Changes In Augmentation Index Research Articles

Effects of General Anesthesia on Noninvasively Measured Central and Peripheral Blood Pressure: A Prospective, Observational-based Cross-over Study

Abstract Background: Blood pressure (BP) monitoring is the basic hemodynamic parameter necessary to monitor the hemodynamic changes occurring under general anesthesia (GA) to maintain adequate perfusion to major organs such as the heart, brain, and kidneys. Physicians heavily rely upon peripheral hemodynamic measurements despite availability of devices suitable for measurement of central blood pressure through non-invasive manner paving a gap in the literature concerning the effects of GA on central pressure. Aims and Objective: In this comparative cross-over study, authors have aimed to find out the degree of changes in central and peripheral BP after the introduction of GA among adult patients of different age groups scheduled for routine surgical procedures with an objective to maintain vital functions more precisely – considering the fact that vital organ perfusions (heart, brain etc.,) depend more on the required values of CBP than that of PBP. Material & Methods: Following approval from IEC, sixty adult patients with ASA physical status 1 or 2 undergoing routine surgical procedures under general anesthesia were enrolled in this prospective cross-over study where each patient was case as well control for measurement and comparison of his/her central and peripheral blood pressure. Patients, being divided into three groups as per age range - 20-40 years (Group A), 40-60 years (Group B), and 60-80 years (Group C) had their normal Riva Rocci BP cuff (Space Lab Inc. USA) placed in one arm for peripheral BP measurement and special Riva Rocci (Uscom Ltd., Australia).) BP cuff for on another arm for Central BP measurement. After patient’s arrival into operation theatre, baseline hemodynamic parameters were taken followed by sequential measurements of CBP and PBP with an interval of 2 minutes till 30-40 mins of operation. There were alternative measurements of these pressures with recording of data from either of the devices as mentioned for further comparison and analysis. Results: From baseline values, it was found that all the three groups were comparable in respect of age, height, weight, PBP and CBP. When measured pressure of all groups combined, that there was a fall in both Central and Peripheral SBP as well as DBP after giving intravenous induction agent (propofol) and rise in both central and peripheral SBP and DBP after laryngoscopy and intubation. Degree of systolic blood pressure change in both peripheral & central that is fall of BP in 3rd reading & rise of BP in 5th reading was greatest in group C, followed by group B, then group A [p - 0.005]. While comparing three subgroups, the baseline Augmentation Index (AI) was highest in group C and lowest in group A. Following the administration of general anesthesia (GA), the change in Augmentation Index (ΔAI), was most pronounced in the third reading corresponding to the time after the administration of the induction agent. Conclusion: Measurement of CBP through peripheral placement of cuff is a unique feasible method to detect real changes of circulation with actual pressure in vital organs. Thus, the study suggests that central blood pressure measurements can provide a more accurate reflection of hemodynamic changes during general anesthesia, especially in older individuals or those with different cardiovascular conditions allowing better vital management of body circulation.

IMPAIRED BETA-ADRENERGIC VASODILATOR FUNCTION IN HYPERTENSIVE PATIENTS WITH SYMPTOMS OF DEPRESSION

Objective: Hypertension and depression are amongst the most common chronic physical and mental conditions worldwide. The two conditions cluster, however the mechanisms underlying the association are not well understood. Hypertension complicated by affective disorders may be characterised by high sympathetic activity. We investigated whether symptoms of depression may be associated with impaired endothelium-dependent beta2-adrenergic vasodilator responses. Design and method: Hypertensive subjects with no previous history of diabetes or cardiovascular disease were recruited from the hypertension outpatient service at St. Thomas’ Hospital, London. Detailed medical history and baseline characteristics including blood pressure (BP), heart rate (HR), routine biochemistry including C-reactive protein (CRP) and low-density lipoprotein (LDL) were obtained during a single study visit. Plasma concentrations of normetadrenaline were measured as a marker of resting sympathetic activity. Depression symptom severity was assessed using the Patient Health Questionnaire-9 (PHQ-9). The pulse wave response to the beta2-adrenergic vasodilator salbutamol (PWRS) was assessed using radial tonometry to measure the change in augmentation index after inhalation of 200μg salbutamol from a metered dose inhaler with spacer device. Results: 100 subjects (62% male, mean ± SD age 41.0±11.6 years) were recruited. 79% were on pharmacological treatment for hypertension. Mean PHQ-9 depression score was 8.8±6.2, consistent with a high prevalence of depression. After adjusting for confounders (age, sex, smoking status, body mass index, BP, HR, CRP, LDL, treatment for hypertension), PWRS was significantly related to depression score (Beta= 0.447, P=0.002). Depression score was also significantly associated with plasma concentrations of normetadrenaline (Beta= 0.605, P<0.001) and after adjusting for plasma normetadrenaline level, the association between PWRS and depression score was no longer significant (Beta= 0.343, P=0.102). Conclusions: These results suggest that in hypertensive subjects with depression, an impaired endothelium-dependent beta2-adrenergic vasodilator response is mediated by a high level of sympathetic activity which could contribute to cardiovascular complications.

Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019.

The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown. Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample. One hundred and one participants (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n = 34) and those recovered from mild symptoms of COVID-19 ( n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P = 0.001). In a sub-sample ( n = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P = 0.006) with no significant difference between hospitalized ( n = 12) and nonhospitalized participants ( n = 10). In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

Acute Effects of Foam Rolling Exercises on Arterial Stiffness, Flexibility and Autonomic Nervous System Function in Young and Middle-Aged Women

PURPOSE: Arterial stiffness is an independent risk factor for cardiovascular disease and inversely associated with flexibility. Self-myofascial release (SMR) using a foam roller is a popular intervention to improve flexibility, restore the muscles, fascia, tendons, and ligaments, and regain soft-tissue extensibility. This study aimed to investigate whether a single bout of SMR has a beneficial effect on arterial stiffness and the function of the autonomic nervous system and the relationships among these variables in young and middle-aged women by age.METHODS: Ten healthy young (23.20±0.59 years) and 10 middle-aged women (44.50±0.91 years) completed an instructed SMR using a foam roller. Brachial-ankle pulse wave velocity (baPWV), augmentation index (AIx), trunk flexibility, shoulder flexibility, heart rate variability, including standard deviation of normal R-R intervals (SDNN), and the root mean square of the standard deviation of the time between heartbeats (RMSSD) were measured before and after one 30-minutes bout of SMR.RESULTS: After one bout of SMR, trunk and shoulder flexibility increased in both groups of women, while AIx decreased significantly (from 6.9±2.9 to -1.9±4.6%, p=.0072, young women group; from 22.1±3.4 to 14.7±1.7%, p=.0049, middle-aged women group). However, the baPWV, RMSSD, and SDNN did not change. In the analysis of correlations between all measured variables, changes in AIx showed negative correlations with flexibility and SDNN.CONCLUSIONS: This study suggests that one bout of SMR using a foam roller positively affected arterial stiffness in women by reducing AIx and improving flexibility.

Central blood pressure lowering effect of telmisartan-rosuvastatin single-pill combination in hypertensive patients combined with dyslipidemia: A pilot study.

This multicenter, phase 4, Prospective Randomized Open, Blinded End‐point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single‐pill combination (SPC) therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID‐19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10‐year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4‐week single‐group run‐in period with telmisartan 40–80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial‐ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between‐group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between‐group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between‐group difference p = .078). Change of AIx had no significant difference (between‐group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.

Effect of Limb-Specific Resistance Training on Central and Peripheral Artery Stiffness in Young Adults: A Pilot Study

This study aimed to investigate the effect of limb-specific resistance training on arterial stiffness in young adults. Twenty-four participants were randomly assigned to three groups: upper-limb resistance training (n = 8 (URT)), lower-limb resistance training (n = 8 (LRT)), and control group (n = 8 (CON)). Both URT and LRT groups performed the limb-specific resistance training at 70–80% of one-repetition maximum twice a week for 8 weeks. The aortic pulse wave velocity and augmentation index (AIx) were measured by the SphygmoCor XCEL to assess central artery stiffness. Peripheral artery stiffness was evaluated by brachial to radial artery pulse wave velocity (ArmPWV) and femoral to posterior tibial artery pulse wave velocity (LegPWV) using Doppler flowmeters. URT significantly reduced AIx (4.7 ± 3.0 vs. 0.3 ± 2.9%, pre vs. post, P = 0.01), and ArmPWV presented a tendency to decrease following URT (10.4 ± 0.3 vs. 8.6 ± 0.8 m/s, pre vs. post, P = 0.06). LRT showed no negative influence on central and peripheral artery stiffness. Changes in serum triglyceride and leg lean body mass after resistance training were significantly associated with changes in AIx and LegPWV, respectively. URT is beneficial in decreasing central artery wave reflection and may help to improve local peripheral artery stiffness even in healthy young adults.

Persistent augmentation of central arterial stiffness following viral clearance by direct-acting antivirals in chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection is associated with risk of cardiovascular diseases. Although direct-acting antivirals (DAA) result in rapid eradication of HCV, their long-term impact on arterial stiffness remains unclear. This study aimed to evaluate changes in parameters of central arterial stiffness from pretreatment, through sustained virological response, to one year after viral clearance. Patients with chronic HCV receiving DAA treatment were enrolled prospectively. Medical history and comorbidities of all patients were collected. Lipid profiles, liver stiffness by transient elastography and central blood pressures using pulse wave analysis of the brachial artery by cuff sphygmomanometry were measured before treatment, at viral clearance and at one year following viral clearance. Augmentation index (AIx), a parameter of aortic stiffness, was calculated as the ratio of augmentation pressure to central pulse pressure. After DAA treatment, all included patients with chronic HCV (n=102) had achieved viral clearance. Cholesterol, low-density lipoprotein (LDL) and triglyceride/high-density lipoprotein (TG/HDL) increased significantly at viral clearance and persisted at one year (all P<.001). AIx was also elevated significantly at viral clearance and persisted one year later (P<.001). Changes in AIx remained significant only in patients with increased values from baseline in either LDL (P<.01) or TG/HDL (P<.001). Central arterial stiffness and lipid profiles in patients with chronic HCV worsen immediately after viral eradication by DAA treatment and persist at one year. Worsening of lipid profiles after DAA treatment contributes to central arterial stiffness in this patient population and persists long term.

Altered Arterial Stiffness, Cerebral Blood Flow and Cognitive Function in Young Smokers in Response to One-Bout of Aerobic Exercise: MICE vs. HIIE

PURPOSE: This study aimed to compare the acute effects of high-intensity interval exercise (HIIE) with moderate-intensity continuous exercise (MICE) on arterial stiffness, cerebral blood flow and cognitive function in young smokers.METHODS: Young smokers (23.1 years &amp; 7.2 pack years) were randomly assigned to either MICE (n=5) or HIIE (n=4) group. MICE was implemented at 70% of HRmax for 30 minutes. HIIE was performed at 70% and 90% of HRmax for 24 minutes. Central artery stiffness was assessed by aortic pulse wave velocity (cfPWV), augmentation index (AIx) at pre and post-exercise, and 30 minutes, 1 hour, 2 hours, 24 hours following the exercises. Cerebral blood flow was continuously monitored using near-infrared spectroscopy technique before and during exercise, and at 30 minutes, 1 hour, 2 hours, and 24 hours following the exercises. Cognitive function was assessed by Stroop Color-Word test at pre-exercise, and 30 minutes and 24 hours following the exercises.RESULTS: There was no significant group by time interaction in cfPWV, AIx, cerebral blood flow (HbO2) level, and cognitive function. Compared with MICE, cfPWV was increased (p=.01) at 30 minutes but AIx was decreased (p=.02) at 1 hour following HIIE. When MICE and HIIE combined, arterial stiffness and cerebral blood flow measures, and cognitive function parameters were improved following even one-bout of exercise (p≤.049). Change in AIx was associated with change in cognitive function at 30 minutes following the exercises (r=.69, p=.06).CONCLUSIONS: Even one-bout of either MIIE or HIIT acutely improves aortic wave reflection, cerebral blood flow and cognitive function in young smokers. The intensity of aerobic exercise does not seem to make meaningful differences in the positive effects on arterial stiffness, cerebral blood flow, and cognitive function in young smokers if both exercises have the same volume.

Insulin Stimulation Reduces Arterial Stiffness In Adults With Metabolic Syndrome

PURPOSE: Adults with metabolic syndrome (MetS) have increased fasting arterial stiffness compared with healthy counterparts, and this, in turn, increases risk for cardiovascular disease (CVD) and cardiac events. Although insulin acts to reduce arterial stiffness in healthy adults, the effects in obese individuals with MetS are unclear. We hypothesized that insulin stimulation would reduce measures of arterial stiffness in relation to aerobic fitness and body fat. METHODS: Thirty-one obese adults (24F; 53.7±6.0yrs; 37.4±4.8kg/m2) were screened for MetS (NCEP ATP III criteria) following an overnight fast. Augmentation index (AIx), augmentation pressure (AP) and brachial systolic (bSBP) and diastolic blood pressure (bDBP) were assessed using SphygmoCor before and after a 2hr euglycemic-hyperinsulinemic clamp (90 mg/dl, 40 mU/m2/min). Aerobic fitness (VO2peak; ml/kg/min) was measured through a treadmill protocol while body fat (BF; %) was determined using DEXA. RESULTS: Compared to fasting, insulin significantly reduced AIx (28.5 ± 9.9 vs. 23.2 ± 9.9%, P<0.01) and AP (15.1 ± 6.7 vs. 21.1 ± 5.8 mmHg, P<0.01). However, there was no effect of insulin on bSBP (P=0.19) or bDBP (P=0.21). Fasting AIx and AP correlated with VO2peak (r=-0.42, P=0.02 and r=-0.37, P=0.04) and BF (r=0.64, P<0.01 and r=0.68, P<0.01). Interestingly, neither the change in AIx nor AP from fasting to insulin stimulation correlated with VO2peak (r=-0.18, P=0.33 and r=-0.12, P=0.95) or BF (r=-0.29, P=0.24 and r=-0.17, P=0.58). CONCLUSION: Insulin stimulation reduces indices of arterial stiffness in adults with MetS. While high aerobic fitness and lower BF may contribute to less arterial stiffness in the fasted state, they were not associated with insulin action. This suggests that insulin impacts arterial stiffness through another mechanism. Future research is warranted to determine the role of insulin on arterial health in order to optimize CVD prevention/treatment. Funding was supported by the National Institutes of Health RO1-HL130296.

The effect of acute aerobic exercise on central arterial stiffness, wave reflections, and hemodynamics in adults with diabetes: A randomized cross-over design

BackgroundIndividuals with diabetes have greater central arterial stiffness, wave reflections, and hemodynamics, all of which promote the accelerated cardiovascular pathology seen in this population. Acute aerobic exercise has been shown to be an effective strategy for reducing central arterial stiffness, wave reflections, and hemodynamics in healthy individuals; however, the effects of acute aerobic exercise in reducing these outcomes is not well established in people with diabetes. Recently, implementation of high-intensity interval exercise (HIIE) has shown superior improvements in cardiovascular health outcomes when compared to traditional aerobic exercise. Yet, the effect of HIIE on the aforementioned outcomes in people with diabetes is not known. The purpose of this study was to (i) describe the central arterial stiffness, wave reflections, and hemodynamic responses to a bout of HIIE and moderate-intensity continuous exercise (MICE) in adults with diabetes; and (ii) compare the effects of HIIE and MICE on the aforementioned outcomes. MethodsA total of 24 adult men and women (aged 29–59 years old) with type 1 (n = 12) and type 2 (n = 12) diabetes participated in a randomized cross-over study. All participants completed the following protocols: (i) HIIE: cycling for 4 × 4 min at 85%–95% of heart rate peak (HRpeak), interspersed with 3 min of active recovery at 60%–70%HRpeak; (ii) MICE: 33 min of continuous cycling at 60%–70%HRpeak; and (iii) control (CON): lying quietly in a supine position for 30 min. ResultsA significant group × time effect was found for changes in central systolic blood pressure (F = 3.20, p = 0.01) with a transient reduction for the HIIE group but not for the MICE or CON groups. There was a significant group × time effect for changes in augmentation index at a heart rate of 75 beats/min (F = 2.32, p = 0.04) with a decrease following for HIIE and MICE but not for CON. For all other measures of central arterial stiffness and hemodynamics, no significant changes were observed (p > 0.05). ConclusionA bout of HIIE appears to lead to a greater transient reduction in central systolic blood pressure than the reduction observed following MICE; however, both HIIE and MICE improved augmentation index at a heart rate of 75 beats/min in people with diabetes. There was no significant difference in response to HIIE and MICE in all outcomes. This provides preliminary evidence on the role of HIIE on such outcomes in people with diabetes.

Effects of Simvastatin on Augmentation Index Are Transient: Outcomes From a Randomized Controlled Trial.

BackgroundStatins improve endothelial function, but their effects on arterial stiffness and aortic blood pressure in middle‐aged adults are uncertain.Methods and ResultsThis was a prospective, randomized, double‐blind, placebo‐controlled trial of middle‐aged (40‐72 years old) adults who were randomly assigned to receive simvastatin 40 mg (n=44) or placebo (n=44) daily for 18 months to evaluate impact on dementia‐related biomarkers (primary end points) and measures of vascular health (secondary end points). This analysis focuses on the predetermined secondary end points of changes in central aortic blood pressure, aortic augmentation index, and brachial artery flow‐mediated dilation. Measurements were performed at baseline and after 6, 12, and 18 months. Multivariable models were used to identify predictors of these prespecified vascular end points. Study groups were similar at baseline; low‐density lipoprotein cholesterol declined in the statin group but not in the placebo group (P<0.01). There were no significant differences in changes in central blood pressure parameters or flow‐mediated dilation (all P>0.2). After 12 months, augmentation index decreased from baseline in the statin group compared with the placebo group (−2.3% [5.5%] versus 1.2% [5.7%], P=0.007), but by 18 months the response in both groups trend toward baseline (−1.1% [5.8%] versus 0.2% [4.8%], P=0.3). Low‐density lipoprotein cholesterol was not associated with changes in augmentation index at any time point.ConclusionsStatin therapy led to a short‐term reduction in augmentation index after 12 months, but this effect did not persist after 18 months despite continued reduction in low‐density lipoprotein cholesterol levels. These findings suggest that statins may have a transient effect on aortic stiffness.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifier: NCT00939822.

Effects of short-term exposure to fine and ultrafine particles from indoor sources on arterial stiffness - A randomized sham-controlled exposure study.

Particulate air pollution is linked to adverse cardiovascular effects, including arterial stiffness. The aim of the study was to investigate the effect of short-term exposure to indoor fine and ultrafine particles on augmentation index (AIx), augmentation pressure (AP), and pulse wave velocity (PWV), early signs of vascular damage. We analyzed the association of particle emissions from typical indoor sources (candle burning - CB, toasting bread - TB, and frying sausages - FS) with changes in pulse wave analysis indices in 55 healthy adults in a randomized cross-over controlled exposure study. Particle mass concentration (PMC), size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) were measured during the 2 h exposure. AIx and AP were measured before, directly, 2, 4 and 24 h after exposure. PWV was measured directly and 24 h after exposure. We performed multiple mixed linear regression analyses of different particle metrics and AIx, AP and PWV. The highest mean PMC was observed during FS reaching a maximum of 210 μg/m3 PM10. The maximal PNC for UFP <100 nm was reached during CB with 2.3 million particles/cm3. PSC was similar across all three exposures (about 3000 μm2/cm³). Strongest associations between different particles metrics and arterial stiffness indices could be observed for UFP from CB and FS and for PMC from TB. The highest mean increase could be observed for the UFP fraction <10 nm, measured during CB, and AIx with an increase of 9.5%-points (95%-CI: 3.1; 15.9). PSC seemed to follow the pattern of PNC. PM10 and PM2.5 from TB led to clear changes in AIx with biggest increases for PM10 of 5.8%-points (95%-CI: 3.2; 8.4) 2 h after exposure and for PM2.5 of 8.1%-points (95%-CI: 2.5; 13.7) directly after exposure. Our study indicates effects of indoor exposure to fine and ultrafine particles on systemic arterial stiffness indices that depend on the indoor source as well as on particle metric. Differences in size-specific physical characteristics of source-specific particles might account for these differential effects. We did not observe clear and stable associations of indoor particle exposure and PWV.

Acute Changes in Augmentation Index and Pulse Wave Velocity Following Controlled Exposures to Cookstove Air Pollution in the Subclinical Tests of Volunteers Exposed to Smoke (Stoves) Study

Acute Changes in Augmentation Index and Pulse Wave Velocity Following Controlled Exposures to Cookstove Air Pollution in the Subclinical Tests of Volunteers Exposed to Smoke (Stoves) Study

Sex differences in the contribution of blood pressure to acute changes in aortic augmentation index.

Augmentation index (AIx), derived from aortic pulse waveform, is related to arterial stiffness and increased cardiac workload. Sex differences were observed in the relationship between blood pressure (BP) and AIx at rest. In addition, positive correlation between BP and AIx in men during a pressor stimulus was observed previously. However, whether BP is important to acute changes of AIx also in women is yet to be investigated. Therefore, we sought to investigate whether there are sex differences on the relationship between BP and AIx. In all, 16 men (age 27 ± 5 yr; height 176 ± 1 cm; weight 77 ± 7 kg; mean ± SD) and 13 women (age 26 ± 5 yr; height 164 ± 0.3 cm; weight 63 ± 7 kg; mean ± SD) underwent 3 min of rest followed by 3 min of cold pressor test (CPT). Heart rate during CPT was similar to rest. CPT increased BP in both groups and the magnitude was similar between groups. AIx and left ventricle energy wasted (EW) increased (men Δ13 ± 5% and women Δ17 ± 3%; p > 0.05 for group; men Δ580 ± 242 dynes cm-2 s-1 and women Δ618 ± 123 dynes cm-2 s-1; p > 0.05 for group) similarly in men and women during CPT. A positive Pearson correlation was found between AIx and BP in men (systolic BP (SBP) r = 0.77, p = 0.01; diastolic BP (DBP) r = 0.79, p = 0.01 and mean arterial pressure (MAP) r = 0.83, p < 0.01), however no correlation was seen in women (SBP r = 0.04, p = 0.89; DBP r = 0.24, p = 0.44 and MAP r = 0.23, p = 0.44). The contribution of BP to acute changes in AIx at higher levels of BP is different between men and women.

Myocardial preload alters central pressure augmentation through changes in the forward wave.

Augmentation index (AIx) is often used to quantify the contribution of wave reflection to central pulse pressure. Recent studies have challenged this view by showing how contractility-induced changes in the forward pressure wave can markedly impact AIx. We hypothesized that changes in preload will also affect AIx through changes in the forward wave and studied this in two experiments. Noninvasively obtained aortic pressure was used to study central haemodynamics and wave morphology. In the first experiment, we examined the effects of head-up tilt with and without unilateral thigh cuff in 12 young healthy volunteers (mean age 26 years, 50% men). In the second experiment, we examined the effects of active standing in 31 middle-aged patients (mean age 57 years, 65% men) before and after phlebotomy. Head-up tilt or active standing significantly decreased AIx [-17.7 ± 10.4 percentage point (pp) in the young population, -4.7 ± 12.3 pp in the middle-aged population, both P < 0.05]. The fall in AIx was associated with increases in HR, diastolic pressure and systemic vascular resistance and a decrease in stroke volume (all P < 0.05). Inflation of a unilateral thigh cuff reduced the decrease in AIx by 10.7 pp, whereas 500 ml of blood loss augmented the fall in AIx by 5.9 pp (both P < 0.05). The changes in AIx were related to a preload-induced change in forward pressure wave shape (earlier peaking and steeper downstroke). Next to inotropic and chronotropic effects, preload emerges as another myocardial factor that obscures the relation between wave reflection and AIx.

Sex differences in aortic augmentation index in adolescents.

Augmentation index (AIx) is a noninvasive measure of pulse wave reflection. AIx is associated with cardiovascular disease. Adult women have a higher AIx than men, but the factors determining this sex-related difference remain to be determined. To examine factors associated with AIx in adolescents, participants in the Childhood Asthma Prevention Study, followed from birth, were assessed at age 14 years, with AIx standardized to a heart rate of 75/min (AIx_75) and pulse wave velocity. Associations of AIx_75 and pulse wave velocity with height, change in height, and measures of puberty were assessed. AIx_75 was higher in women compared to men [-24.5 (12.1) versus -32.3 (12.4)%; P < 0.001]. Lower AIx_75 was significantly related to greater change in height between 8 and 14 years, but not to achieved height. The sex difference in AIx was not independently related to puberty variables. Differences between sexes included early life weight gain, lipids, height, BMI-Z-score, change in height from 8 to 14 years, and age at peak height velocity. Change in AIx_75 from 8 to 14 years was highly associated with change in height (m) from 8 to 14 years (B = -88.8, 95% confidence interval -137.3 to -40.3, P = < 0.001). The difference between sexes established at 8 years was not amplified from 8 to 14 years. AIx is higher in girls than boys at 14 years and is closely associated with change in height between 8 and 14 years. Measures of puberty do not appear to independently influence the sex difference in AIx in adolescents.

Low dose‐eplerenone treatment decreases aortic stiffness in patients with resistant hypertension

Vascular damage is aggravated in animal models of hypertension with mineralocorticoid (MR) excess and in hypertensive patients with primary hyperaldosteronism. MR antagonism has shown to provide effective blood pressure (BP)-control in patients with treatment resistant hypertension (TRH), but the concurrent effects on the vasculature have not been examined. In a randomized, double-blinded, placebo-controlled parallel-group study, 51 patients with TRH received either eplerenone 50 mg or placebo for 6months together with additional antihypertensives titrated to achieve a BP target of <140/90mmHg. Pulse wave velocity (PWV), augmentation index (AIx), augmentation pressure (AP), AP normalized to a heart rate of 75/min (AP@HR75), renal resistive index (RRI), intima-media thickness (IMT) and urinary albumin excretion rate (UAER) were assessed before and after treatment. PWV was reduced only with eplerenone (from 11.3±3.6 to 9.8±2.6m/s, P˂.001), but not with placebo (10.3±2.0 to 10.1±1.8m/s, P=.60), despite similar reductions in BP (-35±20/-15±11mmHg vs -30±19/-13±7mmHg, n.s.). Further, reductions in AP and AP@HR75 were greater with eplerenone, while changes in AIx, RRI, IMT and UAER were similar. Our data show that eplerenone beneficially affects markers of arterial stiffness and wave reflection in patients with TRH, independently of BP lowering. These data add to the evidence that MR antagonism should be the preferred treatment option in TRH.

Influence of sympathetic nerve activity on aortic hemodynamics and pulse wave velocity in women.

Central (aortic) blood pressure, arterial stiffness, and sympathetic nerve activity increase with age in women. However, it is unknown if the age-related increase in sympathetic activity influences aortic hemodynamics and carotid-femoral pulse wave velocity (cfPWV), an index of central aortic stiffness. The goal of this study was to determine if aortic hemodynamics and cfPWV are directly influenced by sympathetic nerve activity by measuring aortic hemodynamics, cfPWV, and muscle sympathetic nerve activity (MSNA) in women before and during autonomic ganglionic blockade with trimethaphan camsylate. We studied 12 young premenopausal (23 ± 4 yr) and 12 older postmenopausal (57 ± 3 yr) women. These women did not differ in body mass index or mean arterial pressure (P > 0.05 for both). At baseline, postmenopausal women had higher aortic pulse pressure, augmented pressure, augmentation index adjusted for a heart rate of 75 beats/min, wasted left ventricular pressure energy, and cfPWV than young women (P < 0.05). During ganglionic blockade, postmenopausal women had a greater decrease in these variables in comparison to young women (P < 0.05). Additionally, baseline MSNA was negatively correlated with the reductions in aortic pulse pressure, augmented pressure, and wasted left ventricular pressure energy during ganglionic blockade in postmenopausal women (P < 0.05) but not young women. Baseline MSNA was not correlated with the changes in augmentation index adjusted for a heart rate of 75 beats/min or cfPWV in either group (P > 0.05 for all). Our results suggest that some aortic hemodynamic parameters are influenced by sympathetic activity to a greater extent in older postmenopausal women than in young premenopausal women.NEW & NOTEWORTHY Autonomic ganglionic blockade results in significant decreases in multiple aortic pulse wave characteristics (e.g., augmented pressure) and central pulse wave velocity in older postmenopausal women but not in young premenopausal women. Certain aortic pulse wave parameters are negatively influenced by sympathetic activity to a greater extent in older postmenopausal women.

Effects of a 4 Week Exercise Intervention on Brachial and Core Blood Pressures

Cardiovascular disease is the leading cause of mortality in the world. Research has consistently shown that high blood pressure is a major cardiovascular risk factor, which emphasizes the need to monitor it in all individuals. Blood pressure measurements are typically obtained using the brachial artery, but core blood pressure obtained using pulse wave analysis (PWA) has been gaining popularity. This is due to the fact that previous research supports that core blood pressure may be a better predictor of cardiovascular events. PURPOSE:To determine if a 4-week functional exercise intervention will change blood pressure measurements obtained in adults using the traditional brachial cuff and the more novel PWA procedure. METHODS:Eleven healthy adults have finished the 4-week self-report exercise intervention. Participants completed pre- and post- fasted and fitness tests. During the fasted appointment, clinic brachial systolic (bSBP) and diastolic blood pressure (bDBP), and core systolic (cSBP) and diastolic blood pressure (cDBP) were measured. Core blood pressure was obtained through PWA, which utilizes a tonometer placed on the radial artery. During the fitness appointment clinic blood pressure was again measured. For the intervention, 3 times a week, participants completed a 6-station exercise circuit, rotating through the stations 3 times. The circuit included functional exercises such as weighted carries, stair climbs, balance, and core strength. RESULTS:Participants’ average age was 32 ±15.7 yrs, and body weight was 156.6 ±28.8 lbs. Adherence to the 4-wk exercise program was 95.5%. We found that body fat decreased from 23.2 to 22.1% and VO2peak increased from 39.8 to 41.6 ml/kgmin. We found improvement in brachial blood pressures with the intervention (bSBP decreased 2.3mmHg from 119.3 ±6.6 to117 ±7.7mmHg, p=0.03; bDBP decreased 2.8mmHg from 70.8 ±6.5 to 68 ±7.5mmHg). We also found improvement in core blood pressures (cSBP decreased 1.1mmHg from 109.6 ±12.1 to108 ±11.7mmHg; cDBP decreased 2.2mmHg from 75.5 ±12 to 73.3 ±7.5mmHg). We found no change in augmentation index. CONCLUSIONS:It appears that four weeks of a functional exercise program improves clinic and core blood pressures. We hypothesize that with a larger sample size obtained from our ongoing study we will find more significant results.

Multi-component Exercise Training and Protein-pacing Improves Fitness Outcomes in Women

Multimodal training (Resistance, Interval, Stretching, and Endurance, RISE) improves body composition in overweight adults. However, it’s unclear how RISE might affect active normal weight women and whether high dietary protein intake (P) might modify the responses to RISE (PRISE), including the effects on performance outcomes. PURPOSE: To determine the effect of RISE alone, or PRISE on performance outcomes, cardio-metabolic health, and body composition in active normal weight women. METHODS: 27 healthy active females (BMI < 30kg/m2; 42±8 yrs) were recruited for this study and randomized to either standard dietary protein intake (CON: 1.0 g/kg/body weight/day) or high dietary protein intake (HP: 2.0 g/kg/bw/d). Baseline assessment of performance assessed via abdominal, upper and lower body muscular strength (situps, pushups, 1 RM bench and leg presses), power (jump squats and bench throws), aerobic power (5km cycling time trial), flexibility (sit and reach), and balance (stork stand), cardiovascular health (blood pressure, and augmentation index (AIx)), body composition (iDEXA: Fat free mass, fat mass, abdominal/visceral fat, %body fat), hunger/satiety ratings (visual analog scales), and cardio-metabolic profile (energy expenditure, fasting lipids, glucose, insulin). RESULTS: At baseline, no differences existed between groups in any variable. Some aspects of performance, while improved from baseline (1RM bench 10±15 [INCREMENT]lbs, 1RM leg press 123±120 [INCREMENT]lbs, SJ peak power 90±207 [INCREMENT]watts, flexibility 3±2 [INCREMENT]cm, balance 5.5±3 [INCREMENT]sec, 5km TT -28±11 [INCREMENT]sec, p<0.05), were not different between groups. However, other improvements in performance were enhanced in the HP group (Situps 6±7 v. 10±7 [INCREMENT]reps, Pushups 8±13 v. 14±12 [INCREMENT]reps, bench throw peak power 11±35 v. 44±34 [INCREMENT]watts, CON v. HP, p<0.05). BP and AIx were improved with training, but the changes in AIx (1±9 v. -5±11 %) and DBP (-5±9 v. -11±11 mmHg) were greater in the HP group (p<0.05). All aspects of body composition were improved, but no group differences existed. CONCLUSION: The RISE protocol improves multiple aspects of performance, cardiovascular health, and body composition and inclusion of high dietary protein (PRISE) seems to confer additional benefit in terms of strength, power, and cardiovascular health. Funding was provided by Isagenix International LLC to PJA