Blood Pressure Response Research Articles

Abstract 40: Sodium-mediated Blood Pressure Increase in Chronic Kidney Disease and Diabetic Kidney Disease Patients Coincides With Vasodysfunction.

Background: Chronic kidney disease (CKD) and diabetic kidney disease (DKD) patients are advised to limit salt intake, because of its detrimental effects on blood pressure (BP) and albuminuria. The salt-sensitive BP response in these patients may be attributed to impaired renal ability to excrete sodium (Na+) resulting in fluid overload and/or vasodysfunction. To define which factor relates to BP sensitivity in both CKD and DKD, we studied the Na+-mediated BP response in these patients as compared to healthy volunteers (HV). Methods: In this randomized crossover study, CKD patients (KDIGO stage G2/3A, proteinuria >0.5 g/d), Type 2 DKD patients (KDIGO stage G2/3A, proteinuria 0.2 - 0.5 g/d) and HV followed a 7-day low sodium diet (LSD, <50mmol/d) and high sodium diet (HSD, >200mmol/d), respectively. After each diet, assessment of the hemodynamic profile included daytime BP (Mobil-O-Graph) and cardiac output (CO) measurements (using NexfinTM), by which SVR was calculated accordingly. Extracellular fluid volume (ECV) change was assessed with multi-frequency body impedance spectroscopy (Fresenius). Results: We included 20 CKD (mean age 48 yrs, median (IQR) proteinuria 0.7 (0.6-1.6) g/d, mean (SD) eGFR 60.7 (16.3) ml/min/1.73m2) and 8 DKD patients (age 68 yrs, proteinuria 0.3 (0.2-0.4) g/d, eGFR 59.0 (15.9) ml/min/1.73m2), and 16 HV (age 41 yrs). Dietary salt intervention was successful with mean difference in urine Na+ excretion of 185, 168, and 209 mmol/day in CKD, DKD and HV respectively. After HSD, mean (SD) systolic BP change was 9.3 mmHg (8.9; p<0.001) in CKD and 13.8 mmHg (10.4; p<0.01) in DKD, while systolic BP change (3.1 mmHg (6)) in HV was not significant. After HSD, we observed significant ECV expansion in all groups without differences between groups (CKD 1.6 L, DKD 1.6 L, HV 1.4 L, p=0.27), while no effects on CO were observed. After HSD, the mean (SD) SVR in CKD increased with 125.7 dyn*sec*cm-5 (247.9, p=0.04) and in DKD with 125.5 dyn*sec*cm-5 (142.6, p=0.04), while in HC a non-significant decline of -109.2 dyn*sec*cm-5 was observed (358.2, p=0.24). Conclusion: The Na+-mediated BP rise in both CKD and DKD coincides with an increase in SVR. The absence of differences in ECV and CO between the three groups indicates that salt sensitivity in both CKD and DKD is not completely based on fluid overload but might be due to an inability to induce vasodilation.

Single-Pill Combination Therapy of Amlodipine, Telmisartan, and Chlorthalidone in the Management of Hypertension: A Systematic Review of Randomized Controlled Trials.

Hypertension is a major cause of cardiovascular disease and death worldwide. Low-dose combination therapy is a promising approach for managing hypertension due to its safety and efficacy. This systematic review evaluates the safety and efficacy of a single-pill, low-dose combination of amlodipine, telmisartan, and chlorthalidone for essential hypertension based on evidence from randomized controlled trials (RCTs). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched the Cochrane, Scopus, PubMed, and Web of Science databases until July 01, 2024, using the following search string: (telmisartan) AND (amlodipine) AND (chlorthalidone) AND (randomized OR randomly). The quality of the RCTs was assessed using the revised Cochrane risk of bias tool. The primary endpoint was the mean change in sitting systolic blood pressure (BP), with secondary endpoints including BP target achievement rates, BP response rates, and serious treatment-related adverse events. Overall, three RCTs met the inclusion criteria and exhibited a low risk of bias. The doses in the combination pill ranged from 2.5 to 5 mg of amlodipine, 20 to 80 mg of telmisartan, and 4.167 to 25 mg of chlorthalidone. Control groups varied, including usual care, amlodipine 10 mg, and dual therapy of telmisartan and amlodipine. Results showed significant reductions in mean sitting systolic and diastolic BP, improved BP control and response rates, and a generally safe profile with no significant differences in serious adverse events. Despite encouraging data, results should be interpreted with caution due to heterogeneity in doses and control groups. Further research should address the long-term effects and explore predictors of response to this therapy.

Comparison of acute hemodynamic effect of prioritizing ventricular resynchronization vs left ventricular filling during optimization of cardiac resynchronization therapy

BackgroundTargeting maximal ventricular resynchronization, with the shortest QRS duration (QRSd), is commonly implemented after cardiac resynchronization therapy (CRT). ObjectiveThe purpose of this study was to compare optimization of ventricular resynchronization with optimization of left ventricular (LV) filling during CRT by measuring their acute hemodynamic effects. MethodsPatients with standard CRT indications, recruited from 2 centers, underwent biventricular pacing (BVP) and left bundle branch pacing (LBBP). We performed a within-patient comparison of acute hemodynamic response of systolic blood pressure (SBP) at the atrioventricular delay (AVD) with the shortest QRSd against the AVD with the most efficient LV filling. In a validation substudy, we also performed electrical assessment using QRS area (QRSa) and hemodynamic assessment with the maximum rate of LV pressure rise (dP/dtmax). ResultsThirty patients (age 65 ± 10 years; 53% male) were recruited. The AVD producing maximal ventricular resynchronization was associated with a significantly shorter QRSd (difference 15 ± 12 ms for BVP and 18 ± 13 ms for LBBP, both P <.01) and a significantly smaller improvement in SBP (difference −3 ± 4 mm Hg for BVP and −2 ± 2 mm Hg for LBBP, both P <.01) compared with the AVD that optimized filling. Similar findings were observed in the substudy, with a significantly smaller improvement in dP/dtmax assessed with QRSd and QRSa (difference −9% ± 7% and −6% ± 4% during BVP, and −5% ± 6% and −3% ± 3% during LBBP, all P <.01). ConclusionTargeting the maximal ventricular resynchronization results in suboptimal acute hemodynamic performance with both BVP and LBBP as CRT. These findings support prioritizing LV filling when programming AVD for CRT.

Abstract P110: Analysis of Community-Level High Blood Pressure Awareness Efforts for Philadelphia's Unhoused Population

Introduction: The University of Pennsylvania Shelter Health Outreach Program (SHOP) is a student-led community health initiative where volunteers go weekly to various sites around Philadelphia and take blood pressure (BP) for unhoused guests at no cost. The objective of the study is to estimate the prevalence of high BP among the unhoused population in Philadelphia and its association with various factors relating to health access. Methods: SHOP BP screening tables were set up at six food and housing sites once a week from September 2022 to December 2023. The study cohort included guests who voluntarily came to the tables for BP measurement. High BP was defined as having a single measurement systolic BP over 130 mmHg and/or having a diastolic blood pressure over 80 mmHg. BP results and responses to survey questions about health status and momentary social situation were stored in a secure cloud server. The data were analyzed using the R statistical software. Results: We surveyed 2,138 guests across the 6 sites. Among the guests who were surveyed, 73.6% had high BP and of these 65% of guests had at least stage 2 hypertension as defined by the American Heart Association Guidelines. In addition, a higher proportion of high BP was observed among guests who were returning to a SHOP table for a repeat screening after one or more weeks. A higher proportion of high BP was also observed for guests who reported having had a physical exam in the past year. At least one-third of the guests reported as returning to the screening site after having received a prior BP screening from a SHOP table. Conclusions: Our results show a high burden of hypertension, especially severe hypertension, in the unhoused population in Philadelphia. Although significant challenges exist to ascertain accurate BP readings at the community level, SHOP demonstrated relatively high retention. This model of BP screening represents a distinct opportunity to introduce community-based interventions to manage hypertension in such a highly disadvantaged population.

Abstract 21: The Detrimental Effects of a Comorbidity of Increased Blood Pressure Variability and High Salt Diet on Cardiovascular and Neurovascular Outcomes

Recent studies have identified increased blood pressure variability (BPV) as a novel risk factor for cognitive decline, independently from absolute BP values. However, the underlying mechanisms are poorly defined. In addition, whether a high salt diet (HSD) contributes to BPV and exacerbates cognitive decline is not known. We tested the hypothesis that vascular damage resulting from blood pressure fluctuations in BPV disrupts critical mechanisms regulating cerebral blood flow (CBF), impairing perfusion and leading to neurovascular dysfunction and cognitive decline. We established a murine BPV model and evaluated the impact of BPV on systemic BP (baroreceptor reflex) and CBF regulation (myogenic and functional hyperemia (FH) responses). Mice were implanted with a cranial window for in-vivo two-photon (2P) imaging. A programmable pump infused 6-8 pulses/day of angiotensin II ((Ang II 18 µg/day) (BPV) or saline (Control) for 25 days, and cardiovascular variables were measured via DSI telemetry. Ang II pulse infusions evoked transient BP increases (Δ43±4 mmHg, MAP; P&lt;0.01,n=8); however, did not induce hypertension in the BPV group. BPV mice displayed increased BPV index (P=0.04,n=12) and cognitive decline (novel object recognition test (P=0.01,n=10)). Telemetry data showed a decrease in bradycardic responses following chronic BPV (P=0.03, n=8). Data from 2P studies showed enhanced myogenic response in parenchymal arterioles of BPV vs Controls (P&lt;0.01,n=9-15 runs) when BP transitions from low to high BP. We observed a blunted FH in BPV vs Control during low BP (P&lt;0.01,n=6-7). During high BP, FH was pronounced in Controls (P&lt;0.01,n=6-7); however, pressure-induced vascular responses were abolished in BPV mice (P&lt;0.01,n=6-7). In separate groups of mice, the Control and BPV protocol was repeated with all mice receiving a high-salt diet (HS; 4% NaCl chow+1% NaCl drinking water: Control+HS or BPV+HS). There were no changes in 24-hr MAP in Control+HS (P&gt;0.85, n=5). Whereas BPV+HS mice developed sustained hypertension (increased 24-hr MAP; P&lt;0.01, n=4). These data demonstrate that BPV alters mechanisms regulating CBF and BP, contributing to cognitive decline and that HSD may exacerbate the detrimental effects of BPV on BP regulating mechanisms. Ongoing studies are examining the comorbid effects of BPV+HS on the cerebrovasculature and direct CBF changes in BPV and BPV+HS mice.

Abstract P327: Comparing the Blood Pressure Response to Antihypertensive Treatment Intensification and Dose Increase to No Action for Uncontrolled Hypertension

Background: The addition of a new antihypertension medication class (CA) or dose increase (DI) in patients with hypertension (HTN) is relatively infrequent when HTN is uncontrolled (blood pressure [BP, mmHg] ≥ 140/90) during outpatient visits. We compared systolic (S)BP changes following CA, DI, or no medication changes for uncontrolled BP. Methods: A patient cohort from 6 diverse healthcare organizations, engaged in a quality improvement program, was identified with previously diagnosed HTN. Uncontrolled outpatient SBP measurements observed at participating program sites were compared to follow-up measurements within 7 to 120 days for evaluating SBP change. ANCOVA and linear regression analyses were used to control clinical and demographic covariates and assess differences in SBP change following treatment decision. Results: A prospective cohort of 124,068 patients with HTN spanning 280,937 events was identified, mean age 63.3 ± 13.9. Class addition reduced SBP 2.0 mmHg (95% CI, 1.81 – 2.24), whereas dose increase did not lower SBP [-0.07 (95% CI, -0.31, 0.16)]. Conclusion: In this study, CA lowered BP modestly, whereas DI appeared ineffective. Since patients were not randomized, our results may under-estimate the effects of CA and DI on BP, i.e., clinicians may have expected a greater decline of SBP than simply regression to the mean for patients with uncontrolled hypertension in the absence of DI or TI. Our data are consistent with reports that CA has a greater effect to lower BP than DI. Our findings also highlight some challenges of interpreting real world data compared to randomized clinical trials.

Abstract P353: Sexual dimorphism of blood pressure responses to angiotensin II in rats subjected to early life circadian stress

Various forms of early life stress (ELS) lead to a greater risk of hypertension, but no studies have examined stress produced by circadian disruption. We hypothesize that circadian stress during adolescence will increase sensitivity to a hypertensive stimulus in adulthood recapitulating other models of early life stress (ELS). We exposed male and female rats 1-2 weeks post-weaning to 6-hour phase advances (shifts) in the light/dark cycle each week for 4 weeks. To assess whether the molecular clock contributes to the response to ELS, we performed these studies in both Bmal1 knockout (KO) rats and littermate wildtype (WT) controls, Bmal1 is a core circadian clock transcription factor. At 10-12 weeks of age, baseline mean arterial pressure (MAP) was measured (telemetry) followed by a 2-wk angiotensin II (AngII) infusion (250 ng/kg/min, s.c.). At baseline, non-ELS KO rats of both sexes had lower MAP compared to WT littermates, but this genotype effect was lost in ELS rats. Thus, exposure to circadian stress early in life has only a modest effect on baseline blood pressure in rats lacking Bmal1. AngII increased MAP in all groups but was significantly attenuated in male ELS rats compared to non-ELS controls of both genotypes (p stress = 0.039, p genotype =0.979, p SxG =0.917, 2-way ANOVA), but this attenuation was not evident in female rats (p stress = 0.497, p genotype =0.041, p SxG =0.772). We also observed a significant phase advance in peak MAP in male non-ELS rats of both genotypes that was absent in ELS males (p Genotype =0.030, p AngII &lt;0.001, p AngIIxGT =0.025). In contrast, there were no significant differences in peak MAP time in any female rats. The response to AngII was attenuated in ELS male, but not female rats. These data do not support our original hypothesis that exposure to circadian stress during adolescence induces hypersensitization to Ang II in rats but does reveal an impact on the timing of peak MAP in male rats. We propose that the attenuated MAP response to AngII seen in male rats following exposure to specific types of circadian stress during the post-weaning period may pre-condition rats against a subsequent hypertensive stimulus.

Abstract 37: Targeted Deletion of NKCC1 in Vascular Smooth Muscle Cells Lowers Blood Pressure in Normotensive and Hypertensive Mice

Background: Salt plays a major role in blood pressure homeostasis and the pathogenesis of arterial hypertension. While numerous mechanisms have been described by which Na + can influence arterial blood pressure, the role of Cl - in blood pressure regulation is still largely unexplored. The Na + -K + -2Cl - cotransporter NKCC1 is an important Cl - import pathway in vascular smooth muscle cells (VSMC). To investigate the role of NKCC1 in blood pressure regulation, we generated mice with an inducible VSMC-specific disruption of Slc12a2 . Methods: Mean arterial blood pressure and heart rate were measured by radiotelemetry in unrestrained mice lacking vascular NKCC1 (KO) and wildtype littermates (WT). Cardiac function was assessed by echocardiography. Plasma renin activity and aldosterone concentrations were quantified by radioimmunoassay. Protein expression of renal sodium transporters and channels was analyzed by Western blotting. Results: Mean arterial blood pressure was markedly decreased in Nkcc1 -deficient mice 6 weeks after induction of gene disruption (from 116±2 mm Hg to 103±4 mm Hg, n=18, p&lt;0.001, 2-way ANOVA and Bonferroni post-test), while it did not change in WT control animals (n=17). Heart rate, stroke volume, fractional shortening, and ejection fraction remained unchanged compared to non-induced controls. We did not observe a compensatory increase in plasma renin activity or aldosterone levels, and the blood pressure response to ANG II receptor 1 antagonism by losartan treatment for 7 days was similar in both groups (ΔMAP KO -8.8±3.0 mm Hg, n=8, ΔMAP WT -12.4±1.9 mm Hg, n=7; p&gt;0.05, 2-way ANOVA). In the kidney, the relative expression of total NCC (1.5- fold , n=7-8; p=&lt;0.05, Student’s t-test) and pNCCThr53 (1.9- fold , n=7-8; p=&lt;0.05, Student’s t-test) were modestly increased. The hypotensive effect of Nkcc1 disruption was maintained after induction of hypertension by either infusion of ANG II for 10 days (ΔMAP KO 43.8±6.5 mm Hg, n=6, ΔMAP WT 50.2±7.2 mm Hg, n=4; p&gt;0.05, 2-way ANOVA) or a high salt diet for 10 days (ΔMAP KO 21.7±7.0 mm Hg, n=8, ΔMAP WT 34.0±7.3 mm Hg, n=5; p&gt;0.05, 2-way ANOVA). Conclusions: Our findings indicate that NKCC1 in vascular smooth muscle contributes significantly to the maintenance of arterial blood pressure. Inhibition of NKCC1 in VSMC may provide additional blood pressure reduction in resistant hypertension.

Effect of endothelin-1 on the blood pressure response to acute hypoxia and hyperoxia in healthy young men.

Endothelin-1 (ET-1) and its receptors are linked to increases in sensitivity of the chemoreceptors to hypoxic stress and the development of hypertension in preclinical models. We hypothesized ET receptor antagonism would lower resting blood pressure (BP) as well as the acute BP response to chemoreflex stress. Twenty-four men (31 ± 5 years, 26 ± 3 kg/m2) completed two study visits (control, bosentan). On each visit, BP was assessed under three conditions: (1) normoxia (FiO2 0.21), (2) chemoreflex excitation via hypoxia (FiO2 0.05-0.21), (3) chemoreflex inhibition via hyperoxia (FiO2 1.00). Bosentan increased plasma ET-1 (0.94 ± 0.90 to 1.27 ± 0.62 pg/mL, p = 0.004), supporting receptor blockade. Resting diastolic (73 ± 5 to 69 ± 7 mmHg, p = 0.007) and mean (93 ± 7 to 88 ± 7 mmHg, p = 0.005) BP were reduced following bosentan compared to control with no change in systolic BP (p = 0.507). The mean BP response to both acute hypoxia (-0.48 ± 0.38 to -0.25 ± 0.31 mmHg/%, p = 0.004) and hyperoxia (area under the curve -93 ± 108 to -27 ± 66 AU, p = 0.018) were attenuated following bosentan. Acute ET receptor inhibition attenuates the rise in BP during chemoreflex excitation as well as the fall in BP during chemoreflex inhibition in healthy young men. These data support a role for ET-1 in control of resting BP, possibly through a chemoreceptor-mediated mechanism.

O98 NEW APPROACHES TARGETING THE RENIN-ANGIOTENSIN SYSTEM: BRAIN ACE2 ACTIVATION FOLLOWING BRAIN AMINOPEPTIDASE A BLOCKADE BY FIRIBASTAT IN SALT-DEPENDENT HYPERTENSION

Background and Objective: In the brain, aminopeptidase A (APA), a membrane-bound zinc metalloprotease, generates angiotensin III from angiotensin II. Brain angiotensin III exerts a tonic stimulatory effect on the control of blood pressure (BP) in hypertensive rats and increases vasopressin release. Blocking brain angiotensin III formation by the APA inhibitor prodrug RB150/firibastat normalizes arterial BP in hypertensive deoxycorticosterone acetate (DOCA)-salt rats. Ang II and Ang III have similar affinities for AT1 receptors and blocking brain AngIII formation by RB150 decreases arterial BP without inducing Ang II accumulation. Methods: We therefore hypothesized that another metabolic pathway of brain angiotensin II, such as the conversion of angiotensin II into angiotensin 1-7 (Ang 1-7) by angiotensin-converting enzyme 2 (ACE2) might be activated following brain APA inhibition. To answer this question, we use surgical animal models that could allow us to monitor awake blood pressure responses to intracerebroventricular (icv) injections and measure enzymatic activity. Results: We found that the intracerebroventricular administration of RB150/firibastat in conscious DOCA-salt rats both inhibited brain APA activity and induced an increase in brain ACE2 activity. Then, we showed that the decreases in BP and vasopressin release resulting from brain APA inhibition with RB150/firibastat were reduced if ACE2 was concomitantly inhibited by MLN4760, a potent ACE2 inhibitor, or if the Mas receptor (MasR) was blocked by A779, a MasR antagonist. Conclusions: Our findings suggest that in the brain, the increase in ACE2 activity resulting from APA inhibition by RB150/firibastat treatment, subsequently increasing Ang 1-7 and activating the MasR while blocking angiotensin III formation, contributes to the antihypertensive effect and the decrease in vasopressin release induced by RB150/firibastat. RB150/firibastat treatment constitutes an interesting therapeutic approach to improve BP control in hypertensive patients by inducing in the brain renin-angiotensin system, hyperactivity of the beneficial ACE2/Ang 1-7/MasR axis while decreasing that of the deleterious APA/Ang II/Ang III/ATI receptor axis.

Abstract 72: Genetic variance in heparan sulfation is associated with salt-sensitivity: a gene-environment analysis in EPIC-Norfolk, UK biobank, and HELIUS

Background: High heritability of salt sensitivity suggests an essential role for genetics in the relationship between sodium intake and blood pressure (BP). The role of glycosaminoglycan (GAG) genes, which are crucial for salinity tolerance througout evolution, remains to be elucidated. Methods: Interactions between 54,126 variants in 130 GAG genes and daily sodium excretion on BP were explored in 20,420 EPIC-Norfolk subjects. UK Biobank (n=414,132) and the multi-ethnic HELIUS study (n=2,239, comprising a balanced representation of people from European, Subsaharan, South Asian, Turkish, and Moroccan descent) were used for validation. Afterwards, urinary GAG composition was studied in HELIUS participants (n=57) stratified by genotype, and upon dietary sodium loading in a time-controlled crossover intervention study (n=12). Results: rs2892799 (NDST3) showed the strongest interaction with sodium on mean arterial pressure (MAP) (FDR 0.03), with higher MAP for the C-allele in high sodium conditions. Also, rs9654628 (HS3ST5) showed an interaction with sodium on systolic BP (FDR 0.03). These interactions were multi-ethnically validated (figures A and B, respectively). Stratifying for rs2892799 genotype, showed higher urinary expression of N-sulfated heparan sulfate epitope D0S0 for the T-allele. Conversely, upon dietary sodium loading, urinary D0S0 expression was higher in participants with stable BP after sodium loading, and sodium-induced effects on this epitope were opposite in individuals with and without BP response to sodium. Conclusion: The C-allele of rs2892799 (NDST3) exhibits higher BP in high sodium conditions when compared to low sodium conditions, whereas no differences were detected for the T-allele. Concomitantly, both alleles demonstrate distinct expressions of D0S0, which, in turn, correlates with sodium-mediated BP elevation. These findings underscore the potential significance of genetic GAG variation in human BP regulation.

Effects of exercise on autonomic cardiovascular control in individuals with chronic, motor-complete spinal cord injury: an exploratory randomised clinical trial.

Secondary analysis of a clinical trial. To assess the impact of 6 months of armcycle ergometry training (ACET), or body weight-supported treadmill training (BWSTT), on autonomic cardiovascular responses to a laboratory sit-up test (SUT) in individuals with chronic (≥1-year post-injury) spinal cord injury (SCI). Tertiary Rehabilitation Centre, Vancouver, Canada. Sixteen individuals with motor-complete (American Spinal Injury Association Impairment Scale A-B) SCI between the fourth cervical and sixth thoracic spinal cord segments, aged 39 ± 11 years, were assessed. Participants were randomized to receive 72 sessions of moderate-to-vigorous intensity ACET (n = 8) or passive BWSTT (n = 8). Changes in mean arterial pressure (finger plethysmography), hemodynamics (Modelflow® method), and heart rate/heart rate variability (HR/HRV; electrocardiography) were measured in response toa SUT before and after 6 months of exercise training. Spontaneous cardiovagal baroreflex sensitivity (cvBRS) was assessed using the sequence method. Neither ACET nor BWSTT impacted hemodynamic responses to SUT or the incidence of orthostatic hypotension (all P > 0.36). ACET increased HR (P < 0.01, ηp2 = 0.34) and high frequency (HF) power HRV responses (P < 0.01, ηp2 = 0.42) to SUT following 6 months of training while BWSTT did not. Consistent with this, cvBRS improved (P < 0.05, ηp2 = 0.16) only following ACET. Improvements in cvBRS were correlated with both the HR (r = 0.726, P < 0.0001) and HF power (r = -0.484, P < 0.01) responses to SUT. Six months of ACET, but not BWSTT, improved cardiovagal baroreflex control of HR but had no effect on BP responses to SUT in individuals with chronic, motor-complete SCI. Canadian Institutes of Health Research (CIHR) CLINICAL TRIAL REGISTRATION: NCT01718977.

Daytime actisensitivity predicts nocturnal dipping patterns and morning surge in blood pressure: the Home-Activity ICT-based Japan Ambulatory Blood Pressure Monitoring Prospective study.

Ambulatory blood pressure (BP) is influenced by physical activity and the BP response to physical activity (actisensitivity) differs between individuals. This study investigated associations between daytime actisensitivity and nighttime BP dipping status and morning BP surge. Twenty-four-hour ambulatory BP monitoring (ABPM) with simultaneously monitored physical activity using a multisensor all-in-one device (TM-2441; A&D Company) was performed at baseline in HI-JAMP study participants. Those with complete BP measurements and complete physical activity monitoring data were included in this analysis. Actisensitivity was calculated as the slope of the regression line between daytime SBP and log-transformed physical activity over a 5 min period before each BP reading. Hyper and negative reactivity were defined as actisensitivity greater than 90th and less than 10th percentile, respectively. Data from 2692 individuals (mean age 69.9 ± 11.9 years; mean BMI 24.8 ± 4.1 kg/m 2 , 53.6% men) were analyzed. Those with hyper reactivity had a high prevalence of the extreme dipper pattern of nighttime BP and exaggerated morning BP surge; those with negative reactivity had higher nighttime BP and a riser pattern of nighttime BP. Results remained significant after adjusting for 24-h physical activity. Differences in diurnal BP variability based on actisensitivity were augmented in individuals aged at least 75 years. This study is the first to investigate associations between actisensitivity and 24-h ambulatory BP profiles using an all-in-one multisensor device in a large real-world population. The associations seen between either hyper or negative actisensitivity and abnormal diurnal BP variability, especially in the elderly, could contribute to increased cardiovascular event risk. University Hospital Medical Information Network Clinical Trials Registry, UMIN000029151 (HI-JAMP study).

Blood pressure behavior during exercise in patients with diastolic dysfunction and a hypertensive response to exercise.

A hypertensive response to exercise is a precursor leading to hypertension, which is a major risk factor for the development of heart failure and diastolic dysfunction. Herein, we aimed to assess blood pressure (BP) in patients with a hypertensive response to exercise and different degrees of diastolic dysfunction. Between January 2009 and December 2014, 373 patients with a hypertensive response to exercise (HRE) and echocardiographic data assessing diastolic function were enrolled at the University Hospital of Zurich. ANCOVA was used to assess the changes in BP response during exercise testing in individuals with different degrees of diastolic dysfunction. Normalization of systolic BP was blunted in patients with grade II and III diastolic dysfunction after 3 min of recovery in univariable [β (95%) - 9.2 (-13.8 to - 4.8) p<.001, -16.0 (-23.0 to 9.0) p<.001, respectively] and adjusted models. In fully adjusted models, when taking maximal effort into account, there were no differences with regard to systolic BP during exercise. Patients without diastolic dysfunction achieved higher heart rates (HRs) [both in absolute terms (p<.001) and as a percentage of the calculated maximum (p=.003)] and greater wattage (p<.001) at maximum exertion. The findings of this cross-sectional study suggest that exercise capacity is compromised in patients with diastolic dysfunction. A hypertensive response to exercise and the finding of a blunted BP recovery may help identify patients at risk of developing heart failure.

Effect of Different Breathing Patterns on Heart Rate and Blood Pressure Response to Resisted Exercises in Females Within the Age Group of 25 to 35 Years

Introduction: Blood pressure and heart rate increases in individuals while performing heavy resisted exercises but acquiring different breathing patterns during exercise shows its effect on blood pressure and heart rate, it may or may not exaggerate. Inhalation or exhalation when coupled with concentric phase of resisted exercise may or may not show similar blood pressure response as compare to inhalation or exhalation when coupled with eccentric phase of resisted exercise whereas Valsalva maneuver can exaggerate the blood pressure response. Objective: To study the inhalation, exhalation and Valsalva maneuver on systolic, diastolic blood pressure and heart rate. Research Design: Quasi experimental. Methodology: 30 female subjects were taken which were asked to do a set of bicep curls with 3 different patterns of breathing with each pattern performed on a separate day. Then the recordings were taken and calculated to see in which pattern of breathing blood pressure and heart rate rises. Result: ANOVA was used and the result showed that diastolic blood pressure increases while exhalation coupled with the concentric phase and inhalation coupled with the eccentric Phase but there is a marked increase in diastolic blood pressure during Valsalva maneuver as compared to the inhalation coupled with the concentric phase and exhalation coupled with the eccentric phase. The result showed that the change in the blood pressure due to the different breathing patterns were significant p&gt;0.05 Conclusion: It is concluded that Valsalva maneuver exaggerates the blood pressure response. Keywords: resisted exercises, Valsalva maneuver, exhalation. breathing patterns.

A novel mouse model recapitulates the effects of rs2254524 variant in the lanosterol synthase gene on salt sensitivity and organ damage.

The blood pressure (BP) response to salt intake (salt sensitivity) shows great variability among individuals and is more frequent in hypertensive patients. Elevated levels of the steroid hormone Endogenous Ouabain (EO) are associated with hypertension (HT) and salt sensitivity. The lanosterol synthase gene ( LSS ) plays a key role in the biosynthesis of steroids and its rs2254524 variant (Val642Leu) is linked to salt sensitivity in humans. This study aims to investigate the pathophysiological significance of the Lss missense variation in a new knock-in mouse model of salt-sensitive HT onset. We generated a mouse model carrying the murine homolog (Val643Leu) of the human LSS variant. C57BL/6N LssV643L/V643L mice were fed different NaCl diets (low-salt, LSD; normal-salt, NSD; high-salt, HSD) and were characterized at functional, histological, and molecular levels. At baseline, mutant mice showed an enlarged kidney compared to the wild-type (WT) counterpart, but the Lss V643L variant did not affect EO biosynthesis nor systolic BP at 3 and 12 months. In HSD, we observed an increased systolic BP only in 12-month-old LssV643L/V643L mice, compared to NSD. Moreover, only the HSD LssV643L/V643L mice showed cardiac hypertrophy and a higher incidence of cardiac fibrosis compared to WT at 12 months. Finally, the Lss mRNA level was differentially regulated by HSD in the adrenal gland, liver, and heart of LssV643L/V643L mice compared to WT. The novel Lss mouse model resembles the salt-sensitive HT phenotype observed in hypertensive patients and provides a good model of salt-sensitive HT and HT-mediated organ damage.

A preliminary investigation of worry, cortical amyloid burden, and stressor-evoked brain and cardiovascular reactivity in older adults

Worry is a transdiagnostic symptom common to many neurocognitive disorders of aging, including early stages of Alzheimer's disease and related dementias (ADRD). Severe worry is associated with amyloid burden in cognitively intact older adults, yet the mechanisms underlying this association are not well understood. We hypothesize that this relationship involves altered brain and cardiovascular reactivity to acute stressors, a brain-body phenotype that also increases risk for cardiovascular disease. Twenty cognitively normal older adults (age 60 to 80) with varying levels of worry severity underwent positron emission tomography using Pittsburgh Compound-B and functional magnetic resonance imaging. We examined associations of worry severity and amyloid burden with cardiovascular reactivity, brain activation, and brain connectivity using a cognitive stressor task. Worry severity was not associated with global amyloid burden, but was associated with greater resting levels of cardiovascular physiology and lower systolic blood pressure reactivity. Worry severity also was associated with altered stressor-evoked activation and effective connectivity in brain circuits implicated in stress processing, emotion perception, and physiological regulation. These associations showed small to medium effect sizes. These preliminary findings introduce key components of a model that may link severe worry to ADRD risk via stressor-evoked brain-body interactions.

The effect of foot immersion and neck cooling on cardiac autonomic function in older adults exposed to indoor overheating: a randomized crossover trial.

Foot immersion and neck cooling are recommended cooling strategies for protecting heat-vulnerable persons during heat waves. While we recently showed that these strategies do not limit core temperature increases in older adults during prolonged heat exposure, we did observe small reductions in heart rate. Expanding on these findings, we examined the effects of foot immersion with and without neck cooling on cardiac autonomic function. Seventeen adults (9 females; 65-81 years) underwent 3 randomized, 6 h exposures to 38 °C and 35% relative humidity with: no cooling (control), foot immersion (20°C water), or foot immersion with a wet towel (20°C) around the neck. Cardiac autonomic responses were measured at baseline and end-exposure. These included heart rate variability, cardiac and systolic blood pressure responses to standing, indexed via the 30:15 ratio and supine-to-standing systolic pressure change, respectively, and baroreflex sensitivity during repeated sit-to-stand maneuvers. The 30:15 ratio was 0.04 [95% CI: 0.01, 0.07] greater with foot immersion and neck cooling (1.08 (SD: 0.04)) relative to control (1.04 (0.06); P=0.018). Similarly, standing systolic blood pressure was elevated 9 [0, 17] mmHg with foot immersion and neck cooling (P=0.043). That said, neither difference remained statistically significant after adjusting for multiplicity (Padjusted≥0.054). No differences in 30:15 ratio or standing systolic blood pressure were observed with foot immersion alone, while heart rate variability and baroreflex sensitivity were unaffected by either cooling intervention. While foot immersion with neck cooling potentially improved cardiac autonomic responses in older adults exposed to simulated indoor overheating, these effects were small and of questionable clinical importance.

Adrenal Vein Sampling Results and Surgical Outcomes in Patients with Nonsuppressed Plasma Renin Activity

PurposeTo determine adrenal vein sampling (AVS) and postadrenalectomy outcomes in patients with a nonsuppressed plasma renin activity (PRA) and elevated aldosterone-to-renin ratio (ARR). Materials and MethodsThe study sample included 23 patients with an ARR of >20 and PRA of >1 ng/mL/h (nonsuppressed group) and 69 patients with an ARR of >20 and PRA of <0.6 ng/mL/h (suppressed group) who underwent AVS from 2006 to 2023. Data regarding baseline clinical characteristics, AVS results, and outcomes after adrenalectomy were analyzed. ResultsThe proportion of patients in the nonsuppressed group who had a lateralization index of >4 was lower than that in the suppressed group, although this was nonsignificant (43% vs 62%; P = .15). The mean lateralization index in the nonsuppressed group was lower compared with that in the suppressed group (8.7 vs 17.4; P = .05). The proportion of patients in the nonsuppressed group with improved or cured hypertension following adrenalectomy was similar to that of patients in the suppressed group who also underwent surgery (6/8, 75%, vs 25/32, 78%; P = .71). All hypokalemic patients (32/32) who underwent adrenalectomy had normalization of their potassium levels following procedure. ConclusionsNearly half of patients with nonsuppressed PRA lateralized with AVS. The patients who did lateralize had similar blood pressure response and correction of hypokalemia following adrenalectomy, regardless of PRA. Therefore, patients with a nonsuppressed PRA (>1 ng/mL/h) should still be considered for AVS provided the ARR is elevated.

The Effects of Acute Beetroot Juice Intake on Glycemic and Blood Pressure Responses When Controlling for Medication in Individuals with Type 2 Diabetes: A Pilot Study.

Physical inactivity and poor dietary choices contribute to the rise in cardiometabolic diseases in the United States. It remains critical to identify strategies that may mitigate the negative impact of these behaviors. Several studies have shown that the consumption of dietary inorganic nitrate may improve vascular health and glucose regulation in animal models and some human studies. However, the improvements in glucose regulation have yet to be corroborated in humans with type 2 diabetes (T2D). Therefore, the purpose of this study was to assess the acute effects of beetroot juice (BRJ) on glycemic and hemodynamic responses in individuals with T2D while controlling for medication. Seven participants with a clinical diagnosis of T2D were recruited into this study and were temporarily removed from blood pressure- and glucose-lowering medications. Hemodynamic measurements (pulsewave velocity) and an oral glucose tolerance test (glycemic response) were measured following consumption of either BRJ or a denitrolized placebo. Saliva and blood samples were collected at baseline and two and four hours post supplementation to measure changes in nitrate and nitrite concentrations. We detected significant improvements in total plasma glucose exposure (p = 0.022) and the SVR change score (p = 0.009) in the BRJ condition. This study demonstrated that BRJ consumption can improve oral glucose tolerance in individuals with T2D while controlling for medication; however, future larger-cohort randomized controlled trials are needed to confirm if BRJ is a viable treatment for glucose control in individuals with T2D.