Blood Pressure Response Research Articles

Assessing Blood Pressure, Mental Health, and HRV Responses to Integrated Acupuncture in Hypertensive Patients: A Pilot Randomized Controlled Trial

Assessing Blood Pressure, Mental Health, and HRV Responses to Integrated Acupuncture in Hypertensive Patients: A Pilot Randomized Controlled Trial

Novel approaches to define responders to interventional treatment in hypertension: insights from the SPYRAL HTN-OFF and HTN-ON MED trials.

Multiple sham-controlled clinical trials have demonstrated significant reductions in both office and 24-h blood pressure (BP) following radiofrequency renal denervation (RDN) in the uncontrolled hypertension population. Notably, the blood pressure response varies widely within individual participants, thus showing a clinical need to identify potential RDN "responders" prior to the procedure. Despite multiple analytic efforts, no single parameter, aside from baseline blood pressure, has been consistently associated with BP reduction following RDN. However, this failure may be due to limitations in empiric definitions of responders. Indeed, commonly applied responder definitions based on the difference between two point-in-time BP measurements are fraught due to visit-to-visit variability in office and 24-h blood pressure endpoints. Several factors should be considered to develop a more clinically useful operational definition of procedural response including relative changes in office and 24-h BP, consideration of the temporal response to RDN, as well as adjustment for baseline BP. The current evidence may provide incentives for future expert consensus to precisely define responders to hypertension treatments.

Abstract 4122543: Can We Diagnose Ticagrelor-induced Dyspnea After Urgent Percutaneous Coronary Intervention with Cardiopulmonary Exercise Testing?

Background: Ticagrelor has been reported to cause shortness of breath (SOB) in 6 to 9 % of patients. Precise mechanisms are not enirely understood. We hypothesize that cardiopulmonary exercise testing (CPET) may be helpful in clinical assessment of patients reporting SOB on ticagrelor. Case presentation: 66-yo female with history of arterial hypertension, DM type 2 and prior MI presented with STEMI and successfully underwent urgent PCI of RCA and LAD. The patient received ticagrelor in loading dose followed by 90 mg b.i.d plus low-dose aspirin. Just after PCI she developed SOB with no evidence of acute cardiac or respiratory compromise. After discharge the patient continued to experience SOB impairing daily activities. In 6 months she was re-assessed. Clinical investigation (physical exam, blood tests, echo, CXR, spirometry) showed no abnormalities that could explain SOB. CPET despite good effort showed low VO 2 peak (7,8 ml*min/kg; 49% from predicted), undetectable anaerobic threshold (AT), severely impaired ventilatory efficacy (VE/VCO 2 =50,1) and marked hyperventilation (resting RER=1,0; PetCO 2 =18,0 mmHg at rest and 22,4 mmHg at peak load). Exercise EKG, blood pressure response, SpO 2 and breathing reserve were normal. Once the patient was switched from ticagrelor to clopidogrel she reported significant improvement. CPET one week after showed increase in VO 2 peak up to 12,5 ml/kg/min., AT of 11,1 ml*min/kg, better ventilatory efficacy (VE/VCO 2 =37,1) and less hyperventilation (PetCO 2 28,1 mmHg at rest and 28,8 mmHg at peak load). CPET performed one month later showed further improvement in VO 2 peak to 13,2 ml*min/kg, normal VE/VCO 2 and no signs of hyperventilation. Discussion: it is believed that ticagrelor-induced dyspnea can be driven by 2 potential mechanisms, first related to inhibition of adenosine reuptake, second - to sensory neuron P2Y12 inhibition. It occurs early after starting the medication and is not associated with structural cardiopulmonary abnormalities. Previous small data showed evidence of Cheyne-Stokes respiration during both night and day related to ticagrelor. Symptoms usually are dose-dependent and disappear after discontinuation of ticagrelor. In our case the patient demonstrated reversible hyperventilation and reduced exercise capacity associated with ticagrelor that was confirmed with CPET. Conclusion: CPET allows differentiating SOB in patients treated with ticagrelor. Further investigations are required to confirm this hypothesis.

Abstract 4134685: Cardiopulmonary Exercise Testing for Characterization and Prognostication in Hypertrophic Cardiomyopathy: A Meta-Analysis

Background: Hypertrophic cardiomyopathy (HCM) carries substantial risk of adverse cardiac events. Consequently, detailed physiologic assessment and accurate risk stratification in HCM are of high clinical importance. Aim: To synthesize current evidence on the utility of cardiopulmonary exercise testing (CPET) for characterization and prognostication of HCM. Methods: PubMed, Embase, Scopus, and Web of Science were systematically searched for eligible studies from database inception to November 2023. Studies that had at least one CPET performed in HCM patients, with corresponding test data reported, were included. Abstracts with no full-text and studies focused on pediatric populations were excluded. The primary outcome was a composite endpoint of cardiovascular adverse events. Hazard ratios (HR) and 95% confidence interval (CI) from Cox proportional hazard model were meta-analyzed. This study was performed following the PRISMA guidelines and registered under PROSPERO (CRD42023487759). Results: Sixty full-length manuscripts focused on CPETs performed in HCM patients were included, comprising 12,914 patients. Despite male predominance (66%) and average age of 48 years, peak VO 2 was only 6.2 [95% CI, 6.0-6.4] metabolic equivalents (21.8 [20.9-22.6] mL/kg/min), consistent with significant functional limitation. In subanalyses, peak VO 2 was 18.9 [18.0-19.9] mL/kg/min in obstructive HCM and 22.5 [20.8-24.2] mL/kg/min in non-obstructive HCM. Compared to commonly used metrics such as NYHA Class, CPET markedly enhances sensitivity to detect impaired cardiac performance ( Figure ). This meta-analysis highlights several easily-derived CPET variables that consistently predict HCM prognosis. An increase of 1 mL/kg/min in peak VO 2 was associated with a lower HR of 0.83 [0.76-0.90] for adverse cardiac events, while a 1 unit increase in the VE/VCO 2 slope was associated with a higher HR of 1.12 [1.03-1.23]. Abnormal blood pressure response to exercise conferred a 2.5-fold [2.0-3.1] increase in adverse events. Conclusion: CPET is a valuable objective method for multi-dimensional physiologic assessment and prognostication in HCM. With further standardization, CPET is well suited for more widespread clinical utilization in HCM patients.

Low-dose sufentanil does not affect tolerance to LBNP-induced central hypovolemia or blood pressure responses during a cold pressor test.

Hemorrhage is a leading cause of death in the prehospital setting. Since trauma-induced pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic regulation of arterial blood pressure and vital organ perfusion. The purpose of this study was to test two unrelated hypotheses: 1) sublingual sufentanil (Dsuvia) impairs tolerance to progressive central hypovolemia and 2) sublingual sufentanil attenuates pain sensation and the accompanying cardiovascular responses to a noxious stimulus. Twenty-nine adults participated in this double-blinded, randomized, crossover, placebo-controlled trial. After sublingual administration of sufentanil (30 μg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) challenge to tolerance (aim 1). After a recovery period, participants completed a cold pressor test (CPT; aim 2). Addressing the first aim, tolerance to LBNP was not different between trials (P = 0.495). Decreases in systolic blood pressure from baseline to the end of LBNP also did not differ between trials (time P < 0.001, trial P = 0.477, interaction P = 0.587). Finally, increases in heart rate from baseline to the end of LBNP did not differ between trials (time P < 0.001, trial P = 0.626, interaction P = 0.424). Addressing the second aim, sufentanil attenuated perceived pain (P < 0.001) in response to the CPT, though the magnitude of the change in mean blood pressure during the CPT (P = 0.078) was not different between trials. These data demonstrate that sublingual sufentanil does not impair tolerance to progressive central hypovolemia. Additionally, sublingual sufentanil attenuates perceived pain, but not the accompanying mean blood pressure responses to the CPT.NEW & NOTEWORTHY Addressing two unique aims, we observed that sublingual sufentanil administration does not impair tolerance or cardiovascular responses to lower-body negative pressure (LBNP)-induced progressive central hypovolemia. Second, despite pain perception being reduced, sublingual sufentanil did not attenuate mean blood pressure responses to a cold pressor test (CPT).

Unraveling autonomic cardiovascular control complexity during orthostatic stress: Insights from a mathematical model

Understanding cardiovascular control mediated by the autonomic system remains challenging due to its inherent complexity. Consequently, syndromes such as orthostatic intolerance continue to evoke debates regarding the underlying pathophysiological mechanisms. This study develops a comprehensive mathematical model simulating the control of the sympathetic branch of the cardiovascular system in individuals with normal and abnormal responses to the head-up-tilt test. We recruited four young women: one control, one with vasovagal syncope, one with orthostatic hypertension, and one with orthostatic hypotension, exposing them to an orthostatic head-up tilt test (HUTT) employing non-invasive methods to measure electrocardiography and continuous blood pressure.Our work encompasses a compartmental model formulated using a system of ordinary differential equations. Using heart rate as input, we predict blood pressure, flow, and volume in compartments representing the veins, arteries, heart, and the sympathetic branch of the baroreflex control system. The latter is modulated by high- and low-pressure baroreceptor afferents activated by changes in blood pressure induced by the HUTT. Sensitivity analysis, parameter subset selection, and optimization are employed to estimate patient-specific parameters associated with autonomic performance. The model has seven sensitive and identifiable parameters with significant physiological relevance that can serve as biomarkers for patient classification.Results show that the model can reproduce a spectrum of blood pressure responses successfully, fitting the trajectory displayed by the experimental data. The controller exhibits behavior that emulates the operation of the sympathetic system. These encouraging findings underscore the potential of computational methods in evaluating pathologies associated with autonomic nervous system control, warranting further exploration and novel approaches.

Predicting blood pressure response to renal denervation based on a new approach.

Identifying predictors of blood pressure (BP) response to renal denervation (RDN) is crucial for patient selection. According to Wilder's principle, baseline BP predicts BP change after any antihypertensive intervention. Thus, any observed BP change after RDN is the sum of the BP change depending on the baseline BP and the specific BP reduction due to RDN. Based on this concept, we propose a new definition of BP responders. In our center, 148 patients with uncontrolled hypertension underwent RDN, and 24-h ambulatory BP (ABP) was measured at baseline, and 6 months after the procedure. The decrease in 24-h systolic BP (SBP) correlated with baseline SBP (P = <0.001, r = -0.374). We determined the RDN-specific effect by subtracting the predicted SBP decrease from the observed SBP decrease. The cohort was divided into RDN responders, neutral responders, and nonresponders. Our study population had a mean age of 59 ± 10.4 years and was 74% male. The RDN-specific (residual) 24-h ABP decreased by -14.9 ± 6.3/-8.2 ± 3.8 mmHg (responder group), 1.0 ± 3.2/0.2 ± 1.9 mmHg (neutral group), and 14.2 ± 10.4/8.3 ± 3.9 mmHg (nonresponder group) 6 months after RDN. Responders had fewer antihypertensive medications (P = 0.018), higher baseline office heart rate (HR) (P = 0.019), higher 24-h ambulatory HR (P = 0.003), lower BMI (P < 0.038), and absence of type 2 diabetes (T2D) (P = 0.020). Our definition of BP responders to RDN separates baseline BP-related changes from RDN-specific changes. Positive predictors for BP response to RDN include low BMI, fewer antihypertensive medications, high baseline office HR, high 24-h ambulatory HR, and absence of T2D.

Changes in motor unit firing pattern are associated with post-exercise blood pressure response in older untreated but not treated hypertensive adults.

This study aimed to determine the difference in motor unit (MU) firing pattern between hypertensive and normotensive individuals, and the relationship between MU firing pattern and post-exercise blood pressure (BP) response in older individuals. Fourteen older untreated (systolic/diastolic BP (SBP/DBP)≥130/80mmHg, 76 (5) years), 11 treated hypertensive (78 (4) years) and 14 normotensive (SBP/DBP<130/80mmHg, 71 (4) years) individuals were studied. Participants performed ramp-up exercises until 50% of maximal voluntary contraction (MVC) of knee extension and five MVCs. During the ramp-up exercise, high-density surface electromyography signals were recorded and each MU firing rate (FR) and recruitment threshold was assessed. The slope of the linear regression between MUFRs and recruitment thresholds was calculated to assess the MU firing pattern. Pre- and post-exercise blood pressure was measured. Change in (∆)SBP from pre- to post-exercise was greater in treated hypertensive than untreated hypertensive individuals (P=0.026). MUFR was lower in treated hypertensive than untreated hypertensive and normotensive individuals (P<0.001). Although the slope was not significantly different between groups (P=0.294), FRs of larger MUs were lower than those of smaller MUs in treated hypertensive and normotensive individuals (P<0.05) but sustained in untreated hypertensive individuals. The FRs of larger MUs and slope were positively correlated with the ∆SBP only in hypertensive individuals (r=0.768 and 0.715; P=0.044 and 0.020). MUFR was lower in treated hypertensive than untreated hypertensive and normotensive individuals. Furthermore, MU firing patterns were associated with the ∆SBP after exercise in older untreated hypertensive individuals, but this relationship was not observed in treated hypertensive and normotensive individuals.

Raised blood pressure affects reactivity to expressive music features

Abstract Background Music has been shown to lower hypertensive patients’ blood pressure in the long-term, but predominant approaches overlook the wide range of complex real-time responses. Mapping the acute dynamics of music features can help discern blood pressure (BP) reactivity. Understanding the mechanisms of music BP effects can broaden the scope for precision medicine. Purpose The aims of this study are to determine: (1) if reshaped music features alter BP reactivity; and, (2) whether BP reactivity differs for individuals with high and normal BP. Methods Participants listened to music with computationally altered tempo and loudness played back on a Disklavier piano. We compared continuous BP measurements in 40 participants (23 females, mean age of 41.3 y (95%CI: 37.2-45.4)), 20 with baseline BP measurement above 140/90 mmHg (H-bBP) and 20 with bBP below (N-bBP), paired by playlist. Continuous BP was recorded while listening to a playlist of 9 reshaped versions of 8 distinct pieces (≈40 min) after a 5-minute baseline silence. Results The mean increase in systolic and diastolic BP during music (reactivity) was significantly higher for N-bBP than H-bBP (mean (95%CI); mmHg): systolic 8.6 (6.2-11.1) vs 5.0 (2.7-7.3); p=0.031; diastolic 7.7 (5.9-9.5) vs 4.6 (2.9-6.3); p=0.0046. No significant difference in pulse pressure (PP) reactivity was found; however, the N-bBP subjects had significantly lower mean PP during music than H-bBP subjects (45.2 (40.2-44.8) vs 54.2 (51.7-56.7) ; p&amp;lt;0.001). Based on mean tempos, N-bBP subjects had significantly lower average PP than H-bBP subjects during slow (&amp;lt;60bpm; 44.6 (40.6-48.6) vs 52.6 (48.9-56.3); p=0.016) and fast (&amp;gt;120bpm; 43.9 (39.9-47.9) vs 57.2 (52.9-61.5); p&amp;lt;0.001) music, though not medium pace music. Similarly, N-bBP participants had significantly lower PP during quiet (&amp;lt;13 dB; 44.0 (39.6-48.4) vs 55.7 (50.7-60.7); p&amp;lt;0.001) and loud (&amp;gt;17 dB; 44.0 (39.6-48.4) vs 55.5 (51.1-59.9); p&amp;lt;0.001) music, but not during moderately loud music. H-bBP and N-bBP participants’ PP measures are more similar during moderately fast and moderately loud music. In addition, N-bBP’s baseline-normalised mean PP was significantly lower only during fast music (3.3 (-2.3-8.6) vs 12.9 (6.9-18.9); p = 0.04). Separating responses to unaltered vs reshaped music––i.e. music made faster and/or louder, in the case of one piece, slower and/or quieter––significant differences are found between N-bBP and H-bBP groups only for reshaped music in baseline-normalised diastolic BP (6.8 (4.7-8.9) vs 3.9 (2.1-5.7); p=0.02) and PP (45.0 (42.2-47.8) vs 54.8 (51.8-57.8); p&amp;lt;0.001). Conclusions H-bBP subjects had less BP reactivity to music, especially in resting vascular tone PP. Reshaping of music can modulate the level of differences between groups, particularly for immoderate tempo and loudness. Music can induce significant changes in BP profile, which indicates that it could potentially be utilised as a tailored anti-hypertensive therapy.Differences between music and baselineDifferences in tempos and loudness cat.

Blood pressure response to exercise in endurance athletes with and without paroxysmal atrial fibrillation.

Abstract Background Atrial fibrillation (AF) is more prevalent among endurance-trained athletes when compared to non-athletes. The underlying pathophysiology and mechanisms for this phenomenon remain unknown but repeated exposure to an exaggerated blood pressure (BP) response during exercise may contribute to the development of AF in this population. Purpose We aimed to assess whether endurance athletes with AF have a higher maximal systolic BP (SBP) or a higher BP relative to exercise intensity compared to endurance athletes without AF. Methods Endurance athletes with paroxysmal AF (n=66, 96% male) from the ProAFHeart, NEXAF Detraining and Master@Heart studies were matched for age and sex to endurance athletes without AF (n=66, 96% male). Participants with a history of hypertension were excluded. All athletes underwent a maximal graded cardiopulmonary exercise test on a cycle ergometer to assess exercise BP using an automated auscultatory BP machine, maximal oxygen uptake (VO2peak) and peak workload. All athletes were in sinus rhythm at the time of testing and BP was measured pre-exercise seated on the bike and every 2 min throughout the test. Exercise BP measurements included the maximum exercise SBP (SBPmax) and the slopes of the relationships between SBP, diastolic BP (DBP) and workload (W) as determined from linear regression analysis (SBP/W-slope and DBP/W-slope, respectively). The resting SBP and DBP were measured in the supine position after 10min of rest. Independent T-test (parametric data) or the Mann-Whitney U-test (non-parametric data) assessed for the differences between the two groups. Results The 66 athletes with AF were of similar age and sex as the 66 athletes without AF, median age (55 [IQR 45, 61] vs 54 [IQR 44, 62] years, p=0.839), 4% female. There was no difference in (mean±SD) VO2peak (46 ±9 vs 49±10 mL/kg/min, p=0.114) and peak workload (365±67 vs 385±83 W, p=0.136), nor resting SBP (131±13 vs 128±13 mmHg, p=0.169) and resting DBP (76±9 vs 75±11 mmHg, p=0.465) between athletes with and without AF respectively (Table 1). Athletes with AF showed no significant difference to athletes without AF for exercise BP responses (Figure 1) including SBPmax (222±22 vs 219±28 mmHg, p=0.479), SBP/W-slope (0.22±0.07 vs 0.24±0.08 mmHg/W, p=0.310) and median DBP/W-slope (-0.01 [IQR -0.02, 0.01] vs -0.01 [IQR -0.03, 0.02] mmHg/W, p=0.703). Conclusion When comparing endurance athletes with and without paroxysmal AF, there were no differences in the maximal BP attained during exercise or in their BP response indexed to external workload (SBP/W-slope) suggesting that exercise-induced hypertension does not explain the athletic predisposition to AF.

Blood pressure and renal function responses in workers exposed to lead for up to six years

Abstract Background Lead is a widespread environmental toxicant. However, there is currently no consensus whether low-level lead exposure raises blood pressure (BP) or induces kidney dysfunction. Purpose The Study for Promotion of Health in Recycling Lead (SPHERL) assessed the BP and renal function (RF) responses for up to six years in the workers without previous occupational lead exposure. Methods BP was the average of 5 consecutive readings and the estimated glomerular filtration rate was derived from serum creatinine (eGFRcrt) and cystatin C (eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 mg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis. Results The 234 workers analyzed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 µg/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92-6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p≥0.51 and p≥0.18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were -0.25/-0.12 mm Hg (CI: -0.94 to 0.44/-0.66 to 0.42 mm Hg). Accordingly, the incidence of stage-1 or -2 hypertension was not associated with the BL change (p≥0.063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 3-fold BL increment were not significant, amounting to -0.70 mL/min/1.73 m2(CI: -1.70 to 0.30 mL/min/1.73 m2) and -1.06 ml/min/1.73 m2 (-2.16 to 0.03 mL/min/1.73 m2). Conclusion The BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.Figure 1Figure 2

Do more with less? Impact of personalized very low doses of amlodipine in the PERSONAL-CovidBP trial

Abstract Introduction The Personal-CovidBP study1 tested remote patient use of a drug-device combination of a smartphone application (App) to record blood pressure (BP), novel personalized milligram-by-milligram drug (amlodipine) dose, and relevant side effects daily during the COVID-19 pandemic. Purpose In supplementary data analyses, we examined the effect of using small doses (1 mg) and small increments (1-2 mg) of amlodipine on the BP response and side effects. Methods In this community-based trial with remote monitoring and remote medical management from the investigational site, hypertensive participants aged 18 years + with poor BP control (prior 7 day mean of 135 mmHg systolic BP or above and/or 85 mmHg diastolic BP and above) were enrolled to intervention with open label dose titration over 14 weeks, allowing personalized dosing of liquid amlodipine (1–2 mg steps from 1–10 mg daily). Results 205 patients were enrolled into the intervention group between October 2020 and July 2021. Average BP in intervention fell from 141/87 to 131/81 (difference −10/6 p &amp;lt; 0.001). Even low doses or small increments: 1 or 2 mg amlodipine or 5 mg to 6 mg, produced meaningful BP responses. Here we report that the addition of amlodipine during the study reduced blood pressure regardless of being amlodipine naive at baseline (n=141), or receiving amlodipine 2.5mg or 5mg at baseline (n=62). The response slopes were comparable, and mean reductions in SBP were consistent across groups: -11.7 (95% CI: -12.9 to -10.6); -9.4 (-11.1 to -7.7); respectively (Figure 1). For the amlodipine naive, the majority (76%) achieved BP control at low doses (&amp;lt;1 to 3mg) with occurrence of side effects increasing with dose (Figure 2). Conclusions Our real-world remote care study demonstrated that very low doses of amlodipine as little as 1 mg were effective and for 1mg-3mg gained BP control in the majority and were associated with fewer side effects which is consistent with previous meta-analyses.2 Personalized treatment titration was effective even at very low doses and also regardless of whether amlodipine naive or not at baseline.Changes in SBP- baseline amlodipine useAmlodipine dose at control vs oedema

How to predict myocardial injury in patients with large ischaemic burden identified during stress echocardiography?

Abstract Background/Introduction Stress echocardiography (SE) is well established diagnostic tool in coronary artery disease (CAD) with broadly agreed consensus for the indications and protocols. There is, however, no clear non-invasive SE parameter in identifying high risk features in patients with large burden of inducible regional wall motion abnormalities (RWMA) that would require prompt treatment or urgent admission. Purpose To identify high risk features during SE associated with myocardial injury following a positive SE with large amount of RWMA. Methods All consecutive patients referred for SE from June 2019 to November 2022 to diagnose coronary artery disease were assessed for inducible RWMAs using a hybrid protocol (low dose Dobutamine and exercise on supine bike with 3 min increments of workload of 25W). Those with ≥4/17 segments of inducible RWMAs underwent measurement of Troponin level 1 hour after the test termination. Somatometric characteristics, risks factors, symptoms, haemodynamic pre- and during SE and results of subsequent coronary angiography were recorded. Results 631 patients were referred for assessment of CAD. 87 patients had ≥4/17 inducible RWMAs out of 152 patients with positive SE. 61/87 who had Troponin measurements were included in the analysis. Mean age was 65 ± 13 yo, 61% were male. There was high prevalence of known CAD (77%) and cardiovascular risks factors as hypertension (59%) and hyperlipidaemia (61%). The median exercise time was 9 minutes, 46% developed chest pain (CP), 49% - ECG changes, 39% - left ventricular (LV) dilatation and 74% - reduction in LVEF. Troponin was positive in 25/61 patients. Invasive coronary angiography confirmed clinical CAD in 51/61 patients. 5 patients had either normal angiogram or non-obstructive CAD, 5 patients were awaiting diagnostic test. The severity of CAD appears to be associated with magnitude of Troponin release (1 vessel disease - 16.5 ng/L, 2 vessels disease - 39.9 ng/L, 3 vessels disease – 58.2 ng/L). All patients (6/61) with higher troponin values (&amp;gt;90ng/L) had multivessel disease involving the left anterior descending (LAD) artery. Interestingly, 2/5 patients without CAD had elevated Troponin suggesting possible ongoing myopathic process. The only non-invasive SE parameters that were significantly related to troponin increase were recovery time (P=0.001) and exercise time (P&amp;lt;0.05) whereas symptoms, BP response and LVEF reduction showed a trend which did not achieve significance. Conclusions In patient with positive SE with large burden of inducible RWMAs prolonged recovery time and low threshold for ischaemia appear to be the most reliable characteristic to identify patients with potential myocardial injury and should be used as a triaging tool for admission or early invasive assessment.

Treadmill exercise test as a screening tool in the development of hypertension

Abstract Background Guidelines promote screening people with high normal BP for the presence of end-organ damage because their presence is associated with a 2- to 3-fold increase in the risk of CVD. Purpose Office blood pressure measurements may be unable to detect early subclinical cardiac damage of adverse prognostic significance in subjects with high normal blood pressure. Methods 100 consecutive subjects with high normal BP [systolic BP=130-139mmHg and/or diastolic BP=85-89mmHg] were examined for early signs of hypertension-mediated organ damage (HMOD). They underwent an echocardiographic study, a negative for ischemia treadmill exercise test (Bruce protocol) where the index SBP/MET-slope [(peak SBP—resting SBP)/(peakMET-1)] was used. Arterial stiffness was evaluated based on carotid-femoral pulse wave velocity (PWV). The sympathetic drive was assessed by MSNA. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in the office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advice to lower their BP. The endpoint was the development of HTN either with Office BP or ABPM. Results Of 100 subjects (54±8 years, 42 males, baseline office BP: 132/82 mmHg, 24-hour BP: 122/76 mmHg), 40 developed HTN in 3 years. 34 subjects developed Hypertensive Response to Exercise (HRE) (BP &amp;gt;210mmHg in men and &amp;gt;190mmHg in women) and all of them developed HTN. The SBP/MET-slope in future hypertensives was increased in all stages till peak exercise independently of sex type (stage1: 6.7vs4.9 p=0.049, stage2: 8.4vs4.8 p=0.001, peak: 6.7vs4.9, p=0.001). Their exercise capacity was reduced (10vs11.3METs, p=0.002) as well as their maximum exercise heart rate (156vs164, p=&amp;lt;0.0001). Those with HRE had higher 24hSBP (124vs121mmHg, p=0.009), Night SBP (117vs111mmHg, p&amp;lt;0.001), Day SBP (127vs124mmHg, p=0.012) Office Pulse Pressure (51vs47mmHg, p=0.01). Additionally, they had increased PWV (8.3vs7.5m/sec, p=&amp;lt;0.0001), MSNA levels (36vs28 bursts, p=&amp;lt;0.0001), LVMI (38vs34 gr/m2.7, p=0.02), and a statistically significant deterioration of 2021 CKD-EPI eGFR (90 vs 97 mL/min/1.73 m², p=0.02). All of them correlated with development of hypertension (p=0.002), while they did not differ regarding their metabolic profile at the follow-up. Conclusion Detecting exaggerated blood pressure response and specifically an increased SBP/MET-slope in the end of second stage of Bruce protocol at treadmill exercise test is associated with increased systemic vascular resistance and early subclinical HMOD which may upgrade an individual’s cardiovascular disease (CVD) risk as they progress to HTN indicating a need for instituting a BP-lowering strategy.

Exaggerated blood pressure response to submaximal exercise must be considered relative to fitness: strong associations with hypertensive target organ damage

Abstract Exaggerated systolic blood pressure (SBP) during submaximal exercise is associated with increased cardiovascular (CV) risk. However, findings are mixed and new evidence indicates that cardiorespiratory fitness should be considered for proper clinical interpretation of exercise SBP responses. This study aimed to determine the relationship between SBP response to submaximal effort corrected for fitness and abnormalities of cardiac structure and function. Methods Each of 231 participants (age 54±12 years; 53% females) with controlled clinic BP, no evidence for ischemic heart disease, valvular heart disease or heart failure underwent cardiopulmonary exercise testing (Bruce protocol), resting and exercise echocardiography and 24h ABPM. Submaximal exercise SBP (measured at the 2nd stage of Bruce protocol) was corrected for two fitness variables: 1) peak VO2 and 2) maximal workload in METs (SBP/peakVO2 and SBP/METs). Results There were no, or weak, associations with exercise SBP and target organ damage. However, there was a progressive deterioration of cardiac function and structure parameters across the exercise SBP tertiles corrected for fitness (Table 1). Both SBP/peakVO2 and SBP/METs significantly correlated with left ventricular (LV) mass, LV diastolic and systolic, and left atrial parameters (Table 2). ROC analysis revealed good performance of corrected SBP response to submaximal exercise in detection of LV hypertrophy and diastolic dysfunction (AUC 0.792 and 0.808, and 0.771 and 0.802 for SBP/peakVO2 and SBP/METs, respectively; Figure). Conclusions Fitness-corrected SBP responses to submaximal exercise can identify more profound target organ damage with respect to cardiac function and structure even among patients with controlled clinic BP. Exaggerated BP response to exercise must be considered relative to fitness for proper clinical interpretation of BP responses to exercise testing.Figure

A flattening systolic blood pressure response at the end of ramp exercise testing is not associated with all-cause mortality

Abstract Purpose Systolic blood pressure (SBP) is expected to rise linearly during ramp exercise, but sometimes plateaus before the end of exercise. We aimed to examine the predictive value of a plateauing SBP response at the end of a cycle exercise test. Methods We analyzed 9,001 consecutive patients aged ≥18 years with maximal cycle ergometer ramp tests, after excluding subjects with valvulopathy, pacemaker, arrhythmia during the test, or body mass index (BMI) &amp;gt;40kg/m², as well as tests with resting SBP &amp;lt;80mmHg or &amp;gt;200mmHg, exercise SBP &amp;lt;100 mmHg, &amp;lt;2 SBP measurements during the second half of the test or a test duration &amp;lt;4 minutes. The data were cross-linked with nationwide registries for mortality and in- and outpatient hospital diagnoses. The difference in SBP between the two last SBP measurements was standardized to the difference in Watts between the same time points, categorized as i) an SBP decrease (drop), ii) an SBP increase of &amp;lt;2.5 mmHg per 10 Watts increase (flat), iii) an SBP increase of 2.5-15 mmHg/10 Watts (intermediate), and iv) an SBP increase &amp;gt;15 mmHg/10 Watts representing the 97.5th percentile (steep). Hazards ratios (HR, [95% confidence interval, CI]) for all-cause mortality were calculated, stratified for exercise capacity (peak Watt % of predicted) with the intermediate SBP response as reference. Adjustments were made for age, sex, BMI, resting SBP, baseline diagnosis of ischemic heart disease, heart failure, chronic obstructive pulmonary disease, and the use of beta-blockers or anti-hypertensive medication. Results Decreasing, flat, intermediate, and steep SBP responses at the end of exercise were present in 1.1%, 25.6%, 70.8% and 2.5% of patients respectively (Table 1). During median follow-up 8.6 years (interquartile range 5.9–11.6 years) there were 844 deaths. When compared to an intermediate SBP response, a flat SBP response was not associated with all-cause mortality in any of the exercise capacity strata: lowest tertile of Wmax%pred unadjusted HR 0.88 (95% CI 0.69–1.11), middle tertile HR 0.91 (95% CI 0.66–1.24), and highest tertile HR 0.95 (95% CI 0.64–1.41), with HRs remaining non-significant after adjustment for covariates (Table 2). Conclusion In patients referred for exercise testing, a flattening SBP response at the end of exercise was not associated with increased all-cause mortality risk compared to an intermediate SBP response, consistent across the different exercise capacity strata.

Effect of selective renal denervation guided by renal nerve stimulation on atrial remodeling

Abstract Background The renal nerves play a crucial role in regulating blood pressure (BP), and the parasympathetic nervous has been confirmed as one of the components of the renal nerves, with close connections to the central solitary nucleus. Renal nerve stimulation (RNS) can activate not only the sympathetic nerves, leading to an elevation in BP, but also the parasympathetic nerves, resulting in a reduction in BP. Multiple clinical studies have demonstrated that compared to pulmonary vein isolation (PVI), renal denervation (RDN) combined with PVI significantly increased the likelihood of freedom from atrial fibrillation, but its mechanism remains unclear. Purpose Exploring the effects of renal sympathetic denervation and renal parasympathetic denervation on atrial neural remodeling and structural remodeling from a histological perspective of atrial myocardium. Methods 24 adult healthy Kunming dogs were randomly divided into three groups: (1) RNS-guided reduced BP response sites ablation (RRA group, n=8), (2) RNS-guided elevated BP response sites ablation (ERA group, n=8), and (3) RNS only, no ablation (RSC group, n=8). Left atrial samples were obtained after a 4-week follow-up period. Results Compared to the RSC group, the ERA group showed a significant decrease in tyrosine hydroxylase (TH), while the RRA group showed a significant decrease in choline acetyltransferase (CHAT) and muscarinic acetylcholine receptor 2 (CM2) (Fig. 1A-1C). Histological results indicated that compared to the RSC group, the ERA group exhibited orderly arrangement of myocardial cells, with a significant reduction in the degree of mitochondrial swelling and a decrease in average myocardial cell area. In contrast, the RRA group showed disordered arrangement of myocardial cells, with some myofibril dissolution, noticeable swelling of cell nuclei and mitochondria, and an increase in average myocardial cell area (Fig. 1D). Further evaluation of left atrial fibrosis degree revealed that compared to the RSC group, the ERA group showed a significant decrease in Collagen I, with a reduction in interstitial fibrosis degree, while the RRA group showed a significant increase in Collagen I expression, with an increase in myocardial interstitial fibrosis degree (Fig.2). Conclusion Renal sympathetic denervation can reduce atrial sympathetic nerve, improve atrial macrostructure, ultrastructure, and fibrosis levels, which may be one of the reasons why RDN combined with PVI is more effective in maintaining sinus rhythm compared to PVI. Renal parasympathetic denervation can decrease atrial parasympathetic nerve, leading to deterioration of atrial tissue structure and exacerbation of fibrosis. This emphasizes the importance of electrical stimulation guidance during the RDN procedure to avoid "side effects" caused by renal parasympathetic nerves ablation.Figure 1Figure 2

Semaglutide for the treatment of resistant hypertension

Abstract Background Treatment options for resistant hypertension (RH) are often limited by medication intolerance and adverse effects. Novel approaches to treatment are required. The disease of obesity affects 70% of patients with RH. Purpose To determine if a weight centric approach using semaglutide improved BP control in patients with RH. Methods Individual participant data from three randomised placebo-controlled trials (STEP 1, 3 and 4) examining the effect of semaglutide 2.4mg on body weight over 68 weeks were included. Participants on &amp;gt;4 anti-hypertensive medications or those with systolic BP (SBP) &amp;gt;130mmHg at baseline and 3 anti-hypertensive medications including a diuretic were considered to have RH. Firstly, the change in SBP comparing those on semaglutide to placebo was analysed with baseline systolic BP as a covariate in an ANCOVA model. Then, the RH group was subdivided into those with SBP above or below 130mmHg at baseline and BP response to semaglutide assessed. Analyses were performed using R Software version 4.0.3. Results In the pooled analysis of 3136 trial participants, 111 met the criteria for RH. Compared to placebo, participants on semaglutide had a SBP reduction of -4.93mmHg, adjusted for SBP baseline to -3.16mmHg (95%CI -8.69 to 2.37). For those with RH and a baseline SBP &amp;gt; 130mmHg on semaglutide, the SBP change was -10.94mmHg. This change was 4.54mmHg for those with a SBP &amp;lt; 130mmHg. The diastolic BP changes were -3.62 and 2.79mmHg respectively (Figure 1). At trial completion, 36% of those on semaglutide did not meet the criteria for RH. Conclusions The effect of semaglutide on BP for patients with RH is modest. A greater BP reduction is evident for those with a higher baseline SBP. Targeting excess body weight with semaglutide is a viable treatment option for patients with RH and uncontrolled BP.

Correlation of exercise blood pressure levels with concomitant cardiovascular disease.

Hypertension is a fatal but preventable risk factor for cardiovascular disease and an important cause of death from cardiovascular disease. Exercise training has a definite clinical effect on blood pressure control. However, inappropriate exercise is ineffective and may also cause disease. The aim of this study was to evaluate the possible factors influencing blood pressure level in an exercise treadmill test and its relationship with accompanying clinical diseases. Five hundred sixty-four patients who underwent exercise treadmill test were selected and divided into the abnormal exercise blood pressure group (n = 156, age 60.46 ± 9.2 years) and normal exercise blood pressure group (n = 408, age 56.57 ± 8.8 years) according to whether the peak exercise systolic blood pressure was more than or equal to 180 mm Hg. General clinical data and associated clinical diseases were collected from both groups. The prevalence of hypertension and coronary atherosclerotic heart disease in the abnormal exercise blood pressure group was significantly higher than that in the normal exercise blood pressure group (all P < .05). At the same time, the smoking rate and glycohemoglobin level of the patients with abnormal exercise blood pressure were significantly increased (all P < .05), but there was no statistically significant difference in age, sex, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and other indicators between the 2 groups (all P > .05). Patients with abnormal exercise blood pressure response have a higher prevalence of hypertension and coronary heart disease. Exercise blood pressure level may be an important factor affecting patients' cardiovascular prognosis.

Physiological characteristics of blood pressure responses after combined exercise in elderly hypertensive patients: a systematic review and meta-analysis.

The aim of this investigation is to explore the efficacy of combined exercise in elderly patients with hypertension. Moreover, we aim to delve into the underlying mechanisms governing blood pressure regulation, with the objective of promoting the adoption of this exercise regimen among elderly hypertensive individuals. In our study, we conducted a thorough search across multiple databases, including PubMed, Web of Science, Cochrane Library, Embase, and Scopus. This extensive search resulted in the preliminary screening of 2,347 articles. Among these, 9 studies were carefully selected for an in-depth analysis. For our meta-analysis, we employed Review Manager 5.3 and Stata 15.0, enabling us to perform detailed subgroup analyses and assess the possibility of publication bias. In comparison to the control group (n = 194), individuals enrolled in the combined exercise group (n = 200) exhibited a notable decrease in both resting systolic blood pressure (SBP) [weighted mean difference (WMD) = -11.17 mm Hg, 95% confidence interval (CI) (-17.13, -5.22), Z = 3.68, P < 0.05] and diastolic blood pressure (DBP) [WMD = -5.93 mm Hg, 95% CI (-9.24, -2.61), Z = 3.51, P < 0.05]. Nonetheless, no statistically significant alteration was observed in pulse pressure (PP) [WMD = -9.05 mm Hg, 95% CI (-22.65, 4.55), Z = 1.3, P = 0.192]. Further subgroup analyses elucidated that combined exercise regimens, characterized by aerobic training intensities below 85% of HRmax, durations of up to 12 weeks, weekly frequencies of either ≥3 or <3 sessions, total session times under 60 min, and a sequence of aerobic exercise followed by resistance training (AE-RT), were particularly effective in enhancing SBP and DBP among elderly patients with hypertension. Additionally, regular engagement in combined exercise led to significant improvements in SBP and DBP across individuals aged 60-70, those older than 70 years, and regardless of whether participants were using antihypertensive medications or not. Combined exercise serves as an efficacious adjunctive therapy for reducing blood pressure among elderly individuals with hypertension, exerting beneficial influences on multiple physiological mechanisms pertinent to blood pressure regulation. Moreover, the integration of aerobic exercise with resistance training presents a more varied training program, thereby eliciting wider-ranging positive effects on both the physical and mental well-being of elderly patients afflicted with hypertension.