Reduction In Pulse Pressure Research Articles

Impact of visual and textural characteristics of street walls on stress recovery

Rapid urbanization increases psychological stress among pedestrians, potentially heightening mental health disorders. This study examines the role of street walls' visual and textural characteristics in stress recovery, using Qingdao as a case study. Virtual reality is employed to simulate five distinct street walls: yellow mortar, brown stone, red brick, green plant, and white mortar. The stress recovery effectiveness of these walls was evaluated through psychological and physiological indicators from 48 young college students. Results indicated that street walls with warm tones, particularly brown stone, significantly aid stress recovery. Psychologically, Restorative Components Scale was highest for brown stone at 1.13. Physiologically, it was linked with notable reductions in diastolic and pulse pressure (decreases of 2.95 mmHg and 2.27 mmHg, respectively), and enhanced parasympathetic activity, as evidenced by the fastest decrease in low frequency/high frequency ratio (LF/HF), and increases in pNN50 and RR (0.14–2.01% and 1.57–11.81 ms, respectively). For urban design, the incorporation of warm-toned materials and natural elements like stone is recommended for their superior restorative benefits.

Physiologic Validation of the Compensatory Reserve Metric Obtained From Pulse Oximetry Waveforms

Background: The compensatory reserve metric (CRM) provides a novel marker of hemodynamic status in prediction of sudden cardiovascular decompensation during central hypovolemia. The CRM has previously been calculated using arterial waveforms obtained from a photoplethysmographic volume-clamp technique. However, the in-field use of pulse oximetry is becoming more prominent in research and medicine. To improve in-field applicability of the CRM, this project aimed to validate pulse-oximetry derived CRM values relative to physiologic data during simulated hemorrhage through application of lower body negative pressure (LBNP). Methods: Forty-nine healthy adults (25 females) underwent a graded LBNP protocol with the following 5-minute stages: -0, -15, -30, -45, -60, -70, -80, -90, and 100 mmHg, or until the onset of pre-syncopal symptoms (tolerance) was reached. Arterial waveforms were sampled using pulse oximetry (Massimo Radical 7). The CRM was calculated using a validated one-dimensional convolutional neural network. A brachial artery catheter was used to measure intraarterial pressure. A 3-lead ECG was used to measure heart rate. SpO2 was measured using pulse oximetry. Cardiac output and stroke volume were estimated using the photoplethysmographic volume-clamp. Data were binned for the last thirty seconds of each completed stage, and at tolerance. Fixed-effect linear mixed models with repeated measures were used to examine the association between CRM values and physiologic variables. A priori significance was set at P<0.05. Results: The median LBNP stage reached was 70 mmHg (Range: 45-100 mmHg). Relative to baseline, at tolerance there was a 50±12% ( P<0.001) mean reduction in stroke volume, 65±27% ( P<0.001) increase in heart rate, 18±8% ( P<0.001) reduction in mean arterial pressure, 21±7% ( P<0.001) systolic blood pressure, 8±9% ( P<0.001) diastolic blood pressure, and 39±12% ( P<0.001) pulse pressure. The CRM obtained using pulse oximetry was significantly associated with a reduction in stroke volume ( P<0.001), increase in heart rate ( P<0.001), and reductions in systolic ( P=0.033), diastolic ( P=0.036), and pulse pressure ( P=0.002). There was no statistically significant association between CRM and cardiac output ( P=0.421), SpO2 ( P=0.408), or mean arterial pressure ( P=0.214). Conclusion: The CRM obtained using pulse oximetry may be a valid, reliable marker of hemodynamic status with promising in-field applications. Future studies warrant investigation of feasibility and applicability within various contexts ranging from the operating room to the battlefield. The presented work was funded in part by the Congressionally Directed Medical Research Program (Award No. DM180240) and Offce of Naval Research (Awards No. N00014-18-D-7001 and N00014-19-C-2017). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Coronary Stenosis on Coronary Vascular Impedance

Introduction: The impedance analysis for circulation system is a powerful tool to comprehensively measure the afterload of the entire circulation system. The spectrum of vascular mechanical parameters derived from the impedance analysis can reveal the compliance and resistance changes in proximal and distal vessels, as well as the wave reflections. However, the similar investigation in the opposition of the coronary circulation is limited, and it is unknown how coronary stenosis affects the vascular impedance of the coronary circulation. In this study, we aimed to quantify and compare the changes in the vascular impedance of coronary circulation from the dynamic pressure and flow relations in healthy and patients with stenosis. Method: The pressure and flow rate waveforms from the main coronary artery were obtained from a lumped-parameter computational model that coupled the systemic circulation with the coronary perfusion within a closed system. Both healthy and diseased (coronary stenosis) pressure-flow relations were examined. A Fourier transform was performed to analyze the pressure and flow data, and the resistance (Z0), characteristic impedance (ZC), wave reflections (RW), total arterial compliance (C), and other hemodynamic parameters were derived. Results: Compared to the healthy subject, the diseased subject presented an increased resistance (Z0 was elevated from 0.44 mmHg ▪ min/ml to 0.59 mmHg ▪ min/ml), increased characteristic impedance (ZC was elevated from 0.07 mmHg ▪ min/ml to 0.14 mmHg ▪ min/ml), and reduced wave reflection (RW was decreased from 0.72 to 0.6). These changes indicate elevated distal arteries and arterioles narrowing and proximal artery stiffening in the entire coronary vasculature. Moreover, the coronary flow and the total arterial compliance (stroke volume divided by pulse pressure) were reduced with the disease progression. These data suggest a reduced coronary perfusion and stiffening of the artery in the coronary circulation. Discussion: The impedance analysis has been widely used for systemic and pulmonary circulations previously to quantify the total afterload of the left and right ventricles, respectively. The distribution of the impedance in different frequencies reflects the anatomical and mechanical properties of the vasculature in the circulation system. This study originally found that the coronary artery impedance is altered by coronary stenosis. The key characteristics include the narrowing of distal coronary arteries and stiffening of proximal coronary arteries. However, since both proximal and distal arteries are altered, the wave reflection was reduced, and this may explain a reduced pulse pressure observed in the diseased subject. The reduction in overall coronary perfusion indicates an impaired blood supply to the ventricle and may be responsible for the dysfunction of the heart. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of needling at an acupuncture point zusanli (ST-36) on blood pressure and heart rate variability in patients with hypertension: A randomized placebo-controlled study

BackgroundAcupuncture is a traditional healing system used to prevent and treat hypertension in many countries. Acupuncture point “Zusanli (ST-36)” is used to nourish blood and yin. However, no known studies reported the effect of needling at only ST-36 on cardiovascular parameters. ObjectivesThis study was performed to find the effectiveness of ST-36 on blood pressure (BP) and heart rate variability (HRV) in patients with hypertension. MethodsA total of 100 participants with primary hypertension aged between 30 years and70 years were randomly assigned into either acupuncture group (AG) or control group (CG). AG underwent only one session of bilateral needling at ST-36 acupuncture point for duration of 20 minutes, while the CG underwent only one session of bilateral needling at non-acupuncture point for the same duration. ResultsResults of the study showed a significant reduction in systolic blood pressure, pulse pressure and mean arterial pressure in the AG compared to the CG. In addition, a significant increase in intervals between adjacent QRS complexes (R-R interval), and a significant reduction in heart rate were observed in AG, unlike CG. ConclusionsNeedling at ST-36 acupuncture point may improve cardiovascular function better than needling at non-acupuncture points in patients with hypertension.

Orthostatic hypotension and subjective symptomatic orthostasis in Parkinson’s disease: Associations and correlations

BackgroundBoth measured orthostatic hypotension and symptomatic orthostasis are common in PD but their relationship is unclear. ObjectiveWe aim to determine clinical predictors of both measured orthostatic hypotension and reported symptomatic orthostasis in PD, including the impact of “on”/“off” status and seasons, and to determine the correlation between measured OH and subjective orthostasis. MethodsWe analyzed BP readings, demographic and disease state predictors for both 1. Measured blood pressure OH criteria and 2. The subjective report of orthostatic symptoms, using logistic regression analyses from an initial “on” motor state clinical visit in all PD patient visits. We then correlated subjective orthostasis symptoms with BP measurements. We also compared intra-subject BP measures in PD patients seen in both “on” and “off” states, and when seen “on” in both summer and winter. Results723 consecutive visits over 2 years identified 250 unique PD individuals. Subjective orthostasis was reported by 44 % and “on” measured OH (>20 drop in SBP or 10 DBP upon standing) was seen in 30 %. Measured OH did not significantly correlate with any assessed clinical feature or specific medicine. Subjective orthostasis correlated most with older age, dementia, and L-dopa use. Subjective orthostasis correlated equally with absolute lower measured standing SBP and the drop in SBP from sitting to standing. Compared to the “off” state, “on” state showed lower sitting and standing SBP, more than DBP, but no significant change in BP drop upon standing. Seasons did not impact measured BP. ConclusionsBoth OH and symptomatic orthostasis are common. Dopaminergic medications did not cause traditionally defined OH but lowered all SBP (sitting and standing) and thus reduced pulse pressure, possibly by increasing arteriole compliance simply by reducing motor tone, as this BP-lowering effect may be specific to Parkinsonism.

Testosterone Replacement Therapy: Effects on Blood Pressure in Hypogonadal Men.

While testosterone therapy can improve the various pathologies associated with adult-onset testosterone deficiency (TD), Summary of Product Characteristics (SPC) of five testosterone preparations caution that treatment may be associated with hypertension. This paper evaluates the impact of testosterone undecanoate (TU) on blood pressure (BP) in men with adult-onset TD. Of 737 men with adult-onset TD in an on-going, observational, prospective, cumulative registry, we studied changes in BP using non-parametric sign-rank tests at final assessment and fixed time points. We used multiple regression analysis to establish factors (baseline BP, age, change/baseline waist circumference [WC] and hematocrit [HCT] and follow-up) potentially associated with BP change in men on TU. TU was associated with significant reductions in systolic, diastolic BP and pulse pressure, regardless of antihypertensive therapy (at baseline or during follow-up), larger reductions were seen with concurrent antihypertensive therapy. In men never on antihypertensive agents, median changes (interquartile range [IQR]) in systolic BP, diastolic BP and pulse pressure were -12.5 (-19.0, -8.0), -8.0 (-14.0, -3.0), and -6.0 (-10.0, -1.0) mmHg, respectively at final assessment, with only baseline BP values inversely associated with these changes (HCT and WC were not significantly associated). In men not on TU, systolic BP, diastolic BP, and pulse pressure significantly increased. In the TU treated men only 1 of the 152 men (not on antihypertensive agents at baseline) were started on antihypertensives during follow-up. In contrast 33 of the 202 men on antihypertensives (at baseline or follow-up) had the antihypertensive agent discontinued by the end of the follow-up. TU was associated with lowering of BP during follow-up irrespective of antihypertensive therapy, with greater reductions in men with higher baseline BP. In the context of SPC warnings, our long-term data provide reassurance on the effect of TU on BP.

Transcutaneous auricular Vagus Nerve Stimulation and Median Nerve Stimulation reduce acute stress in young healthy adults: a single-blind sham-controlled crossover study.

Stress is a major determinant of health and wellbeing. Conventional stress management approaches do not account for the daily-living acute changes in stress that affect quality of life. The combination of physiological monitoring and non-invasive Peripheral Nerve Stimulation (PNS) represents a promising technological approach to quantify stress-induced physiological manifestations and reduce stress during everyday life. This study aimed to evaluate the effectiveness of three well-established transcutaneous PNS modalities in reducing physiological manifestations of stress compared to a sham: auricular and cervical Vagus Nerve Stimulation (taVNS and tcVNS), and Median Nerve Stimulation (tMNS). Using a single-blind sham-controlled crossover study with four visits, we compared the stress mitigation effectiveness of taVNS, tcVNS, and tMNS, quantified through physiological markers derived from five physiological signals peripherally measured on 19 young healthy volunteers. Participants underwent three acute mental and physiological stressors while receiving stimulation. Blinding effectiveness was assessed via subjective survey. taVNS and tMNS relative to sham resulted in significant changes that suggest a reduction in sympathetic outflow following the acute stressors: Left Ventricular Ejection Time Index (LVETI) shortening (tMNS: p = 0.007, taVNS: p = 0.015) and Pre-Ejection Period (PEP)-to-LVET ratio (PEP/LVET) increase (tMNS: p = 0.044, taVNS: p = 0.029). tMNS relative to sham also reduced Pulse Pressure (PP; p = 0.032) and tonic EDA activity (tonicMean; p = 0.025). The nonsignificant blinding survey results suggest these effects were not influenced by placebo. taVNS and tMNS effectively reduced stress-induced sympathetic arousal in wearable-compatible physiological signals, motivating their future use in novel personalized stress therapies to improve quality of life.

Hypotensive Effects of Aquatic Exercise Training in Older Adults.

Although regular exercise can help reduce blood pressure, older adults often struggle with adhering to land-based exercise due to barriers such as arthritis pain, functional limitations, and fear of falling. Aquatic exercise is a good alternative mode of exercise that may reduce barriers and improve adherence. However, limited evidence is available on the effectiveness of aquatic exercise in reducing blood pressure in older adults with isolated systolic hypertension. This study aimed to determine the effects of an 8-week aquatic exercise program on arterial blood pressure in older adults. Twenty-five participants were randomized to a control (n=12, 81±8 years) or aquatic exercise group (n=13, 83±7 years). The exercise group received aquatic cognitive-motor training at a moderate-intensity for 45 minutes per session three times per week for eight weeks. The non-exercising control group received a one-hour fall prevention seminar and was asked to maintain their normal physical activity level. Baseline characteristics were not different between the groups. After eight weeks, the exercise group had reductions in systolic blood pressure (135±11 vs. 126±13 mmHg, p<0.01) and pulse pressure (68±8 vs. 60±8 mmHg, p<0.01) without significant change in diastolic blood pressure. There were no significant changes in the control group. Aquatic cognitive-motor training performed at a moderate-intensity was effective in inducing clinically meaningful reductions in systolic blood pressure and pulse pressure in older adults.

Educational Program with Text Messaging for Community-Dwelling Patients with Hypertension: A Pilot Randomized Controlled Trial

Controlling blood pressure minimizes the risk of cardiovascular events among patients with hypertension. Despite regular follow-ups, the hypertension management for patients aged ≥45years is limited as evidenced from a decreased control rate. This pilot study aimed to test a theory-guided educational program for community-dwelling patients with hypertension. Sixty-nine patients with hypertension aged ≥45years and having high blood pressure (>130/80mmHg) were recruited in this two-arm pilot randomized controlled trial. Participants in the intervention group underwent a program guided by the Health Promotion Model, whereas those in the control group received usual care. Data were collected at baseline, week 8, and week 12 and used to assess the blood pressure, pulse pressure, self-efficacy, and adherence to hypertension management. Data were analyzed using a generalized estimating equation based on the intention-to-treat principle. Process evaluation was conducted to assess the feasibility and acceptability of the educational program. The results obtained using the generalized estimating equation revealed that the educational program led to reduction in the systolic blood pressure (β=-7.12, p=.086) and pulse pressure (β=-8.20, p=.007)and to improve self-efficacy (β=2.61, p=.269) at week 12. The program had a small-to-moderate effect on the reduction of systolic blood pressure (effect size=-0.45) and pulse pressure (effect size=-0.66)and self-efficacy (effect size=0.23). The participants were highly satisfied with the educational program. The educational program was found to be feasible and acceptable and may be incorporated into current hypertension management practices at the community level. ClinicalTrials.gov with identifier: NCT04565548.

The effect of isometric exercise training on arterial stiffness: A randomized crossover controlled study.

Isometric exercise training (IET) is an effective intervention for the management of resting blood pressure (BP). However, the effects of IET on arterial stiffness remain largely unknown. Eighteen unmedicated physically inactive participants were recruited. Participants were randomly allocated in a cross-over design to 4 weeks of home-based wall squat IET and control period, separated by a 3-week washout period. Continuous beat-to-beat hemodynamics, including early and late systolic (sBP 1 and sBP 2, respectively) and diastolic blood pressure (dBP) were recorded for a period of 5 min and waveforms were extracted and analyzed to acquire the augmentation index (AIx) as a measure of arterial stiffness. sBP 1 (-7.7 ± 12.8 mmHg, p = 0.024), sBP 2 (-5.9 ± 9.9 mmHg, p = 0.042) and dBP (-4.4 ± 7.2 mmHg, p = 0.037) all significantly decreased following IET compared to the control period. Importantly, there was a significant reduction in AIx following IET (-6.6 ± 14.5%, p = 0.02) compared to the control period. There were also adjacent significant reductions in total peripheral resistance (-140.7 ± 65.8 dynes·cm-5, p = 0.042) and pulse pressure (-3.8 ± 4.2, p = 0.003) compared to the control period. This study demonstrates an improvement in arterial stiffness following a short-term IET intervention. These findings have important clinical implications regarding cardiovascular risk. Mechanistically, these results suggest that reductions in resting BP following IET are induced via favorable vascular adaptations, although the intricate details of such adaptations are not yet clear.

Age-related changes to cerebral artery stiffness and structure in mice

Introduction: With advancing age, there are changes in the structural and material properties of the arterial wall. While the age-related increase in stiffness is well described for large arteries, less is known about the structural changes to cerebral arteries with age. In response to increased blood pressure, as occurs with aging, arteries typically undergo remodeling that includes smooth muscle cell proliferation and collagen accumulation. This remodeling contributes to increased stiffness and reduces pulse pressure dampening, potentially leading to damage to arterioles and capillaries. We hypothesized that old cerebral arteries would display greater stiffness, wall thickness, collagen content, and smooth muscle content compared with young cerebral arteries. Methods: We studied old male (n=10, 24-27 months) and young male (n=9, 4-7 months) C57BL/6 mice. For measures of stiffness, isolated posterior cerebral arteries were exposed to pulsatile pressure (37.5 to 87.5 mmHg, 400 pulses/min) for 30 minutes. Artery diameters during the pulsation were recorded and used to calculate distension, β-stiffness index, and Peterson modulus of elasticity (EP). In sections of the middle cerebral arteries, total wall thickness and total collagen were measured in Masson’s trichrome-stained arteries. Collagen-1 and α-smooth muscle actin content were measured by immunofluorescence in middle cerebral artery sections. Data were analyzed by a Shapiro-Wilks test for normality, and young and old groups were compared by student’s t-test. Group comparisons for β-stiffness, EP, and percent change in diameter were made using a Mann-Whitney test. A p&lt;0.05 was considered statistically significant. Data are mean±SD. Results: Cerebral arteries from young mice, compared with old mice, had a higher distensibility during the application of pulsatile pressure, measured by the percent change in diameter (8.0±4.0% vs. 5.1±2.5%, p=0.03) or absolute change in diameter (12.0±5.4 μm vs. 7.8±3.8 μm, p=0.03). Cerebral artery stiffness, calculated by β-stiffness index (13.1±6.5 AU vs. 21.9±13.8 AU, p=0.03) and EP (777±384 kPa 102 vs.1293±816 kPa 102, p=0.03) was lower in young mice compared with old mice. There was no difference in cerebral artery wall thickness between groups (6.9±3.0 μm vs. 9.6±2.3 μm, p=0.08). Cerebral arteries from old mice had greater amounts of α-smooth muscle actin compared to young mice (1.4±0.2 AU vs. 1.0±0.2 AU, p=0.009). Interestingly, cerebral arteries from old mice had lower collagen-1 compared to young mice (0.8±0.1 vs. 1.0±0.1 AU, p=0.01), but the opposite trend was observed for total collagen (26.3±13.6 AU vs. 17.6±9.6, p=0.06). Conclusion: These results demonstrate that advancing age results in increased functional stiffness of cerebral arteries. An age-related increase in smooth muscle is a potential cause of higher cerebral artery stiffness. This project was funded by NIH R01 AG064016 and the Oregon Medical Research Foundation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Factors associated with arterial stiffness assessed by pulse pressure amplification in healthy children and adolescents: a cross-sectional study

BackgroundIncreasing evidence suggests that reducing pulse pressure amplification (PPA) plays an important role in pathogenesis and progression of cardiovascular disease. This is a cross-sectional, observational, and analytical study in which we evaluated the associated factors with a greater chance of reducing PPA in 136 healthy children and adolescents aged 8 to 19 years old stratified by gender and age group.MethodsArterial stiffness and vascular and hemodynamic parameters were non-invasively measured using Mobil-O-Graph® (IEM, Stolberg, Germany), a cuff-based oscillometric device. PPA was expressed as the peripheral-to-central pulse pressure ratio (PPp / PPc). Participants with PPA < 1.49 were considered as part of the arterial stiffness group.ResultsIn a univariate model, the increase in total vascular resistance, the reflection coefficient and the augmentation pressure were more likely to have arterial stiffness in all groups. The factors most likely to have arterial stiffness (as assessed by the reduction of the PPA) in the multivariate model were increasing age, the reflection coefficient and cardiac index in the total sample, male group and child and adolescent groups. In addition to age in the female group, cardiac output, stroke volume, and AIx@75 were the factors most likely to present arterial stiffness.ConclusionsThe results show for the first time in children and adolescents that the factors most likely to reduce PPA are related to the reflection wave, which determines aortic pressures and, therefore, left ventricular afterload.

Safety evaluation of the Guardian device on the common carotid artery in sheep

BackgroundPulse pressure intensity in middle-aged adults is a risk factor for dementia. The Guardian device (The Brain Protection Company, Sydney, Australia) has been developed to reduce pulse pressure, as a potential therapy. ObjectivesThe aim of this study was to evaluate the safety of the Guardian, a novel pulse modulation device designed to reduce the intensity of the pulse pressure that penetrates into the cerebral small vessels. The Guardian is a helix that gently wraps around the common carotid artery (CCA) to slightly change its shape, to absorb pulsatility, without lowering flow. MethodsThe Guardian was implanted bilaterally on the CCAs of 10 mature sheep for chronic implant periods of 3, 6 or 8 months. The ratio of internal device diameter to outer diameter of the CCA varied from 63% to 92% (n = 20). The implant position on the vessel was marked surgically at implant. Gross pathology and histopathology of the CCA were examined at 3- and 6-months post explant. Most devices were explanted using open surgery, however minimally invasive surgical explant techniques were examined in 2 animals to assess the potential of this approach for explant in humans if required. ResultsThe Guardian was successfully implanted with no adverse events, and minimally invasive explant appeared to be viable for removal. Following implant, the device was surrounded by a thin fibrous capsule, with similar pathology at 3- and 6-months. Minimal or no movement was observed. CCA sections appeared histologically normal, with no evidence of thrombosis, stenosis, fibrosis, chronic inflammatory response, or vessel degeneration. ConclusionsThe feasibility of surgical implantation and biomaterial safety of the Guardian was confirmed over 8 months. Minimally invasive explant of the Guardian has the potential to be viable. Further work is required to demonstrate efficacy in vitro and/or in vivo before evaluation in humans.

Weight-dependent and weight-independent effects of dulaglutide on blood pressure in patients with type 2 diabetes

BackgroundPatients with type 2 diabetes (T2D) treated with glucagon-like peptide-1 receptor agonists may experience reductions in weight and blood pressure. The primary objective of the current study was to determine the weight-dependent and weight-independent effects of ~ 6 months treatment with dulaglutide 1.5 mg treatment in participants with T2D.MethodsMediation analysis was conducted for five randomized, placebo-controlled trials of dulaglutide 1.5 mg to estimate the weight-dependent (i.e., mediated by weight) and weight-independent effects from dulaglutide vs. placebo on change from baseline for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure. A random-effects meta-analysis combined these results. To investigate a dose response between dulaglutide 4.5 mg and placebo, mediation analysis was first conducted in AWARD-11 to estimate the weight-dependent and weight-independent effects of dulaglutide 4.5 mg vs. 1.5 mg, followed by an indirect comparison with the mediation result for dulaglutide 1.5 mg vs. placebo.ResultsBaseline characteristics were largely similar across the trials. In the mediation meta-analysis of placebo-controlled trials, the total treatment effect of dulaglutide 1.5 mg after placebo-adjustment on SBP was − 2.6 mmHg (95% CI − 3.8, − 1.5; p < 0.001) and was attributed to both a weight-dependent effect (− 0.9 mmHg; 95% CI: − 1.4, − 0.5; p < 0.001) and a weight-independent effect (− 1.5 mmHg; 95% CI: − 2.6, − 0.3; p = 0.01), accounting for 36% and 64% of the total effect, respectively. For pulse pressure, the total treatment effect of dulaglutide (− 2.5 mmHg; 95% CI: − 3.5, − 1.5; p < 0.001) was 14% weight-dependent and 86% weight-independent. For DBP there was limited impact of dulaglutide treatment, with only a small weight-mediated effect. Dulaglutide 4.5 mg demonstrated an effect on reduction in SBP and pulse pressure beyond that of dulaglutide 1.5 mg which was primarily weight mediated.ConclusionsDulaglutide 1.5 mg reduced SBP and pulse pressure in people with T2D across the placebo-controlled trials in the AWARD program. While up to one third of the effect of dulaglutide 1.5 mg on SBP and pulse pressure was due to weight reduction, the majority was independent of weight. A greater understanding of the pleotropic effects of GLP-1 RA that contribute to reduction in blood pressure could support developing future approaches for treating hypertension.Trial registrations (clinicaltrials.gov) NCT01064687, NCT00734474, NCT01769378, NCT02597049, NCT01149421, NCT03495102

Relationship Between Ascending Thoracic Aortic Diameter and Blood Pressure: A Mendelian Randomization Study.

Observational studies identified elevated blood pressure (BP) as a strong risk factor for thoracic aortic dilation, and BP reduction is the primary medical intervention recommended to prevent progression of aortic aneurysms. However, although BP may impact aortic dilation, aortic size may also impact BP. The causal relationship between BP and thoracic aortic size has not been reliably established. Genome-wide association studies summary statistics were obtained for BP and ascending thoracic aortic diameter (AscAoD). Causal effects of BP on AscAoD were estimated using 2-sample Mendelian randomization using a range of pleiotropy-robust methods. Genetically predicted increased systolic BP, diastolic BP, and mean arterial pressure all significantly associate with higher AscAoD (systolic BP: β estimate, 0.0041 mm/mm Hg [95% CI, 0.0008-0.0074]; P=0.02, diastolic BP: β estimate, 0.0272 mm/mm Hg [95% CI, 0.0224-0.0320]; P<0.001, and mean arterial pressure: β estimate, 0.0168 mm/mm Hg [95% CI, 0.0130-0.0206]; P<0.001). Genetically predicted pulse pressure, meanwhile, had an inverse association with AscAoD (β estimate, -0.0155 mm/mm Hg [95% CI, -0.0213 to -0.0096]; P<0.001). Multivariable Mendelian randomization analyses showed that genetically predicted increased mean arterial pressure and reduced pulse pressure were independently associated with AscAoD. Bidirectional Mendelian randomization demonstrated that genetically predicted AscAoD was inversely associated with pulse pressure (β estimate, -2.0721 mm Hg/mm [95% CI, -3.1137 to -1.0306]; P<0.001) and systolic BP (β estimate, -1.2878 mm Hg/mm [95% CI, -2.3533 to -0.2224]; P=0.02), while directly associated with diastolic BP (0.8203 mm Hg/mm [95% CI, 0.2735-1.3672]; P=0.004). BP likely contributes causally to ascending thoracic aortic dilation. Increased AscAoD likely contributes to lower systolic BP and pulse pressure, but not diastolic BP, consistent with the hemodynamic consequences of a reduced aortic diameter.

Aneurysm Sac Pressure during Branched Endovascular Aneurysm Repair versus Multilayer Flow Modulator Implantation in Patients with Thoracoabdominal Aortic Aneurysm.

Open thoracoabdominal repair is the gold standard in the TAAA treatment. However, there are endovascular techniques, that sometimes may be an alternative, such as branched endovascular aneurysm repair (BEVAR) or implantation of the multilayer flow modulator (MFM). In this study, we aimed to assess differences in the aneurysm sac pressure (ASP) between patients undergoing BEVAR and MFM implantation. The study included 22 patients with TAAA (14 patients underwent BEVAR, while eight MFM implantation). The pressure sensor wire was placed inside the aneurysm. A measurement of ASP and aortic pressure (AP) was performed during the procedure. The systolic pressure index (SPI), diastolic pressure index (DPI), and pulse pressure index (PPI) were calculated as a quotient of the ASP and AP values. After the procedure, SPI and PPI were lower in the BEVAR group than in the MFM group. During a procedure, a drop in SPI and PPI was noted in patients undergoing BEVAR, while no changes were revealed in the MFM group. This indicates that BEVAR, but not MFM, is associated with a reduction in systolic and pulse pressure in the aneurysm sac in patients with TAAA.

Aerobic exercise training reduces cerebrovascular impedance in older adults: a 1-year randomized controlled trial.

Older adults have higher cerebrovascular impedance than young individuals which may contribute to chronic brain hypoperfusion. Besides, middle-aged athletes exhibit lower cerebrovascular impedance than their sedentary peers. We examined whether aerobic exercise training (AET) reduces cerebrovascular impedance in sedentary older adults. We conducted a proof-of-concept trial that randomized 73 older adults to 1 yr of AET (n = 36) or stretching and toning (SAT, n = 37) interventions. Cerebrovascular impedance was estimated from simultaneous recordings of carotid artery pressure (CAP) via applanation tonometry and cerebral blood flow velocity (CBFV) in the middle cerebral artery via transcranial Doppler using transfer function analysis. Fifty-six participants completed 1-yr interventions, and 41 of those completed cerebrovascular impedance measurements. AET group showed a significant increase in V̇o2peak after the intervention [estimated marginal mean (95% confidence interval); from 22.8 (21.6 to 24.1) to 24.9 (23.6 to 26.2) mL·kg-1·cm-1, P < 0.001], but not SAT [from 21.7 (20.5 to 22.9) to 22.3 (21.1 to 23.7) mL·kg-1·cm-1, P = 0.114]. Coherence between changes in CBFV and CAP was >0.90 in the frequency range of 0.78-3.12 Hz. The averaged cerebrovascular impedance modulus (Z) in this frequency range decreased after 1-yr AET [from 1.05 (0.96 to 1.14) to 0.95 (0.92 to 1.06) mmHg·s·cm-1, P = 0.023], but not SAT [from 0.96 (0.87 to 1.04) to 1.01 (0.92 to 1.10) mmHg·s·cm-1, P = 0.138]. Reductions in Z were correlated positively with reductions in carotid pulse pressure (r = 0.628, P = 0.004) and inversely with mean CBFV (r = -0.563, P = 0.012) in the AET group. One-year AET reduces cerebrovascular impedance in older adults, which may benefit brain perfusion.NEW & NOTEWORTHY Estimation of cerebrovascular impedance is essential for understanding dynamic cerebral blood flow regulation. This randomized controlled trial demonstrated that aerobic exercise training reduced cerebrovascular impedance in older adults, which may benefit brain perfusion.

Results of PRospect trial to Elucidate the utility of EchocarDiography-based Cardiac ouTput in acute heart failure (PREDICT)

BackgroundThe predictive value of echocardiographic parameters for early worsening heart failure (WHF), worsening of symptoms of heart failure requiring intensification of therapy during an admission for acute decompensated heart failure (ADHF), has not been elucidated. MethodsSixteen centers in Japan prospectively enrolled 303 ADHF hospitalized patients who did not receive positive inotropic agents as an initial therapy. Physical and Doppler echocardiographic examinations were performed before the initial therapy and the association of low output findings and occurrence of early WHF were tested. ResultsEarly WHF occurred in 63 patients with a median duration of 6 (IQR: 2–23) hours from the administration of the initial therapy. In patients with left ventricular (LV) ejection fraction <40% (N = 153), echocardiographic stroke volume index, and cardiac index showed greater c-index [95% confidence interval, 0.71 (0.61–0.79) and 0.72 (0.63–0.80), respectively] compared to single low perfusion finding (symptomatic hypotension, reduced pulse pressure, and impaired mentation) other than cool extremities. When physical findings were combined (low perfusion score), the predictive ability improved to the similar levels of echocardiographic LV output parameters [c-index: 0.69 (0.60–0.76)]. However, addition of cardiac index significantly improved the prognostic ability when added to low perfusion score [0.82 (0.74–0.87), p < 0.001]. In contrast, in patients with LV ejection fraction ≥40% (N = 150), low perfusion score, rather than LV output parameters, was predictive of early WHF [c-index: 0.73 (0.56–0.85)]. ConclusionsWe demonstrated the predictive value of echocardiographic LV output indices for early WHF in ADHF patients with LV systolic dysfunction. These data support the motivation for routine use of echocardiography for initial assessment of ADHF.

Метаболические эффекты генерического препарата телмисартан (ХИПотел) или его комбинации с S-амлодипином (Семлопин) или гидрохлоротиазидом в ТЕРапии пациентов с мягкой и умеренной артериальной гипертензией (результаты исследования ХИПСТЕР-АГ)

Цель: оценить метаболические эффекты генерического препарата телмисартан (Хипотел производства компании «Кусум Фарм», Украина) в качестве монотерапии или в комбинации с S-амлодипином (Семлопин производства компании «Кусум Фарм», Украина) у пациентов с мягкой и умеренной артериальной гипертензией (АГ). Материалы и методы. В исследование было включено 40 пациентов с мягкой и умеренной АГ. После семидневного периода отмены всех медикаментозных средств пациенты проходили первоначальное обследование и деление на группы методом слепых конвертов в зависимости от назначенной антигипертензивной терапии. В конце периода отмены оценивали повторно критерии включения в исследование. Если пациент отвечал критериям включения и не имел критериев исключения, то происходила рандомизация пациента. Назначали Хипотел в дозе 40–80 мг один раз в сутки в течение 2 недель. При недостижении целевого уровня артериального давления (АД) меньше 140/90 мм рт.ст. добавляли Семлопин 2,5–5 мг один раз в сутки еще в течение 1 месяца. Если не было достижения целевого уровня АД, добавляли гидрохлортиазид в дозе 12,5 мг один раз в сутки. Срок наблюдения составил 6 месяцев. Пациентам было проведено в начале и в конце исследования суточное мониторирование АД, определение глюкозы, инсулина крови, определен уровень НОМА, липидный спектр крови, выполнено биохимическое исследование крови, общий анализ крови и мочи. Результаты. Средний возраст больных составил 55,85 ± 2,09 года. Средняя масса тела составляла 87,30 ± 2,77 кг. Средний индекс массы тела — 29,41 ± 0,63 кг/м2. Средние цифры офисного систолического (САД) и диастолического (ДАД) АД в начале исследования составили 155,88 ± 1,63 мм рт.ст. и 92,60 ± 1,43 мм рт.ст. соответственно. Средняя офисная частота сердечных сокращений (ЧСС) — 71,40 ± 1,29 уд/мин. Средние уровни АД при амбулаторном мониторировании составляли для САД 139,37 ± 1,49 мм рт.ст., для ДАД — 82,47 ± 1,84 мм рт.ст. Средняя суточная ЧСС — 71,38 ± 1,32 уд/мин. Хипотел 40–80 мг в нашем исследовании в качестве монотерапии или в комбинации с Семлопином и/или гидро­хлортиазидом имел нейтральный эффект на инсулиновую чувствительность и уровень глюкозы и инсулина крови в течение 24 недель лечения. Не наблюдалось негативного влияния лечения на уровень липидного спектра крови. В подгруппе пациентов без инсулинорезистентности отмечалось достоверное уменьшение центрального АД, а индекс аугментации (АІх) имел тенденцию к уменьшению. В подгруппе пациентов с инсулинорезистентностью наблюдалось выраженное и достоверное уменьшение как центрального АД, так и индекса аугментации. Центральное САД (цСАД) связано с упруго-эластичными свойствами артерий, показателями офисного АД и степени его снижения, степенью гипертрофии левого желудочка, показателями системного воспаления и эректильной функции у мужчин. Метаболические показатели крови были связаны с показателями жесткости артерий, цСАД, офисным САД, степенью снижения пульсового АД при суточном мониторировании. Степень снижения НОМА коррелировала с АІх в конце лечения (r = –0,451, р = 0,018), скоростью клубочковой фильтрации после лечения (r = –0,362, р = 0,042), степенью снижения пульсового АД при суточном мониторировании (r = –0,484, р = 0,004). Степень снижения НОМА зависела от снижения уровня инсулина крови, коррелировала со степенью снижения пульсового АД при суточном мониторировании (r = –0,485, р = 0,004). Уровень глюкозы крови до лечения коррелирует с офисным САД после лечения (r = 0,439, р = 0,005), уровень глюкозы после лечения коррелировал с уровнем офисного САД после лечения (r = 0,357, р = 0,03). Степень снижения уровня глюкозы коррелировала с цСАД в начале лечения (r = –0,445, р = 0,018), уровнем офисного диастолического АД через 4 недели лечения (r = 0,461, р = 0,004), степенью снижения цСАД (r = 0,559, р = 0,002). Чем более значительно снижался уровень глюкозы крови в конце исследования, тем больше была степень снижения цСАД в конце лечения. Выводы. Телмисартан в монотерапии или в комбинации с S-амлодипином в подгруппе пациентов без инсулинорезистентности способствовал достоверному уменьшению центрального АД, а индекс аугментации имел тенденцию к уменьшению. В подгруппе пациентов с инсулинорезистентностью наблюдалось выраженное и достоверное уменьшение как центрального АД, так и индекса аугментации. Глюкоза, инсулин крови и НОМА были связаны с показателями жесткости артерий, центральным САД, офисным САД, степенью снижения пульсового АД при суточном мониторировании.

Effect of empagliflozin on ketone bodies in patients with stable chronic heart failure

BackgroundRecent studies indicated that sodium glucose cotransporter (SGLT)2 inhibition increases levels of ketone bodies in the blood in patients with type 1 and 2 diabetes. Other studies suggested that in patients with chronic heart failure (CHF), increased myocardial oxygen demand can be provided by ketone bodies as a fuel substrate. Experimental studies reported that ketone bodies, specifically beta-hydroxybutyrate (β-OHB) may increase blood pressure (BP) by impairing endothelium-dependant relaxation, thereby leading to increased vascular stiffness. In our study we assessed whether the SGLT 2 inhibition with empagliflozin increases ketone bodies in patients with stable CHF and whether such an increase impairs BP and vascular function.MethodsIn a prospective, double blind, placebo controlled, parallel-group single centre study 75 patients with CHF (left ventricular ejection fraction 39.0 ± 8.2%) were randomised (2:1) to the SGLT-2 inhibitor empagliflozin 10 mg orally once daily or to placebo, 72 patients completed the study. After a run-in phase we evaluated at baseline BP by 24 h ambulatory blood pressure (ABP) monitoring, vascular stiffness parameters by the SphygmoCor system (AtCor Medical, Sydney, NSW, Australia) and fasting metabolic parameters, including β-OHB by an enzymatic assay (Beckman Coulter DxC 700 AU). The same measurements were repeated 12 weeks after treatment. In 19 of the 72 patients serum levels of β-OHB were beneath the lower border of our assay (< 0.05 mmol/l) therefore being excluded from the subsequent analysis.ResultsIn patients with stable CHF, treatment with empagliflozin (n = 36) was followed by an increase of β-OHB by 33.39% (p = 0.017), reduction in 24 h systolic (p = 0.038) and diastolic (p = 0.085) ABP, weight loss (p = 0.003) and decrease of central systolic BP (p = 0.008) and central pulse pressure (p = 0.008). The increase in β-OHB was related to an attenuated decrease of empagliflozin-induced 24 h systolic (r = 0.321, p = 0.069) and diastolic (r = 0.516, p = 0.002) ABP and less reduction of central systolic BP (r = 0.470, p = 0.009) and central pulse pressure (r = 0.391, p = 0.033). No significant changes were seen in any of these parameters after 12 weeks of treatment in the placebo group (n = 17).ConclusionIn patients with stable CHF ketone bodies as assessed by β-OHB increased after treatment with empagliflozin. This increase led to an attenuation of the beneficial effects of empagliflozin on BP and vascular parameters.Trial registration The study was registered at http://www.clinicaltrials.gov (NCT03128528).