Acute Blood Pressure Lowering Research Articles

Effects of acute carotid baroreceptor stimulation on sympathetic nerve traffic in resistant and uncontrolled hypertension: a systematic review and meta-analysis.

In resistant hypertensive patients acute carotid baroreflex stimulation is associated with a blood pressure (BP) reduction, believed to be mediated by a central sympathoinhbition.The evidence for this sympathomodulatory effect is limited, however. This meta-analysis is the first to examine the sympathomodulatory effects of acute carotid baroreflex stimulation in drug-resistant and uncontrolled hypertension, based on the results of microneurographic studies. The analysis included 3 studies assessing muscle sympathetic nerve activity (MSNA) and examining 41 resistant uncontrolled hypertensives. The evaluation included assessment of the relationships between MSNA and clinic heart rate and BP changes associated with the procedure. Carotid baroreflex stimulation induced an acute reduction in clinic systolic and diastolic BP which achieved statistical significance for the former variable only [systolic BP: -19.98 mmHg (90% CI, -30.52, -9.43), P < 0.002], [diastolic BP: -5.49 mmHg (90% CI, -11.38, 0.39), P = NS]. These BP changes were accompanied by a significant MSNA reduction [-4.28 bursts/min (90% CI, -8.62, 0.06), P < 0.07], and by a significant heart rate decrease [-3.65 beats/min (90% CI, -5.49, -1.81), P < 0.001]. No significant relationship was detected beween the MSNA, systolic and diastolic BP changes induced by the procedure, this being the case also for heart rate. Our data show that the acute BP lowering responses to carotid baroreflex stimulation, although associated with a significant MSNA reduction, are not quantitatively related to the sympathomoderating effects of the procedure. This may suggest that these BP effects depend only in part on central sympathoinhibition, at least in the acute phase following the intervention.

Abstract 149: Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage

Background: Blood pressure (BP) reduction is associated with better neuroimaging and clinical outcomes in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). Because this evidence comes from studies that overwhelmingly enrolled deep hemorrhages, the impact of BP reduction in patients with lobar ICH remains understudied. Methods: We re-analyzed data from the pivotal Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) study. We included all patients with available neuroimaging data. Participants were randomized to either intensive (systolic BP target 110-139 mmHg) or standard (systolic BP target 140-179 mmHg) acute BP lowering. The main outcome measures were hematoma expansion &gt; 6 mL in the first 24 hours (HE), poor functional outcome (3-month mRS 4-6) and renal adverse events (RAE) until day 7 or hospital discharge. We fitted multivariable logistic regression models to test for association between the intervention and our outcomes of interest. Covariates included sex, age, race and ethnicity, and baseline ICH volume. Results: Among 1,000 patients enrolled in ATACH-2, 875 (87.5%) with complete data were included (88.9% deep hemorrhages and 11.1% lobar hemorrhages). The baseline characteristics of the intensive and standard treatment groups remained balanced as in the original study (all comparisons p &gt;0.05). Multivariable logistic regression showed that intensive BP reduction decreased the risk of HE (OR 0.60, 95%CI 0.39-0.90; p=0.02) and increased the risk of RAE (OR 2.53, 95%CI 1.40-4.77; p=0.003) in patients with deep, but not lobar ICH (HE, OR: 0.89; 95% CI= 0.31 - 2.52; p=0.83 and RAE, OR: 0.46; 95% CI= 0.04 - 5.10; p=0.53). Intensive BP reduction was not associated with improved mRS in either deep (OR: 0.96; 95 % CI= 0.68 - 1.37; p= 0.82) nor lobar (OR: 0.66; 95% CI= 0.16 - 2.42; p= 0.54) ICH. Conclusion: The impact of intensive blood pressure lowering differs in deep and lobar ICH. These results emphasize the need for a better understanding about biologic differences in ICH, which may have therapeutic implications.

Slow on the Draw-ED Management of Elevated BP in Older Adults.

The purpose of this study is to review data surrounding the emergency department management of elevated blood pressure in older adults, including the management of hypertensive crisis andoutpatient management of markedly elevated blood pressure. Acute lowering of blood pressure in older adults with markedly elevated blood pressure may lead to serious complications without improvements in hospital length of stay, return visits, or mortality. Older adults presenting with elevated blood pressures without evidence of end-organ damage should be referred for outpatient management of their blood pressure. Treatment of hypertensive emergency should follow standard guidelines with additional considerations for aging physiology. Acute lowering of elevated blood pressure in older adults without evidence of end-organ damage has the potential for harm. If the emergency physician opts to acutely treat, they should consider the increased risk of side effects in older adults and avoid Beers list medications including short-acting nifedipine and clonidine.

Abstract P359: Resident Management Of Hypertensive Urgency

Objective: Hypertensive urgency is generally defined as a severely elevated blood pressure without evidence of end-organ damage. Consensus statements do not recommend the acute lowering of blood pressure nor referral to the emergency room. Rapid lowering of blood pressure in patients who are chronically hypertensive carries the risk of hypoperfusion and therefore ischemia to vital organs. The objective of this study was to assess residents’ perception of the management of hypertensive urgency. Methods: An anonymous survey was sent via email to all active resident physicians of an academic internal medicine residency program. It comprised of 8 questions regarding the outpatient and inpatient treatment of hypertensive urgency. Results: A total of 47 residents responded to the survey. Most respondents (44 of 47) knew that evaluating for reversible causes of elevated blood pressure is the first step of management. Fewer residents (37 of 47) said the next course of action would be to up-titrate the oral blood pressure regimen. When asked about real life practice, 35 of 47 attested to conservative management with 12 of 47 respondents regularly using IV antihypertensives to treat hypertensive urgency. The most common contributing reason (25 of 47) to pushing IV antihypertensives was pressure from colleagues and staff, with only 2 residents denying ever administering IV antihypertensives. Residents were also aggressive in the management of hypertensive urgency in the outpatient setting with 15 of 47 respondents reporting most commonly referring patients to the ER for blood pressure lowering (31.91%) and 5 of 47 reporting administering clonidine in the office for quick blood pressure lowering. Conclusion: Resident physicians in our program should be less aggressive in treating hypertensive urgency, especially in the outpatient setting. We suspect that the notion that hypertensive urgency warrants immediate blood pressure lowering is prevalent as pressure from staff/colleagues was the largest cited reason to giving IV antihypertensives in urgency. Further efforts should be pursued to educate residents about the current guidelines regarding hypertensive urgency.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

Initial antihypertensive agent effects on acute blood pressure after intracerebral haemorrhage

IntroductionCurrent guidelines recommend blood pressure (BP) lowering in patients after acute intracerebral haemorrhage (ICH) without guidance on initial choice of antihypertensive class. This study sought to determine if initial antihypertensive...

Efficacy and Safety of Immediate-Release Nifedipine in Critically Ill Patients

Background: Immediate-release nifedipine (IRN) is a calcium channel blocker with potent vasodilatory and antihypertensive properties. Safety concerns led to a black box warning for increased risk of myocardial infarction, stroke, and arrhythmias. Objective: The aim of this study was to evaluate the safety and efficacy of IRN for acute blood pressure lowering in critically ill patients. Methods: A retrospective, single-center study was performed in critically ill patients who received at least one dose of IRN. The primary endpoint was the change in systolic blood pressure (SBP) measured at baseline and 1 hour after first administration of IRN. Secondary outcomes included clinically significant hypotension, defined as an absolute reduction in SBP ≥ 15% or vasopressor initiation within 1 hour after administration; incidence of arrhythmias, stroke, or myocardial injury; and time to transition off antihypertensive infusions. Results: IRN resulted in a median [interquartile range] SBP change of −10 [−21 to −1] mmHg between baseline 142 mmHg [124-155] and 1 h post-administration 127 mmHg [114-144]; P < .001. Twenty-seven percent of patients experienced clinically significant hypotension, with hypotension observed in 24% and vasopressors initiated in 4% of patients. Sixteen percent of patients experienced new-onset arrhythmia and 18% experienced myocardial injury following IRN during hospitalization. Median time to transition off intravenous (IV) continuous infusion antihypertensives was 8.5 [0-31.5] hours. Conclusion: IRN led to a reduction in SBP which may have been associated with clinically significant hypotension and need for vasopressor support. Further studies with direct comparisons to alternatives are needed to determine the true association of adverse events with IRN.

Intensive Blood Pressure Lowering and DWI Lesions in Intracerebral Hemorrhage: Exploratory Analysis of the ATACH-2 Randomized Trial.

With the increasing use of magnetic resonance imaging in the assessment of acute intracerebral hemorrhage, diffusion-weighted imaging hyperintense lesions have been recognized to occur at sites remote to the hematoma in up to 40% of patients. We investigated whether blood pressure reduction was associated with diffusion-weighted imaging hyperintense lesions in acute intracerebral hemorrhage and whether such lesions are associated with worse clinical outcomes by analyzing imaging data from a randomized trial. We performed exploratory subgroup analyses in an open-label randomized trial that investigated acute blood pressure lowering in 1000 patients with intracerebral hemorrhage between May 2011 and September 2015. Eligible participants were assigned to an intensive systolic blood pressure target of 110-139mm Hg versus 140-179mm Hg with the use of intravenous nicardipine. Of these, 171 patients had requisite magnetic resonance imaging sequences for inclusion in these subgroup analyses. The primary outcome was the presence of diffusion-weighted imaging hyperintense lesions. Secondary outcomes included death or disability and serious adverse event at 90days. Diffusion-weighted imaging hyperintense lesions were present in 25% of patients (mean age 62years). Hematoma volume > 30 cm3 was an adjusted predictor (adjusted relative risk 2.41, 95% confidence interval 1.00-5.80) of lesion presence. Lesions occurred in 25% of intensively treated patients and 24% of standard treatment patients (relative risk 1.01, 95% confidence interval 0.71-1.43, p = 0.97). Patients with diffusion-weighted imaging hyperintense lesions had similar frequencies of death or disability at 90days, compared with patients without lesions. Randomized assignment to intensive acute blood pressure lowering did not result in a greater frequency of diffusion-weighted imaging hyperintense lesion. Alternative mechanisms of diffusion-weighted imaging hyperintense lesion formation other than hemodynamic fluctuations need to be explored. Clinical trial registration ClinicalTrials.gov (Ref. NCT01176565; https://clinicaltrials.gov/ct2/show/NCT01176565 ).

Regional Differences in the Response to Acute Blood Pressure Lowering After Cerebral Hemorrhage.

ObjectiveTo compare the impact of intensive blood pressure (BP) lowering right after intracerebral hemorrhage (ICH) on clinical and hematoma outcomes among patients from different geographic locations, we performed a prespecified subanalysis of a randomized, multinational, 2-group, open-label trial to determine the efficacy of rapidly lowering BP in hyperacute ICH (Antihypertensive Treatment of Acute Cerebral Hemorrhage [ATACH]-2), involving 537 patients from East Asia and 463 recruited outside of Asia.MethodsEligible patients were randomly assigned to a systolic BP target of 110 to 139 mm Hg (intensive treatment) or 140 to 179 mm Hg (standard treatment). Predefined outcomes were poor functional outcome (modified Rankin Scale score 4–6 at 90 days), death within 90 days, hematoma expansion at 24 hours, and cardiorenal adverse events within 7 days.ResultsPoor functional outcomes (32.0% vs 45.9%), death (1.9% vs 13.3%), and cardiorenal adverse events (3.9% vs 11.2%) occurred significantly less frequently in patients from Asia than those outside of Asia. The treatment-by-cohort interaction was not significant for any outcomes. Only patients from Asia showed a lower incidence of hematoma expansion with intensive treatment (adjusted relative risk [RR] 0.56, 95% confidence interval [CI] 0.38–0.83). Both Asian (RR 3.53, 95% CI 1.28–9.64) and non-Asian (RR 1.71, 95% CI 1.00–2.93) cohorts showed a higher incidence of cardiorenal adverse events with intensive treatment.ConclusionsPoor functional outcomes and death 90 days after ICH were less common in patients from East Asia than those outside of Asia. Hematoma expansion, a potential predictor for poor clinical outcome, was attenuated by intensive BP lowering only in the Asian cohort.ClinicalTrials.gov IdentifierNCT01176565.Classification of EvidenceThis study provides Class II evidence that, for patients from East Asia with ICH, intensive blood pressure lowering significantly reduces the risk of hematoma expansion.

Extended Renal Artery Denervation Is Associated with Artery Wall Lesions and Acute Systemic and Pulmonary Hemodynamic Changes: A Sham-Controlled Experimental Study.

Objectives We sought to assess acute changes in systemic and pulmonary hemodynamics and microscopic artery lesions following extended renal artery denervation (RDN). Background RDN has been proposed to reduce sympathetic nervous system hyperactivation. Although the effects of RDN on systemic circulation and overall sympathetic activity have been studied, data on the impact of RDN on pulmonary hemodynamics is lacking. Methods The study comprised 13 normotensive Landrace pigs. After randomization, 7 animals were allocated to the group of bilateral RDN and 6 animals to the group of a sham procedure (SHAM). Hemodynamic measures, cannulation, and balloon-based occlusion of the renal arteries were performed in both groups. In the RDN group, radiofrequency ablation was performed in all available arteries and their segments. An autopsy study of the renal arteries was carried out in both groups. Results The analysis was performed on 12 pigs (6 in either group) since pulmonary thromboembolism occurred in one case. A statistically significant drop in the mean diastolic pulmonary artery pressure (PAP) was detected in the RDN group when compared with the SHAM group (change by 13.0 ± 4.4 and 10.0 ± 3.0 mmHg, correspondingly; P = 0.04). In 5 out of 6 pigs in the RDN group, a significant decrease in systemic systolic blood pressure was found, when compared with baseline (98.8 ± 17.8 vs. 90.2 ± 12.6 mmHg, P = 0.04), and a lower mean pulmonary vascular resistance (PVR) (291.0 ± 77.4 vs. 228.5 ± 63.8 dyn∗sec∗cm−5, P = 0.03) after ablation was found. Artery dissections were found in both groups, with prevalence in animals after RDN. Conclusions Extensive RDN leads to a rapid and significant decrease in PAP. In the majority of cases, RDN is associated with an acute lowering of systolic blood pressure and PVR. Extended RDN is associated with artery wall lesions and thrombus formation underdiagnosed by angiography.

Treatment with SGLT2 Inhibitor Empagliflozin Modulates Renal Sympathetic Nerve Activity in Diabetic Rabbits

In patients with type 2 diabetes, antihyperglycemic treatment with the sodium‐glucose cotransporter 2 (SGLT2) inhibitor empagliflozin is associated with a reduction in cardiovascular mortality of 38% (EMPA‐REG OUTCOME trial). In individuals with poorly controlled type 2 diabetes, sympathetic nervous system (SNS) activation is associated with poor cardiovascular outcomes. We explored the notion that the mechanisms underlying the cardiovascular benefits of empagliflozin treatment may involve an action on the SNS.Diabetes was induced by a single dose of alloxan in New Zealand White rabbits. We determined the changes in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) as well as baroreflex responses to changes in BP and norepinephrine spillover in conscious rabbits. The effects of one‐week treatment with empagliflozin were compared to those of another blood glucose‐lowering treatment insulin, the proximally‐acting natriuretic acetazolamide, the ACE inhibitor perindopril, vehicle treatment and to an untreated diabetic group.Diabetic rabbits (n=39) were treated with daily insulin to maintain a stable elevation in blood glucose (20.5±0.4mM vs 6.5±0.4mM in controls) over 4 weeks. Diabetes was associated with 9% greater BP than in non‐diabetic rabbits (P=0.02) but no difference in RSNA or HR. One‐week treatment with empagliflozin lowered blood glucose by 43% (without insulin), and there was a 49% increase in water intake. There was no difference in BP, HR or RSNA between empagliflozin‐treated and untreated diabetic rabbits or those treated with acetazolamide. However, insulin lowered blood glucose similarly to empagliflozin (32%) and increased HR (+10%) while perindopril lowered BP (−9%). There was marked augmentation (+69%) of the maximum RSNA response to baroreceptor unloading in diabetic rabbits compared to non‐diabetic (P&lt;0.01). Empagliflozin attenuated the baroreflex by 34% and acetazolamide had a similar blunting effect (−29%, both P&lt;0.05). Empagliflozin also attenuated the HR baroreflex (−8%) but insulin and perindopril had no effect on either baroreflex. Diabetes did not alter BP or HR variability but empagliflozin and acetazolamide treatment increased mid frequency HR power. Norepinephrine spillover to plasma was similar in diabetic and non‐diabetic rabbits but was elevated after both empagliflozin (+147%) and acetazolamide (+134%, P&lt;0.05).In conclusion, empagliflozin effectively normalized the maximal RSNA response to acute BP lowering without altering resting hemodynamic or sympathetic activity in conscious diabetic rabbits. The similarity of these effects with those of acetazolamide suggests that the mechanism underlying the cardiovascular benefits of empagliflozin is linked to its natriuretic action.Support or Funding InformationThis work was supported by Boehringer Ingelheim.

Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study

Background and purposePrevious studies have found ischemic stroke is associated with atrial fibrillation. However, the causal association between ischemic stroke and atrial fibrillation is not clear. Furthermore, the network relationship among ischemic stroke, atrial fibrillation and its risk factors need further attention. This study aims to examine the potential causal association between ischemic stroke and atrial fibrillation and further to explore potential mediators in the causal pathway from ischemic stroke to atrial fibrillation.MethodsSummary statistics from the ISGC (case = 10,307 and control = 19,326) were used as ischemic stroke genetic instruments, AFGen Consortium data (case = 65,446 and control = 522,744) were used for atrial fibrillation, and other consortia data were used for potential mediators (fasting insulin, white blood cell count, procalcitonin, systolic and diastolic blood pressure, body mass index, waist circumference, and height). Under the framework of network Mendelian randomization, two-sample Mendelian randomization study was performed using summary statistics from several genome-wide association studies. Inverse-variance weighted method was performed to estimate causal effect.ResultsBlood pressure mediates the causal pathways from ischemic stroke to atrial fibrillation. The total odds ratio of ischemic stroke on atrial fibrillation was 1.05 (95% confidence interval [CI], 1.02 to 1.07; P = 1.3 × 10−5). One-unit increase of genetically determined ischemic stroke was associated with 0.02 (DBP: 95% CI, 0.001 to 0.034, P = 0.029; SBP: 95% CI, 0.006 to 0.034, P = 0.003) upper systolic and diastolic blood pressure levels. Higher genetically determined systolic and diastolic blood pressure levels were associated with higher atrial fibrillation risk (DBP: RR, 1.18; 95% CI, 1.03 to 1.35; P = 0.012. SBP: RR, 1.18; 95% CI, 1.01 to 1.38; P = 0.04). Specially, we also found the bidirectional causality between blood pressure and ischemic stroke.ConclusionsOur study provided a strong evidence that raised blood pressure in stroke patients increases the risk of atrial fibrillation and active acute blood pressure lowering can improve the outcome in ischemic stroke patients.

Effect of Betanin, a Beetroot Component, on Vascular Tone in Isolated Porcine Arteries.

Beetroot has attracted much attention because of its blood pressure-lowering properties. Although beetroot contains various nutritional compounds, including inorganic nitrate, some of their physiological properties are not fully understood. In this study, we examined whether betanin, a beetroot component, has a regulatory effect on vascular tone. Mechanical responses of isolated porcine coronary, mesenteric, and pulmonary arteries were assessed by organ chamber technique. In some cases, the vascular reactivity was observed in the presence of a physiological concentration of betanin (10 µM). Betanin did not induce vasorelaxation at physiological concentrations both in endothelium-intact and -denuded coronary, mesenteric, and pulmonary arteries. The endothelium-dependent agonists, bradykinin and A23187 induced vasorelaxation of endothelium-intact coronary arteries, both of which were not affected by exposure to betanin. Likewise, endothelium-independent vasorelaxation induced by sodium nitrite and sodium nitroprusside was also not affected by the presence of betanin. In addition, exposure of endothelium-intact coronary arteries to betanin did not attenuate prostaglandin F2α- and endothelin-1-induced vasocontraction. These findings suggest that betanin does not have a vasorelaxant activity. It is unlikely that betanin is a component directly responsible for the beetroot-induced acute blood pressure-lowering effect in a nitrate-independent manner.

54 Acute Blood Pressure Lowering in Spontaneous Acute Intra-cerebral Haemorrhage: A Re-audit in a Tertiary Referral Stroke Centre

Abstract Background Acute blood pressure (BP) lowering to a target of &lt;150mmHg systolic improves outcomes in patients with acute spontaneous intra-cerebral haemorrhage (sICH). It is thought that the beneficial effect of BP-lowering in sICH is time-sensitive and mediated through the prevention of haematoma expansion. The American Heart Association guidelines state that BP lowering to &lt;150 mmHg or lower is safe and can improve functional outcome. Our aim was to re-evaluate the performance of clinicians in meeting target SBP levels of &lt;150mmHg in patients with acute sICH within 1 hour of presentation, following the introduction of a BP-lowering protocol in our centre. Methods We undertook a retrospective chart review of consecutive patients with an acute sICH admitted to our centre between September 2017 and May 2018. Any patient who did not receive active medical management from the outset of presentation due to immediate initiation of palliative measures were excluded. The time from presentation to target BP and BP measured at 1 hour were recorded. Any protocol violations were also documented Results 11 patients were included (mean age 77.5years, 55% female). The mean BP at presentation and 1 hour was 186/93mmHg and 161/93mmHg respectively. The median and mean times from presentation to first achieved target BP was 129 and 120minutes respectively. At least 1 protocol violation occurred in 66.6% of cases. The most common protocol violation was the failure to escalate to an intravenous infusion of a BP-lowering agent in a timely manner when bolus therapy had failed. Conclusion An introduction of a BP protocol for patients with an acute sICH did not improve performance on achieving rapid SBP-lowering to target levels of &lt;150mmHg. Strategies to improve awareness of this protocol are required to improve adherence and its successful implementation.

Acute Management of Hypertension Following Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is responsible for approximately 15% of strokes annually in the United States, with nearly 1 in 3 of these patients dying without ever leaving the hospital. Because this disproportionate mortality risk has been stagnant for nearly 3 decades, a main area of research has been focused on the optimal strategies to reduce mortality and improve functional outcomes. The acute hypertensive response following ICH has been shown to facilitate ICH expansion and is a strong predictor of mortality. Rapidly reducing blood pressure was once thought to induce cerebral ischemia, though has been found to be safe in certain patient populations. Clinicians must work quickly to determine whether specific patient populations may benefit from acute lowering of systolic blood pressure (SBP) following ICH. This review provides nurses with a summary of the available literature on blood pressure control following ICH. It focuses on intravenous and oral antihypertensive medications available in the United States that may be utilized to acutely lower SBP, as well as medications outside of the antihypertensive class used during the acute setting that may reduce SBP.

Recent advances in spontaneous intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a stroke subtype associated with significant morbidity and mortality. The purpose of this review is to provide an update on important research on ICH over the past three years. Topics covered include risk factors, imaging predictors of hematoma expansion, scoring schema to predict hematoma expansion, hemostatic therapies, acute blood pressure lowering, intraventricular administration of alteplase for intraventricular hemorrhage, and the current status of surgical therapies.

Impact of hydration status on haemodynamics, effects of acute blood pressure-lowering treatment, and prognosis after stroke.

AimsAlthough high blood pressure (BP) is common in acute stroke and associated with poor outcome, the Efficacy of Nitric Oxide in Stroke (ENOS) trial showed no beneficial effect of antihypertensive treatment in this situation. Antihypertensive agents have accentuated effects in dehydrated patients. We assessed the impact of dehydration on haemodynamics, the effects of antihypertensive treatment, and prognosis in the ENOS trial.MethodsENOS randomized 4011 patients with acute stroke and raised systolic BP to a glyceryl trinitrate (GTN) patch or no GTN patch, and to continue or to stop existing antihypertensive treatment within 48 h of onset. The primary outcome was functional outcome (modified Rankin Scale, mRS) at day 90. Blood markers of dehydration at baseline were collected at two sites (n = 310) and their relationship with haemodynamics and outcome was assessed.ResultsThere were no significant associations between dehydration markers and fall in blood pressure from baseline to day 1, and no significant interaction with allocated treatment. Overall, increasing urea was associated with an unfavourable shift in mRS [odds ratio 3.43, 95% confidence interval (CI) 1.42, 8.32; P = 0.006] and increased risk of death at day 90 (hazard ratio 4.55, 95% CI 1.51, 13.66; P = 0.007).ConclusionsBlood pressure‐lowering treatment was safe in dehydrated patients, with no precipitous changes in BP, thus supporting its use in acute stroke prior to blood markers of dehydration becoming available. Increased baseline urea was associated with poor prognosis after stroke.

Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes

Response to intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH) might vary with the degree of underlying cerebral small vessel disease. To characterize cerebral microbleeds (CMBs) in acute ICH and to assess the potential for interaction between underlying small vessel disease (as indicated by CMB number and location) and assignment to acute intensive BP targeting for functional outcomes and hematoma expansion. Preplanned subgroup analyses in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial were performed. The ATACH-2 was an open-label international randomized clinical trial that investigated optimal acute BP lowering in 1000 patients with acute ICH. Analyses followed the intent-to-treat paradigm. Participants were enrolled between May 2011 and September 2015 and followed up for 3 months. Eligible participants were aged at least 18 years with ICH volumes less than 60 mL on computed tomography (CT) and a Glasgow Coma Scale score of at least 5 on initial assessment, in whom study drug could be initiated within 4.5 hours of symptom onset. Eight hundred thirty-three participants were excluded, leaving 167 who had an interpretable axial T2*-weighted gradient-recalled echo sequence on magnetic resonance imaging to assess CMBs for inclusion in these subgroup analyses. The primary outcome of interest was death or disability (modified Ranking Scale score, 4-6) at 3 months. The secondary outcome of interest was hematoma volume expansion of at least 33% on a CT scan obtained 24 hours after randomization compared with the entry scan. A total of 167 patients were included; their mean (SD) age was 61.9 (13.2) years, and 98 (58.7%) were male. Cerebral microbleeds were present in 120 patients. Forty-six of 157 (29.3%) patients had poor outcome (modified Ranking Scale score, ≥4), and hematoma expansion was observed in 29 of 144 (20.1%) patients. Risk of poor outcome was similar for those assigned to intensive vs standard acute BP lowering among patients with CMBs (relative risk, 1.19; 95% CI, 0.61-2.33; P = .61) and those without CMBs (relative risk, 1.42; 95% CI, 0.43-4.70; P = .57), and no significant interaction was observed (interaction coefficient, 0.18; 95% CI, -1.20 to 1.55; P = .80). Risk of hematoma expansion was also similar, and no significant interaction between treatment and CMBs was observed (interaction coefficient, 0.62; 95% CI, -1.08 to 2.31; P = .48). Cerebral microbleeds are highly prevalent among patients with ICH but do not seem to influence response to acute intensive BP treatment. ClinicalTrials.gov Identifier: NCT01176565.

Tubular NHE3 is a determinant of the acute natriuretic and chronic blood pressure lowering effect of the SGLT2 inhibitor empagliflozin

The sodium glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, is a new antihyperglycemic drug that also lowers blood pressure and has beneficial effects in patients with heart failure (EMPA‐REG OUTCOME). These effects may relate at least in part to its natriuretic effect. In the brush border of the early proximal tubule, SGLT2 may interact with the Na+‐H+‐exchanger NHE3, which reabsorbs about 30% of Na+ in the proximal convoluted tubule. Here we determine whether the acute or chronic natriuretic effect of empagliflozin depends on intact tubular NHE3.MethodsWe generated mice with NHE3 knock‐down in the tubular system (NHE3‐KO; using Pax8‐Cre) and compared them with littermate controls (WT). In a first series, we determined acute effects of empagliflozin (0.3 mg/kg, given by oral gavage together with a water load to facilitate quantitative urine collection over 3 hours) or vehicle on urinary pH and excretion of fluid, Na, and bicarbonate in metabolic cage studies (n=9–11/group). In a second series, we treated mice for 4 months with empagliflozin (150 mg/kg of diet) or vehicle and measured systolic blood pressure (SBP) by automated tail cuff in trained awake mice and renal renin mRNA expression by RT‐qPCR (n=10/group for renin mRNA and 15–26/group for SBP).ResultsSeries 1In WT, empagliflozin significantly enhanced urinary pH and the excretion of glucose, fluid, Na and bicarbonate compared with vehicle control. In NHE3‐KO, urine pH and bicarbonate excretion were significantly greater than in WT in response to vehicle; however, these two parameters were not significantly changed in response to empagliflozin. Moreover, empagliflozin actually reduced urine Na excretion in NHE3‐KO.Series 2In WT, empagliflozin lowered SBP and enhanced renal renin mRNA expression, consistent with a sustained natriuretic effect. In vehicle‐treated NHE3‐KO, SBP was lower and renal renin mRNA higher compared with WT; however, these two parameters were not significantly changed in response to empagliflozin.ConclusionThe data are consistent with the notion that the acute natriuretic and the chronic blood pressure lowering effect of the SGLT2 inhibitor empagliflozin involve a functional interaction with tubular NHE3, and can occur in the absence of hyperglycemia. The chosen dose of empagliflozin only induced a mild glucosuria, i.e. glucose reabsorption through downstream SGLT1 had just been fully saturated. Since SGLT1 transports Na and glucose in a ratio of 2:1 versus 1:1 for SGLT2, shifting glucose reabsorption from SGLT2 to downstream SGLT1 can explain an anti‐natriuretic effect of empagliflozin that has been unmasked by the absence of tubular NHE3.Support or Funding InformationNIH R01DK112042, R01DK106102, P30DK079337, the Department of Veterans Affairs, Boehringer Ingelheim Pharma GmbH &amp; Co.KGThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Retrospective review of the use of as-needed hydralazine and labetalol for the treatment of acute hypertension in hospitalized medicine patients.

The aim of this study was to evaluate the use of as-needed (PRN) labetalol and hydralazine [intravenous (IV) or oral] in hospitalized medicine patients for the treatment of severe asymptomatic hypertension and to examine the potential negative outcomes associated with their use. The electronic health record of 250 medicine patients hospitalized at the University of Colorado Hospital between November 2014 and April 2016 who received at least one dose of PRN IV or oral hydralazine or labetalol were retrospectively reviewed. The primary outcome was to describe the use of PRN antihypertensive medications in this population. A total of 573 PRN doses of antihypertensive medication were administered. Oral hydralazine was the most common (521 doses, 90.9%). A total of 36% of PRN administrations were given for a systolic blood pressure (SBP) <180 mmHg and diastolic blood pressure (DBP) <110 mmHg (cut-point for acute severe hypertension). No serious adverse events were related to PRN antihypertensive administration. Despite receiving at least one PRN antihypertensive medication during hospitalization, 40.8% of patients were not continued on their home antihypertensive medication(s) while hospitalized, and 62.4% of patients did not have their home regimens intensified at discharge. As-needed oral hydralazine is frequently prescribed for acute blood pressure lowering with administration thresholds often less than what are used to define acute severe hypertension. Many patients are prescribed PRN antihypertensive medication instead of being continued on their home regimens, and most patients do not have the intensity of their home regimens increased. Providers need to be educated about the use of PRN antihypertensive medication for the management of severe asymptomatic hypertension in the hospital setting.