Systolic Blood Pressure Response Research Articles

Sex Differences in Muscle Metaboreflex Activation after Static Handgrip Exercise.

Larger blood pressure (BP) responses to relative-intensity static exercise in men versus women are thought to involve altered muscle metaboreflex activation, but whether this is because of an intrinsic sex difference in metabolite production or differences in muscle strength and absolute load is unknown. Continuous BP and heart rate were recorded in 200 healthy young men and women (women: n = 109) during 2 min of static handgrip exercise at 30% of maximal voluntary contraction (MVC), followed by 2 min of postexercise circulatory occlusion (PECO). Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (n = 39; women, n = 21), permitting calculation of signal-averaged resting sympathetic transduction (MSNA-diastolic BP). Sex differences were examined with and without statistical adjustment for MVC. Multivariate regression analyses were performed to identify predictors of BP responses. Men had larger systolic BP responses (interactions, P < 0.0001) to static handgrip exercise (24 ± 10 vs 17 ± 9 mm Hg [mean ± SD], P < 0.0001) and PECO (20 ± 11 vs 16 ± 9 mm Hg, P < 0.0001). Adjustment for MVC abolished these sex differences in BP (interactions, P > 0.7). In the subset with MSNA, neither burst frequency or incidence responses to static handgrip exercise or PECO differed between men and women (interactions, P > 0.2). Resting sympathetic transduction was also similar (P = 0.8). Multiple linear regression analysis showed that MVC or the change in MSNA, were predictors of BP responses to static handgrip, but only MVC was associated with BP responses during PECO. Sex differences in absolute contraction load contribute to differences in BP responses during muscle metaboreflex isolation using PECO. These data do not support an intrinsic effect of sex as being responsible for exercise BP differences between men and women.

Association between awakening cortisol levels and cardiovascular performance in sugarcane rural workers.

Sudden deaths without known causes have been reported among rural workers in the last decade, especially in low and middle-income countries. The current study aimed to analyse the association between awakening cortisol response and cardiovascular performance in rural workers before and after the harvesting period. Fifty-four rural male workers and 48 residents were included (non-rural workers) from a sugarcane production area in São Paulo, Brazil. Morning salivary cortisol were analysed before and 7 months after the beginning of burnt sugarcane harvesting. Cardiovascular performance (blood pressure, pulse pressure and heart rate HR) was evaluated using the Incremental Shuttle Walking Test (ISWT). Our findings revealed a negative association between CAR and cardiovascular performance in rural workers at the harvesting period. Specifically, morning cortisol levels significantly increased after seven months of intense harvesting activity, allied to improvements in physical performance, systolic blood pressure and heart rate reactivity to a cardiopulmonary task. No association was observed in the resident group. Altogether, these findings suggest that, at least in the short-term, rural workers presented an adaptive response to the physical demands of sugarcane harvesting work. Longitudinal studies are essential to investigate the long-term effects of harvesting activity on rural workers' health.

Altered Vascular Reactivity to Circulating Angiotensin II in Familial Hypercholesterolemia.

We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we investigated the effects of a 3-hour infusion of Ang II on blood pressure and forearm skin microvascular function in 16 otherwise healthy patients with FH and matched healthy controls. Skin microvascular hyperemia was studied by laser Doppler fluxmetry during local heating. Microvascular resistance was determined by the ratio of mean arterial pressure to microvascular hyperemia. Macrovascular reactivity was assessed by changes in brachial blood pressure. Compared with the controls, the FH group had increased baseline systolic blood pressure (127 ± 14 vs. 115 ± 12 mm Hg; P = 0.02), while systolic blood pressure responses were similar (+24 ± 9 vs. +21 ± 7 mm Hg; P = 0.26) after 3 hours of Ang II infusion. At baseline, there were no group differences in microvascular hyperemia or resistance. However, after 3 hours of Ang II infusion, heat-induced microvascular hyperemia was less pronounced in FH (126 ± 95 vs. 184 ± 102 arbitrary units; P = 0.01), while microvascular resistance during heat-induced hyperemia was increased (1.9 ± 0.9 vs. 0.9 ± 0.8, P = 0.01), as compared to controls. Both these responses were further pronounced 1 hour after stopping Ang II. In conclusion, despite similar blood pressure responses to Ang II in the FH group and controls, microvascular dilatation capacity was impaired in the FH group, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and microvascular complications in FH.

Altered Cardiovascular Reactivity to and Recovery from Cold Face Test-Induced Parasympathetic Stimulation in Essential Hypertension.

Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test (CFT) in essential hypertension. Moreover, we tested whether chronic stress modulates CFT-reactivity dependent on hypertension status. The CFT was conducted by applying a cold face-mask for 2 min in 24 unmedicated, otherwise healthy hypertensive men and in 24 normotensive controls. Systolic and diastolic blood pressure (BP) and heart rate (HR) were measured repeatedly. Chronic stress was assessed with the Trier-Inventory-for-Chronic-Stress-Screening-Scale. Hypertensives did not exhibit diastolic BP decreases after CFT-cessation (p = 0.59) as did normotensives (p = 0.002) and failed to show HR decreases in immediate response to CFT (p = 0.62) when compared to normotensives (p < 0.001). Systolic BP reactivity and recovery patterns did not differ between hypertensives and normotensives (p = 0.44). Chronic stress moderated HR (p = 0.045) but not BP CFT-reactivity (p′s > 0.64) with chronically stressed normotensives showing similar HR reactivity as hypertensives. Our findings indicate impaired diastolic BP and HR reactivity to and recovery from CFT in hypertensives and a moderating effect of chronic stress on HR reactivity potentially reflecting reduced relaxation ability of the cardiovascular system.

Monotherapy treatment with chlorthalidone or amlodipine in the systolic blood pressure intervention trial (SPRINT).

This post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) examined the performance of chlorthalidone (C) versus amlodipine (A) monotherapies. ANOVA was used to analyze the differences in systolic blood pressure (SBP) response between C and A. Logistic regression was used to examine monotherapy failure (adding a second antihypertensive agent or switching to a different antihypertensive agent) rates. Four hundred ninety‐one participants were treated with C monotherapy (n = 210, mean dose = 22 mg/day) or A monotherapy (n = 281, mean dose = 7 mg/day). There was a significant difference in mean SBP reduction between the C and A monotherapies at the third visit (higher reduction with A, adjusted p = .018). Unadjusted analysis showed a higher failure with C in the standard treatment group. Although the average SBP at failure was higher and above the 140 mm Hg cutoff that indicated monotherapy failure with A (142.60) compared with C (138.40), more participants on C failed despite having SBP below the 140 cutoff. This was probably due to decisions made by the investigative teams to change the antihypertensive regimen, because, in their opinion, the clinical picture required it. After adjusting for baseline characteristics, C had higher failure than A only in the standard treatment group (1.64 odds ratio [OR], 95% CI 1.06–2.56, p = .028). A sub‐analysis including participants who had never used antihypertensive treatment before randomization had similar results (2.57 OR, 95% CI 1.34–5.02, p = .004). Overall, in SPRINT chlorthalidone was associated with higher monotherapy failure than amlodipine in the standard treatment group because of decisions of the investigative teams.

Long-term effects of hyperpolarization-activated inward current blockade on cardiac parasympathetic activity

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS - UEFISCDI Background The autonomic control of the pacemaker current, If, and the molecular mechanisms underlying parasympathetic If modulation are well understood. Conversely, the effects of chronic If blockade on the parasympathetic nervous system and on the heart rate (HR) response to acute parasympathetic changes are still largely unknown. Such interactions could significantly influence the course of patients undergoing chronic therapy with the If blocker ivabradine. Purpose We aimed to assess the effects of long-term If blockade using ivabradine on cardiac autonomic modulation and on the cardiovascular response to acute in vivo and in vitro parasympathetic stimulation. Methods Radiotelemetry ECG transmitters were implanted in 6 Control and 10 ivabradine-treated male Wistar rats (IVA; 3 weeks, 10 mg/kg/day); sympathetic and parasympathetic heart rate variability parameters were assessed. At the end of the study, the right atrium was removed and right atrial HCN(1-4) RNA expression levels were analyzed. The HR and systolic blood pressure (SBP) responses to in vivo electrical stimulation of the right vagus nerve (2–20 Hz) and the spontaneous sinus node discharge rate (SNDR) response to in vitro cholinergic receptors stimulation using carbamylcholine (10-9–10-6 mol/L) were assessed in 6 additional Control and 10 IVA rats. Results At the end of the study, mean 24-h HR was significantly lower in the IVA compared with the Control rats (301.3 ± 7.5 bpm vs. 341.5 ± 8.3 bpm; p&amp;lt; 0.01). Ivabradine administration led to a significant increase in vagal tone and shifted the sympatho-vagal balance towards vagal dominance (awake, asleep, and over 24-h; all p&amp;lt; 0.05). In the Control rats, in vivo vagus nerve stimulation induced a progressive decrease in both the SBP (p = 0.0001) and the HR (p&amp;lt; 0.0001). Meanwhile, in the IVA rats, vagal stimulation had no effect on the HR (p = 0.16) and induced a significantly lower drop in SBP (p&amp;lt; 0.05). Ivabradine-treated rats also presented a significantly lower SNDR drop in response to carbamylcholine (p&amp;lt; 0.01) and significantly higher HCN4 expression (p = 0.02). Conclusion Long-term If blockade using ivabradine caused a significant increase in vagal tone and shifted the autonomic balance towards vagal dominance in rats. Given the highly proarrhythmic effects of vagal activation at the atrial level, these findings could provide an explanation for the increased risk of atrial fibrillation associated with ivabradine use in clinical trials. In addition, ivabradine reduced the HR response to direct muscarinic receptors stimulation, canceled the cardioinhibitory response and blunted the hemodynamic response to in vivo vagal stimulation, and led to significant sinus node HCN4 up-regulation. These data suggest that ivabradine-induced HCN4 and the consequent If up-regulation could render the sinus node less sensitive to acute vagal inputs and could thus protect against excessive bradycardia induced by acute vagal activation.

Sudomotor and cardiovascular autonomic function in de novo Parkinson's disease assessed by sudoscan and cardiovascular reflexes

ObjectiveThe prevalence of autonomic involvement in early stage of Parkinson ‘s disease (PD) is still debated. Aim of this study is to assess the autonomic functions in de novo PD patients (dnPD) in comparison with PD patients on therapy (PDot) and healthy controls (HC). MethodsTwenty-eight dnPD and 24 PDot, to whom Unified Parkinson's Rating Scale (UPDRS) was administered, and 23 HC underwent electrochemical skin conductance (ESC) measured with sudoscan, cardiovascular reflexes (head-up tilt test HUTT, Valsalva maneuver, deep breathing, hand grip, and cold face),and Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT) questionnaire. ResultsThe mean SCOPA-AUT total score was significantly higher in dnPD group compared with HC group (p < 0.001) and significantly lower than PDot (p = 0.004). No significant difference of ESC mean values were found between dnPD and HC group. DnPD had a significantly lower diastolic blood pressure (BP) response at handgrip test (p = 0.005) compared with HC. Hands and feet ESC significantly negatively correlated with disease duration (p = 0.014; p = 0.025) and feet ESC significantly negatively correlated with UPDRS III (p = 0.039). Systolic and diastolic BP responses at 3rd minute of HUTT correlated significantly negatively with disease duration (p < 0.001; p = 0.003) and with UPDRSIII (p = 0.001; p < 0.001). BP response to Valsalva maneuver negatively correlated with UPDRSIII (p = 0.006). ConclusionAlthough dnPD patients complain of thermoregulatory symptoms, we found no alteration in the sudomotor function investigated with sudoscan. Furthermore, a deficit of the sympathetic vasoconstrictive response to the isometric exercise was detected, suggesting an early involvement of the autonomic cardiovascular components in dnPD.

Changes in vitality in response to acute stress: an investigation of the role of anxiety and physiological reactivity

ABSTRACT Background: Feeling alive and invigorated, or vitality, is examined within the framework of a stress paradigm. The current study investigated whether endocrine and cardiovascular responses to acute psychological stress predict declines in vitality. Methods: A sample of 90 undergraduate students completed an in-lab stressor. We measured anxiety, state vitality, cortisol levels, heart rate, and blood pressure before the task, and measured changes in state vitality, cortisol, heart rate, and blood pressure in response to the stressor. We investigated whether pre-task anxiety predicted changes in state vitality, and whether such changes were explained by physiological responses. Results: Results indicate that cognitive and somatic anxiety preceding a stressor predict changes in vitality, which is mediated by the magnitude of diastolic (95% CI [0.017, 0.517]; [0.006, 0.454]) and systolic (95% CI [0.038, 0.705]) blood pressure responses to the task. Cortisol reactivity was associated with somatic anxiety (F(6, 83) = 3.34, p < .01, β = 0.401) but was not related to changes in vitality. Conclusions: Together, these results contribute to the understanding of how physiological reactivity to a stressor can deplete vitality.

Blood pressure responses to static and dynamic knee extensor exercise between sexes: Role of absolute contraction intensity

Males have larger blood pressure (BP) responses to relative intensity static handgrip exercise compared to females. Controlling for maximal voluntary contraction (MVC) absolute strength abolishes these differences. Whether similar observations exist during large muscle mass exercise or dynamic contractions remain unknown. BP, heart rate, muscle oxygenation (near-infrared spectroscopy), and rectus femoris electromyography (EMG) were recorded in 28 males and 17 females during 10% and 30% MVC static (120s) and isokinetic dynamic (180s; 1:2 work-to-rest ratio; angular velocity: 60º/s) knee extensor exercise. At baseline and during exercise, continuous BP and heart rate were measured using finger photoplethysmography and single-lead electrocardiography, respectively. MVC, as well as all submaximal exercise testing, was measured and performed on a dynamometer at 80⁰ of knee flexion, and voluntary activation was assessed using the interpolated twitch technique, with ≥90% voluntary activation of the knee extensors set as the acceptable activation threshold. Static and dynamic exercises were completed on separate visits, in a randomized order. The change from baseline of each variable was calculated for every 30 s during each submaximal test. Sex differences were then examined with and without statistical adjustment of MVC using analyses of covariance (ANCOVA). The males were taller and heavier than the females and had higher resting systolic BP (all P<0.05), while BMI, resting diastolic and mean arterial BP, and heart rate were similar between sexes (all P>0.05). Knee extensor MVC was higher in males than females (165 ± 40 vs. 94 ± 22 Nm, P<0.0001). Males had larger systolic BP responses (interaction, P<0.001) and muscle deoxygenation (interaction, P<0.01) than females during 10% static exercise, with no difference in EMG (interaction, P=0.73). Peak systolic BP was correlated to MVC (r=0.53, P=0.0002), and adjustment for MVC abolished sex differences in systolic BP (interaction, P=0.5). BP, heart rate, muscle oxygenation/deoxygenation, and EMG responses did not differ between sexes during 30% static exercise (interaction, All P>0.2), including following adjustment for MVC (All P>0.1). Males had larger systolic BP responses during dynamic exercise at 10% and 30% (interaction, Both P=0.01), which were abolished after adjustment for MVC (interaction, Both P>0.08). Systolic BP responses at 180s were correlated with MVC and stroke volume responses during 10% (r=0.31, P=0.04; r=0.61, P<0.0001, respectively) and 30% (r=0.4, P=0.007; r=0.59, P<0.0001, respectively). In conclusion, MVC can influence systolic BP responses to 10% but not 30% MVC static, as well as 10% and 30% MVC dynamic knee extensor exercise. MVC should be considered when comparing BP responses between males and females. Finally, the mechanisms mediating the larger pressor responses in stronger individuals across different exercise modalities warrant further investigation.

Hyperoxia Exaggerates Systolic Blood Pressure Response in Patients with Peripheral Arterial Disease

It is well known that acute oxidative stress evokes different effects in patients with atherosclerotic disease and in normal subjects. The effects of acute hyperoxia, an important acute oxidative stressor, on hemodynamics have not been well studied in patients with peripheral arterial disease (PAD). We recruited 20 PAD patients (14M, 6F, 66 ± 6yrs), and 16 age-matched control subjects (10M, 6F, 65 ± 8yrs). The ankle-brachial pressure index (ABI) in the most affected limbs of the patients was 0.58 ± 0.15, compared to 1.04 ± 0.09 in the controls. Blood pressure and ECG were monitored at baseline and during hyperoxia (100% oxygen for 5 mins, as an acute oxidative stress test). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), heart rate (HR), and rate-pressure product (RPP) were averaged across the final minute of baseline and hyperoxia, and were compared across time and between groups using Repeated Measures Analyses of Variance (RMANOVA). Results indicated a significant interaction for SBP (F1,1=4.65, P=0.04), which was explained by a significant increase in SBP from baseline to hyperoxia in the PAD group (126 ± 13 mmHg vs. 137 ± 16 mmHg, respectively, P<0.001) that was not observed in the control group (115 ± 9 mmHg vs. 120 ± 7 mmHg at baseline and hyperoxia, respectively, P=0.06). In contrast, no significant interactions were observed for DBP (P=0.43), MBP (P=0.47), HR (P=0.71), or RPP (P=0.11). Considering 53% of PAD patients were on antihypertensive medicine, whereas none of the control subjects were on chronic antihypertensive agents, the likely effects of hyperoxia on systolic pressure may have been underestimated in our study.

Long-Term Effects of Ivabradine on Cardiac Vagal Parasympathetic Function in Normal Rats.

Background: The complex interactions that exist between the pacemaker current, I f, and the parasympathetic nervous system could significantly influence the course of patients undergoing chronic therapy with the I f blocker ivabradine. We thus aimed to assess the effects of chronic ivabradine therapy on autonomic modulation and on the cardiovascular response to in situ and in vitro parasympathetic stimulation. The right atrial expression of HCN genes, encoding proteins for I f, was also evaluated. Methods: Sympathetic and parasympathetic heart rate variability parameters and right atrial HCN(1-4) RNA levels were analyzed in 6 Control and 10 ivabradine-treated male Wistar rats (IVA; 3 weeks, 10 mg/kg/day). The heart rate (HR) and systolic blood pressure (SBP) responses to in situ electrical stimulation of the vagus nerve (2–20 Hz) were assessed in 6 additional Control and 10 IVA rats. The spontaneous sinus node discharge rate (SNDR) response to in vitro cholinergic receptors stimulation using carbamylcholine (10−9–10−6 mol/L) was also assessed in these later rats. Results: Ivabradine significantly increased vagal modulation and shifted the sympatho-vagal balance toward vagal dominance. In Control, in situ vagus nerve stimulation induced progressive decrease in both the SBP (p = 0.0001) and the HR (p< 0.0001). Meanwhile, in IVA, vagal stimulation had no effect on the HR (p = 0.16) and induced a significantly lower drop in SBP (p< 0.05). IVA also displayed a significantly lower SNDR drop in response to carbamylcholine (p< 0.01) and significantly higher right atrial HCN4 expression (p = 0.02). Conclusion: Chronic ivabradine administration enhanced vagal modulation in healthy rats. In addition, ivabradine reduced the HR response to direct muscarinic receptors stimulation, canceled the cardioinhibitory response and blunted the hemodynamic response to in situ vagal stimulation. These data bring new insights into the mechanisms of ivabradine-related atrial proarrhythmia and suggest that long-term I f blockade may protect against excessive bradycardia induced by acute vagal activation.

BFF: Bayesian, Fiducial, and Frequentist Analysis of Cognitive Engagement among Cognitively Impaired Older Adults.

Engagement in cognitively demanding activities is beneficial to preserving cognitive health. Our goal was to demonstrate the utility of frequentist, Bayesian, and fiducial statistical methods for evaluating the robustness of effects in identifying factors that contribute to cognitive engagement for older adults experiencing cognitive decline. We collected a total of 504 observations across two longitudinal waves of data from 28 cognitively impaired older adults. Participants’ systolic blood pressure responsivity, an index of cognitive engagement, was continuously sampled during cognitive testing. Participants reported on physical and mental health challenges and provided hair samples to assess chronic stress at each wave. Using the three statistical paradigms, we compared results from six model testing levels and longitudinal changes in health and stress predicting changes in cognitive engagement. Findings were mostly consistent across the three paradigms, providing additional confidence in determining effects. We extend selective engagement theory to cognitive impairment, noting that health challenges and stress appear to be important moderators. Further, we emphasize the utility of the Bayesian and fiducial paradigms for use with relatively small sample sizes because they are not based on asymptotic distributions. In particular, the fiducial paradigm is a useful tool because it provides more information than p values without the need to specify prior distributions, which may unduly influence the results based on a small sample. We provide the R code used to develop and implement all models.

GENOME-WIDE ASSOCIATION STUDY FOR PHARMACOGENETIC RESPONSE OF BLOOD PRESURE TO BETA BLOCKER AND CALCIUM CHANNEL BLOCKER DRUGS

Objective: There is substantial inter-individual variability in blood pressure (BP) responses to anti-hypertensive drugs and it is hypothesised that there could be genetic influences. One goal of pharmacogenetics is to aid in treatment selection. However very few variants have been identified. After the success of genome-wide association studies (GWAS) for BP, it is hoped GWAS could also reveal genes associated with BP treatment response. Design and method: A discovery analysis was performed including participants from ASCOT and NORDIL studies. Six different analyses were performed for systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) responses to monotherapy beta blockers (BBs) and calcium channel blockers (CCBs). BP response was defined as post-treatment BP minus baseline BP. All analyses adjusted for age, sex, baseline BP and principal components. ASCOT analyses were also adjusted for dose and previous antihypertensive use, and excluded patients taking either BB/CCB drug at baseline, whereas NORDIL participants were previously untreated and subsequently treated on the same drug dose. Genotyped data was imputed to 1000 Genomes, testing ∼7million common variants. Results from ASCOT and NORDIL were meta-analysed, with total N = 2,556 for BBs and N = 3,369 for CCBs. Any variants reaching P &lt; 1 × 10-5 for SBP and DBP response to BBs were tested for replication in available ICAPS consortium data (N = 1,328). Results: Strong correlation between baseline BP and BP response shows patients with higher BP have greater BP reduction post-treatment. No variants reached genome-wide significance in any of the GWAS analyses, and none replicated in ICAPS data. Lookups of ∼1,000 published BP-associated variants were performed, but none reached Bonferroni significance level. Ongoing analyses are testing BP genetic risk scores for association with treatment response. Comparison of GWAS results shows correlation between SBP vs DBP response (r2 = 0.48) and SBP vs PP response (r2 = 0.76), but none between response to BBs vs CCBs. Conclusions: Despite being the largest GWAS of antihypertensive response, we found no significant associations, showing that larger studies are still required to increase power for discoveries. Model comparisons show different genes are likely to influence response to different antihypertensive drugs, with different genetic architecture.

CHANGES IN RENAL HEMODYNAMICS DURING A COLD PRESSURE TEST ARE DETECTABLE BY DOPPLER AND CONTRAST-ENHANCED ULTRASOUND

Objective: The cold pressure test (CPT) is a classic cardiovascular stress test known to increase blood pressure and heart rate secondary to an increase in nervous sympathetic activity. Its effect on renal hemodynamics using both Doppler ultrasound (DU) and contrast-enhanced ultrasound (CEUS) has not been reported previously. We hypothesized that a CPT would induce changes in renal hemodynamics detectable by DU and CEUS. The objective was to measure the renal responses during a CPT using DU and CEUS. Design and method: This was a single center prospective study in healthy participants. Renal resistive index (RRI) and mean acceleration time (MAT) were measured 4 times during 2 minutes baseline conditions (water at body temperature) and 4 times during 2 minutes CPT conditions (water at 4°C). The same protocol was then repeated after 5 minutes washout period for the measurement of the perfusion index (PI), relative blood volume and mean transit time using CEUS. Renal hemodynamic responses during baseline and CPT were compared using a t-test or a Wilcoxon matched-pair signed-rank test if variables were not normally distributed. Results: 24 healthy participants (15 women, 9 men) were included. Mean age and body mass index were respectively (mean ± standard deviation) 33.9 ± 11.8 years and 24.3 ± 3.4 kg/m2. The CPT increased mean blood pressure by 19.8 ± 4.4 mmHg, heart rate by 14.0 ± 3.8 beats per min. The CPT decrease RRI from 0.60 ± 0.04 to 0.58 ± 0.04 (p = 0.018). This decrease was associated with the systolic blood pressure (rho: -0.43, p = 0.038) and heart rate response (rho = -0.52, p = 0.009). Mean acceleration time did not change. Perfusion index (median and interquartile range) increased from 2578 UI (1789; 4901) to 4148UI (2499; 6739) (p &lt; 0.001). Relative blood volume increased, but mean transit time did not change. Conclusions: This is the first demonstration that the CTP induces detectable changes in renal hemodynamics using both DU and CEUS. The CPT combined to DU and CEUS may be a valuable tool to assess the renal response to increased sympathetic drive in hypertensive or chronic kidney disease patients.

Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients

Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4+ effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8+ effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.

Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.

Pregnancy-associated plasma protein-A2 (PAPP-A2) is the homolog of PAPP-A in the vertebrate genome and its role in protecting against salt-induced hypertension in salt-sensitive rats has been confirmed. We sought to examine the associations of plasma PAPP-A2 levels and its genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in humans. Eighty participants (18-65 years old) sequentially consuming a usual diet, a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day). In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families in Northern China in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension over 14 years. The plasma PAPPA2 levels significantly decreased with the change from baseline to a low-salt diet and decreased further when converting from the low-salt to high-salt diet. SNP rs12042763 in the PAPP-A2 gene was significantly associated with systolic BP responses to both low-salt and high-salt diet while SNP rs2861813 showed a significant association with the changes in SBP and pulse pressure at 14-year follow-up. Additionally, SNPs rs2294654 and rs718067 demonstrated a significant association with the incidence of hypertension over the 14-year follow-up. Finally, the gene-based analysis found that Pappa2 was significantly associated with longitudinal SBP changes and the incidence of hypertension over the 14-year follow-up. This study shows that dietary salt intake affects plasma PAPP-A2 levels and that PAPP-A2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations.

Blood Pressure Responses to Static and Dynamic Knee Extensor Exercise between Sexes: Role of Absolute Contraction Intensity.

Males have larger blood pressure (BP) responses to relative-intensity static handgrip exercise compared with females. Controlling for absolute load (maximal voluntary contraction (MVC)) abolishes these differences. Whether similar observations exist during large muscle mass exercise or dynamic contractions, and the mechanisms involved, remains unknown. BP, heart rate, muscle oxygenation (near-infrared spectroscopy), and rectus femoris EMG were recorded in 28 males and 17 females during 10% and 30% MVC static (120 s) and isokinetic dynamic (180 s; 1:2 work-to-rest ratio; angular velocity, 60°·s-1) knee extensor exercise. Static and dynamic exercises were completed on separate visits, in a randomized order. Sex differences were examined with and without statistical adjustment of MVC (ANCOVA). Males had larger systolic BP responses (interaction, P < 0.0001) and muscle deoxygenation (interaction, P < 0.01) than did females during 10% static exercise, with no difference in EMG (interaction, P = 0.67). Peak systolic BP was correlated with MVC (r = 0.55, P = 0. 0001), and adjustment for MVC abolished sex differences in systolic BP (interaction, P = 0.3). BP, heart rate, muscle oxygenation/deoxygenation, and EMG responses were similar between sexes during 30% static exercise (interaction; all, P > 0.2), including following adjustment for MVC (all, P > 0.1). Males had larger systolic BP responses during dynamic exercise at 10% and 30% (interaction; both, P = 0.01), which were abolished after adjustment for MVC (interaction; both, P > 0.08). Systolic BP responses were correlated with absolute MVC and stroke volume responses during 10% (r = 0.31, P = 0.04; r = 0.61, P < 0.0001, respectively) and 30% (r = 0.48, P = 0.001; r = 0.59, P < 0.0001, respectively). Absolute contraction intensity can influence systolic BP responses to 10% but not 30% MVC static, as well as 10% and 30% MVC dynamic knee extensor exercise, and should be considered in cross-sectional comparisons of exercise BP.

Association of Blood Pressure and Heart Rate Responses to Submaximal Exercise With Incident Heart Failure: The Framingham Heart Study.

BackgroundExercise stress tests are conventionally performed to assess risk of coronary artery disease. Using the FHS (Framingham Heart Study) Offspring cohort, we related blood pressure (BP) and heart rate responses during and after submaximal exercise to the incidence of heart failure (HF).Methods and ResultsWe evaluated Framingham Offspring Study participants (n=2066; mean age, 58 years; 53% women) who completed 2 stages of an exercise test (Bruce protocol) at their seventh examination (1998–2002). We measured pulse pressure, systolic BP, diastolic BP, and heart rate responses during stage 2 exercise (2.5 mph at 12% grade). We calculated the changes in systolic BP, diastolic BP, and heart rate from stage 2 to recovery 3 minutes after exercise. We used Cox proportional hazards regression to relate each standardized exercise variable (during stage 2, and at 3 minutes of recovery) individually to HF incidence, adjusting for standard risk factors. On follow‐up (median, 16.8 years), 85 participants developed new‐onset HF. Higher exercise diastolic BP was associated with higher HF with reduced ejection fraction (ejection fraction <50%) risk (hazard ratio [HR] per SD increment, 1.26; 95% CI, 1.01–1.59). Lower stage 2 pulse pressure and rapid postexercise recovery of heart rate and systolic BP were associated with higher HF with reduced ejection fraction risk (HR per SD increment, 0.73 [95% CI, 0.57–0.94]; 0.52 [95% CI, 0.35–0.76]; and 0.63 [95% CI, 0.47–0.84], respectively). BP and heart rate responses to submaximal exercise were not associated with risk of HF with preserved ejection fraction (ejection fraction ≥50%).ConclusionsAccentuated diastolic BP during exercise with slower systolic BP and heart rate recovery after exercise are markers of HF with reduced ejection fraction risk.

Hemodynamic responses to In-Bed Cycle Exercise in the acute phase after moderate to severe stroke: A randomized controlled trial.

Hemodynamic responses to exercise in the acute phase after moderate to severe stroke have remained poorly investigated. The aim of this randomized controlled study, in which 52 (32 women) patients with moderate to severe stroke were randomized to three weeks of 20 minutes in‐bed cycle exercise 5 days per week or to usual care, was to explore the systolic blood pressure (SBP) response to exercise and to evaluate the impact of the intervention on the resting and post‐test systolic and diastolic blood pressures and heart rate, and on the systolic blood pressure response to exercise. We found that resting SBP decreased from baseline to post‐intervention in both the intervention group (147.7 ± 18.1 mmHg to 125.3 ± 17.1 mmHg, P < .001) and in the control group (147.8 ± 23.7 mmHg to 131.4 ± 14.8 mmHg, P < .001) without a significant difference between the groups (interaction P = .308). However, there was a significant difference (interaction P = .010) regarding how Δ SBP (change in SBP from pre‐test to post‐test) changed from baseline to post‐intervention. In the intervention group, Δ SBP increased from −1.0 ± 15.0 mmHg to 8.5 ± 9.4 mmHg, P = .009, whereas in the control group, Δ SBP decreased from 7.1 + 10.9 mmHg to 4.5 + 11.8 mmHg, P = .395. We conclude that patients randomized to in‐bed cycle exercise seemed to normalize their blood pressure response to exercise to a larger extent than patients in the control group.

Effort investment in uncontrollable situations: The moderating role of motivation toward closure

According to the principle of energy-conservation principle, effort investment is usually reduced in situations that are perceived as uncontrollable. This is because when success is recognized as impossible, any effortful actions are no longer justified. However, we predicted that individual differences in uncertainty tolerance, i.e., the need for closure (NFC), may moderate effort investment in uncontrollable situations. We tested this prediction in two experimental studies in which we exposed participants with differing levels of NFC to uncontrollable events, and indexed effort through the assessment of systolic blood pressure (SBP) responses. As predicted, in the uncontrollability (vs. controllability) condition, effort investment decreased significantly among low- but not high-NFC participants. Since gaining certainty and achieving closure is not a critical epistemic goal for low-NFC individuals, exerting extra effort to gain certainty is therefore no longer justified. On the other hand, high-NFC participants do not withhold their efforts, as they are highly motivated to obtain certainty. These results may help to account for contradictory findings in effort-investment behaviour and add substantively to the literature concerning motivation toward closure.