Changes In Pressure Research Articles

Orthostatic blood pressure changes and incident atrial fibrillation in patients with hypertension: Insights from the SPRINT trial

Abstract Background Exaggerated orthostatic changes in systolic blood pressure (SBP) were associated with adverse cardiovascular events. However, the predictive role of SBP hyperactivity to standing on incident atrial fibrillation (AF) is unclear. Purpose We aim to assess the association between orthostatic SBP changes and incident AF. Methods We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. Participants with standing SBP <110 mm Hg were not eligible for randomization according to the SPRINT protocol. Participants without AF who had seated and standing SBP measurements at baseline and available baseline or follow-up ECG were included in this analysis. Orthostatic SBP changes were defined as standing SBP minus seated SBP. Patients were grouped into tertiles of orthostatic SBP changes. AF was ascertained from the standard 12-lead ECG obtained at baseline, year 2, year 4, a close-out visit, and any visit when suspected of serious adverse events. We used Cox proportional regression models and restricted spline curves to assess the association of orthostatic SBP changes with incident AF. Results Among 8,455 participants included in this analysis, 327 incident AF cases occurred during follow-up. The restricted spline curve depicted a U-shaped relationship between orthostatic SBP changes and incident AF in the unadjusted model (P for nonlinearity = 0.012) (Figure 1). After adjusting for age, female, race, smoking, alcohol use, history of cardiovascular disease, history of chronic kidney disease, and body mass index, a SBP increase ≥ 6 mm Hg to standing was independently associated with a 43% higher risk of incident AF (HR: 1.43; 95% CI: 1.07-1.90; P = 0.014) compared to nonsignificant orthostatic SBP changes (>-4 mm Hg to <6 mm Hg). A SBP decrease ≥ 4 mm Hg to standing showed a nonsignificant higher risk of developing AF compared to SBP changes of >-4 mm Hg to <6 mm Hg (Figure 2). In subgroup analysis, the results presented a similar tendency to the main result. Sensitivity analyses also generated consistent results while additionally adjusting for seated and standing blood pressure or heart rate. Conclusion In this post hoc analysis of the SPRINT trial, exaggerated SBP increase to standing independently predicts incident AF.Figure 1Figure 2

Influence of orthostatic blood pressure changes on the effects of intensive blood pressure control in patients with type 2 diabetes

Abstract Background Intensive blood pressure (BP) control has been proven to reduce the risks of major cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM) (1). Excessive orthostatic BP changes should be fully addressed, given its high prevalence and associations with adverse events among T2DM patients (2-5). However, the benefits of intensive BP control among T2DM patients with significant orthostatic BP changes have been equivocal. Purpose To examine whether orthostatic BP changes modify the efficacy of intensive BP control on CVD outcomes in patients with T2DM. Methods The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) is a 2×2 factorial designed trial that aimed to evaluate the effects of intensive glycemia and BP control on major CVD events among T2DM patients (6). We enrolled participants with at least one record of orthostatic BP values for analysis. The composite CVD outcome in this study comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalized congestive heart failure. Associations between orthostatic BP changes and the composite CVD outcome and all-cause death, respectively, were presented by restricted cubic spline curves based on multivariable Cox models. We examined if the effects of intensive BP control varied across the orthostatic BP change for the composite CVD outcome and all-cause death. Results Among 4330 participants, 877 (20.3%) experienced episodes of orthostatic hypotension (OH) at baseline or during follow-up. There was no significant difference in the proportions of OH participants between the intensive and standard BP arms. U-shaped associations were observed between orthostatic systolic BP changes and the composite CVD outcome, as well as all-cause mortality (Figure 1). In the standard glycemia arm, intensive BP control was significantly associated with a lower risk of composite CVD outcome (HR 0.76, 95%CI 0.59-0.97). There was a beneficial association of intensive BP control with all-cause mortality without statistical significance (HR 0.85, 95%CI 0.56-1.30). The favorable effect of intensive BP control was not influenced by orthostatic BP changes (P for interaction 0.51 for the composite CVD outcome and 0.97 for all-cause mortality) (Figure 2). Beneficial effects of intensive BP control were not observed for participants in the intensive glycemia arm on the composite CVD outcome (HR 0.99, 95%CI 0.76-1.28) and all-cause mortality (HR 1.19, 0.79-1.80). Conclusion Orthostatic BP changes should not be a barrier to intensive BP control for T2DM patients treated with guideline-recommended standard glycemia control.

Development of Electrically Conductive Wood-Based Panels for Sensor Applications.

This study investigates the development of electrically conductive panels for application as emergency detection sensors in smart house systems. These panels, composed of wood chips coated with polymeric methylene diphenyl isocyanate, were modified with carbon black and carbon fibers to enable detection of moisture, temperature, and pressure variations. Manufactured via hot pressing, the panels retained standard mechanical properties and exhibited stable performance under diverse environmental conditions. Carbon black-filled panels achieved electrical percolation at a lower filler concentration (5%) compared to carbon fiber-filled panels. The incorporation of carbon black reduced the electrical resistivity to 8.6 ohm·cm, while the addition of carbon fibers further decreased it to 7.7 ohm·cm. In terms of sensor capabilities, panels containing carbon fibers demonstrated superior sensitivity to moisture and pressure changes. However, carbon black was ineffective for temperature sensing. Among the carbon fiber-filled panels, those with 20 wt.% concentration exhibited the best performance for moisture and pressure detection, whereas panels with 40 wt.% carbon fiber content displayed the most reliable and consistent temperature-sensing properties.

Total sugar intake significantly associated with systolic blood pressure in small sample population

Abstract Background Hypertension contributes to 45% of all deaths from heart disease and up to 51% of deaths from strokes. Dietary factors, such as sodium (Na+) and potassium (K+) can play a role, but recent studies have also highlighted the importance of sugar intake on blood pressure. Very few studies have evaluated the impact of these factors and their ratio on cardiometabolic biomarkers. This study aims to assess the impact of dietary sugar intake, Na+, K+ and NA+/K+ ratio on hypertension and cardiometabolic biomarkers. Methods Fasting venous blood was collected to measure glucose, triacylglycerols (TAG), total cholesterol, HDL-c, ApoA1, ApoB, or hs-CRP, with enzymatic and turbidimetric techniques, and oxidized LDL by ELISA, and IL-6 and TNFa by Luminex system, the latter’s in a subset sample. Blood pressure (SBP, DBP, and HR) was measured at least twice with an automatic recorder. Dietary intake was obtained using semi-quantitative FFQ, comprising 82 items, and reported to the previous year. Data was analysed using R software through descriptive analysis and partial correlations adjusted to the participant’s BMI. A significant level of 0.05 was used. Results 78 participants, aged from 19 to 80 years old (M = 48,5±13,5) were evaluated, with 47% taking hypertensive medication. BMI ranged from 19,7 to 41,1 Kg/m2 (M = 29,2±5,4). The average intake of Na+, K+ and NA+/K+ ratio were 3805±1397 mg, 3980±1300 mg and 1.65±0,38, respectively. Total mean sugar intake (% energy) represents 21,4%. No significant correlation was found between Na+ or K+ with SBP, HR, and the cardiometabolic biomarkers (p > 0.05). A positive correlation was found between % sugar intake and SBP (rs = 0,29, p < 0,05), which remains significant after adjusting for BMI, and a positive correlation, in the borderline of significance, with TAG (rs = 0,23, p = 0,0561). Conclusions N+, K+, and their ratio do not associate with SBP, HR and cardiometabolic biomarkers. However, % of sugar intake is positively associated with SBP. Key messages • Sodium and potassium may not always be associated with changes in blood pressure. • Sugar intake might have an important role in the etiopathology of hypertension.

Periprocedural changes in systolic pulmonary artery pressure in transcatheter aortic valve implantation

Abstract Background Pulmonary hypertension (PH) is common in patients with aortic stenosis and associated with increased mortality following transcatheter aortic valve replacement (TAVR). PH often improves after TAVR and systolic pulmonary artery pressure (sPAP) can change, but to what extent these changes in sPAP following TAVR affect long-term prognosis is unclear. Purpose To investigate the association between periprocedural changes in sPAP and long-term prognosis after TAVR. Methods Patients undergoing TAVR between 2012-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. sPAP was estimated from echocardiography before and after TAVR and categorized as: (1) No PH before and unchanged (≤5 mmHg change) after, (2) No PH before and worsened (>5 mmHg increase) after, (3) PH before and improved (>5 mmHg decrease) after, (4) PH before and unchanged after and (5) PH before and worsened after. An sPAP cutoff at >50 mmHg was applied for PH. Patients were followed for a median of 3.1 years for the primary endpoint heart failure hospitalizations (HFH) and the secondary endpoint all-cause mortality. Cox regression analyses were performed and adjusted for age, sex, body mass index, atrial fibrillation, eGFR class, diabetes, frailty, left ventricular ejection fraction and chronic obstructive pulmonary disease. Results In total, 4926 patients were included (mean age 82 years, 50% female) among whom 2596 (53%) patients had no PH and unchanged, 864 (18%) had no PH and worsened after, 912 (19%) had PH and improved after, 401 (8%) had PH and unchanged after and 153 (3%) had PH and worsened after. The mean sPAP levels preoperatively in each group were 36, 31, 60, 58, 57 mmHg respectively. Mean change in patients with no PH and worsened was +16 mmHg, in patients with PH and improved -20 mmHg and in patients with PH and worsened +14 mmHg. Cumulative incidence rates of HFH at 5 years among the five groups were 18%, 25%, 32%, 41%, and 52%, respectively (p<0.001). In adjusted analyses, there was a stepwise increase in the risk of HFH (Figure 1A) and all-cause mortality (Figure 1B) for no PH and worsened, PH and improved, PH and unchanged and PH and worsened as compared with no PH and unchanged. Conclusion Increase of periprocedural sPAP in patients with and without known PH before TAVR was associated with worse prognosis whereas reduction of sPAP was associated with improved outcomes.

Pharmacometabolomics Approach to Explore Pharmacokinetic Variation and Clinical Characteristics of a Single Dose of Desvenlafaxine in Healthy Volunteers

This study investigated the effects of a single dose of desvenlafaxine via oral administration on the pharmacokinetic parameters and clinical and laboratory characteristics in healthy volunteers using a pharmacometabolomics approach. In order to optimize desvenlafaxine’s therapeutic use and minimize potential adverse effects, this knowledge is essential. Methods: Thirty-five healthy volunteers were enrolled after a health trial and received a single dose of desvenlafaxine (Pristiq®, 100 mg). First, liquid chromatography coupled to tandem mass spectrometry was used to determine the main pharmacokinetic parameters. Next, ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry was used to identify plasma metabolites with different relative abundances in the metabolome at pre-dose and when the desvenlafaxine peak plasma concentration was reached (pre-dose vs. post-dose). Results: Correlations were observed between metabolomic profiles, such as tyrosine, sphingosine 1-phosphate, and pharmacokinetic parameters, as well as acetoacetic acid and uridine diphosphate glucose associated with clinical characteristics. Our findings suggest that desvenlafaxine may have a broader effect than previously thought by acting on the proteins responsible for the transport of various molecules at the cellular level, such as the solute carrier SLC and adenosine triphosphate synthase binding cassette ABC transporters. Both of these molecules have been associated with PK parameters and adverse events in our study. Conclusions: This altered transporter activity may be related to the reported side effects of desvenlafaxine, such as changes in blood pressure and liver function. This finding may be part of the explanation as to why people respond differently to the drug.

The influence of the daily salt-intake on the antihypertensive action and atrial natriuretic peptide level in patietns with angiotensin receptor neprilysin inhibition

Abstract Background The angiotensin receptor–neprilysin inhibitor (ARNI) is a drug which acts through angiotensin receptor blocking effect and the increase in atrail natriuretic peptide (ANP) through neprilysin inhibitor in hypertension (HT). These combined effects result in a reduced risk of hospitalization for heart failure or death from cardiovascular causes. ANP is also known for its various cardioprotective effects including vasodilator and natriuretic action. Acording to Guyton's pressure-natriuresis curve, the efficacy of angiotensin receptor blocker drugs is diminished in HT cases with high daily salt inatke. However, whether the effect of ARNI on HT is attenuated in patients with high daily salt intake remains unclear. Purpose The present study investigated the influence of a daily salt intake on the antihypertensive action and ANP level in patients with ARNI. Methods Fourty-four consecutive essential HT patients on ARNI were enrolled. Blood pressure and ANP level were measured at baseline (before taking ARNI) and 3 weeks later. ARNI (200mg) was prescribed and maintained during the study. In addtion, the daily salt intake was calculated using creatinine and natrium levels in urine, age, and body weight according to Japanese hypertensive guideline at baseline and 3 weeks later. Results The average age was 70±8 years old. About 50% (N=23) was male. The mean sytolic and diastolic blood pressure was 148±14mmHg and 89±10mmHg, respectively. The mean daily salt intake was 9.5±2.2 g/day at baseline. The mean ANP level was 529±300pg/ml. At follow up (3 weeks later), the mean systolic and diastolic blood pressure significanly went down to 132± 18 mmHg and 70± 9 mmHg, respectively (p=0.03). ANP level also increased from 529±300pg/ml to 793±580pg/ml. However, the mean daily salt intake was almost same as the baseline at 9.4±3.2 g/day. The patients were divided into 2 groups; high daily salt intake (N=20 with mean daily salt intake 10.5±1.7g/day)) and low daily salt intake (N=24 with 8.4±3.1g/day) groups compared to the baseline. The absolute and percentage changes in systolic blood pressure were almost same in the high and low daily salt intake groups (-12.7±15.8mmHg vs -13.7±14.2mmHg, p=0.75; -5.8±6.5% vs.-7.0±9.6%, p=0.58, respectively). However, the change rate in ANP level was significantly higer in the high daily salt intake group than in the low daily salt intake group (155±63 vs. 12±16%, p=0.01). Conclusion ARNI demonstrates effectiveness in lowering the blood pressure even in patients with higher salt intake, unlike angiotensin receptor blocker. In cases with high salt intake, the notable increase in ANP levels may contribute to decreasing blood pressure through vasodilator and natriuretic action.

Intracoronary nicardipine to induce hypaeremia

Abstract Background Several pharmacological agents and routes of administration have been used to induce transient maximal hyperaemia, but most suffer from shortcomings that limit their clinical usage. Nicardipine, a dihydropyridine calcium channel blocker, has been proposed as a coronary hyperaemic agent with the advantage of not causing any adverse effects. Purpose We compared intracoronary (IC) nicardipine with IC papaverine for obtaining fractional flow reserve (FFR) and pullback pressure gradient (PPG). Methods and results This is a prospective, single-center study enrolling stable patients presenting with intermediate coronary artery disease (CAD) undergoing invasive functional assessment. The lowest FFR, duration of the hyperemic plateau, and PPG were assessed after IC nicardipine (400 µg to the left coronary or 300 µg to the right coronary artery) and IC papaverine (12 mg to the left coronary artery and 8 mg to the right coronary artery). Results Overall, 107 patients with 108 vessels (216 FFR and 216 PPG paired measurements) were analyzed. The correlation in FFR between nicardipine and papaverine was r = 0.95 (95% CI 0.92 to 0.96, p < 0.001) with a mean difference of 0.02 FFR units (limit of the agreement [LOA]: -0.04 to 0.08). Similarly, the correlation in PPG between nicardipine and papaverine was r = 0.86 (95% CI 0.71 to 0.93, p < 0.001) with a mean difference of 0.01 PPG units (limit of the agreement [LOA]: -0.14 to 0.17). The hyperaemic plateau was significantly longer with nicardipine (101.4 ± 62.1 s nicardipine vs 41.5 ± 14.3 s papaverine, p < 0.001). No significant differences were observed in the magnitude of changes in blood pressure and heart rate (p=NS). No complications occurred with the administration of IC nicardipine or papaverine. Conclusion FFR and PPG values obtained following nicardipine administration exhibited excellent agreement with those obtained using papaverine. Moreover, the hyperaemic response induced by nicardipine led to a significantly prolonged steady state in comparison to papaverine. Given its widespread availability, cost-effectiveness, safety profile and frequent utilization in clinical settings, nicardipine emerges as the optimal vasodilator for coronary physiology testing.FFR by Nicardipine vs PapaverinePPG by Nicardipine vs Papaverine

Platelet membrane coated r-SAK to improve thrombolytic efficacy by targeting thrombus

Abstract Background Thrombolytic therapy is one of the most effective treatments to achieve rapid thrombus clearance and recanalization of blocked vessels in thrombotic diseases. However, the application of thrombolytic strategy has been limited due to unsatisfied thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications.[1] With the development of nanotechnology and biotechnology, platelet membrane nanoparticles have been developed to enable the targeted delivery of thrombolytic agents to local thrombus sites.[2] Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology. In this study, platelet membrane coated r-SAK (PLT-r-SAK) was constructed, and its thrombolytic efficacy was evaluated in in-vitro and in-vivo experiments. Purpose We aimed to construct a thrombus-targeting agent of PLT-r-SAK and investigate its thrombolytic efficacy. Methods PLT-r-SAK was prepared by encapsulating r-SAK into platelet membrane vesicles using a membrane extrusion method. An in-vitro thrombolytic experiment was performed to examine the thrombolytic efficacy of PLT-r-SAK, and a totally occluded femoral artery thrombosis model of rabbit was developed to evaluate the in-vivo thrombolytic efficacy of PLT-r-SAK. The changes in femoral artery pressure were adopted to assess the vessel opening status. Besides, the effect of the antiplatelet drugs on the thrombolytic efficacy of PLT-r-SAK was explored. Finally, near-infrared fluorescence imaging system was used to verify the thrombus-targeting effect of PLT-r-SAK. Results PLT-r-SAK was firstly constructed, which exhibited a uniformly dispersed spherical morphology with a diameter of 185.8 ± 1.5 nm and a zeta potential of -26.1 ± 0.8 mV. In the in-vitro animal experiment, the thrombolysis rate of PLT-r-SAK was significantly higher than that of the same (low) dose and 4-fold (high) dose r-SAK (Figure 1a, 1b). In the in-vivo experiment, the initial recanalization time of PLT-r-SAK was significantly shorter than that of the low dose and high dose r-SAK, and the duration of the reperfusion time of PLT-r-SAK was prolonged compared to low dose and high dose r-SAK (Figure 1c). Another in-vitro experiment showed that the increased thrombolysis rate of PLT-r-SAK could be inhibited by platelet poor plasma (PPP) from aspirin- and ticagrelor-treated patients. Finally, both the in-vitro and in-vivo near-infrared fluorescence imaging showed significantly higher radiant efficiency in the PLT-r-SAK group as compared to the NS group (Figure 2). Conclusions Platelet membrane coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the platelet membrane and can be inhibited by aspirin- and ticagrelor-treated plasma.Thrombolytic efficacy of PLT-r-SAKThrombus-targeting evidence of PLT-r-SAK

Cardiac risk confrontation in primary care as a teachable moment towards improved health outcomes

Abstract Background Urgent life events, such as acute coronary events, can evoke a teachable moment (TM) for lifestyle change. This study aims to investigate whether less urgent events, such as being confronted with an increased risk of cardiovascular disease, can evoke a TM, what psychosocial factors are associated with it, and whether experiencing such a TM predicts improved health outcomes. Methods The study included 114 patients who were informed about their elevated cardiovascular risk during a primary care visit. Participants completed a survey assessing whether they experienced a TM and several psychosocial factors linked to experiencing it: perceived risk, affective impact, changed self-concept. Participants monitored their weight and blood pressure for six months using an at-home self-monitoring device. Univariate and multivariate regression analyses were conducted to examine the associations between the psychosocial factors and the lifestyle change intentions with changes in blood pressure and weight. Results Of the participants, 55.3% experienced increased lifestyle change intentions. Lower risk perception ((B = -0.27; CI = -0.39-(-0.15)) and higher change in self-concept (B = 0.34; CI = 0.23-0.44) were associated with higher intention to change lifestyle. Higher risk perception (B = 0.23; CI = 0.06-0.42) and higher change in self-concept (B = 0.54; CI = 0.37-0.72) predicted a lower weight reduction at six months. A higher change in self-concept predicted a higher blood pressure reduction (B = -3.32; CI = -6.55-(0.09)). Lastly, a higher lifestyle change intention predicted bigger reductions blood pressure (B = -5.04; CI = -9.08-(-0.29)). Conclusions Results suggest that less urgent cardiac events, such as a confrontation with an increased cardiac risk, can be experienced as a TM that urges lifestyle change intentions and affects health outcomes. Risk confrontations in primary care therefore offer a unique opportunity to provide lifestyle counseling at the right moment. Key messages • A confrontation with an increased cardiac risk in primary care can be experienced as a teachable moment. • Experiencing a teachable moment after a cardiac risk confrontation in primary care affects health outcomes.

Radiological indicators of chronicity in patients with acute symptomatic pulmonary embolism treated with ultrasound-assisted catheter-directed thrombolysis: a study of 180 consecutive cases

Abstract Background Radiological signs of chronic thrombi are present in up to 20% of patients that present acutely with pulmonary embolism (PE). Ultrasound-Assisted Catheter-Directed Thrombolysis (USAT) can swiftly reverse right ventricular dysfunction in patients with acute PE. Purpose To investigate the frequency of radiological signs of chronic PE and pre-existing chronic thromboembolic pulmonary hypertension in patients treated with USAT and their impact on early and long-term hemodynamic and clinical outcomes. Methods The index CT scans of patients receiving USAT for acute intermediate-high and high-risk PE at a tertiary academic institution (2017-2022) were adjudicated by three expert radiologists blinded for treatment scheme and outcomes. Changes in invasively-measured mean pulmonary artery pressure (mPAP) at 24 hours post USAT, presence of post-PE impairment (PPEI), and CTEPH diagnoses after at least 3 months were studied. A total of 15 radiological signs of chronicity were assessed, including 6 major criteria that have been previously validated to raise the suspicion of pre-existing CTEPH. In this study, acute-on-chronic PE was defined when at least 3 of the 6 validated radiological criteria for chronicity were present together with acute findings. Pre-existing CTEPH was defined based on the results of follow-up (vs. index) CT scan and on the anatomical consistency of pathology specimens after pulmonary endarterectomy. PPEI was defined by the presence of residual respiratory symptoms and right ventricular dysfunction during follow-up. Results Of 180 consecutive patients (median age 65 years, 61% men, 17% high-risk PE), 31 had at least 3 of 6 radiological criteria at the time of acute presentation; Table 1. The median modified Miller Score was 24 points and baseline mPAP was 35 mmHg in both groups. The absolute mPAP reduction after USAT was 11 (Q1-Q3: 5-17) mmHg in patients with <3 and 10 (Q1-Q3: 5, 17) mmHg in those with ≥3 criteria; Table 2. Three (1.7%) patients were diagnosed with CTEPH after a median of 3 months and underwent pulmonary endarterectomy: in all 3 patients, CTEPH was pre-existing. At least 3 of the 6 previously validated criteria were present in all CTEPH patients at index CT. In the 3 patients with acute PE on pre-existing CTEPH, the median baseline mPAP was much higher (median 53 mmHg) than in the remaining patient group and the absolute reduction after USAT was 9 mmHg, corresponding to a relative reduction of 19%. During follow-up, PPEI was more frequent in patients with <3 signs (n=4, 2.7%) than in those with ≥3 signs (n=4, 12.9%). Conclusion(s) The evaluation of six radiological parameters in initial CT scans successfully identified all cases of pre-existing CTEPH in patients presenting with acute PE. However, these parameters did not prove effective in determining which patients would benefit from USAT in terms of mPAP reduction.Baseline characteristicsHemodynamic and clinical outcomes

Effects of multilevel OSA surgery on patients with poor cardiopulmonary performance: A prospective pilot study

ObjectiveMultilevel airway surgery for obstructive sleep apnea/hypopnea syndrome (OSA) has benefits in improving sleep quality, but its effect on polysomnography (PSG) and 6-minute walk test (6MWT) parameters, including walking distance and cardiopulmonary performance, in patients with poor pre-operative cardiopulmonary performance remains understudied, which should be further investigated. MethodsThis prospective pilot study enrolled 27 consecutive OSA patients with poor pre-operative 6MWT results. All patients received multilevel OSA surgery, and the alterations of sleep parameters and 6MWT profiles were studied. The pre- and post-operative values of polysomnographic data and 6MWT profiles were analyzed using the Wilcoxon signed-rank tests. The relationships among changes of the indices of PSG and 6MWT were further investigated with the Spearman's correlations. ResultsAfter surgery, the sleep parameters and certain cardiopulmonary indices improved. When analyzing the correlations among changes of the indices of PSG and 6MWT, the improvement of daytime sleepiness (with ESS) was found related to farther walking distance (ρ=-0.414, p = 0.032) and higher percentage of “distance/target distance” (ρ=-0.435, p = 0.023). Moreover, the change of maximal expiratory pressure was the only index associated with the changes of AHI (apnea/hypopnea index, /hr.; ρ=-0.407, p = 0.035) and AHI in REM (ρ=-0.502, p = 0.009) among the cardiopulmonary performance parameters. ConclusionThis pilot study showed that OSA patients with poor pre-operative cardiopulmonary status undergoing multilevel sleep surgery could experience improvement in the sleep study and 6MWT to some extent. The relatively better walking distance and cardiopulmonary performance after the operation might potentially result from the improvement of daytime sleepiness and better respiration.

The TMEM63B Channel Facilitates Intestinal Motility and Enhances Proliferation of Intestinal Stem Cells.

The intestines are in a constant state of motion and self-renewal. The mechanical breakdown of food facilitates intestinal movement and aids digestion. It is believed that mechanical stimulation, triggered by changes in osmotic pressure within the intestines, plays a crucial role in regulating gastrointestinal motility. While TRPs and PIEZO1/2 have been identified as mechanosensitive ion channels involved in this process, there still exist numerous unidentified channels with similar properties. In this study, we demonstrate that the TMEM63B expressed in intestinal stem cells contributes to the regulation of intestinal motility and digestion. The deletion of TMEM63B in intestinal stem cells not only decelerates intestinal motility and impairs digestion but also attenuates the proliferation of intestinal stem cells and exacerbates DSS-induced colitis in mice. Collectively, our findings unveil the pivotal role of TMEM63B in governing optimal digestive function and modulating intestinal motility.

Incident HFpEF and time-dependent changes in markers of LVDD severity in women and men with pre-clinical LVDD

Abstract Background Over time, left ventricular diastolic dysfunction (LVDD) can progress towards heart failure with preserved ejection fraction (HFpEF). Yet, the identification of those at high risk of progression is challenging, and guidance on follow-up or preventive treatment is lacking. Purpose To study the incidence of HFpEF and changes over time in markers of LVDD severity in women and men with pre-clinical LVDD. In addition, we evaluate whether blood pressure and kidney function affect progression of LVDD. Methods We reinvited 146 participants from the HELPFul study (58% women and 42% men) with pre-clinical LVDD after a median follow-up of 4.3 [IQR: 3.9-4.7] years (Figure 1). The follow-up measurements were similar to baseline and encompassed a structured interview, physical examination, blood draw, electrocardiogram and (exercise) echocardiography. We determined HFpEF incidence and report changes over time in cardiovascular risk factors as well as echocardiographic characteristics and biomarkers of LVDD. Additionally, we studied whether changes in blood pressure and kidney function affected LVDD progression using generalized mixed models. LVDD progression was defined as an increase in plasma NT-proBNP levels and HFA-PEFF major functional and morphological abnormalities. All analyses were performed for women and men combined as well as stratified by sex. Results Fifteen (10%) of the 146 participants developed HF of whom 13 had HFpEF (9 women and 4 men) during follow-up. Over time, systolic and diastolic blood pressure levels remained stable while mean kidney function (eGFR) declined from 89±14 to 81±17 mL/min/1.73m2. Median NT-proBNP plasma levels increased from 71 [IQR: 44, 120] to 100 [IQR: 51, 157] pg/mL. The prevalence of major functional abnormalities according to the HFA-PEFF score increased from 84 to 91%, while the prevalence of morphological abnormalities increased from 25% to 39% (Figure 2). A higher systolic blood pressure in women and a higher diastolic blood pressure in men was associated with an increase in NT-proBNP plasma levels over time. Additionally, lower eGFR levels were related to increased NT-proBNP plasma levels over time in both men and women. There was a significant rise in the prevalence of major functional and morphological abnormalities with time, but blood pressure and kidney function did not affect this change over time. Conclusions A small proportion of women and men with preclinical LVDD developed incident HF over a 5-year follow-up period. High blood pressure and reduced kidney function were associated with increased levels of NT-proBNP over time. This highlights the need to further explore cardiorenal protection as a method to prevent HFpEF.Study design and HF outcomesLongitudinal changes in LVDD markers

10 years after treatment with renal denervation of the sympathetic nerves for resistant hypertension: what happened to the patients and their office blood pressure? An observational study

Abstract Background Catheter-based renal denervation of the sympathetic nerves (RDN) for resistant hypertension has long been controversial. A renewed clinical and scientific interest in defining the appropriate role of RDN in the treatment of resistant hypertension has become evident in recent years. The efficacy and safety of RDN treatment is mainly based on available data up to three years, whereas data concerning the long-term effect and safety are scarce. Purpose We therefore wanted to investigate the long time change in blood pressure (BP) in patients treated with RDN for resistant hypertension. Methods A review of data from the electronic patient journal concerning all RDN treated patients was initiated and completed in October 2023. Every registration of an office BP listed in the patient file, antihypertensive treatment, cardiovascular events, and renal function between 2012 and 2023 were registered. For each patient the average of all office post RDN blood were averaged for every year and for their complete follow-up. The outcome in blood pressure was the change in BP from baseline pre RDN office to follow-up Results Between January 2012 and October 2013, 19 consecutive patients underwent RDN treatment, 10 men and 9 women with a median age of 63 years (range 35-74 years). At baseline the median systolic office BP was 181 mmHg (range 162–230 mmHg) and the diastolic office BP 97 mmHg (range 82-123 mmHg) on a median of 5 (range 0-7 ) antihypertensive drugs. During follow-up the number of antihypertensive drugs were reduced in 7, unchanged in 10, and increased in 2 patients. Two patients left the outpatient clinic with normal BP after 2 years. Two patients developed heart failure after 7 years and were censored at that time-point. 15 (79%) patients had office BP recorded up to 9 or 10 years. In the 15 (79%) patients with available office BP 9 to 10 years after RDN the median systolic and diastolic office BPs were reduced by 39 mmHg (range -2 to - 66 mmHg) and 18 mmHg (range -11 to - 55 mmHg) respectively, relative reduction 22% (range 5-36%) and 20% (range 6-32), respectively. Conclusion During a follow-up of 9 to 10 years after RDN without a step-up in antihypertensive medication a relative decrease of ~20% in systolic and diastolic BP was observed.

Safety and feasibility of drug eluting and perfusion therapy for left main disease: JDEPTH-LM pilot study

Abstract Background Reducing cardiovascular events arising from ostial lesions of the left circumflex artery (LCx) remains an issue following percutaneous coronary intervention (PCI) for left main disease (LMD). Despite expert consensus recommendation for the drug coated balloon (DCB) use to address it, there are concerns in using DCB following the standard practice of crossover-stenting from the left main trunk (LMT) to left anterior descending artery (LAD). Specifically, utilizing a DCB in isolation for the ostial LCx after stenting may result in additional carina shift. The combination of a conventional balloon for LMT-LAD and a DCB for LMT-LCx in KBT could potentially cause hemodynamical instability due to prolonged occlusion time for the entire left coronary artery system. Accordingly, we hypothesized the combined usage of DCB and perfusion balloon (PB) could provide a safe and effective approach for drug-eluting therapy in ostial LCx lesion. This approach aims to facilitate prolonged inflation while maintaining coronary blood flow during KBT for LMD. Purpose The aim of this study was to assess the safety and feasibility of prolonged KBT with DCB and PB for LMD. Methods In this single-center prospective observational study, we enrolled patients of de-novo LMD with ostial LCx lesion, requiring crossover stenting for the LMT-LAD followed by conventional KBT (C-KBT). IVUS-guided procedure was mandated as per the study protocol. Following confirming the achievement of optimal left main PCI by IVUS, a double-effect KBT (W-KBT) was employed. This technique involved the use of a PB for the LMT-LAD and a DCB for the LMT-LCx, sized in a 1:1 ratio to the balloons used in C-KBT. Patients in cardiogenic shock, those requiring a two-stent technique for LMD, and individuals without achievement of TIMI3 flow in the LCx after C-KBT were excluded. The primary endpoint was procedural success, defined as device delivery and balloon inflation time ≥30 sec. Secondary endpoints included the total balloon inflation time (W-KBT time), the incidence of ST-change cases, time to ST-change (ST-change time), changes in blood pressure and heart rate (delta BP and delta HR, respectively), and the frequency of inotrope usage following W-KBT. Results Between January 2023 and December 2023, 12 patients were included among 73 patients with LMD who underwent PCI during this study period. Mean age was 73.8±7.2 years (91.7% men) and median SYNTAX score was 29 (IQR: 26.3 to 34.5). The incidence of ACS was 8.3%. Procedural success was achieved in 100% of cases. The results of secondary endpoints were as follows: median W-KBT time: 60 sec (IQR: 60 to 60); the incidence of ST-change: 50% (no cases with ST-elevation); mean ST-change time: 41.2±7.1 sec; mean delta BP: -13.7±11.4 mmHg; mean delta HR: -3.4±5.9 bpm; and the use of inotrope: 0%. Conclusion Within the limited sample size of this pilot study, the safety and feasibility of the "first-in-man" technique of W-KBT were confirmed.Procedure of W-KBTStrength of W-KBT

Effects of Abelmoschus manihot (L.) and its combination with irbesartan in the treatment of diabetic nephropathy via the gut-kidney axis.

Clinical observations have recently shown that Abelmoschus manihot (L.) in the form of Huangkui capsule (HKC) and in combination with irbesartan (EB) is an effective therapy for diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). The present study aims to explore the mechanisms underlying the therapeutic efficacies of HKC and its combination with EB in DN via the gut-kidney axis. HKC, EB, and their combination or vehicle were administered in db/db mice, which is an animal model for the study of T2D and DN. Comparative analyses of the gut microbiota, serum metabolites, and kidney transcriptomics before and after drug administration were performed. After treatment with HKC, EB, and their combination for 4 weeks, the urinary albumin-to-creatinine ratios decreased significantly in the db/db mice with DN. In terms of the gut microbiota, the abundances of Faecalitalea, Blautia, and Streptococcus increased but those of Bacteroidetes, Firmicutes, Enterobacteriaceae, and Desulfovibrio decreased. Parallelly, serum metabolites, mainly including quercetin 3'-glucuronide and L-dopa, were elevated while cortisol and cytochalasin B were reduced. Furthermore, the S100a8, S100a9, Trem1, and Mmp7 genes in the kidneys were downregulated. These altered elements were associated with proteinuria/albuminuria reduction. However, EB had no effects on the changes in blood pressure and specific differentially expressed genes in the kidneys. The present study provides experimental evidence that HKC regulates the gut microbiota, circulating metabolites, and renal gene activities, which are useful for better understanding of the action mechanisms of A. manihot in the treatment of DN through the gut-kidney axis.

Regional variation of age-related blood pressure trajectories and their association with blood pressure control rates, disability-adjusted life years and death

Abstract Background/Introduction While the relationship between blood pressure (BP) changes and increasing age is well described, age-related BP trajectories may vary substantially across different populations and associated with differential CV risk and outcomes. Purpose The dataset of the May Measurement Month (MMM) international campaigns enables a unique investigation of regional, socio-economic and sex differences in age-BP trajectories and their association with major public-health outcomes. Method Global BP data from more than 4,5 million adult (≥18 years) screenees obtained during the cross-sectional MMM campaigns in 2017, 2018, 2019, and 2021 were used for analysis. Average BP and slopes of BP changes across age groups were calculated within regional, socio-economic and sex strata. BP slopes of individuals between 30 and 70 years of age were derived from adjusted linear regression models, along with baseline BP estimates at young age. These BP slopes were correlated in regression models adjusted for baseline BP at young age with country-specific all-cause rates of DALYs (Disability-Adjusted Life Years), death (both from Global Burden of Disease Study 2019), life expectancy (World Bank data SP.DYN.LE00.IN 2019) and BP control rates (NCD Risk Factor Collaboration). Results Age-related BP changes differed distinctly across global geographic regions, income levels, and between sexes. The steepest increase in BP with age was observed in populations from Africa and Europe, whereas a more gradual rise in BP with increasing age was seen in South-East Asian populations. Women had lower BP levels than men at younger ages (twenties and thirties), but subsequently experienced a more pronounced age-related BP increase resulting in diminishing sex differences across older age groups. Geographically divergent age-related BP trajectories were significantly associated with major national public health indicators. Globally, the steeper the age-related BP slope, the stronger the association with poor BP control (β = -0.46 [95% CI: -0.74; -0.19], p=0.001), increased DALY’s (β = 66155.68 [95% CI: 44847.0; 87464.36], p<0.001) and death rates. (β = 1017.3 [95% CI: 351.72; 1682.89], p=0.003). Conclusion Age-related BP trajectories vary considerably across global populations and contribute considerably to the variability in BP-related risks and adverse outcomes across regions. Effective public health strategies may require region-specific targeting of lifestyle and other factors contributing to adverse BP trajectories to improve health outcomes.Average blood pressure by ageAssiciations with public health metrics

Blood pressure and renal function changes in patients with severe chronic kidney disease undergoing radiofrequency renal denervation: 12 months outcomes from the Global SYMPLICITY Registry DEFINE

Abstract Background Radiofrequency renal denervation (RF RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension (HTN). The impact of renal function on safety and efficacy of RDN is unknown. Purpose To assess BP and renal function in patients with HTN following RDN. Methods All patients treated with RF RDN (n=3332) from the observational Global SYMPLICITY Registry Denervation Findings in Real World (GSR DEFINE) were included. Patients were categorized into CKD stages by the corresponding estimated glomerular filtration rate (eGFR; mL/min/1.73m2): <45 (CKD stage 3b and higher; n=339), 45-59 (CKD stage 3a; n=467), ≥60 (CKD stage 2 and lower; n=2334). BP (office, 24h ambulatory BP), eGFR changes from baseline through 12 months were compared between groups. Comparisons between groups were made after adjusting for baseline BP and change in number of antihypertensive drug classes from baseline. Results At baseline, office systolic SBP (OSBP) in eGFR groups <45, 45-59, and ≥60 ml/min/1.73 m2 was: 164±25, 163±26 and 165±25 mmHg, respectively (p=0.083). 24-h ambulatory systolic BP (ASBP) was: 156±19, 153±20 and 154±19 mmHg, respectively (p=0.082). Mean eGFR was: 32.5±11.2, 53.6±4.4, and 86.8±18.6 ml/min/1.73 m2, respectively. A total of 1.1% of patients were on dialysis. Patients in eGFR group <45 ml/min/1.73 m2 were significantly older, had higher rates of ischemic heart disease, heart failure, diabetes, on more antihypertensive drug classes compared to higher eGFR groups. Patients were on 5.0±1.3, 4.6±1.3, and 4.5±1.4 antihypertensive drugs in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (p<0.001). At 12 months, all had significant OSBP drop from baseline within the different eGFR groups (p<0.001). OSBP changed by -10.8±27.8, -10.5±25.9 and -14.7±26.6 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (adjusted p=0.095; Figure 1A). Similarly at 12 months, all patients had significant ASBP reductions from baseline across the eGFR groups (p<0.01). ASBP changed by -5.2±18.0, -6.9±18.8, and -8.5±18.8 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 subgroups, respectively (adjusted p=0.16). At 12 months, eGFR did not significantly change from baseline in eGFR <45 and 45-59 ml/min/1.73 m2 groups (Figure 1B): 0.1±14.6 (p=0.92) and -0.6±12.8 ml/min/1.73 m2 (p=0.45), respectively. Estimated GFR changed from baseline by -5.6±15.5 ml/min/1.73 m2 in eGFR ≥60 ml/min/1.73 m2 group (p<0.001). Between group differences in eGFR changes were statistically significant (adjusted p<0.001), but by a numerically small difference. The no. of antihypertensive drug classes changed by -0.2±1.3, -0.1±1.0 and -0.1±1.0 in eGFR <45 and 45-59 ml/min/1.73 m2 groups, respectively. Conclusion Patients with uncontrolled HTN with different CKD severity including those with eGFR <45 ml/min/1.73 m2 had significant SBP reductions from baseline through 12 months, whilst renal function was preserved.Figure 1

Cumulative effect of lifetime smoking history on arterial stiffness and subclinical atherosclerosis in patients with arterial hypertension

Abstract Introduction Although the effect of smoking status on blood pressure (BP) changes is well known an adverse association between cumulative smoke exposure (by pack-years) and functional and structural changes in arteries of patients with high BP has not been consistently demonstrated. Aim of the study was to explore the contributions of cumulative smoke exposure to the vascular consequences of arterial hypertension. Methods Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV), augmentation index (AIx) and carotid intima media thickness (cIMT) were measured in 485 adults aged less than 60 years old without a history of cardiovascular disease. The cohort was divided into three groups according to office systolic BP (SBP) and diastolic BP (DBP): normal (SBP <130 and DBP <85 mmHg, n=242), high normal (130≤SBP<140 or DBP 85≤DBP<90mmHg, n=96), and hypertension (SBP≥140 or DBP≥90mmHg, n=147). The cohort was subdivided according to pack-years of smoking history as never smokers (0.0 pack-years), light smokers (<20 pack-years), moderate smokers (20-40 pack-years), and heavy smokers (> 40 pack-years). Results The three BP groups had similar age and metabolic parameters (body mass index, fasting blood glucose and LDL-C). Figure shows PWV, AIx and carotid IMT by smoking exposure, stratified by BP level. The lowest PWV level was observed in never smokers with normal BP; whereas heavy smokers with hypertension exhibited the highest PWV. Also of note, heavy smokers with normal BP exhibited comparable PWV to light and never smokers with hypertension. Furthermore, in smokers with more than 20 pack-years tobacco exposure, PWV was higher among patients with high normal BP compared to subjects with normal BP (all P<0.01). In contrast to the monotonic increases in PWV and AIx by BP and pack-years smoking history, carotid IMT was generally similar among BP groups on the basis of cumulative exposure category. This finding may indicate a plateau in subclinical atherosclerotic burden over cumulative tobacco exposure for all BP categories. Conclusion Tobacco cumulative exposure adversely modify the effect of BP on arterial stiffness. Given that most adults who smoke start before the age 18 years, efforts to promote smoking cessation should continue to target younger adults with high BP.BP, tobacco exposure-vascular changes