Similar Blood Pressure Research Articles

PS-BPC12-2: EFFICACY AND SAFETY OF SINGLE-PILL COMBINATION OF OLOMAXÂ (OLMESARTAN, AMLODIPINE, AND ROSUVASTATIN) IN HYPERTENSIVE PATIENTS WITH LOW-TO-MODERATE CARDIOVASCULAR RISK

Objective: Of the ten hypertensive patients who have to take statins in Korea, about two are not actually prescribed. The use of polypills including lipid-lowering and blood pressure (BP)-lowering drug improves medication adherence, and consequently ameliorates in cardiovascular risk levels. This study was to evaluate the efficacy and safety of single-pill triple-combination of olmesartan/amlodipine/rosuvastatin (OLOMAX®) in comparison to single-pill dual-combination of olmesartan/amlodipine (SEVIKAR®) in hypertensive patients with low-to-moderate cardiovascular risk. Design and method: This multicenter, active-control, randomized study included 106 hypertensive patients with low-to-intermediate cardiovascular risk, who were randomly assigned to receive either OLOMAX®(20/5/5 mg, treatment 1), OLOMAX®(20/5/10 mg, treatment 2), or SEVIKAR®(20/5 mg, control) once daily for 8 weeks. The low and moderate cardiovascular risk groups were defined according to the definition of the 4th Korean dyslipidemia treatment guidelines. Primary endpoint was assessed as the difference of the percent change of LDL-C(low-density lipoprotein-cholesterol) level at 8 weeks from baseline among the three groups. Results: The difference in the least square mean % change of LDL-C in the treatment 1 and 2 groups compared to the control group at 8 weeks was -32.6 ± 3.7% and -45.9 ± 3.3%, respectively (all p < 0.001). There was significant difference in the achievement rate of LDL-C levels < 100 mg/dL at 8 weeks between the three groups (65.8% for the treatment 1 group, 86.7% for the treatment 2 group, and 6.25% for the control group, p < 0.001). The results of total cholesterol, triglycerides, high-density lipoprotein-cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A1 showed the superiority in the treatment 1 and 2 groups compared to the control group. Meanwhile, there was no significant difference in systolic and diastolic BPs and diabetes-related variables including fasting glucose, fructosamine, and hemoglobinA1c at 8 weeks between the three groups. Adverse drug reaction (ADR) developed only 1 case (constipation) in the treatment 1 group and serious ADR did not occur in the three groups. Medication adherence rates were highly excellent in the three groups (98.0% for the treatment 1 group, 99.7% for the treatment 2 group, and 96.3% for the control group, p > 0.05). Conclusions: Single-pill triple-combination of olmesartan/amlodipine/rosuvastatin were superior to single-pill dual-combination of olmesartan/amlodipine in LDL-C lowering effect, with similar BP reduction effects and excellent safety profiles in hypertensive patients with low to moderate cardiovascular risk.

PS-C36-8: BLOOD PRESSURE REDUCTION AFTER RENAL DENERVATION IN PATIENTS WITH OR WITHOUT CHRONIC KIDNEY DISEASE: THE ERLANGER EXPERIENCE

Background: Hypertension is associated with major cardiovascular and renal adverse events and the 24h-ambulatory blood pressure (BP) is superior than the office BP in predicting these complications. Overactivitiy of the sympathetic nervous system is linked with elevation of systemic BP and is also present in patients with chronic kidney disease (CKD). The aim of this study was to compare the BP lowering effects of renal denervation (RDN) in patients with and without CKD. Methods: Radiofrequency or ultrasound device based renal denervation was performed in 47 patients with and 127 without CKD in our center. Office and 24h-ambulatory BP were assessed after 3, 6 and 12 months by validated devices. CKD was defined by clinical diagnosis or according to the estimated glomerular filtration rate (eGFR: 15–60 ml/min/1.73m2; CKD-EPI formula). Results: Until today, 174 patients with a mean age of 59.0 ± 10 were followed up for at least 12 months. At baseline mean eGFR was 55.8 ± 21 ml/min/1.73m2 in patients with CKD and 87.3 ± 13 ml/min/1.73m2 in patients without CKD. There was no significant eGFR decline in either of the groups during follow up. In patients with CKD eGFR was after 12 months 54.4 ± 23 ml/min/1.73m2 (p = 0.699 vs baseline). Office and 24h-systolic and -diastolic BP were significantly reduced from baseline in patients with or without CKD at all time points after RDN (all p < 0.01). There was no significant difference in the reduction of 24 h, day- and nighttime ambulatory BP between the 2 groups at any time point (see table below). With exception of rare local adverse events (e.g. haematoma at the puncture site), we had no safety signals, especially in our patients with CKD, e.g. there was no dissection, embolism or periprocedural cardiovascular complications. Conclusion: In our single center registry, we observed a similar BP reduction in 24 h, day- and nighttime ambulatory BP as well as in office BP in patients with and without CKD at any time point up to 12 months. There was no safety signal related to RDN. In particular, we did not observe a significant eGFR decline in both CKD positive or negative patients. We conclude that RDN is an effective and safe treatment option for patients with hypertension and chronic kidney disease.

PS-P07-3: EFFICACY AND SAFETY OF NIFEDIPINE GASTROINTESTINAL THERAPEUTIC SYSTEM VERSUS RAMIPRIL IN CHINESE AND EUROPEAN PATIENTS WITH HYPERTENSION

Objective: In a post-hoc analysis of a multinational, randomized trial, we investigated whether the efficacy and safety of nifedipine gastrointestinal therapeutic system (GITS) and ramipril differed between Chinese and European patients with hypertension. Method: Previously treated (2-week washout) and untreated patients with hypertension were randomly assigned to treatment with nifedipine GITS 30 mg or ramipril 10 mg for 12 months, if they had elevated clinic (≧ 140/90 mmHg) and daytime (≧ 135/85 mmHg) ambulatory systolic/diastolic blood pressure (BP) and standard deviation of home (> 7 mmHg) and daytime systolic BP (> 12 mmHg). BP was measured at each of the clinic visits at baseline and during follow-up. Ambulatory and 7-day home BP monitoring were performed at baseline and 10 weeks and 12 months of follow-up. Results: The 67 Chinese and 101 European patients significantly differed in age (50.9 vs. 54.6 years), body mass index (24.5 vs. 27.0 kg/m2), clinic diastolic BP (87.9 vs. 92.5 mmHg), clinic heart rate (75.0 vs. 70.8 beats/minute) and nighttime diastolic BP (79.3 vs. 75.9 mmHg). However, within each ethnicity, patients were comparable between the nifedipine GITS and ramipril groups (P≧ 0.05). In both Chinese and European patients, BP was similarly reduced in the nifedipine GITS and ramipril groups, except that daytime systolic/diastolic BP reductions were 7.4/4.1 mmHg greater in the ramipril than nifedipine GITS group in Chinese (P = 0.02). The safety profile significantly (P for drug*ethnicity interaction ≦ 0.046) differed between the Chinese and European patients for the incidence of all adverse events (lower on nifedipine GITS in Chinese), ankle edema (higher on nifedipine GITS in Europeans) and dry cough (higher on ramipril in Chinese). Conclusion: In the Chinese and European patients with hypertension, nifedipine GITS and ramipril had similar BP lowering efficacy, but different safety profile and tolerability.

Assessment of Cardiorespiratory Dysfunctions of Health Professionals above the Age of 40 years by means of Electrocardiography and Spirometry

Background: The increasing prevalence of chronic respiratory diseases, particularly chronic bronchitis andemphysema (COPD), is reflected as a growing concern regarding its diagnosis and control. Moreover medicalpersonnel working in different medical set up are at greater risk of stress and disease related susceptibility.Materials and Methods: Descriptive observational study based on ‘convenience sampling done on Healthprofessional viz. Doctors, Nurses and Technicians attached with Medical College, Kolkata and Ruby GeneralHospital, Kolkata between Feb 2015 to May 2016. Overall 50 doctors, 25 nurses and 25 technicians were taken fromMedical College, Kolkata. Pulmonary function tests were done by Spirotech ©, a software after rest for 10-15 minand briefing about to the technique of FVC (maximum inhalation followed by maximum exhalation) and MVV(voluntary hyperventilation for 15 seconds) tests were carried out. Spirometric parameters recorded for analysiswere FVC, FEV1, FEV1/FVC, PEFR, FEF25%-75% and MVV. The controls were selected from relatives of Out PatientDepartment (OPD) of Medical College who were non-health professionals. They followed the same procedure asthe cases.Results: It shows among cases of Medical College, 8 people are hypertensive and 42 people are normotensive,whereas in control group 5 people are hypertensive and 44 people are normotensive and 1 person had hypotension,which is not statistically significant (P Value 0.419). It shows among Medical college cases Mean FEV1 / FVC ratiois 114.50 (SD 12.63) whereas that of control is 103.90 (SD 15.94), which is statistically significant (P Value 0.000).Conclusion: Medical personnel are more obese particularly in corporate hospital. Medical personnel have similarblood pressure level as in general population. RBBB pattern is the most predominant QRS abnormality which isnot uncommon. Medical personnel have lower mean FEV1%, FEV1/ FVC and PEFR % than general population.Predominant spirometry abnormality in our study is restrictive pattern.

Adrenal Vein Sampling Results and Surgical Outcomes in Patients with a Normal Plasma Aldosterone Concentration

PurposeTo determine the utility of adrenal vein sampling (AVS) and outcomes after adrenalectomy in patients with normal plasma aldosterone concentration (PAC) and elevated aldosterone-to-renin ratio (ARR). Materials and MethodsThe study sample included 106 patients with ARR greater than 20 and PAC between 5 and 15 ng/dL (normal PAC group) who underwent AVS from 2005 to 2021. These patients were compared with a cohort of 106 patients with ARR >20 and PAC >15 ng/dL (high PAC group) who underwent AVS during the same period. Data regarding baseline clinical characteristics, lateralization indices from AVS, and outcomes after adrenalectomy were analyzed. ResultsAVS was technically successful in 210 patients (210/212, 99%). A smaller proportion of patients in the normal PAC group showed a lateralization index of >4 compared with those in the high PAC group (44% vs 64%, P <.01). A similar proportion of patients in the normal PAC group experienced improved or cured hypertension after adrenalectomy compared with that in the high PAC group (94% vs 88%, P =.31). Hypokalemia was cured in all patients in the normal PAC group after adrenalectomy compared with 98% of patients in the high PAC group (100% vs 98%, P = 1). ConclusionsAlthough lateralization is less frequent for patients with normal PAC, patients who do lateralize show similar blood pressure response and correction of hypokalemia after adrenalectomy, regardless of initial plasma aldosterone levels. Therefore, patients with PAC <15 ng/dL should still be considered for AVS provided the ARR is elevated.

Clinical Utility of Short-Term Blood Pressure Measures to Inform Long-Term Blood Pressure Management.

Decisions about hypertension management are substantially influenced by blood pressure (BP) levels measured before and soon after starting BP lowering drugs. We aimed to assess the utility of short-term BP changes in individuals in terms of long-term treatment response. Post hoc analyses of 2 randomized trials with 4-to-6 weeks active run-in for all participants, followed by randomization to active BP lowering treatment (combination perindopril±indapamide) or placebo. We categorized individuals by degree of systolic BP (SBP) change during active run-in treatment and assessed associations with subsequent postrandomization placebo-corrected BP reduction, cardiovascular events, and tolerability. We included individuals with baseline BP ≥140/90 mm Hg from the PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study; 4275 individuals with cerebrovascular disease) and ADVANCE trial (The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation; 6610 individuals with diabetes). During the active run-in period, the proportion of participants with initial SBP changes in 4 categories (SBP increase, 0-9.9 mm Hg decrease, 10-19.9 mm Hg decrease, and ≥20 mm Hg decrease) were 17%, 27%, 28%, and 28% in PROGRESS and 21%, 22%, 24%, and 33% in ADVANCE. Randomization to active therapy achieved similar placebo-corrected long-term BP reductions across the 4 initial SBP change groups in both trials (P-values for heterogeneity >0.1). There was no significant difference in achieving BP <140/90 mm Hg at follow-up, major cardiovascular events, nor treatment tolerability according to the SBP change during active run-in period (all P-values >0.1). An individual's apparent BP change immediately after commencing therapy has limited clinical utility. Therefore, more emphasis should be given to use of evidence-based regimens and measures over the long-term to ensure sustained BP control. URL: https://www. gov; Unique identifier: NCT00145925.

Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation

Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial. To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications. This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m2 or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment. uRDN vs sham procedure in conjunction with added medications to target BP control. Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety. A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m2 had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of -2.4 [16.6] vs -7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups. In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group. ClinicalTrials.gov Identifier: NCT02649426.

Central hemodynamics and the discrepancy between central blood pressure and brachial blood pressure.

Despite similar brachial blood pressure, central hemodynamics could be different. The objective of the present study was to investigate the factors, which could influence the discrepancy between central BP (cBP) and brachial blood pressure. Six hundred forty-seven patients (364 males, 48 ± 12 years old) were enrolled. Using applanation tonometry, cBP was noninvasively derived. The median difference between brachial systolic BP (bSBP) and central systolic BP (cSBP) was 8 mm Hg. We defined the discrepancy between bSBP and cSBP as differences >8 mm Hg. For adjustment of cBP, population was divided into 3 groups according to the cBP: group 1, <140 mm Hg of cSBP; group 2, 140 > cSBP < 160 mm Hg; group 3, =160 mm Hg of cSBP. All the central hemodynamic parameters of the patients, including augmentation pressure, augmentation index (AI), heart rate (75 bpm) adjusted augmentation index (AI@HR75), and subendocardial viability ratio, were measured. Using multivariate logistic regression analysis, we evaluated the factors which could influence the discrepancy between bSBP and cSBP. Age, gender, augmentation pressure, AI, and AI@HR75 were correlated with the discrepancy between bSBP and cSBP. AI@HR75 was significantly correlated with the discrepancy between bSBP and cSBP (β-coefficient = −0.376, P < .001 in group 1; β-coefficient = −0.297, P < .001 in group 2; and β-coefficient = −0.545, P < .001 in group 3). In groups 1 and 2, male gender was significantly correlated with the discrepancy between bSBP and cSBP (β-coefficient = −0.857, P = .035 in group 1; β-coefficient = −1.422, P = .039 in group 2). In present study, arterial stiffness might affect the discrepancy between bSBP and cSBP. Also, male gender was closely related to the discrepancy between bSBP and cSBP especially with cSBP <160 mm Hg. Not only cSBP, the discrepancy between cSBP and bSBP should be considered for understanding the central hemodynamics.

Erectile dysfunction, generalized vascular disease and the long term effects of smoking exposure on arterial properties: time is of the essence

Abstract Introduction Erectile dysfunction (ED) is considered an early manifestation of generalized vascular disease and may precede clinically overt cardiovascular disease (CVD) by 2 to 5 years. We examined macrovascular changes according to time of ED onset and the impact of smoking on the severity of penile vascular damage and large artery wall changes. Methods We measured carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (cIMT), augmentation index (AIx) and brachial flow-mediated dilation (FMD) in 378 males with ED (age: 54±7 years). All participants had no clinical manifestations or a history of atherosclerotic disease. They were assessed using the Sexual Health in Men (SHIM)-5 score for ED severity and the penile colour Doppler ultrasonography after intracavernous injection of prostaglandin E1 for measurement of peak systolic velocity (PSV). Low PSV values indicate impaired penile blood inflow and severe vasculogenic ED. ED duration was defined as the time interval between age at diagnosis and study entry. Results The study population was divided into three groups according to duration of ED. Group 1: &amp;lt;2 years, Group 2: 2–5 years and Group 3: &amp;gt;5 years. Comparison of various parameters among the three groups using one-way ANOVA or the Kruskal–Wallis test did not demonstrate statistically significant differences in age, prevalence of hypertension, diabetes, smoking, peripheral blood pressure (BP) and metabolic parameters (fasting blood glucose, lipid profile, testosterone levels). Total tobacco cigarette exposure was greater in males with ED duration &amp;gt;5 years (Group 3), compared to Group 2 and 1 patients (23.8 vs 22.5 vs 20.7 pack-years, P&amp;lt;0.01). PWV, AIx and cIMT increased and FMD decreased across the three groups (Figure 1). The three groups had comparable PSV value. We then divided the study population into four subgroups according to tobacco exposure (never smokers; light smokers&amp;lt;20 pack-years, moderate smokers 20–40 pack-years and heavy smokers &amp;gt;40 pack-years). The subgroups have similar age and BP. The three smoking subgroups had significantly higher PWV (P&amp;lt;0.001), AIx (P&amp;lt;0.01), cIMT (P&amp;lt;0.01) and lower FMD (P&amp;lt;0.05) and PSV (P&amp;lt;0.05) compared to never smokers. Post hoc analysis revealed higher PWV, AIx and cIMT and lower FMD in heavy smokers compared to moderate and light smokers (all p&amp;lt;0.05). PSV was similar across the three smoking subgroups. Conclusions The study shows that longer ED duration is associated with a more pronounced vascular dysfunction and subclinical vascular wall changes and that heavy tobacco cigarette exposure significantly deteriorates macrovascular parameters. Furthermore there was a significant impairment of penile vasculature even in light smokers. These findings may partly explain why the same process that contribute to CVD may cause earlier ED symptoms and imply that smoking cessation should be a premising non pharmacological intervention in men with ED. Funding Acknowledgement Type of funding sources: None.

Cell-Specific Actions of the Prostaglandin E-Prostanoid Receptor 4 Attenuating Hypertension: A Dominant Role for Kidney Epithelial Cells Compared With Macrophages.

Background A beneficial role for prostanoids in hypertension is suggested by clinical studies showing nonsteroidal anti-inflammatory drugs, which block the production of all prostanoids, cause sodium retention and exacerbate hypertension. Among prostanoids, prostaglandin E2 and its E-prostanoid receptor 4 receptor (EP4R) have been implicated in blood pressure control. Our previous study found that conditional deletion of EP4R from all tissues in adult mice exacerbates angiotensin II-dependent hypertension, suggesting a powerful effect of EP4R to resist blood pressure elevation. We also found that elimination of EP4R from vascular smooth muscle cells did not affect the severity of hypertension, suggesting nonvascular targets of prostaglandin E mediate this antihypertensive effect. Methods and Results Here we generated mice with cell-specific deletion of EP4R from macrophage-specific EP4 receptor knockouts or kidney epithelial cells (KEKO) to assess the contributions of EP4R in these cells to hypertension pathogenesis. Macrophage-specific EP4 receptor knockouts showed similar blood pressure responses to alterations in dietary sodium or chronic angiotensin II infusion as Controls. By contrast, angiotensin II-dependent hypertension was significantly augmented in KEKOs (mean arterial pressure: 146±3 mm Hg) compared with Controls (137±4 mm Hg; P=0.02), which was accompanied by impaired natriuresis in KEKOs. Because EP4R expression in the kidney is enriched in the collecting duct, we compared responses to amiloride in angiotensin II-infused KEKOs and Controls. Blockade of the epithelial sodium channel with amiloride caused exaggerated natriuresis in KEKOs compared with Controls (0.21±0.01 versus 0.15±0.02 mmol/24 hour per 20 g; P=0.015). Conclusions Our data suggest EP4R in kidney epithelia attenuates hypertension. This antihypertension effect of EP4R may be mediated by reducing the activity of the epithelial sodium channel, thereby promoting natriuresis.

The effect of placental transfusion on hemodynamics in premature newborns: a randomized controlled trial

Despite of growing evidence of the beneficial effects of placental transfusion techniques, there is no available sufficient data about their effects on vulnerable hemodynamics and myocardium of premature infants. The purpose of this work is to study ventricular functions and hemodynamics after applying different placental transfusion techniques, delayed cord clamping (DCC), cut cord milking (C-UCM), and intact cord milking (I-UCM). Sixty-four infants delivered whether by C-section or vaginal delivery were randomly assigned to undergo C-UCM (20–30 cm), I-UCM (3–4 strippings), and DCC (30–60 s). Functional echocardiography was done on day 1 and day 3 of life for 57 infants. Primary outcome variable was superior vena cava flow measurement in infants having placental transfusion in the first 24 h of life and between 64 and 72 h. Secondary outcomes were other echocardiographic and clinical hemodynamic parameters, and biventricular functions in those infants. Of a total 196 preterm infants ≤ 32 weeks delivered in the study period, from January 2021 to August 2021, 57 infants were eligible and survived till the second examination. They were randomly assigned to the three groups. Neonates randomly assigned to DCC had significantly higher superior vena cava flow and lower right ventricular systolic function in the first 24 h of life. This finding vanished at day 3. Neonates undergone different methods of placental transfusions had similar hemoglobin, admission temperature, and mean blood pressure in the first 24 h of life.Conclusion: Despite their potential benefits, placental transfusions have shown to alter the hemodynamics and adversely affect myocardial function of premature neonates.Trial registration: This trial was registered in the clinical trial gov NCT04811872.What is Known:• Placental transfusion techniques might have benefits regarding prematurity- related morbidities and mortality.What is New:• Placental transfusion might adversely affect the myocardium and alter hemodynamics in premature infants.

Impact of dedicated multidisciplinary service on patient selection and outcomes for surgical treatment of primary aldosteronism

BackgroundPrimary aldosteronism is the most common surgically curable cause of endocrine hypertension. Management of the unilateral subtype of primary aldosteronism with adrenalectomy requires multidisciplinary input. It is unclear if a dedicated endocrine hypertension service confers better outcomes compared to standard care offered by individual clinicians. MethodsIn this retrospective study, patients from the Monash University Endocrine Surgery Database were divided into either the endocrine hypertension service group, where patients were managed by a dedicated multidisciplinary team, or the standard group, where patients were managed by individual clinicians. The comparisons included patient selection for surgery, perioperative blood pressure control, and surgical cure rate. ResultsDespite similar perioperative blood pressure, patients in the endocrine hypertension service group (n = 41) were on fewer antihypertensive medications (1 vs 2, P = .011) compared to the standard group (n = 55). A larger proportion of patients in the endocrine hypertension service group had either bilateral adrenal nodules or no adrenal lesions on computed tomography (41% vs 18%, P = .013). Patients in the standard group had larger adrenal lesions on computed tomography (median 15 mm vs 10 mm, P = .032). Postoperatively, the biochemical cure rate was higher in the endocrine hypertension service group at 6 to 12 months (97% vs 76%, P = .021). ConclusionPatients managed by endocrine hypertension service were more likely to be diagnosed with surgically curable primary aldosteronism without a unilateral adrenal adenoma on imaging, required fewer medications for perioperative blood pressure control, and experienced superior postoperative outcomes. Referral to a dedicated endocrine hypertension service is recommended for patients with primary aldosteronism who wish to pursue a surgical cure.

Efficacy of Dapagliflozin in Patients with Diabetes Mellitus Complicated with Coronary Artery Disease and Its Impact on the Vascular Endothelial Function.

Objective To investigate the efficacy of dapagliflozin for diabetes mellitus complicated by coronary artery diseases and its impact on vascular endothelial function. Methods Between August 2020 and August 2021, 80 patients with coronary heart disease complicated by type 2 diabetes mellitus were recruited and randomly assigned to receive either dapagliflozin (5 mg daily) plus original oral hypoglycemic agents (dapagliflozin group) or original oral hypoglycemic agents alone (control group). Outcome measures included blood pressure, blood glucose, cholesterol levels, vascular endothelial function, cardiovascular events, and drug-related adverse events. Results The two groups had similar outcome indices upon admission (P > 0.05). After 20 weeks of medication, the two groups of patients showed similar blood pressure, hemoglobin A1c (HbA1c), and low-density lipoprotein (LDL-C) levels versus those before treatment (P > 0.05), and no significant differences were found in intergroup comparison neither (P > 0.05). Dapagliflozin plus conventional hypoglycemic agents resulted in a significantly higher reactive hyperemia index (RHI) value, fewer cases with abnormal vascular endothelial function, and fewer major cardiovascular events during treatment versus the sole use of conventional hypoglycemic agents (P < 0.05). There was no significant difference in drug-related adverse events between the two groups (P > 0.05). Conclusion Dapagliflozin improves the vascular endothelial functions of patients with diabetes mellitus complicated by coronary artery disease with a high safety profile and favorable efficacy.

Abstract A2: Non-canonical AT 1 R/b-arrestin2 Activation In Brain As A Regulator Of Blood Pressure

The brain renin angiotensin system (RAS) is known for its role in cardiovascular and metabolic regulation. Angiotensin II (Ang II) is the major active product of the RAS, exerting most of its physiological effects through the angiotensin type-1 receptor (AT 1 R). Canonical or G protein-mediated signaling of the AT 1 R within the brain is known to induce dipsogenic and pressor responses to Ang II stimulation. Non-canonical or β-arrestin mediated signaling is thought to counterbalance the detrimental effects of canonical signaling. However, the role of the non-canonical AT 1 R/β-arrestin pathway within the brain is understudied. Therefore, we hypothesized that β-Arrestin activation within the brain contributes to blood pressure (BP) regulation. Global β-arrestin1 ( Arrb 1) and β-arrestin2 ( Arrb 2) knockout (KO) mice were employed to evaluate BP upon treatment with 1) deoxycorticosterone acetate (DOCA)-salt and 2) Ang II. Age- and sex-matched C57BL/6J mice served as controls. First, mice were instrumented with radiotelemetry implants and BP was continuously recorded. At baseline, Arrb2 -KO mice exhibited similar BP when compared to WT (WT=128±5.5 vs Arrb 2-KO=131±5.4 mmHg; n=8 and 9, respectively). However. Arrb2-KO mice exhibited exacerbated responses to DOCA-salt compared to WT (WT=152±12 vs Arrb 2-KO=163±10 mmHg; n=8 and 9, respectively; p=0.03). Second, BP was evaluated upon acute intracerebroventricular (ICV) injection of Ang II (1ug). Arrb -2KO mice showed a higher BP response to Ang II compared to WT (WT=143±12 vs Arrb 2-KO=168±10 mmHg; n=5 and 6, respectively). These findings suggest that activation of β-arrestin2 might counterbalance the effects of canonical activation of the AT 1 R through G proteins. Overall, β-arrestin2 in the brain appears to protect against cardiovascular diseases since the genetic ablation of β-Arrestin2 resulted in an exacerbated BP, particularly with brain-specific injection of Ang II.

Urban-rural differences in hypertension prevalence in low-income and middle-income countries, 1990-2020: A systematic review and meta-analysis.

The influence of urbanicity on hypertension prevalence remains poorly understood. We conducted a systematic review and meta-analysis to assess the difference in hypertension prevalence between urban and rural areas in low-income and middle-income countries (LMICs), where the most pronounced urbanisation is underway. We searched PubMed, Web of Science, Scopus, and Embase, from 01/01/1990 to 10/03/2022. We included population-based studies with ≥400 participants 15 years and older, selected by using a valid sampling technique, from LMICs that reported the urban-rural difference in hypertension prevalence using similar blood pressure measurements. We excluded abstracts, reviews, non-English studies, and those with exclusively self-reported hypertension prevalence. Study selection, quality assessment, and data extraction were performed by 2 independent reviewers following a standardised protocol. Our primary outcome was the urban minus rural prevalence of hypertension. Hypertension was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure as ≥90 mm Hg and could include use of antihypertensive medication, self-reported diagnosis, or both. We investigated heterogeneity using study-level and socioeconomic country-level indicators. We conducted meta-analysis and meta-regression using random-effects models. This systematic review and meta-analysis has been registered with PROSPERO (CRD42018091671). We included 299 surveys from 66 LMICs, including 19,770,946 participants (mean age 45.4 ± SD = 9 years, 53.0% females and 63.1% from rural areas). The pooled prevalence of hypertension was 30.5% (95% CI, 28.9, 32.0) in urban areas and 27.9% (95% CI, 26.3, 29.6) in rural areas, resulting in a pooled urban-rural difference of 2.45% (95% CI, 1.57, 3.33, I-square: 99.71%, tau-square: 0.00524, Pheterogeneity < 0.001). Hypertension prevalence increased over time and the rate of change was greater in rural compared to urban areas, resulting in a pooled urban-rural difference of 5.75% (95% CI, 4.02, 7.48) in the period 1990 to 2004 and 1.38% (95% CI, 0.40, 2.37) in the period 2005 to 2020, p < 0.001 for time period. We observed substantial heterogeneity in the urban-rural difference of hypertension, which was partially explained by urban-rural definition, probably high risk of bias in sampling, country income status, region, and socioeconomic indicators. The urban-rural difference was 5.67% (95% CI, 4.22, 7.13) in low, 2.74% (95% CI, 1.41, 4.07) in lower-middle and -1.22% (95% CI, -2.73, 0.28) in upper-middle-income countries in the period 1990 to 2020, p < 0.001 for country income. The urban-rural difference was highest for South Asia (7.50%, 95% CI, 5.73, 9.26), followed by sub-Saharan Africa (4.24%, 95% CI, 2.62, 5.86) and reversed for Europe and Central Asia (-6.04%, 95% CI, -9.06, -3.01), in the period 1990 to 2020, p < 0.001 for region. Finally, the urban-rural difference in hypertension prevalence decreased nonlinearly with improvements in Human Development Index and infant mortality rate. Limitations included lack of data available from all LMICs and variability in urban and rural definitions in the literature. The prevalence of hypertension in LMICs increased between 1990 and 2020 in both urban and rural areas, but with a stronger trend in rural areas. The urban minus rural hypertension difference decreased with time, and with country-level socioeconomic development. Focused action, particularly in rural areas, is needed to tackle the burden of hypertension in LMICs.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Discovery of small-molecule modulators of the secretin receptor: Purmorphamine as novel anti-hypertensive agent

The Secretin/Secretin receptor (SCTR) axis is well-known for its important role in water/salt homeostasis and blood pressure control. Recent studies revealed that absence of Secretin could lead to hypertension in animals and the administration of external Secretin leads to a sharp drop in blood pressure. Therefore, Secretin receptor has emerged as a crucial drug target of interest. In this report, using structure based drug design strategy, we have identified a small compound-based Secretin receptor modulator (i.e. purmorphamine or KSD179019). The virtual docking of KSD179019 with SCTR crystal structure and homology models revealed similar binding interactions. Based on active pharmacophores of KSD179019, several derivatives were designed and sythesized. SAR studies revealed that KSD179019 is the most effective SCTR modulator and chosen for further biological evaluation, including drug like properties and anti-hypertensive effect. KSD179019 not only has a similar blood pressure lowering effect as SCT peptide, but more importantly, it has a much longer half-life (∼8 h) and can be taken orally. Preliminary preclinical studies revealed extended bioavailability and low toxicity of this compound.

Transcutaneous Vagus Nerve Stimulation Ameliorates the Phenotype of Heart Failure With Preserved Ejection Fraction Through Its Anti-Inflammatory Effects.

A systemic proinflammatory state plays a central role in the development of heart failure with preserved ejection fraction (HFpEF). Low-level transcutaneous vagus nerve stimulation (LLTS) suppresses inflammation in animals and humans, mediated by an α7nAchR (alpha7 nicotinic acetylcholine receptor)-dependent pathway. We examined the effects of LLTS on cardiac function, inflammation, and fibrosis in the presence of α7nAchR pharmacological blockade in a rat model of HFpEF. Dahl salt-sensitive rats at 7 weeks of age were treated with high-salt diet for 6 weeks to induce HFpEF, followed by 4 weeks of (1) LLTS, (2) LLTS with the α7nAchR blocker methyllycaconitine, (3) sham, and (4) olmesartan. Blood pressure, cardiac function by echocardiography, heart rate variability, and serum cytokines were measured at 13 and 17 weeks of age. Cardiac fibrosis, inflammatory cell infiltration, and gene expression were determined at 17 weeks. LLTS attenuated the increase in blood pressure; improved cardiac function; decreased inflammatory cytokines, macrophage infiltration, and fibrosis; and improved survival compared with other groups. Methyllycaconitine attenuated these effects, whereas olmesartan did not improve cardiac function or fibrosis despite maintaining similar blood pressure as LLTS. Heart rate variability was similarly improved in the LLTS and LLTS plus methyllycaconitine groups but remained low in the other groups. LLTS reversed the dysregulated inflammatory signaling pathways in HFpEF hearts. Neuromodulation with LLTS improved cardiac function in a rat model of HFpEF through its anti-inflammatory and antifibrotic effects. These results provide the basis for further clinical trials in humans.

Comparing effect of definition of diurnal periods by diary, fixed periods, and actigraphy on ambulatory blood pressure parameters in a Chinese population.

Background:Reliable measurement of daytime and night-time blood pressure (BP), and degree of BP dipping during sleep during ambulatory blood pressure monitoring (ABPM) requires an accurate definition of sleep time (diurnal definition). However, superiority of any diurnal definition on ABPM remains unclear. The present study compared mean daytime and night-time SBP and DBP using different methods for diurnal definition: patient's diary, wide-defined and narrow-defined fixed periods, and actigraphy, in a Chinese population with diagnosed essential hypertension. We hypothesize that BP values from actigraphy are different from BP obtained by other methods and associated with end-organ damage (i.e. impaired renal function, proteinuria, left ventricular hypertrophy).Methods:From April 2017 to October 2019, 203 Chinese patients diagnosed with hypertension were recruited prospectively from Lek Yuen Clinic and 179 completed a 48-h ABPM study, wearing a validated actigraph and completed a sleep diary. Presence of end-organ damage was retrieved from the computerized clinical management system. The differences in the mean BP values provided by different diurnal definition were compared using paired t tests and Bland–Altman plots. The prevalence of elevated BP, dipping status categories, overall percentage agreement and the Kappa statistic were calculated by pairwise comparisons between different diurnal definitions. The reproducibility was also estimated and logistic regression was used to examine the relationship between BP values from different diurnal definitions and end-organ damage.Results:Mean daytime and night-time BP values were similar regardless of the definition used (mean difference <2 mmHg). Kappa statistics and overall percentage agreement found excellent agreement between different definitions to diagnose elevated daytime BP (Kappa ranged from 0.80 to 0.91) and night-time BP (Kappa ranged from 0.74 to 0.89). Good agreement to diagnose nondipping was also detected (Kappa ranged from 0.65 to 0.78). Furthermore, ABPM values were most reproducible when diurnal periods were defined by patient's diary (intra-class correlation coefficient = 0.82–0.93). Daytime and night-time BP values obtained using different diurnal definitions did not differ in their association to end-organ damage.Conclusion:Differing definitions of diurnal periods provide similar mean BP values among a Chinese hypertensive population and have good agreement for diagnosis of elevated BP and dipping status. In individual patients, clinicians should be aware that different definitions of diurnal periods can lead to a 3–5 mmHg difference in patient's BP values and may affect the diagnosis of elevated BP in patients with BP close to diagnostic thresholds. The current study supports using the patient's diary to define diurnal periods, which provided the best reproducibility.

Effects of sleep deprivation and 4‐7‐8 breathing control on heart rate variability, blood pressure, blood glucose, and endothelial function in healthy young adults

This study investigated the effects of sleep deprivation on heart rate variability (HRV), blood pressure (BP), fasting blood glucose (FBG), and endothelial function as well as the immediate effects of 4‐7‐8 breathing control on HRV and BP. In total, 43 healthy participants aged 19–25 years were classified into two groups: Twenty two in the with sleep deprivation group and 21 in the without sleep deprivation (control) group. Resting heart rate (HR), BP, HRV, FBG, and endothelial function were examined. Subsequently, participants practiced 4‐7‐8 breathing control for six cycles/set for three sets interspersed between each set by 1‐min normal breathing. Thereafter, the HR, BP, and HRV were immediately examined. The HRV, HR, and BP variables and FBG were not significantly different between the two groups. However, endothelial function was significantly lower in the sleep deprivation group than that in the control group (p < 0.05). In response to 4‐7‐8 breathing control, low‐ and very‐low‐frequency powers significantly decreased (p < 0.05), whereas high‐frequency power significantly increased (p < 0.05) in the control group. Moreover, time domain, total power, and very‐low‐frequency power significantly decreased (p < 0.05) in the sleep deprivation group. Both groups had significantly decreased HR and systolic BP (p < 0.05). HRV, HR, and BP variables showed no significant differences between the groups. Healthy young adults with and without sleep deprivation may have similar HRV, BP, and FBG values. However, sleep deprivation may cause decreased endothelial function. Furthermore, 4‐7‐8 breathing control can help participants improve their HRV and BP, particularly in those without sleep deprivation.