Changes In Systolic Blood Pressure Research Articles

PS-C28-9: AMBULATORY BP DERIVED SALT SENSITIVITY INDEX AS A PREDICTOR OF THE BP RESPONSE TO RENAL DENERVATION

Objective: Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce clinic and ambulatory blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis and severity, but cumbersome to assess by gold-standard methodology. 24-hour average heart rate and mean arterial pressure dipping, taken by ambulatory blood pressure monitoring (ABPM), can stratify patients into high, moderate and low salt sensitivity index (SSI) risk categories. Here we aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world cohort of RDN patients. Design and Methods: 60 participants (70.0 ± 10.3 years, 76.3% male) had repeat ABPM assessment as part of a renal denervation long-term follow and compared to their pre-RDN baseline for calculating systolic BP changes. Average time since RDN was 8.7 years ± 1.09 years. Participants were stratified into low, moderate and high SSI Risk groups, respectively. MAP dipping less than 10% and heart rate (HR) greater than 70 indicated high-risk, MAP dipping greater than 10% and HR less than 70 indicated low risk. Remaining participants were classified as moderate risk. Systolic BP changes in risk groups were compared by One-way ANOVA. Multiple regression was computed for systolic BP response, baseline SBP and High SSI Risk status. Results: One-way ANOVA indicated a significant treatment effect (p = 0.03) between low, moderate and high salt-sensitivity index risk calculated by ABPM measures with systolic BP reduction of 9.64 ± 3.74 mmHg, 8.41 ± 3.48 mmHg, and 28.20 ± 9.55 mmHg, respectively. Baseline SBP was not significantly different between SSI Risk groups (p = 0.18), but trended upward with increasing SSI. High SSI risk independently correlated with systolic BP reduction (p = 0.02). Conclusions: Our preliminary investigation indicates that SSI risk may serve as a simple and easily accessible measure for prediction of the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug-naive RDN cohorts.

To Compare the Effects of Adding Handheld and Ankle Weights During Treadmill Walking on Blood Pressure and Rate of Perceived Exertion in Normal Healthy Adults: An Experimental Study

Context: Walking is the most commonly reported activity which requires no special facilities and is achievable by all groups with little injury risk. Nowadays, adding weights to different locations while walking is popular in general fitness and rehabilitation programs, which again increases energy expenditure as well as oxygen consumption in a shorter quantity of time. Aims: The aim of this study was to compare the effect of adding handheld and ankle weights during treadmill walking on blood pressure and rate of perceived exertion in normal healthy adults. Settings and Design: The experimental study took place in the laboratory and was designed to be carried on for three sessions to measure the changes in blood pressure and ratings of perceived exertion (RPE) while walking with and without weight. Subjects and Methods: Thirty-three participants who satisfied the inclusion criteria were recruited to perform the exercise session with handheld and ankle and without weights and it consisted of 8 min of exercise testing with and without weights for two sessions. Statistical Analysis Used: The statistical test data were screened for normal distribution by Shapiro–Wilk test. Data were normally distributed for the systolic blood pressure (SBP), diastolic blood pressure (DBP), and RPE. Hence, parametric tests were applied for SBP, DBP, and RPE within-session and between-session analysis. Within-session analysis was done by paired t-test and between-session analysis was done by unpaired t-test. Results: Intra-session analysis by paired t-test in both sessions shows statistically significant changes in SBP and RPE (P < 0.05). Moreover, DBP was found significant while using handheld weights compared to no weights. While inter-session analysis by unpaired t-test showed significant changes in DBP compared to that of SBP, RPE using handheld weights during treadmill walking. Conclusions: Study shows addition of handheld weights proves to be more effective in adults who cannot run, or do not like to run, or are limited in walking speed, and may benefit from the addition of hand-held weight (HHW) and ankle weight (AW).

PS-C25-10: ASSOCIATION BETWEEN SKELETAL MUSCLE MASS AND BLOOD PRESSURE DECLINE OVER A FIVE-YEAR PERIOD FOR COMMUNITY-DWELLING OLDER ADULTS

Objective: To determine the association between skeletal muscle mass and systolic blood pressure decline over a 5-year period in older adults over 75 years old. Methods: Of those who got health checkups at private A clinic from May 2020 to March 2021, 118 subjects for whom data on systolic blood pressure (SBP) levels consequently collected for five years were included. Skeletal muscle mass was measured at the health checkup in this clinic, and the Skeletal Muscle Index (SMI) was calculated by dividing the sum of limb muscle mass by the square of height using the multi-frequency bioimpedance method. Lower SMI was classified as a relative skeletal muscle mass index less than 7.0 kg/m2 and 5.7 kg/m2 in men and women, respectively. SBP levels used the mean of office SBP at A clinic visits in 2020 and 2015. 5-year SBP changes were calculated and categorized into two groups: SBP decline group (decline of -3 or more) and SBP maintenance group. The main outcome was SBP decline, and the association with SMI was examined by chi-square test and logistic regression analysis adjusted for age and gender. Results: The mean age of the subjects was 81.1 ± 4.5 years, 76 (64.4%) were female, 76(64.4%) were taking anti-hypertensive medication, 40(33.9%) were lower SMI, and 39 (33.1%) for SBP decline group. The SBP decline group had a lower BMI and a higher percentage of lower SMI than the maintenance group (p < 0.05). Furthermore, logistic regression analysis showed that lower SMI was independently associated with SBP decline (odds ratio: 2.44, 95% CI: 1.07–5.54). Conclusion: Our results suggest that there may be an association between lower SMI and SBP decline over a 5-year period in community-dwelling older adults over 75 years old. Long term changes of SBP might be the useful biomarker for muscle mass decline for older adults, although further mechanistic investigations are necessary.

Effects of education on pain and anxiety before and after video-assisted thoracoscopic surgery.

Video-assisted thoracoscopic surgery (VATS) is a common surgical procedure. To find out how educating patients using multimedia affects their pain and anxiety before and after VATS surgery. The study included 50 patients who underwent VATS between December 2017 and December 2018. The subjects were divided into two groups: the multimedia information group (MIG) and the control group (n = 25). The subjects underwent STAI-T testing, preoperative and postoperative STAI-S testing, and pulmonary function tests (PFT) before surgery and after surgery. The patients in the MIG had higher baseline anxiety levels than those in the control groups. There were no significant differences between the two groups in terms of demographic information, surgical characteristics, or vital signs. There was a statistically significant difference in the preoperative (p = 0.001) and the postoperative (p = 0.0001) pain scores between MIG and control groups. The postoperative STAI-S scores of MIG increased, but this increase was not significant. In both groups, there was no significant difference in the changes in systolic blood pressure (p = 0.656) or respiratory rate (p = 0.05). There was no difference between post-training and pre- and post-operative pain scores in both groups. Providing multimedia information before surgery has some effect on pain. However, providing multimedia information does not reduce postoperative anxiety.

H1 and H2 antihistamines pretreatment for attenuation of protamine reactions after cardiopulmonary bypass: a randomized-controlled study.

Protamine administration post-cardiopulmonary bypass (CPB) can potentially cause hemodynamic instability. Histamine released from mast cells is believed to be responsible for hypotension after protamine administration. The aim of this study was to examine the effects of pretreatment with H1 and H2 antihistamines on changes in systemic arterial pressure following protamine administration. This study was a randomized, triple-blinded, placebo-controlled study, conducted at a university hospital. Forty adult patients undergoing elective coronary artery bypass grafting (CABG) or single valve surgery were included. The patients were randomly allocated (20 patients in each group) to receive a single dose of combined chlorpheniramine 10 mg and ranitidine 50 mg or normal saline intravenously immediately after separation from CPB prior to protamine administration. Trajectory changes in systolic blood pressure (SBP), mean arterial pressure (MAP), and vasoactive-inotropic score (VIS) from baseline until 35 minutes following protamine administration (24-time points) were compared between the two groups. Serial serum tryptase levels were also obtained at baseline, 30 and 60 minutes after protamine was given. Forty patients were included in the analysis. Demographic and baseline blood pressure were similar between the two groups. At 30 minutes after protamine administration, there were no significant differences in both crude SBP [mean difference: -7.1 mmHg, 95% confidence interval (CI), -1.1 to 15.3 mmHg, P=0.09] and SBP after adjustment for the European System for Cardiac Operative Risk Evaluation (EuroSCORE II), CPB time, and VIS (mean difference: -3.9 mmHg, 95% CI, -11.9 to 4.0 mmHg, P=0.33). There were also no significant differences in crude MAP (mean difference: -2.1 mmHg, 95% CI, -6.9 to 2.7 mmHg, P=0.39) and adjusted MAP (mean difference: -0.7 mmHg, -5.9 to 4.4 mmHg, P=0.78) between the two groups. None of the patients in both groups had a significant increase in serum tryptase from baseline. No differences in median serum tryptase levels at baseline, 30 and 60 minutes were demonstrated between the two groups. Pretreatment with H1 and H2 antihistamines does not attenuate blood pressure responses to protamine administration in patients after CPB. Mechanisms other than histamine release from mast cells might be responsible for protamine-induced cardiovascular changes. ClinicalTrials.gov NCT03583567.

Phenylephrine and Ephedrine for Prevention of Hypotension in Women during Lower Segment Caesarean Section under Spinal Anaesthesia: A Randomised Clinical Study

Introduction: Hypotension is the most common serious adverse event associated with Spinal Anaesthesia (SA) and is associated with nausea and vomiting leading to pulmonary aspiration, respiratory depression and cardiac arrest. Phenylephrine (PE) and Ephedrine (EP) are vasopressors commonly used for prevention of hypotension associated with SA. Aim: To compare the efficacy and safety of PE and EP in prevention of hypotension induced by SA in women during Lower Segment Caesarean Section (LSCS) surgery. Materials and Methods: The present randomised clinical study was conducted on 60 women, between 18-36 years of age and a Heart Rate (HR) of 60-100 per minute randomised to receive either 100 mcg Intravenous (i.v.) bolus of PE, or 12 mg i.v. of EP during intrathecal block. Women having intraoperative hypotension were injected additional doses of vasopressor. Cardiovascular parameters were recorded at baseline (before block) and then at 1, 5, 10, 15, 30, 40 and 60 minutes. Further, safety was also assessed based on hypotension events and adverse events reported during immediate postoperative period. Data analysis was done using IBM SPSS 17 and a p-value <0.05 was considered statistically significant. Results: The mean age of the study participants in PE and EP group was 26.67±5.40 and 26.23±4.59 years, respectively. Significant differences were observed between PE and EP groups for change in Systolic Blood Pressure (SBP) after 1, 10, 30, 40 and 60 minutes. Overall, there was a slight fall in SBP with PE, whereas, with EP there was a slight rise in SBP. Also, the Diastolic Blood Pressure (DBP) was maintained with EP throughout the 60 minute period, whereas with PE there was an initial rise in DBP followed by a slight fall in DBP. The Mean Arterial Pressure (MAP) was well maintained with PE throughout, whereas with EP there was a fall in MAP after 15 minutes. However, these changes were not clinically significant. The Pulse Rate (PR) was lower with PE compared to EP group at time points of 1, 5, 15 and 20 minutes. The mean respiratory rates and blood oxygen saturation were similar with PE and EP administration (p>0.05). A total of 13 (43.3%) patients in the PE group and 14 (46%) in the EP group had adverse events excluding hypotensive patients. Conclusion: According to the findings of the present study, the i.v. bolus of 100 mcg PE and 12 mg EP administered immediately after SA are equally effective in prevention of maternal hypotension and do not cause any significant cardiovascular and respiratory effects.

Characterizing the Blood Pressure Response to Physical Counterpressure Manoeuvres Using Surface Electromyography in Adults With Long Covid

Orthostatic intolerance (OI) is common in Long Covid. Physical counterpressure manoeuvres (PCM) may improve OI in other disorders. We characterised the blood pressure-rising effect of PCM using surface electromyography (sEMG) and investigated its association with fatigue in adults with Long Covid. Participants performed an active stand with beat-to-beat hemodynamic monitoring and sEMG of both thighs, including PCM at 3-minutes post-stand. Multivariable linear regression investigated the association between change in systolic blood pressure (SBP) and change in normalised root mean square (RMS) of sEMG amplitude, controlling for confounders including the Chalder Fatigue Scale (CFQ). In 90 participants (mean age 46), mean SBP rise with PCM was 13.7 (SD 9.0) mmHg. In regression, SBP change was significantly, directly associated with change in RMS sEMG ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\beta =0.25$ </tex-math></inline-formula> , 95% CI 0.07–0.43, P = 0.007); however, CFQ was not significant. PCM measured by sEMG augmented SBP without the influence of fatigue.

S-21-5: COMPARISON OF THIRD-DOSE TRIPLE VERSUS THIRD-DOSE DUAL ANTIHYPERTENSIVE COMBINATION THERAPIES IN PATIENTS WITH ESSENTIAL HYPERTENSION DURING 8-WEEK FOLLOW-UP

Objective: We compared efficacy and safety of low-dose triple versus low-dose dual antihypertensive combination therapies in patients with essential hypertension. Design and method: This trial was a multicenter, randomized, double-blind, parallel, phase II study. After a 4-week placebo run-in period, 243 patients were randomized to the third -dose triple combination (ALC group, amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg), third-dose dual combination (AL group, amlodipine 1.67 mg + losartan potassium 16.67 mg), (LC group, losartan potassium 16.67 mg + chlorthalidone 4.17 mg), or (AC group, amlodipine 1.67 mg + chlorthalidone 4.17 mg) for 8 weeks. The primary outcome was to compare the mean changes in systolic blood pressure (SBP) from baseline to week 8. Results: Baseline patient characteristics and blood pressure did not show significant differences among 4 groups. The mean SBP reductions of ALC group, AL group, LC group and AC group were -18.30 ± 13.23, -13.03 ± 13.30, -16.29 ± 12.36, and -13.80 ± 13.21 mmHg at week 8 from baseline, respectively. The ALC group showed significant SBP reductions in comparison to the AL and AC groups at week 4 (p = 0.0097 and p = 0.0179, respectively) and week 8 (p = 0.0170 and p = 0.0357, respectively). The mean diastolic blood pressure (DBP) reduction from baseline was significantly greater in the ALC group when compared to the AL group (-7.93 ± 7.05 and -4.95 ± 7.96 mmHg, respectively, p = 0.0307). The proportion of responders for SBP was significantly greater in the ALC group (42.6%) compared to the AL (22.0%), LC (23.3%) and AC (27.1%) groups (p = 0.0126, 0.0210 and 0.0445, respectively) at week 4. Furthermore, the proportion of responders for SBP and DBP was significantly greater in the ALC group (59.7%) compared to the AL (39.3%) and AC (42.4%) groups (p = 0.0222 and 0.0491, respectively) at Week 8. Study drug-related adverse reactions were rare and did not show significant differences among 4 study groups. Conclusions: Low-dose triple antihypertensive combination therapy when compared to the low-dose dual combination therapies demonstrated early effective BP control without increasing adverse drug reactions in patients with essential hypertension during 8-week follow-up.

Remote Patient Monitoring for Hypertension: Feasibility and Outcomes of a Clinic-Based Pilot in a Minority Population.

In the US 48% of adults have hypertension, with direct costs in excess of $130 billion per year. Remote patient monitoring (RPM) has been discussed as a useful tool in the treatment of hypertension, but few studies evaluate its cost effectiveness or efficacy in minority, lower socio-economic (SES) populations. Our study aims to evaluate the clinical and financial outcomes of RPM in hypertension management in a primarily minority, low-SES population. In this prospective cohort pilot study, patients with uncontrolled primary hypertension (defined via Joint National Committee 8 guidelines) were randomly selected from a single academically affiliated primary care clinic. Patients were enrolled on a rolling basis for 90 days. Patients were given blood pressure cuffs and transmission hubs and asked to transmit daily blood pressure readings. Patients were called weekly by research assistants and concerns were escalated to the primary care physician. The control group was the remaining 299 uncontrolled hypertensive patients from the same clinic population analyzed via retrospective chart records at the conclusion of the interventional study period. The primary outcome was blood pressure control. Secondary outcomes were relative improvement in systolic pressure and direct costs. A total of 13 patients were enrolled into the RPM intervention; these patients were 54% female, 100% African American, and 77% Medicaid. When assessed via intention-to-treat analysis, patients in the intervention group had non-inferior blood pressure control at 90 days (46% experimental vs 31% control, P = .33) and average change in systolic blood pressure at 90 days (13.5 vs 3.7 mmHg, P = .174) while experiencing a significant reduction in office-based visits at 90 days (1.5 vs 5.9, P < .001) as compared to control. Results on per-protocol analysis also showed non-inferior BP control (63% vs 31%, P = .135). Financially, the program generated margins of $29 per patient at 90 days. Patients in our minority- and Medicaid-predominant cohort achieved noninferior blood pressure control as compared to retrospective control at 90 days and a significant reduction in all-cause clinic visits at 90 days. The program generated little revenue per patient, with main barriers to implementation including patient compliance and payor denial.

PS-P12-7: IDENTIFYING THE EVIDENCE-POLICY GAP IN TASK-SHARING WITH COMMUNITY HEALTH WORKERS FOR MANAGEMENT OF HYPERTENSION: A MIXED-METHOD STUDY

Objective: Few studies are addressing the evidence-policy gap in task-sharing with community health workers (CHWs) to manage hypertension. We aimed to identify the gap by 1) performing a scoping review of peer-reviewed journals and 2) conducting in-depth interviews with key informants who have been involved in national CHW programs. Design and Methods: We searched PubMed for studies published from 2010–2021 following the PRISMA extension for scooping review guideline. We included all type of studies on task-sharing with CHWs for hypertension management. We extracted data on types, places, and the frequency of CHWs’ activities and other relevant indicators. The primary outcomes were changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), BP control, and medication adherence. In the corresponding countries, key informants with policy and implementation experience in national CHW programs were identified and interviewed. Result: A single reviewer screened 2,316 records, of which 166 were assessed for eligibility, and 85 were included in the final review. There were 29 randomized controlled trials, 2 quasi-experimental trials, 11 pre-post studies, 2 prospective cohorts, 19 cross-sectional studies, and 22 qualitative studies. CHWs performed health education and BP measurement in 80% (60/75) and 63% (47/75) of studies, respectively. 89% (33/37) used digital BP device. Patients’ home (64%, 47/71) was used the most with a median of one visit per month, followed by public space (11%, 8/71) and home/clinic (6%, 4/71). One CHW was responsible for an average of 116 participant with the range from 3 to 612. Significant reduction in SBP was seen in 56% (9/16) of the included trials. Eight informants from six countries (Brazil, India, Iran, Liberia, Thailand, Zimbabwe) participated in in-depth interviews. Brazil, India, Iran, Thailand, and Zimbabwe involved CHWs in health education, whereas only Thailand and Iran involved in BP measurement and both use manual BP devices. In these five countries, one CHW was responsible for an average of 1,250 people with the range from 250 to 3,000 in a national program. Conclusion: Despite clinically relevant BP reduction in CHW programs, there was suboptimal translation of this evidence into policy. The size of the population served per CHW and the type of BP device differed between research studies and national programs. Global health partners (i.e. those who generate evidence) and local governments need to work together to bridge the gap between evidence and policy. Figure 1: Forest plot of difference in systolic and diastolic blood pressure change in included studies.

PS-BPP04-9: THE RXPATH RANDOMIZED TRIAL OF THE HYPERTENSION CANADA PROFESSIONAL CERTIFICATION PROGRAM: A NOVEL IMPLEMENTATION STRATEGY FOR HYPERTENSION GUIDELINES

The uptake of clinical practice guidelines into practice is poor for many chronic conditions, including hypertension. We designed a guidelines-based educational program for primary care clinicians, the Hypertension Canada Professional Certification Program (HC-PCP, www.hypertension.ca/professional-certification-program). It consists of four online modules, an online prospective patient registry, and expert evaluations of the blood pressure measurement technique and case management by the learner. We then evaluated its impact on patient level outcomes. Objective: The objective of RxPATH was to determine the effect of the HC-PCP for pharmacists on systolic blood pressure reduction in patients with poorly controlled hypertension. Design and Methods: Design: Stepped wedge cluster randomized trial (unit of randomization was the pharmacy). Setting: Community pharmacies in Alberta, Canada Population: Pharmacists with prescriptive authority volunteered to participate. We enrolled patients with poorly controlled hypertension (BP &gt; 140/90mmHg or &gt; 130/80mmHg in those with diabetes), identified by their pharmacist. Intervention: Pharmacists were enrolled in the HC-PCP. They then provided this care to their patients with poorly controlled hypertension. Control: Pharmacists were given a copy of the Hypertension Canada Guidelines and provided usual care to their patients prior to undertaking the HC-PCP. Outcomes: The primary outcome was difference in change in systolic blood pressure between intervention and control groups at 3 months. We also evaluated patient satisfaction using the Consultant Satisfaction Questionnaire (CSQ). Results: We enrolled 890 patients from 61 pharmacies (104 pharmacists). Mean age was 61.6 (SD 14.1) years, 46% were female, 35.5% had diabetes, and mean baseline BP was 152.4 (SD 13.8)/87.0 (SD 10.6)mmHg. Change in systolic BP was 9.9 (SD 16.5) for the intervention group, compared to 9.9 (SD 16.2) mmHg in the control group, p = 0.29. Patient satisfaction using the CSQ was high at 76 (of 90 maximum). Conclusions: Most educational programs do not get evaluated at the patient level. RxPATH demonstrated that the HC-PCP intervention did not result in a greater reduction in systolic BP compared to control. While both groups did have clinically meaningful reductions in BP, possible reasons for lack of a difference with the intervention include: COVID-19 staffing/workload issues in pharmacies, selection bias for pharmacists interested in hypertension/contamination of usual care group, and short follow-up duration. Feedback on the HC-PCP from pharmacists was positive, patient satisfaction was high, and we plan to make this program widely available to primary care providers.

PS-C19-10: SEASONAL VARIATION IN THE EFFECT OF ANTIHYPERTENSIVE TREATMENT WITH THE IRBESARTAN/HYDROCHLOROTHIAZIDE COMBINATION

Objective: There is increasing awareness of seasonal variation in blood pressure. In the present analysis, we investigated seasonal variation in antihypertensive treatment effect of the irbesartan/hydrochlorothiazide combination in patients with stage 2 and 3 hypertension. Design and Methods: The study participants were hypertensive patients enrolled in a 12-week therapeutic study. Antihypertensive treatment was initiated with the irbesartan/hydrochlorothiazide 150/12.5 mg/day, with the possible up-titration to 300/12.5 mg/day and 300/25 mg/day at 4 and 8 weeks of follow-up. The month of treatment commencement was classified as spring/summer (May to August) and autumn/winter (September to December). Results: Of the 501 enrolled patients, 313 and 188 commenced antihypertensive treatment in spring/summer and autumn/winter, respectively. The mean changes in systolic/diastolic blood pressure at 8 and 12 weeks of follow-up were greater in patients who commenced treatment in autumn/winter (-32.3/-16.5 and -34.2/-16.7 mmHg, respectively) than those in spring/summer (-28.4/-13.9 and -27.1/-12.8 mmHg, respectively), with a between-season difference of 3.9 (95% confidence interval [CI], 1.4–6.4, P = 0.002)/2.6 (95% CI, 0.9–4.2, P = 0.002) mmHg and 7.0 (95% CI, 4.7–9.3, P &lt; 0.0001)/3.9 (95% CI, 2.4–5.4, P &lt; 0.0001) mmHg, respectively. Further subgroup analyses showed a greater between-season difference in the changes in systolic blood pressure in patients aged 55 years and older (n = 255) than those &lt; 55 years (n = 246, 12.6 vs. 6.9 mmHg, P = 0.02), and in patients with chronic kidney disease (n = 175) than those with normal renal function (n = 326, 12.1 vs. 7.4 mmHg, P = 0.06). Conclusions: There is indeed seasonality in antihypertensive treatment effect, with a greater blood pressure reduction in patients who commenced treatment in cold than warm seasons.

Predictive Value of Exercise Blood Pressure Changes for Orthostatic Hypotension in Patients With Parkinson’s Disease

Orthostatic hypotension (OH) is common in patients with Parkinson's disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD. This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET). According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively. CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group (p<0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH (p<0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649-0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively. This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH.

APSH-OP-5: MEASURES OF LONG-TERM SYSTOLIC BLOOD PRESSURE VARIABILITY AND THEIR ASSOCIATIONS WITH THE RISK OF INCIDENT TYPE 2 DIABETES MELLITUS

Objective: The present study investigates the association between long-term systolic blood pressure (SBP) variability and the risk of type 2 diabetes mellitus (T2DM) by using different indicators of the variability including standard deviation (SD), coefficient of variation (CV), maximum and minimum difference (MMD), root mean square error (RMSE), variability independent of the mean (VIM), and average real variability (ARV). Design and method: A cohort of 3017 Japanese individuals (2446 male, 571 female) aged 36 to 65 was followed from 2007 through 2019. SD, CV, MMD, RMSE, VIM, and ARV of long term SBP changes were calculated per individual using SBP values obtained consecutively from 2003 to 2007. A multivariable Cox proportional model was applied to estimate hazard ratio (HR) and the corresponding 95% confidence interval (CI) for tertiles of the each variability measure, SD, CV, MMD, RMSE, VIM, and ARV, adjusted for age, sex, smoking status, regular exercise, family history of diabetes, sleep disorders, sodium intake, body mass index (BMI), BMI slope, fasting blood glucose (FBG), and 2007 SBP. Results: Of the variability measures examined, the highest RMSE tertile compared to the lowest was significantly associated with T2DM incidence (multivariable-adjusted HR: 1.79, 95% CI: 1.15–2.78). Also, the highest ARV tertile compared to the lowest was associated with T2DM incidence (multivariable-adjusted HR: 1.54, 95% CI: 1.00–2.35). The SD, CV, MMD and VIM were not significantly associated with T2DM incidence independent of the covariates. Conclusion: This study revealed that long-term SBP variability is possibly an independent risk factor for the future occurrence of T2DM, and such property can only be measured by either RMSE or ARV.

Comparative study of the effect of two different doses of intravenous labetalol on the cardiovascular response to endotracheal extubation.

Providing a stable hemodynamic in extubation is important. We aimed to compare the effect of two different doses of intravenous labetalol on the cardiovascular response to endotracheal extubation. This double-blind randomized trial was performed in 2019-2020 in Isfahan on 72 patients under general anesthesia. Patients using Random Allocation software were divided into three groups and received 0.1 mg/ kg or 0.2 mg/kg labetalol and normal saline intravenously 10 min before extubation. Hemodynamic variables including heart rate (HR), Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and peripheral blood oxygen saturation(SPO2) was measured for each patient before induction of anesthesia and 1, 3, 5 and 10 minutes after extubation. SBP changes were significantly different between the three groups at 1, 3, 5 minutes after extubation (P=0.036, P=0.009, P=0.005 respectively) unlike the other two groups, patients who received 0.2 mg/kg labetalol did not have an increase in DBP after extubation (P>0.05). DBP was significantly different between the three groups one minute after extubation (P=0.03). At minutes 1 and 3 following extubation, there was a significant difference in the MAP between the three groups. (P=0.029 and P=0.012 respectively). There was no significant difference between the three groups regarding heart rate (P>0.05). Tracheal extubation is usually associated with an increase in hemodynamic variables. Both doses of labetalol attenuate the hemodynamic response accompanying tracheal extubation. But labetalol 0.2 mg/kg in reducing hemodynamic response to extubation acted more effectively than labetalol 0.1mg/kg.

S-57-3: GUT MICROBIAL METABOLITES LOWER 24-HOUR SYSTOLIC BLOOD PRESSURE IN HYPERTENSIVE PATIENTS

Objective: Clinical evidence supports that dietary fibre intake lowers blood pressure (BP). Dietary fibres remain intact until they reach the colon. There, they are fermented by gut microbial communities to produce metabolites, particularly short-chain fatty acids (SCFAs). Previous studies, including our own, have demonstrated that supplementation with the SCFAs acetate and butyrate lower BP in experimental models. However, whether dietary supplementation with SCFAs in humans elicits the same reduction in BP is undetermined. We aimed to establish whether a SCFAs-enriched dietary supplement lowers 24-hour BP in participants with essential hypertension. Design and method: Twenty untreated hypertensive participants, diagnosed by 24-hour BP using a Mobil-O-Graph device, were recruited for a phase II randomized placebo-controlled double-blind crossover trial. Participants were randomized to receive a daily intervention of 40 g/day of acetylated and butyrylated high amylose maize starch (HAMSAB) or 40 g/day of regular flour or cornflour (placebo). The dietary intervention lasted three weeks, with a three-week washout period following completion. The primary endpoint was a change in 24-hour systolic BP. Secondary endpoints included SCFA levels and changes in gut microbiome. Results: Participants were on average 55.8 ± 11.2 (mean ± SD) years of age, had a body mass index (BMI) of 25.7 ± 2.5km2/m, and 30% were female. The baseline 24-hour systolic BP was 136 ± 6mmHg. The dietary intervention was well-tolerated and had high acceptability with 93% compliance. There was no difference in 24-hour systolic BP between the baseline visits (P = 0.55) and the placebo (P = 0.18). After 3-weeks on the HAMSAB diet, the placebo-subtracted treatment 24-hour systolic BP difference was 6.1 ± 9.9mmHg (P = 0.027). These observations were independent of age, sex, BMI and study arm. Day and night systolic BP were reduced by 6.5 ± 12.3mmHg (P = 0.01) and 5.7 ± 9.8mmHg (P = 0.02), respectively, and 24-h central BP by 7.2 ± 14.7 mmHg (P = 0.005). There was no change in stroke volume, cardiac output or heart rate; however, HAMSAB reduced total vascular resistance (P = 0.049). Compared to the placebo, the HAMSAB diet elevated acetic and butyric acid levels by 7.8-fold (P = 0.016). HAMSAB also shifted the gut microbial ecosystem (P = 0.037) and increased the prevalence of the acetate and butyrate producers Parabacteroides distasonis and Ruminococcus gauvreauii (q-value &lt; 0.05). Conclusions: We observed a clinically relevant reduction in 24-hour systolic BP in participants with essential hypertension treated with the gut microbial-derived metabolites acetate and butyrate. These metabolites may represent a novel option for lowering BP. Low fibre diets and reduced gut microbial metabolites may be one of the principal reasons for the hypertension epidemic in Western countries.

S-28-2: EFFECT OF ESAXERENONE ON NOCTURNAL BLOOD PRESSURE COMBINED WITH RENIN-ANGIOTENSIN SYSTEM INHIBITOR OR CALCIUM CHANNEL BLOCKER IN UNCONTROLLED HYPERTENSION

Objective: To evaluate the nighttime blood pressure(BP)-lowering effects of esaxerenone with different concomitant antihypertensive treatments, we conducted a post hoc analysis of a multicenter, open-label, long-term phase 3 study (NCT02722265) of esaxerenone, a highly selective mineralocorticoid receptor blocker, alone or in combination with a calcium channel blocker (CCB) or a renin-angiotensin system (RAS) inhibitor in patients with essential hypertension. Design and method: Patients had previously untreated essential hypertension, or had received only one RAS inhibitor or CCB as a baseline antihypertensive agent at the start of the study. All patients had a sitting systolic BP of 140 to &lt; 180 mmHg and a sitting diastolic BP of 90 to &lt; 110 mmHg, a 24-h ambulatory BP of ≧130/80 mmHg. In this post hoc analysis, patients were classified into 3 treatment groups; esaxerenone monotherapy, combination with a CCB and combination with RAS inhibitor and targeted on the patient without any additional antihypertensive treatment at Week 28. For these 3 groups, mean changes in 24-hour, early morning, daytime, and nighttime systolic BP in 24-h ambulatory BP, mean changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and changes in dipping pattern (extreme dippers, dippers, non-dippers, risers) were evaluated at 28 Week to include as many patients as possible available for analysis. Results: Of the total 368 patients in the study, 248 patients were included in this analysis and there were 153 in esaxerenone monotherapy, 48 in combination with a CCB and 48 in combination with a RAS inhibitor. Nighttime systolic BP statistically significantly decreased in all groups at Week 28 compared to baseline, with combination with a RAS inhibitor group showing the greatest change (-20.6 mmHg). Those changes were numerically greater than the daytime systolic blood pressure in all groups. The decrease in NT-proBNP from baseline to Week 28 was statistically significant in all group (p &lt; 0.001, respectively) and the decrease in combination with RAS inhibitor was numerically greater than that of monotherapy. A statistically significant shift in dipping pattern and changes from riser/non-dipper to dipper/extreme dipper pattern were found at Week 28 in Monotherapy (p &lt; 0.05) and the same trend of shifting was shown in combination with RAS inhibitor (p = 0.1615). The prevalence of riser/non-dipper pattern was decreased from 58.2% to 47.7% in monotherapy and from 54.2% to 39.6% in combination with RAS inhibitor. Conclusions: Esaxerenone would provide a useful treatment option for nocturnal hypertension, especially in combination with RAS inhibitor, in uncontrolled hypertension.

PS-C26-4: ASSOCIATIONS BETWEEN ARTERIAL STIFFNESS INDICES AND CHRONIC KIDNEY DISEASE CATEGORIES IN ESSENTIAL HYPERTENSIVE PATIENTS

Background: This study investigated the association between arterial stiffness indices and asymptomatic chronic kidney disease (CKD) risk categories in hypertensive patients by using oscillometric device. Methods: Arterial stiffness indices, including 24-hour brachial and aortic systolic blood pressure (SBP) and pulse wave velocity (PWV), were measured by an oscillometric Mobil-O-Graph device, brachial-ankle PWV (baPWV) by a volume-plethysmographic method, and renal resistive index (RI) by ultrasonography, in 184 essential hypertensive patients (66.0 ± 17.1 years, 47.3% male). CKD was categorized into 3 stages based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, using a combination of estimated glomerular filtration and albuminuria. Results: The 24-hour aortic PWV (aPWV), baPWV, and RI increased with worsening severity of CKD risk category (all P &lt; 0.01 for trend). Multivariate logistic regression analysis found that a 1 SD increase of nighttime aortic SBP (odds ratio [OR] 1.52), PWV (OR 4.80), or RI (OR 1.75) was an independent predictor of high or very-high CKD stage (all P &lt; 0.05). After adjustment for potential confounders, day-to-night change in brachial SBP as well as in aPWV differed among groups (P &lt; 0.05, respectively). In a multivariate regression model, day-to-night changes in aortic SBP and PWV, and RI were independently associated with day-to-night brachial SBP change. Conclusions: In hypertension, circadian hemodynamics in high CKD stage are characterized by higher nighttime values of aortic SBP and PWV and disturbed intrarenal hemodynamics. Further, the blunted nocturnal BP reduction in these patients might be mediated via disturbed intrarenal hemodynamics and circadian hemodynamic variation in aortic SBP and arterial stiffness.

A study of post exercise hypotension in normotensive offspring of hypertensives after acute exercise.

Post exercise hypotension (PEH) is a well-known entity in hypertensive and borderline hypertensive patients. Since the results are inconsistent in normotensives and there is a genetic predisposition of the individuals to hypertension, we hypothesized that PEH is expected to occur in those normotensives who are offspring of hypertensive parents. In this study, we therefore aimed to compare the magnitude of PEH after an acute bout of moderate intensity continuous exercise (MICE) in the offspring of hypertensives vs. offspring of normotensives. Sixty normotensive participants of both genders (male and female in equal proportion), aged 18-40 yr, were divided into two groups based on their family history of hypertension. The cases (Group 1, n=30) consisted of the normotensives who were offspring of hypertensive parents while the normotensives who were offspring of normotensive parents were taken as the controls (Group 2, n=30). The hypertensive patients were excluded from the study. The individuals underwent a control session (sitting at rest for 5-10 min), followed by a single acute bout of MICE based on the target heart rate (60-70% of maximum heart rate) on a treadmill at the same time of the day (in the morning). The pre- and post-exercise measurements (after 10 min post exercise) of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) were taken in all the participants using mercury sphygmomanometer in sitting position on the left arm. The intergroup and intragroup net effects of exercise on BP were compared with P<0.05 considered significant. The mean SBP was reduced by 5 mmHg than the baseline in the offspring of hypertensives (cases) as compared to the controls after exercise (P=0.01). The fall in mean DBP and MAP was insignificant across both the groups, but the magnitude of PEH measured as delta changes (BP before and after exercise) in SBP (~5 mmHg) and MAP (~4 mmHg) were significantly higher for the cases as compared to the controls (P=0.01). PEH occurs in higher magnitude in normotensives who are genetically predisposed to hypertension, such as offspring of hypertensive parents, and may find regular exercise-induced PEH as an important primary preventive tool to prevent or delay the development of hypertension.

AW-AD-4: RENOPROTECTIVE EFFECTS OF CANAGLIFLOZIN VIA LESSENING HYPERINSULINEMIA IN DIABETIC PATIENTS WITH HEART FAILURE: A POST-HOC ANALYSIS OF THE CANDLE TRIAL

Objective: The mechanisms by which sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce proteinuria in patients with type 2 diabetes mellitus (T2DM) remain unclarified. We evaluated factors associated with proteinuria regression in patients with T2DM treated with canagliflozin. Design and method: This study was a post-hoc analysis of the CANDLE trial (UMIN000017669), which compared the effect of 24 weeks treatment canagliflozin and glimepiride for changes in NT-proBNP in patients with T2DM and chronic heart failure (CHF). Factors associated with regression of proteinuria at 24 weeks were evaluated with multivariate logistic models. Results: The rate of regression of proteinuria was higher and that of progression was lower in the canagliflozin versus the glimepiride group. There were no differences in the change in systolic and diastolic blood pressure and eGFR category between groups at baseline. Systolic blood pressure and insulin levels significantly decreased in the canagliflozin group but not in the glimepiride group. Insulin level, HOMA-β, HOMA-IR, and estimated plasma volume were decreased at 24 weeks in the proteinuria regression subclass but not in the proteinuria progression subclass, suggesting that regression of proteinuria is associated with the declines in these values in the canagliflozin group. Systolic and diastolic blood pressure did not change significantly in either the proteinuria progression or regression groups in both the canagliflozin and glimepiride groups. Higher insulin level was solely associated with proteinuria regression in the multivariate logistic regression model. Conclusion: In patients with T2DM and CHF, regression of proteinuria with canagliflozin treatment was associated with the pre-treatment insulin level. These results suggest new mechanistic intuitions into the beneficial effects of canagliflozin on renal outcomes and warrant discussion for selecting preferred patient profiles, including pre-treatment insulin levels.