BP Reduction Research Articles

POOLED, LONG-TERM ANALYSIS OF THE GLOBAL SYMPLICITY CLINICAL TRIAL PROGRAM OF RADIOFREQUENCY RENAL DENERVATION FOR THE TREATMENT OF UNCONTROLLED HYPERTENSION

Objective: The Global Symplicity Clinical program is the largest investigation of radiofrequency renal denervation (RDN) to treat uncontrolled hypertension (HTN) to date. Collectively, over 4,000 patients enrolled into Spyral First-in-Man, the Global SYMPLICITY Registry (GSR) DEFINE, and multiple randomized controlled and sham controlled trials including HTN-Japan, Symplicity HTN-3, and the SPYRAL HTN-OFF and ON MED studies. We leveraged the entire Symplicity Global Clinical program patient dataset to develop a multivariate, patient-level, mixed model assessing (1) long-term BP reductions after RDN, and (2) whether specific patient characteristics correlate with future BP reductions after the procedure. Design and method: Repeated BP measurements from each patient in the Global Symplicity Clinical program were analyzed using linear mixed models fitted with 24-h ambulatory systolic (S)BP and office SBP as outcome variables. Baseline SBP, baseline number of antihypertensive (AH) medications, and AH medications over time were included as fixed effects. Additional patient characteristics were included as potential significant fixed effects. To account for multiple BP measurements per patient and multiple studies, nested random effects were included using an auto-regressive correlation structure. Results: The mixed model included data from 4156 patients treated with either the first-generation Symplicity Flex or the next-generation Symplicity Spyral catheter. Estimated, office and 24-h ambulatory SBP changes through 36 months, after adjusting for AH medication effects, were biphasic with a steep reduction after RDN through the first 6 months (Figure), followed by a steady reduction in SBP afterward through 36 months. Higher baseline SBP was correlated with greater BP reductions. History of AF (-3.7 mmHg compared to no AF, p=0.0048) and increasing eGFR at baseline (-0.039 mmHg for every 1 ml/min increase in baseline eGFR, p=0.040) significantly correlated with lower 24-h ambulatory SBP. Conclusions: This is the most comprehensive analysis of radiofrequency RDN to date. Higher baseline SBP was strongly correlated with greater BP reductions. The results demonstrate the durability of RDN as an adjunctive therapy to treat HTN patients. Prospective studies need to validate whether certain patient characteristics are associated with improved response to RDN.

EVALUATION OF THE EFFICACY AND TOLERABILITY OF A FIXED DOSE COMBINATION OF AMLODIPINE AND INDAPAMIDE IN PATIENTS OLDER THAN 55 YEARS

Objective: There is very limited real-life data on hypertension management in Bangladeshi population. Considering this fact, this study evaluated the effectiveness of treatment with an indapamide/amlodipine single-pill combination (SPC) in Bangladeshi patients over the age of 55 years, in an OPD setting with uncontrolled systolic hypertension in real-life clinical practice. Methods: This was a 3-month, multicenter, observational, open-label study conducted in 3 divisional cities of Bangladesh among patients with grade I or II hypertension who were either uncontrolled on previous antihypertensive treatment or treatment-naïve. The effectiveness of indapamide/amlodipine SPC was assessed by the change in office systolic blood pressure (SBP) and the rate of target SBP (< 140 mmHg) achievement at 2 weeks, 1 month and 3 months, in four age groups: 55-59 years, 60-69 years, 70-79 years, and 80 years or older. Design and method: The COMBINE study recruited 213 patients, of whom 185 took indapamide/amlodipine 1.5/5 mg SPC fora full three-month course of therapy. Mean age was 62.4±7.4 years, 76 men [41.1%] and 109 women [58.9%]. The absolute decrease of SBP during 3 months of taking indapamide/amlodipine single-pill combination (SPC) was 29.3 mm Hg, DBP - 12.9 mm Hg. After 3 months of treatment significant SBP decreases from baseline were observed in each age group: ? 31.8 mmHg (from 156.7 to 124.9), ? 26.4 mmHg (from 152.7 to 126.3), ? 29.5 mmHg (from 152.8 to 123.3), and ? 25.8 mmHg (from 151.7 to 125.9) in the 55-59, 60-69, 70-79, and 80 years and older age groups, respectively. Leg edema was observed in 3 patients (1.62%), electrolyte imbalance was observed in 4 patients (2.16%) and 1 patients observed sudden fall of blood pressure. Conclusion: This COMBINE study results showed that indapamide/amlodipine SPC was associated with significant and rapid reductions in BP even in a different age range of Bangladeshi patients in routine clinical practice. This study result is consistent with already achieved data of this SPC globally.

Cerebrovascular Compliance during Progressive Hypotension in Patients with Autonomic Failure

Background: Cerebral perfusion during reductions in arterial pressure (AP) can be supported transiently by a Windkessel mechanism that increases cerebrovascular compliance (Ci). This defense mechanism exists in healthy participants during rapid standing and in patients during vasovagal syncope. However, it remains unknown whether the rise in Ci with falling AP exhibits a threshold effect. Thus, we tested the hypothesis that increased Ci is passive to a reduction in AP and starts to increase only after a threshold has been reached. To test this hypothesis, it was necessary to study a population that tolerates progressive large reductions in BP without a loss of consciousness. Therefore, we analyzed Ci changes during a graded head-up tilt (HUT) from patients with autonomic failure (AF). Methods: Finger AP and right middle cerebral artery blood velocity (MCAv) were recorded from 5 AF patients (n = 5 male, 61 ± 23 years, 25 ± 5 kg/m2) at supine rest and during graded-HUT (30, 45, 60 degrees). Tilt gradients increased incrementally every 5 minutes until AP reached a critically low value prompting termination of HUT. The total time in HUT was 11 ± 4 min. Individual AP and MCAv waveforms during supine rest and graded HUT (one waveform every 5 s) were assessed with a modified Windkessel model to calculate Ci and cerebrovascular resistance (CVR). Pulse pressure (PP) was calculated as systolic AP − diastolic AP. A threshold value for the increase in Ci was determined as five consecutive cardiac cycles greater than the average supine Ci plus 2 standard deviations. Results: Graded HUT resulted in an overall reduction in AP (85 ± 18 to 50 ± 7 mmHg), PP (72 ± 22 to 32 ± 19 mmHg), mean MCAv (62 ± 12 to 35 ± 7 cm/s), and CVR (1.4 ± 0.1 to 1.0 ± 0.3 mmHg/cm/s; all p < 0.05 vs supine). Ci increased by 905 ± 756% (p = 0.04 vs supine). The threshold effect was evident as Ci began to increase progressively after PP fell by 15 ± 3 mmHg and AP fell by 12 ± 2 mmHg. Conclusions: Our results provide evidence that Ci increases after a threshold reduction in PP and AP in the apparent absence of autonomic support. These data support the idea that increasing Ci during reductions in AP represents a pressure-dependent Windkessel mechanism. Of interest, our findings provide clinical insight into how AF patients compensate for such large reductions in pressure without the assistance of CVR as a defense mechanism. NSERC USRA — Western University, Natural Sciences and Engineering Research Council of Canada (NSERC, Grant No. RGPIN-2018-06255). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

SPONTANEOUS, INDEPENDENT, SINGLE-CENTER RDN REGISTRY OF A RESISTANT HYPERTENSION MULTIDISCIPLINARY TEAM

Objective: Uncontrolled resistant hypertension (URH) is defined as Systolic Blood Pressure above 140mmHg despite at least 3 maximally tolerated doses of antihypertensive drugs including a diuretic. Renal sympathetic denervation (RDN) has proved efficacy in the sponsored SPYRAL and RADIANCE studies. However, little evidence is available from independent studies. Furthermore, patients with glomerular filtrate rate <45ml/min have been systematically excluded. This study aims to evaluate the safety and the efficacy of catheter-based radiofrequency RDN in patients with URH, including those with renal impairment. Design and method: Consecutive unselected patients with URH undergoing RDN were enrolled, assessed in a multidisciplinary team involving cardiologist, nephrologist and hypertension specialists, that excluded secondary forms. Efficacy was defined as change of office (OBP) and ambulatory blood pressure monitoring (ABPM) after RDN, safety as the absence of device-related major complication (BARC classification), end-stage renal disease, stroke, acute myocardial infarction and any cause of death within 1 month. 107 patients underwent RDN from 2012 to December 2023. The population had multiple comorbidities: 45% were smokers, 43% diabetic, 35% had peripheral artery disease, 30% coronary artery disease, 57% CKD. The average number of antihypertensive medications was 4.83±1.2 Baseline ABPM and OBP were 151.18±20,97/87,88±14,39mmHg and 155,92±24/85,25±15,5 mmHg, respectively Results: . At 12-month a significant reduction of systolic OBP and ABPM, respectively by -17.51±3.70 mmHg (P=0.001) and -7.03±3.37 mmHg (P=0.04) was noticed. BP reduction at 12-month follow-up was observed also among eGFR <45 ml/min, with a reduction by -18.73±7.14mmHg (P=0.02) in systolic OBP and by -17.81±7.49 (P=0.03) in ABPM. The therapeutic burden was slightly reduced baseline to 4 (3-5) at follow-up (p<0.01). No major complications were observed and renal function was stable up to 12 months, compared to baseline (1.87±2.37 vs. 2.44±3.56; -0.57±0.32; p=0.08). Conclusions: RDN on top of medical therapy is safe and feasible in patients with URH, even in a high-risk CKD population with multiple comorbidities. A significant reduction of SBP also in this subgroup up to 12 months was reported without undesired effects. Furthermore, our experience underlines the central role of multidisciplinary team evaluation for the appropriate management of URH.

EFFECTIVENESS & TOLERABILITY OF METOPROLOL ER, TELMISARTAN & CHLORTHALIDONE IN PATIENTS OF ESSENTIAL HYPERTENSION WITH STABLE CAD: INDIAN REAL-WORLD STUDY STRATIFIED BY BMI

Objective: We conducted real world study to assess effectiveness (on blood pressure [BP; mmHg]) and tolerability of fixed dose combination (FDC) of 25/50 mg Metoprolol + 40 mg Telmisartan + 12.5 mg Chlorthalidone in treating hypertension and stable coronary artery disease (CAD). Body mass index (BMI) is one of the factors that affects hypertension and CAD. Hence, we performed this subgroup analysis to assess effectiveness of the FDC based on patients’ BMI. Design and method: A retrospective, multicenter study retrieved data over 15 months from electronic medical records of 1,810 adult patients with systolic BP greater or equal to 140 and/or diastolic BP greater or equal to 90 and stable CAD; 1,784 were treated with FDC for 24 ± 2 weeks. Mean change in BP from baseline, proportion of patients achieving target BP (systolic BP < 140 and diastolic BP < 90) and incidence of adverse events were analyzed in patients with BMI < 18.5 kg/m2 (underweight n= 9); 18.5-22.9 kg/m2 (normal n= 249), 23.0-24.9 kg/m2 (overweight n= 464) and greater or equal to 25 kg/m2 (obese n=1,062). Results: Mean changes in systolic (underweight, -33.6; normal, -29.9; overweight, -27.7; obese, -31) and diastolic BP (underweight, -12.2; normal, -11.5; overweight, -12; obese, -12.2) from baseline to 24 ± 2 weeks were significant (p<0.001), Fig 1. Proportion of patients achieving target BP at 24 ± 2 weeks in all except underweight category was >84%. Fourteen patients had adverse events; hypotension being most common. Conclusions: In a real-world setting, the FDC of Metoprolol + Telmisartan + Chlorthalidone was effective in reducing blood pressure and was well-tolerated in treating hypertension with CAD across all BMI categories. The study demonstrated significant reductions in both systolic and diastolic BP for patients with different BMI levels, highlights the potential benefits of FDC in managing hypertension in various body weight groups.

POSTERIOR REVERSIBILE LEUKOENCEPHALOPATHY SYNDROME AND HYPERTENSIVE CRISIS DUE TO OBSTRUCTIVE SLEEP APNEA:SEARCHING FOR A LINK

Objective: Posterior Reversible Encephalopathy Syndrome(PRES) is a clinic-radiological syndrome characterized by headache, nausea/vomiting, confusion, cognitive changes, seizures,cortical blindness. MRI shows bilateral hyper-intense lesions at the parieto-occipital sub-cortical level on T2 and FLAIR sequences. PRES is associated with severe hypertension, while obsstructive sleep apnesa(OSA) is a common cause of secondary hypertension but rarely causes hypertensive encephalopathy. We present a case of a 42-year-old woman who suffered of hypertensive emergency during hospitalization for dyspnea. Design and method: Clinical history revealed obesity, COPD, OSA in treatment with CPAP, HF with depressed EF (44%), adrenal hyperplasia and retroduodenal lesion under investigation. She was active smoker and BP was uncontrolled by valsartan 160 mg, furosemide 25 mg,bisoprolol 2,5 mg. During the hospitalization in November 2023, patient presented headache, seizures, respiratory distress with high BP values (220/120 mmHg, HR 78 bpm). Results: Laboratory tests revealed only a mild increase of plasma cortisol levels (27.5 mcg/dL, range 0-24); low-dose overnight dexamethasone suppression test was normal (1.5 mcg/dl). Despite anti-hypertensive therapy with B-blocker urinary metanephrine levels were normal (184 mcg/24 h, range 0-320) and 18f-FDG PET-TAC for retroduodenal lesion was normal. Cerebral CT did not show ischemic or hemorrhagic lesions while MRI documented radiological characteristics compatible with PRES (Figure 1). Electroencephalogram showed no epileptic abnormalities. Antihypertensive intravenous treatment with urapidil (25 mg as bolus injection followed by 25 mg/h as continuous infusion) was performed for 36h and followed by oral treatment with canrenoate 25 mg, amlodipine 5 mg and doxazosin 4 mg, added to the above therapy. At discharge, BP was normalized (120/84 mmHg). Checking the electronic card of CPAP, the patient used the device for more than four hours only in 35% of the nights. Conclusions: OSA is a risk factor for acute cardiovascular and cerebrovascular diseases like PRES. CPAP application has been shown to induce small reductions (about 3 mmHg) in BP, but in clinical practice the adherence of treatment is very low (30-60%). On the other hand, the improvement of BP values during hospitalization, raises the suspicion that adherence to pharmacological treatment at home was in the same way poor.

WHY HAPPENS A PROGRESSIVE DECREASE OF BLOOD PRESSURE AFTER RENAL DENERVATION

Objective: Long-term follow-up data from the SYMPLICITY 3 trial (Bhatt et al, Lancet, 2022) and the Global Symplicty Register data (Mahfoud et al, JACC, 2020) show a further decrease in BP over time up to 3 years post procedure. Yet these observations lack a mechanistic explanation. A decrease in vascular resistance could possibly explain the observed phenomenon. Scanning Laser Doppler Flowmetry (SLDF) allows the non-invasive assessment of vascular resistance and capillary density by using the retinal vasculature as a mirror of the systemic circulation. Design and method: Retinal parameters were assessed using SLDF together with office and 24-hour ambulatory BP before and 6 as well as 12 months after renal denervation in 63 patients with treatment resistant hypertension (TRH) (NCT01687725). SLDF allows the assessment of retinal capillary flow (RCF), pulsed retinal capillary flow (systolic retinal capillary flow – diastolic retinal capillary flow) (pRCF), retinal vascular resistance, capillary area (CapA) and intercapillary distance (ICD). Results: Mean age of the study cohort was 60±11 years, mean BMI 30.6±4.9 kg/m2. Patients took 5.8 antihypertensive medications on average. There was a significant reduction of systolic and diastolic 24-hour ambulatory as well office BP 6 as well as 12 months after RDN (table 1). There was no significant reduction in the number of antihypertensive medications taken between baseline and 12 months after RDN (5.8vs.5.7 antihypertensive pills, p=0.159). Retinal vascular resistance was reduced 6 months after RDN (table 1), pRCF was reduced 6 as well as 12 months after RDN and capillary density improved 12 months after RDN. Conclusions: In high-risk patients with TRH endovascular RDN improved vascular resistance and reversed capillary rarefaction in the retinal circulation, a prognostic marker of further end-organ damage. The reduction of pRCF indicates a decrease of shear stress on the vascular wall by the pulsed blood flow. Increment of capillary density was observed not already 6 months, but only 12 months after RDN. We conclude that, improvement of capillary rarefaction happens slowly after RDN and requires long-term effective BP control and, that reduction in vascular resistance might explain the prolonged BP reduction after RDN.

EFFECT OF SEQUENTIAL NEPHRON BLOCKADE X DUAL RENIN-ANGIOTENSIN SYSTEM BLOCKADE + BISOPROLOL IN THE TREATMENT OF RESISTANT HYPERTENSION, A RANDOMIZED CONTROLLED TRIAL (RESHYPOT)

Objective: The primary aim was to compare sequential nephron blockade (SNB) versus dual renin-angiotensin system blockade (DRASB) plus bisoprolol in patients with resistant hypertension to observe reductions in systolic and diastolic blood pressure (SBP and DBP) levels after 20 weeks of treatment. Design and method: This trial was an open-label, prospective, randomized, parallel-group, clinical study with optional drug uptitration. Participants were evaluated during five visits at 28-day intervals. Results: The mean age was 55.5 years in the SNB and 58.4 years in the DRASB + bisoprolol group (p=NS). Significant office BP reductions were observed in both groups. SNB group, SBP decreased from 174.5±21.0 to 127.0±14.74 mmHg (p<0.0001), and DBP decreased from 105.3±15.5 to 78.11±9.28 mmHg (p<0.0001). DRASB group, SBP decreased from 178.4±21.08 to 134.4 ± 23.25 mmHg (p<0.0001) and DBP decreased from 102.7±11.07 to 77.33±13.75 mmHg (p<0.0001). Ambulatory blood pressure monitoring (ABPM) showed also significant SBP and DBP reductions in both groups (p<0.0001). Central systolic blood pressure had a greater reduction in the SNB group pre x post-intervention (128.8± 22.1 x 117.4± 17.9) (p = 0.03). Conclusions: In patients with RHTN adherent to treatment, SNB and DRASB plus bisoprolol showed excellent therapeutic efficacy, although SNB was associated with earlier SBP reduction and a greater reduction in Central systolic blood pressure.

Renal Denervation for Uncontrolled Hypertension

What Is the Issue?
 
 It is estimated that 23% of adults in Canada have hypertension. About 1/3 of this population have uncontrolled hypertension, a condition in which (BP) blood pressure levels continue to remain high despite treatment. People with high BP despite being prescribed 3 or more blood pressure-lowering (antihypertensive) medicines are considered to have uncontrolled resistant hypertension.
 Renal denervation is a therapy that involves disrupting activity in the sympathetic nerves in the renal artery using a minimally invasive catheter-based procedure to treat high BP.
 We wanted to know if renal denervation would effectively and safely reduce BP in people with uncontrolled hypertension.
 
 What Did We Do?
 
 We identified and summarized the literature comparing the clinical effectiveness and safety of renal denervation in individuals with uncontrolled hypertension to help guide decisions on the use of this intervention.
 An information specialist searched for peer-reviewed and grey literature sources published between January 1, 2019, and February 5, 2024. The search was limited to English-language documents. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.
 
 What Did We Find?
 
 The evidence for this report was based on 2 systematic reviews and 3 randomized controlled trials (RCTs).
 Renal denervation could lead to a reduction in BP compared to sham in adults with uncontrolled nonresistant hypertension.
 It is uncertain if renal denervation is an effective treatment for resistant hypertension and suspected hypertensive heart disease due to the methodological limitations of the included studies.
 Serious side effects of renal denervation were rare.
 
 What Does This Mean?
 
 Our findings agree with evidence-based guidelines and real-world evidence that suggest renal denervation can be considered a treatment option for patients with uncontrolled nonresistant hypertension. Other factors, including costs and resources, equity, acceptability, and patient selection, should be considered when implementing renal denervation in Canada, where it remains an emerging medical technology.
 Future research should assess important patient outcomes, such as quality of life.

Effect of Alcohol-Mediated Renal Denervation on Blood Pressure in the Presence of Antihypertensive Medications: Primary Results from the TARGET BP I Randomized Clinical Trial.

Renal denervation (RDN) has demonstrated clinically relevant reductions in blood pressure among individuals with uncontrolled hypertension despite lifestyle intervention and medications. The safety and effectiveness of alcohol-mediated RDN has not been formally studied in this indication. TARGET BP I is a prospective, international, sham-controlled, randomized, patient- and assessor-blinded trial investigating the safety and efficacy of alcohol-mediated RDN. Patients with office systolic blood pressure (SBP) ≥150 and ≤180 mmHg, office diastolic BP ≥90 mmHg and mean 24-hour ambulatory SBP ≥135 and ≤170 mmHg, despite prescription of 2-5 antihypertensive medications were enrolled. The primary endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 3 months post procedure. Secondary endpoints include mean between-group differences in office and ambulatory BP at additional time points. Among 301 patients randomized 1:1 to RDN or sham control, RDN was associated with a significant reduction in 24-hour ambulatory SBP at 3 months (mean ± standard deviation -10.0 ± 14.2 mmHg versus -6.8 ± 12.1 mmHg, treatment difference -3.2 mmHg, 95% confidence interval [CI] -6.3, 0.0 mmHg; P=0.0487). Subgroup analysis of the primary endpoint revealed no significant interaction across predefined subgroups. At 3 months, the mean change in office SBP was -12.7 ± 18.3 mmHg and -9.7 ± 17.3 mmHg (difference, -3.0, 95% CI -7.0, 1.0; P=0.173), for RDN and sham, respectively. No significant differences in ambulatory or office diastolic BP were observed. Adverse safety events through 6 months were uncommon with 1 instance of accessory renal artery dissection in the RDN group (0.7%). No significant between-group differences in medication changes or patient adherence were identified. Alcohol-mediated RDN was associated with a modest but statistically significant reduction in 24-hour ambulatory systolic BP compared with sham control. No significant differences between groups in office BP or 6-month major adverse events were observed.

Effect of Continuous Positive Airway Pressure on Blood Pressure in Patients with Resistant Hypertension and Obstructive Sleep Apnea: An Updated Meta-analysis.

The effect of continuous positive airway pressure (CPAP) on resistant hypertension in patients at high risk with obstructive sleep apnea (OSA) needs further investigation. We aimed to determine the effect of CPAP on blood pressure in patients with resistant hypertension and OSA. Databases including PubMed, EMBASE, MEDLINE, the Cochrane Library, and CMB were searched. Data were pooled using a random-effects or fixed-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals (CIs). A total of 12 trials and 718 participants were included. Compared with control, CPAP significantly reduced 24-h systolic blood pressure (SBP) (WMD: - 5.92 mmHg [ - 8.72, - 3.11]; P＜0.001), 24-h diastolic blood pressure (DBP) (WMD: - 4.44 mmHg [- 6.26 , - 2.62]; P ＜0.001), daytime SBP (WMD: - 5.76 mmHg [ - 9.16, - 2.36]; P ＜0.001), daytime DBP (WMD: - 3.92 mmHg [- 5.55, - 2.30];nighttime SBP (WMD: - 4.87 mmHg [ - 7.96 , - 1.78]; P = 0.002), and nighttime DBP (WMD: - 2.05 mmHg [- 2.99, - 1.11]; P＜0.001) in patients with resistant hypertension and OSA. CPAP improved theblood pressure bothin the short(＜3 months) and long term (≥ 3 months). No significant impact on mean heart rate was noted (WMD: -2.76 beats per min [- 7.50, 1.97]; P = 0.25). CPAP treatment was associated with BP reduction in patients with resistant hypertension and OSA.

Antihypertensive effect of Dapagliflozin in Type II diabetic patients with Hypertension

Hypertension (HTN) and type II diabetes mellitus (T2DM) are two main cardiovascular risk factors that coexist frequently. The aim of this study is evaluation the antihypertensive effect of dapagliflozin in hypertensive type 2 diabetic patients (controlled/inadequately uncontrolled), and study its effect on contributing factors in that effectiveness (ex. weight loss and SNS damping). Primary endpoints included the effect of dapagliflozin on hemoglobin A1C (HbA1c) and blood pressure. Secondary endpoints included the effect of drug on weight body, pulse rate and pulse pressure. Patients were randomly selected from the outpatient of the Endocrinology Department at Tishreen University Hospital in Syria, and divided into two groups: dapagliflozin group (n=45) received 5 or 10mg dapagliflozin once daily as an add-on therapy to oral anti-diabetic drugs (OAD)and antihypertensive drugs, and control group (n=38) received OAD and antihypertensive drugs. After 12 weeks follow-up, dapagliflozin-treated versus control-treated showed significant reduction in HbA1C (-0.7% vs -0.3%, p<0.05, mean seated SBP (-9.4 vs -1.2mmHg, p=0.0001) and mean seated DBP(-6 vs-0.3mmHg, p=0.0001). Dapagliflozin also reduced body weight compared with control (-2.6 vs -0.6kg, p=0.0001) andthere was a significant positive correlation between weight loss and BP reduction. The effect on pulse rate was modest and similar between two groups but dapagliflozin have lowered pulse pressure values. There was no significant dose-response with any studied parameter, too. 5mg dapagliflozin once daily improved glycemic control, reduced body weight, SBP more than DBP and thus improved pulse pressure. All that without any significant effect on pulse rate.

Dapagliflozin and Blood Pressure in Patients with Chronic Kidney Disease and Albuminuria

Background and AimsSodium–glucose cotransporter 2 inhibitors decrease blood pressure in patients with type 2 diabetes, but the consistency and magnitude of blood pressure lowering with dapagliflozin in patients with chronic kidney disease (CKD) is unknown. We conducted a prespecified analysis of the DAPA-CKD trial to investigate the effect of dapagliflozin on systolic blood pressure (SBP) in patients with CKD, with and without type 2 diabetes. MethodsA total of 4304 adults with baseline estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g were randomized to either dapagliflozin 10 mg or placebo once daily; median follow-up was 2.4 years. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or death from a kidney or cardiovascular cause. Change in SBP was a prespecified outcome. ResultsBaseline mean (SD) SBP was 137.1 mmHg (17.4). By Week 2, dapagliflozin compared to placebo reduced SBP by 3.6 mmHg (95% CI 2.8-4.4 mmHg), an effect maintained over the duration of the trial (2.9 mmHg, 2.3-3.6 mmHg). Time-averaged reductions in SBP were 3.2 mmHg (2.5-4.0 mmHg) in patients with diabetes and 2.3 mmHg (1.2-3.4 mmHg) in patients without diabetes. The time-averaged effect of dapagliflozin on diastolic blood pressure (DBP) was 1.0 mmHg (0.6-1.4 mmHg); 0.8 mmHg (0.4-1.3 mmHg) in patients with diabetes and 1.4 mmHg (0.7-2.1 mmHg) in patients without diabetes. Benefits of dapagliflozin on the primary composite and secondary endpoints were evident across the spectrum of baseline SBP and DBP. ConclusionIn patients with CKD and albuminuria, randomization to dapagliflozin was associated with modest reductions in systolic and diastolic BP.

Effect of mindfulness-based interventions on people with prehypertension or hypertension: a systematic review and meta-analysis of randomized controlled trials

BackgroundHypertension and prehypertension have been widely recognized as the main contributors of global mortality. Evidence shows mindfulness-based interventions may reduce blood pressure and improve mental health. However, the effect of mindfulness-based interventions on blood pressure and mental health has not been fully understood.MethodsPotential studies published before May 24th 2023 were identified by searching Embase, Ovid Emcare, PsycINFO, CINAHL, Web of Science, Cochrane, PubMed, China National Knowledge Infrastructure, Wanfang database, and VIP China Science. Additionally, two grey databases were searched: Mednar, WorldWideScience.org. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias Assessment tool. The random-effects meta-analyses were conducted using Review Man 5.4 software and the key outcomes are presented as mean difference or standard mean difference and the 95% confidential interval.ResultsSearches returned 802 studies in total, of which 12 were included (N = 715). The duration of interventions was 8 weeks in 10 trials and 6 weeks in one trial. Pooled effect sizes indicated reductions in systolic blood pressure (MD = − 9.12, 95% CI [− 12.18, − 6.05], p < 0.001), diastolic blood pressure (MD = − 5.66, 95% CI [− 8.88, − 2.43], p < 0.001), anxiety (SMD = − 4.10; 95% CI [− 6.49, − 1.71], p < 0.001), depression (SMD = − 1.70, 95%CI [− 2.95, − 0.44], p < 0.001) and perceived stress (SMD = − 5.91, 95%CI [− 8.74, − 3.09], p < 0.001) at post-intervention. The findings from subgroup analyses are favorable for mindfulness-based interventions regardless of gender and baseline blood pressure with regard to BP reduction, with a more profound effect observed in participants with higher pre-intervention blood pressure.ConclusionsThe results provide evidence for the positive role of mindfulness-based interventions in hypertension management. More large randomized control trials with sufficient statistical power and long-term follow-up are needed.Trial registrationThe protocol had been registered with Prospero on October 2nd 2021 (registration NO. CRD42021282504).

Effects of vasodilators on beat-to-beat and every fifteen minutes blood pressure variability induced by noradrenaline infusion in rats

Increased blood pressure variability (BPV) was shown to be associated with cardiovascular morbidities and/or mortalities. There are various types of BPV depending on time intervals of BP measurements, ranging from beat-to-beat to visit-to-visit or year-to-year. We previously found that continuous infusion of noradrenaline (NA) for 14 days increased short-term BPV every 15 min in rats. The aims of this study were to examine (1) whether NA infusion increases very short-term beat-to-beat BPV, (2) the effects of azelnidipine and hydralazine on NA-induced BPV, and (3) whether baroreceptor reflex sensitivity (BRS) is affected by NA or NA plus those vasodilators. Nine-week-old Wistar rats infused subcutaneously with 30 μg/h NA were orally treated with or without 9.7 mg/day azelnidipine or 5.9 mg/day hydralazine over 14 days. BP levels were continuously monitored via abdominal aortic catheter with a telemetry system in an unrestrained condition. Standard deviations (SDs) were used to evaluate beat-to-beat BPV and BPV every 15 min which was obtained by averaging BP levels for 10-s segment at each time point. BRS was determined by a sequence analysis. Continuous NA infusion over 14 days increased average BP, beat-to-beat BPV, and BPV every 15 min, lowering BRS. Comparing the two vasodilators, hydralazine reduced BP elevation by NA; meanwhile, azelnidipine alleviated BPV augmentation, preserving BRS, despite a smaller BP reduction. Thus, NA infusion increased both very short- and short-term BPV concomitantly with impaired BRS, while azelnidipine had an inhibitory effect, possibly independent of BP-lowering, on those types of BPV and impairment of BRS.

Retrospective study assessing the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers to reduce toxicity from tyrosine kinase inhibitors in metastatic renal cell carcinoma.

411 Background: The main toxicities associated with tyrosine-kinase inhibitors (TKIs) in the treatment of renal cell carcinoma (RCC) are proteinuria and hypertension. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have established reno-protective and anti-hypertensive effects and can help with toxicity in mRCC. We hypothesize that use of ACEIs/ARBs is an effective method to decrease the degree of proteinuria and hypertension in patients treated with TKIs for metastatic/advanced renal cell carcinoma (mRCC). Methods: Single Institution retrospective study; mRCC patients (pts) who received TKI and ACEIs/ARBs and had urine protein measurements available at baseline and at 4-6 wk follow up post ACEs/ARBs were included in the analysis. Primary endpoints included improvement in grade of proteinuria and BP in mRCC pts on TKI treatment at baseline and with addition of ACEIs/ARBs. Secondary endpoints included number of dose interruptions (DI), BUN and creatinine changes. Paired statistical tests were used to compare the selected outcome variables between baseline and post ACE/ARB measures: for example, nonparametric Wilcoxon Signed-rank test for paired quantitative data and McNemar test for paired binary data. Results: Out of 71 screened patients between 2020-2023, N of 22 mRCC (N=22, 72.7% male, 77.3% white; 9% Hispanic; N=14 for TKI+ immunotherapy; N=8 TKI alone) pts were selected. ACEIs/ARBs treatment was associated with significantly reduced levels of proteinuria at 4–6wk follow-up. At baseline vs. follow-up, pts were found to have significantly lower proteinuria overall after ACEI/ARBs (p=0.0147), and 45.4% of pts had clinically insignificant proteinuria vs. 22.7% at baseline. Additionally, DI rates for TKI were significantly lower for pts placed on ACEIs/ARBs, with an 81% chance that pts with prior DI would not experience similar event in the follow-up period (p=0.003). Reductions in BP, creatinine, and TKI dosing were seen but not statistically significant (p&gt;0.05 for all measures). Conclusions: In our small study, degree of proteinuria was notably reduced with administration of ACEIs/ARBs. Further findings show fewer DI of TKIs with ACEIs/ARBs use. Our findings suggest a potential role for ACEIs/ARBs in managing toxicity in patients undergoing TKI based therapy for mRCC. Future studies are needed to evaluate the use of ACE/ARB from the time of initiation of TKI based therapy to reduce the toxicities and improve the adherence to mRCC treatment which may result in better outcomes.

Abstract 2: Intracranial Hemorrhage Managed By A Mobile Stroke Unit

Background: Mobile stroke units (MSUs) improve outcomes in thrombolytic-eligible ischemic stroke patients. Outcomes of MSU management in patients with intracranial hemorrhage (ICH) have not been reported. Methods: We conducted a retrospective review of ICH patients enrolled in the Benefits of Stroke Treatment Using a Mobile Stroke Unit (BEST-MSU), a prospective multicenter controlled trial comparing MSU with standard EMS management (SM). The primary outcome was utility weighted modified Rankin Scale (uw-mRS) at 90 days; secondary outcomes were hematoma expansion, length of inpatient stay, favorable discharge disposition or 90-day mRS, and mortality. Groups were compared using Chi-square or Fisher’s exact tests for categorical variables, and two sample t-test or Wilcoxon rank sum test for continuous variables. Adjusted analysis was performed to evaluate the relationship between the intervention group and uw-mRS at 90 days. Kaplan-Meier curves and log-rank test were used to compare the survival by 90 days between groups. Results: 201 ICH patients were identified; 102 in the MSU and 99 in the SM groups. MSU patients had more antiplatelet/antithrombotic (AP/AT) use (30.4% vs 15.2%, p=0.016); edema was more frequent in the SM group (72.7% vs 52.0%, p = 0.004). Initial ICH volume was similar between MSU and SM groups (11.50 mL [5.0, 22.0] vs. 9.0 mL [5.0, 20.0], p = 0.62). Anti-hypertensives were given earlier on the MSU (39.0 min [31.00, 45.00] vs 61.0 min [46.50, 75.25], p&lt;0.001), and resulted in shorter time to systolic blood pressure (SBP) &lt; 150mmHg (52 min vs. 121 min, p&lt;0.001). The mean uw-mRS at 90 days was 0.364 ± 0.361 in the MSU and 0.465 ± 0.360 in the SM group (p=0.50, adjusted for AP/AT and edema). There was no difference in hematoma expansion, length of stay, discharge disposition or 90-day mRS. Higher mortality was noted after 5 days post-ictus in the MSU group (26.5% vs. 14.1%, p = 0.04). Conclusion: In ICH patients, MSU management resulted in faster treatment and time to target SBP with similar clinical outcomes except higher late mortality. Further study of the impact of prehospital ICH management including BP reduction and AT/AP reversal are required.

A telehealth-delivered intervention to extend the veteran HIV treatment cascade for cardiovascular disease prevention: V-EXTRA-CVD study protocol for a randomized controlled trial

Background: Veterans living with HIV have up to twice the risk of atherosclerotic cardiovascular disease (ASCVD) compared to those without HIV. Objective: Our study seeks to test a non-physician led virtual self-management implementation strategy to reduce ASCVD risk among people living with HIV (PWH). We aim to conduct a randomized control trial among PWH (n = 300) with a diagnosis of hypertension (HTN) who are enrolled in Veterans Health Administration (VHA) clinics, on suppressive antiretroviral therapy (ART), randomized 1:1 to intervention vs. education control for a 12-month duration. Methods: Using human centered design approach, we have adapted a previous 5-component telehealth focused, non-physician led intervention to a Veteran population. The education control arm receives enhanced education in addition to usual care. The primary outcome is 6 mmHg reduction in systolic BP over 12-month in the intervention arm compared to the control arm. The secondary outcome is a 12-month difference in non-HDL cholesterol. While each component of our intervention has an evidence base, they have not been tested together in an HIV context. Conclusion: The proposed multicomponent intervention has the potential to improve cardiovascular outcomes in PWH using novel virtual care methods in a patient centered care approach.

MONITORING OF CEREBRAL PERFUSION PRESSURE IN PATIENTS WITH ACUTE ISCHEMIC STROKE

we studied patients with ischemic stroke with antihypertensive medication for high arterial hypertension. Material and methods:we studied 28 patients in the general intensive care unit of multidisciplinary TMA with acute cerebral ischemia syndrome caused by ischemic-type ACCD. The age of the patients was on average 61±7 years. There were 20 males and 8 females. The level of consciousness was assessed using the Glasgow scale. It ranged from 4 to 10 points. Results:the given data clearly indicate a more pronounced decrease of SBP, DBP, ICP during intravenous infusion of Tahiben at the stages of the study. A significant difference in the duration of drug effects in the studied groups was noted. Thus, when using Tahiben, the target level of SBP and DBP could be maintained up to 220±54 minutes, while in the standard treatment group it was maintained for 68±8 minutes. Conclusions:intravenous administration of Tahiben (urapidil) at the early hospital stage in patients with arterial hypertension against the background of standard baseline therapy of ACCD is an effective and safe method of urgent therapy, providing dosage BP reduction by 15-25% of the initial one.

Different systolic blood pressure targets and outcomes: a systematic review and meta-analysis of randomized trials

Abstract Background Blood pressure (BP)-lowering is accompanied by a reduction of fatal or nonfatal outcomes in hypertensive patients. However, the achieved systolic BP target associated with higher outcome benefits remains unsettled. Purpose The aim was to determine the effects of BP-lowering treatment on outcome incidence at different achieved systolic BP strata. Methods A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, search between 1966 and 11/2022) for the effect of BP-lowering treatment against placebo or less aggressive treatment on the composite outcome of major cardiovascular (CV) events (i.e., myocardial infarction, stroke, and heart failure). Selected studies reported outcomes in patients with or without a history of previous CV disease. Studies were categorized according to the achieved level of systolic BP in the active or more actively treated group. Risk ratios (RR) were calculated with their 95% confidence interval (CI) under the random-effects model. Results We included 51 primary prevention studies (i.e., 16 trials in which systolic BP was lowered to values no less than 140 mmHg, n=36,189 patients; 22 trials with achieved systolic BP between 130 and 140 mmHg, n=84,952; and 13 trials with achieved systolic BP less than 130 mmHg, n=41,660) and 44 secondary prevention studies (i.e., 11 trials in which systolic BP was lowered to values no less than 140 mmHg, n=12,518 patients; 19 trials with achieved systolic BP between 130 and 140 mmHg, n=71,449; and 14 trials with achieved systolic BP less than 130 mmHg, n=39,085). For a standard systolic/diastolic BP reduction of 10/5 mmHg, the relative risk of the composite outcome was reduced in all achieved systolic BP strata, without a significant trend from higher to lower systolic BP targets, in both prevention groups. In addition, there was no difference in the absolute risk reduction of the combined outcome, as calculated by the number of events prevented in every 1000 patients treated for 5 years, between the systolic BP targets in each prevention group. However, only in primary prevention did a significant negative incremental trend from higher to lower systolic BP targets for the residual risk of the combined outcome become apparent. Conclusions Although antihypertensive treatment provides CV protection to all hypertensive patients, the lower systolic BP target is associated not only with outcome benefits but also with a lower rate of residual risk in primary prevention only.