar or greater magnitudes of blood pressure reduction in the absence of significant glycosuria. Potential additional mechanisms are proposed and reviewed. Two separate meta-analyses in over 10,000 participants combined demonstrate an average of 4/2 mmHg reduction in blood pressure by SGLT2i. This includes consistency between measurements of in-office and ambulatory blood pressure monitoring. This reduction extends to decreases in nocturnal blood pressure of 2.6 mmHg systolic pressure. These reductions in blood pressure by SGLT2i are also present when added to ongoing treatment with ACE inhibitors or ARBs. In one study, dapagliflozin, when added to a regimen of a renin-angiotensin-aldosterone system (RAAS) antagonist and a diuretic, further lowered in-office systolic pressure by 2.4 mmHg. In contrast, when prescribed to those on a RAAS antagonist plus a calcium channel blocker or RAAS antagonist plus a beta blocker, systolic pressure decreased 5.4 mmHg. Lastly, post hoc analyses of major cardiovascular outcome trials across the spectrum of estimated glomerular filtration rates from 30 to 80 ml/min/1.73 m2 demonstrated similar magnitudes of BP reduction in spite of far less reduction in glucosuria among those with advanced kidney disease. Moreover, recent data implicate the potential for increased ketones associated with SGLT2i contributing to blood pressure lowering in advanced-stage kidney disease. SGLT2i are well established to lower blood pressure. Their mechanism appears to be multifactorial and has a hemodynamic as well as metabolic component contributing to this reduction.

Abstract 005: Loss of Interleukin 21 Protects Against Hypertension and Associated Inflammation and End Organ Damage

T cell derived cytokines such as interferon gamma (IFNγ) and interleukin 17A (IL17A) are upregulated by and can promote angiotensin II-induced hypertension and end-organ damage. Interleukin 21 (IL21) is produced primarily by T follicular helper (Tfh) cells and has the potential to promote IL17A and IFNγ production from T effector cells while inhibiting T regulatory cells. IL21 is also a potent activator of germinal center (GC) B cells. Thus, we hypothesize that IL21 promotes hypertension and hypertensive end-organ damage through its effect on T cell polarization and GC B cell activation. The data indicate that indeed IL21 -/- mice exhibit a 30 mmHg reduction in blood pressure in response to 4 weeks of angiotensin II (Ang II) infusion compared to age-matched wild type (WT) mice (p=0.0275). IL21 mRNA expression increases 1.5 fold in splenic T cells in response to Ang II infusion (p=0.015). Moreover, Tfh cells and GC B cells are increased in the aortas of WT mice after Ang II infusion (p=0.0136 and p=0.0067, respectively). Further, IL17A production from splenic CD4+ T cells and IFNγ production from splenic CD8+ T cells was reduced in IL21 -/- mice compared to WT mice (p=0.0025 and p=0.0237, respectively) following Ang II infusion. Renal function was assessed by measuring albuminuria. WT mice developed 2-fold more albuminuria compared to IL21 -/- mice in response to Ang II infusion (p=0.0349). Lastly, Ang II infusion impaired endothelium-dependent relaxation to acetylcholine in mesenteric vessels from WT mice (52.9% vs 17.5%; p=<0.0001). IL21 -/- mice demonstrated moderately impaired endothelium-dependent relaxation at baseline (34.9%) but interestingly, there was no further impairment in these vessels following Ang II infusion. Taken together, these studies suggest that IL21 and the Tfh cell–GC B cell axis may play a key role in hypertension and hypertensive end-organ damage.

Dexmedetomidine Reduces Shivering during Mild Hypothermia in Waking Subjects.

Background and PurposeReducing body temperature can prolong tolerance to ischemic injury such as stroke or myocardial infarction, but is difficult and uncomfortable in awake patients because of shivering. We tested the efficacy and safety of the alpha-2-adrenergic agonist dexmedetomidine for suppressing shivering induced by a rapid infusion of cold intravenous fluids.MethodsTen subjects received a rapid intravenous infusion of two liters of cold (4°C) isotonic saline on two separate test days, and we measured their core body temperature, shivering, hemodynamics and sedation for two hours. On one test day, fluid infusion was preceded by placebo infusion. On the other test day, fluid infusion was preceded by 1.0 μg/kg bolus of dexmedetomidine over 10 minutes.ResultsAll ten subjects experienced shivering on placebo days, with shivering beginning at a mean (SD) temperature of 36.6 (0.3)°C. The mean lowest temperature after placebo was 36.0 (0.3)°C (range 35.7-36.5°C). Only 3/10 subjects shivered on dexmedetomidine days, and the mean lowest temperature was 35.7 (0.4)°C (range 35.0-36.3°C). Temperature remained below 36°C for the full two hours in 6/10 subjects. After dexmedetomidine, subjects had moderate sedation and a mean 26 (13) mmHg reduction in blood pressure that resolved within 90 minutes. Heart rate declined a mean 23 (11) bpm after both placebo and dexmedetomidine. Dexmedetomidine produced no respiratory depression.ConclusionDexmedetomidine decreases shivering in normal volunteers. This effect is associated with decreased systolic blood pressure and sedation, but no respiratory depression.

Antihypertensive Effect of Celery Seed on Rat Blood Pressure in Chronic Administration

This study investigated the effects of different celery (Apium graveolens) seed extracts on blood pressure (BP) in normotensive and deoxycorticosterone acetate-induced hypertensive rats. The hexanic, methanolic, and aqueous-ethanolic extracts were administered intraperitoneally and their effects on BP and heart rate (HR) were evaluated in comparison with spirnolactone as a diuretic and positive control. Also, the amount of n-butylphthalide (NBP), as an antihypertensive constituent, in each extract was determined by HPLC. The results indicated that all extracts decreased BP and increased the HR in hypertensive rats, but had no effect on normotensive rats. The data showed that administration of 300 mg/kg of hexanic, methanolic, and aqueous-ethanolic (20/80, v/v) extracts of the celery seed caused 38, 24, and 23 mmHg reduction in BP and 60, 25, and 27 beats per minute increase in the HR, respectively. Also, the HPLC analysis data revealed that the content of NBP in the hexanic extract was 3.7 and 4 times greater than methanolic and aqueous-ethanolic extracts. It can be concluded that celery seed extracts have antihypertensive properties, which appears to be attributable to the actions of its active hydrophobic constitutes such as NBP and can be considered as an antihypertensive agent in chronic treatment of elevated BP.

Resistant hypertension: baroreflex stimulation as a new tool

Uncontrolled hypertension remains a significant public health challenge. In recent years, a new baroreflex stimulator has been used to treat these patients. Initial observations suggest that the electrical field stimulation of carotid baroreceptors acutely attenuates sympathetic activation of the vasculature, heart and kidney while augmenting cardiac vagal regulation. During the long-term treatment an average blood pressure (BP) drop of 30-40/15-25 mmHg was observed with a responder rate (>10 mmHg reduction in BP) of up to 80% after 1 year of treatment. Some of this effect can be explained by a 'placebo' effect as suggested by the double-blind Pivotal Trial. The complication rate with the first generation device was 20-30%. With a second generation device, these problems have been reduced to <10%. Even though additional data from controlled clinical trials will be required before more widespread use can be recommended, this treatment option is now approved in Europe for the treatment of severe resistant hypertension and is performed in selected centres with experienced vascular surgeons and hypertension specialists.

Impact of androgen-induced oxidative stress on hypertension in male SHR

Men have higher blood pressure than women, and androgens and oxidative stress have been implicated as playing roles in this sexual dimorphism. The spontaneously hypertensive rat (SHR) is an animal model of both androgen- and oxidative stress-mediated hypertension. Therefore, the present studies were performed to test the hypothesis that androgens cause hypertension in SHR in part by stimulating superoxide production via NADPH oxidase. Castration of male SHR reduced blood pressure by 15% and attenuated both basal and NADPH-stimulated superoxide production in kidney cortical homogenates. Expression of p47(phox) and gp91(phox) but not p22(phox) subunits of NADPH oxidase were significantly lower in kidney cortex from castrated males compared with intact males. Moreover, inhibition of NADPH oxidase with apocynin caused approximately 15 mmHg reduction in blood pressure and reduced basal and NADPH-stimulated superoxide production in intact male SHR, but had no effect on blood pressure or superoxide production in castrated males. These data support the hypothesis that androgens cause oxidative stress and thereby increase blood pressure in male SHR via an NADPH oxidase-dependent mechanism.

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

The dose-dependent antihypertensive actions of olmesartan medoxomil, an angiotensin II (AT-II) receptor blocker

P-242 Key Words: Olmesartan, Angiotensin Receptor Blocker, Antihypertensive

Kallistatin is a potent new vasodilator.

Kallistatin is a serine proteinase inhibitor which binds to tissue kallikrein and inhibits its activity. The aim of this study is to evaluate if kallistatin has a direct effect on the vasculature and on blood pressure homeostasis. We found that an intravenous bolus injection of human kallistatin caused a rapid, potent, and transient reduction of mean arterial blood pressure in anesthetized rats. Infusion of purified kallistatin (0.07-1.42 nmol/kg) into cannulated rat jugular vein produced a 20-85 mmHg reduction of blood pressure in a dose-dependent manner. Hoe 140, a bradykinin B2-receptor antagonist, had no effect on the hypotensive effect of kallistatin yet it abolished the blood pressure-lowering effect of kinin and kallikrein. Relaxation of isolated aortic rings by kallistatin was observed in the presence (ED50 of 3.4 x 10(-9) M) and in the absence of endothelium (ED50 of 10(-9) M). Rat kallikrein-binding protein, but not kinin or kallikrein, induced vascular relaxation of aortic rings. Neither Hoe 140 nor Nomega-nitro--arginine methyl ester, a nitric oxide synthase inhibitor, affected vasorelaxation induced by kallistatin. Kallistatin also caused dose-dependent vasodilation of the renal vasculature in the isolated, perfused rat kidney. Specific kallistatin-binding sites were identified in rat aorta by Scatchard plot analysis with a Kd of 0.25+/-0.07 nM and maximal binding capacity of 47.9+/-10.4 fmol/mg protein (mean+/-SEM, n = 3). These results indicate that kallistatin is a potent vasodilator which may function directly through a vascular smooth muscle mechanism independent of an endothelial bradykinin receptor. This study introduces the potential significance of kallistatin in directly regulating blood pressure to reduce hypertension.

Sustained High‐Dose Nitroglycerin Transcutaneous Patch Therapy in Angina Pectoris: Evidence for Attenuation of Effect Over Time

The safety and efficacy of using continuous high-dose transcutaneous nitroglycerin in doses up to 100 mg/24 hours in chronic stable angina was assessed in 20 patients using serial treadmill testing. Patients had first to show a response to sublingual nitroglycerin with a 20% improvement in exercise time. All patients were then titrated with 20 mg (40 cm2), 60 mg (120 cm2), 80 mg (160 cm2) or 100 mg (200 cm2) patches, until intolerable headache in association with a 10 mmHg reduction in blood pressure and a ten-beat increment in heart rate. Drug was then discontinued for 2 days and patients underwent three repeat stress tests to reestablish a consistent drug-free baseline. Patients were then randomized in double-blind fashion to receive either active patch (N = 11) in previous titration dose or placebo patch (N = 9), with treadmill tests performed at 0 (1 hour after previous patch removal), 4, and 24 hours after patch application at baseline and at weeks 1 and 2. Venous blood was obtained for measurement of plasma nitroglycerin levels. After the first 24 hours of active patch therapy, there was a significant reduction in systolic blood pressure (P = .05), a significant increase in heart rate (P = .01), and a minor increase in exercise tolerance (P = .06) compared to placebo. At weeks 1 and 2, there was an attenuation of drug effect in all of these parameters. Plasma nitroglycerin levels demonstrated consistently high plasma levels over each 24-hour dosing interval, on day 1, week 1, and week 2.(ABSTRACT TRUNCATED AT 250 WORDS)