Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

Arterial Stiffness and Incident Glaucoma: A Large Population-Based Cohort Study.

PURPOSE: To investigate whether arterial stiffness, assessed oscillometrically, is associated with incident glaucoma in the Vitamin D Assessment (ViDA) Study cohort, aged 50 to 84 years. DESIGN: Prospective, population-based cohort study. METHODS: Arterial stiffness was assessed in 4,713 participants without known glaucoma (mean ± SD age = 66 ± 8 years) from 5 April 2011 to 6 November 2012 by way of aortic PWV (aPWV), estimated carotid-femoral PWV (ePWV) and aortic PP (aPP). Incident glaucoma was identified through linkage to national prescription and hospital discharge registers. Relative risks of glaucoma for each arterial stiffness measure were estimated by Cox proportional hazards regression, over the continuum of values and by quartiles. RESULTS: During a mean ± SD follow-up of 10.5±0.4 years, 301 participants developed glaucoma. Arterial stiffness, as measured by aPWV (Hazard ratio (HR) per SD increase, 1.36, 95% CI 1.14-1.62) and ePWV (HR per SD increase, 1.40, 95% CI 1.14-1.71) but not aPP (HR per SD increase, 1.06, 95% CI 0.92-1.23) was associated with incident glaucoma. When arterial stiffness was analyzed as a categorical variable, the highest quartiles of aPWV (HR, 2.62, 95% CI 1.52-4.52; Ptrend = .007), ePWV (HR, 2.42, 95%CI 1.37-4.27; Ptrend = .03), and aPP (HR, 1.68, 95%CI 1.10-2.5; Ptrend = .02) were associated with the development of glaucoma. CONCLUSIONS: Arterial stiffness measured with a simple oscillometric device predicted the development of glaucoma and could potentially be used in clinical practice to help identify people at risk of this condition. It may also present a new therapeutic research avenue, including in respect of systemic antihypertensives.

Arterial stiffness and incident chronic kidney disease: a large population-based cohort study.

BACKGROUND/AIMS: Evidence from large population-based cohorts as to the association of arterial stiffness and incident chronic kidney disease (CKD) is mixed. This large population-based study aimed to investigate whether arterial stiffness, assessed oscillometrically, was associated with incident CKD. METHODS: The study population comprised 4838 participants from the Vitamin D Assessment (ViDA) Study without known CKD (mean ± SD age = 66 ± 8). Arterial stiffness was assessed from 5 April, 2011 to 6 November, 2012 by way of aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure. Incident CKD was determined by linkage to national hospital discharge registers. Cox proportional hazards regression was used to assess the risk of CKD in relation to chosen arterial stiffness measures over the continuum and quartiles of values. RESULTS: During a mean ± SD follow-up of 10.5 ± 0.4 years, 376 participants developed incident CKD. Following adjustment for potential confounders, aortic pulse wave velocity (hazard ratio (HR) per SD increase 1.69, 95% CI 1.45-1.97), estimated carotid-femoral pulse wave velocity (HR per SD increase 1.84, 95% CI 1.54-2.19), and aortic pulse pressure (HR per SD increase 1.37, 95% CI 1.22-1.53) were associated with the incidence of CKD. The risk of incident CKD was, compared to the first quartile, higher in the fourth quartile of aortic pulse wave velocity (HR 4.72, 95% CI 2.69-8.27; Ptrend < 0.001), estimated carotid-femoral pulse wave velocity (HR 4.28, 95% CI 2.45-7.50; Ptrend < 0.001) and aortic pulse pressure (HR 2.71, 95% CI 1.88-3.91; Ptrend < 0.001). CONCLUSIONS: Arterial stiffness, as measured by aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure may be utilised in clinical practice to help identify people at risk of future CKD. TRIAL REGISTRATION: www.anzctr.org.au identifier:ACTRN12611000402943.

Non-invasive pulse arrival time as a surrogate for oscillometric systolic blood pressure changes during non-pharmacological intervention.

Background.Non-invasive continuous blood pressure (BP) monitoring is of longstanding interest in various cardiovascular scenarios. In this context, pulse arrival time (PAT), i.e., a surrogate parameter for systolic BP (change), became very popular recently, especially in the context of cuffless BP measurement and dedicated lifestyle interventions. Nevertheless, there is also understandable doubt on its reliability in uncontrolled and mobile settings.Objective.The aim of this work is therefore the investigation whether PAT follows oscillometric systolic BP readings during moderate interventions by physical or mental activity using a medical grade handheld device for non-invasive PAT assessment.Approach.A study was conducted featuring an experimental group performing a physical and a mental task, and a control group. Oscillometric BP and PAT were assessed at baseline and after each intervention. Interventions were selected randomly but then performed sequentially in a counterbalanced order. Multivariate analyses of variance were used to test within-subject and between-subject effects for the dependent variables, followed by univariate analyses for post-hoc testing. Furthermore, correlation analysis was performed to assess the association of intervention effects between BP and PAT.Mainresults.The study included 51 subjects (31 females). Multivariate analysis of variances showed that effects in BP, heart rate, PAT and pulse wave parameters were consistent and significantly different between experimental and control groups. After physical activity, heart rate and systolic BP increased significantly whereas PAT decreased significantly. Mental activity leads to a decrease in systolic BP at stable heart rate. Pulse wave parameters follow accordingly by an increase of PAT and mainly unchanged pulse wave analysis features due to constant heart rate. Finally, also the control group behaviour was accurately registered by the PAT method compared to oscillometric cuff. Correlation analyses revealed significant negative associations between changes of systolic BP and changes of PAT from baseline to the physical task (-0.33 [-0.63, 0.01],p< 0.048), and from physical to mental task (-0.51 [-0.77, -0.14],p= 0.001), but not for baseline to mental task (-0.12 [-0,43,0,20],p= 0.50) in the experimental group.Significance.PAT and the used digital, handheld device proved to register changes in BP and heart rate reliably compared to oscillometric measurements during intervention. Therefore, it might add benefit to future mobile health solutions to support BP management by tracking relative, not absolute, BP changes during non-pharmacological interventions.

Screening for Peripheral Vascular Stiffness in Lipedema Patients by Automatic Electrocardiogram-Based Oscillometric Detection.

Body mass index (BMI) is seen as a predictor of cardiovascular disease (CVD) in lipedema patients. A valid predictor of CVD is increased aortic stiffness (IAS), and previous research described IAS in lipedema. However, it is not known if this applies to all patients. In this cross-sectional single-center cohort study, peripheral pulse wave velocity (PWV) as a non-invasive indicator of aortic stiffness was measured in 41 patients with lipedema, irrespective of stage and without pre-existing cardiovascular conditions or a history of smoking and a maximum body mass index (BMI) of 35 kg/m2. Automatically electrocardiogram-triggered oscillometric sensor technology by the Gesenius-Keller method was used. Regardless of the stage of lipedema disease, there was no significant difference in PWV compared to published standard values adjusted to age and blood pressure. BMI alone is not a predictor of cardiovascular risk in lipedema patients. Measuring other anthropometric factors, such as the waist-hip ratio or waist-height ratio, should be included, and the existing cardiovascular risk factors, comorbidities, and adipose tissue distribution for accurate risk stratification should be taken into account. Automated sensor technology recording the PWV represents a valid and reliable method for health monitoring and early detection of cardiovascular risks.

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Automatic ECG-based detection of left ventricular hypertrophy and its predictive value in haemodialysis patients.

Objective.Left ventricular hypertrophy (LVH) is one of the most severe risk factors in patients with end-stage kidney disease (ESKD) regarding all-cause and cardiovascular mortality. It contributes to the risk of sudden cardiac death which accounts for approximately 25% of deaths in ESKD patients. Electrocardiography (ECG) is the least expensive way to assess whether a patient has LVH, but manual annotation is cumbersome. Thus, an automated approach has been developed to derive ECG-based LVH parameters. The aim of the current study is to compare automatic to manual measurements and to investigate their predictive value for cardiovascular and all-cause mortality.Approach.From the 12-lead 24 h ECG measurements of 301 ESKD patients undergoing haemodialysis, three different LVH parameters were calculated. Peguero-Lo Presti voltage, Cornell voltage, and Sokolow-Lyon voltage were automatically derived and compared to the manual annotations. To determine the agreement between manual and automatic measurements and their predictive value, Bland-Altman plots were created and Cox regression analysis for cardiovascular and all-cause mortality was performed.Main results.The median values for the automatic assessment were: Peguero-Lo Presti voltage 1.76 mV (IQR 1.29-2.55), Cornell voltage 1.14 mV (IQR 0.721-1.66), and Sokolow-Lyon voltage 1.66 mV (IQR 1.08-2.23). The mean differences when compared to the manual measurements were -0.027 mV (0.21 SD), 0.027 mV (0.13 SD) and -0.025 mV (0.24 SD) for Peguero-Lo Presti, Cornell, and Sokolow-Lyon voltage, respectively. The categorial LVH detection based on pre-defined thresholds differed in only 13 cases for all indices between manual and automatic assessment. Proportional hazard ratios only differed slightly in categorial LVH detection between manually and automatically determined LVH parameters; no differences could be found for continuous parameters.Significance.This study provides evidence that automatic algorithms can be as reliable in LVH parameter assessment and risk prediction as manual measurements in ESKD patients undergoing haemodialysis.

Handheld Device Measures Cardiovascular Effects of Cognitive and Physical Stress.

Stress is an increasing burden for our society and related to cardiovascular (CV) parameters and diseases. Effects of mental or physical stress were observed in CV parameters during task completion and recovery. These effects were measured using a novel handheld device, which can be incorporated in mHealth solutions.

Device-guided slow breathing with direct biofeedback of pulse wave velocity - acute effects on pulse arrival time and self-measured blood pressure.

BACKGROUND: There isevidence that device-guided slow breathing using biofeedback acutely reduces blood pressure (BP) and pulse wave velocity [i.e. increased pulse arrival time (PAT)]. OBJECTIVES: The objectives of the study presented here were to test whether the results of changes observed in PAT in earlier studies are reproducible over 1 week and how changes in pulse wave velocity/PAT translate into absolute self-measured BP changes. METHODS: Patients with a systolic BP 130-160 mmHg or treated essential hypertension (21 females/23 males) were trained to perform unattended device-guided slow breathing exercises for 10 min daily over 5 days. Furthermore, they were skilled to perform self-measurement of BP before and after the breathing exercise using a validated upper-arm device. RESULTS: Office BP at screening [median (1, 3. Q)] was 137 (132, 142)/83 (79, 87) mmHg. We observed a significant ( P < 0.05) increase in PAT of 5 ms (SD 12.5 ms) on average after 10 min of guided breathing and an additional 1 ms ( P < 0.05, SD 8 ms) during the following 5 min of spontaneous breathing compared to baseline. PAT before the exercise remained constant over 5 days paralleled by constant self-measured BP before the exercise. Device-guided breathing was associated with a significant reduction of self-measured SBP of 5 mmHg ( P < 0.01, SD 8 mmHg). Data furthermore demonstrated that these changes were highly reproducible over 1 week. CONCLUSIONS: Device-guided slow breathing and biofeedback lead to reproducible and favorable changes (increase) in PAT and SBP (decrease).

Prediction of Cardiovascular Events by Pulse Waveform Parameters: Analysis of CARTaGENE.

Background Waveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown. Methods and Results We analyzed participants aged between 40 and 69 from the population-based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10-year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c-index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow-up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores. Conclusions Some waveform parameters are independently associated with MACEs in a population-based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.

Attractor Reconstruction for Quantifying the Arterial Pulse Wave Morphology During Device-Guided Slow Breathing.

Attractor reconstruction is a new way to quantify the morphology of a cardiovascular waveform by plotting all data points in the three-dimensional phase space, generating a trajectory of overlapping loops. The aim of this study is to show the feasibility of an automatic approach to quantify pulse wave attractors from a device-guided breathing study, and to link attractor features to pulse waveform features. The recently developed feature extraction technique is applied to arterial pulse waveform data of 30 patients with treated hypertension. The patients performed a device-guided slow breathing exercise. The generated attractors were categorized into three different shapes: triangular attractors, bent attractors and attractors with overlapping arms. The average height of the attractors continuously and progressively dropped from 41.8 [35.4, 55.1] AU to 34.5 [25.4, 47.3] AU (p < 0.001) during the breathing exercise. We have shown that the novel approach to quantify pulse wave attractors is feasible and can be used to detect changes in the morphology of arterial pulse waveforms. Device-guided slow breathing exercise has a shrinking effect on the average height of the attractors, which may indicate a reduction in blood pressure.

Twenty-Four-Hour Pulsatile Hemodynamics Predict Brachial Blood Pressure Response to Renal Denervation in the SPYRAL HTN-OFF MED Trial.

BACKGROUND: Renal denervation (RDN) lowers blood pressure (BP), but BP response is variable in individual patients. We investigated whether measures of pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, predict BP drop following RDN. METHODS: From the randomized, sham-controlled SPYRAL HTN-OFF MED Pivotal trial, we performed a post hoc analysis of BP waveforms from 111 RDN patients and 111 sham controls, obtained with a brachial cuff-based sphygmomanometer. Waveforms were acquired during ambulatory BP monitoring at diastolic BP level and processed with validated ARCSolver algorithms to derive hemodynamic parameters (augmentation index; augmentation pressure; backward and forward wave amplitude; estimated aortic pulse wave velocity). We investigated the relationship between averaged 24-hour values at baseline and the change in 24-hour BP at 3 months in RDN patients, corrected for observed trends in the sham group. RESULTS: There was a consistent inverse relationship between baseline augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity and BP response to RDN: the decrease in 24-hour systolic BP/diastolic BP was 7.8/5.9 (augmentation index), 8.0/6.3 (augmentation pressure), 6.7/5.4 (backward wave amplitude), 5.7/4.7 (forward wave amplitude), and 7.8/5.2 (estimated aortic pulse wave velocity) mm Hg greater for patients below versus above the respective median value (P<0.001 for all comparisons, respectively). Taking augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity into account, a favorable BP response following RDN, defined as a drop in 24-hour systolic blood pressure of ≥5 mm Hg, could be predicted with an area under the curve of 0.70/0.74/0.70/0.65/0.62 (P<0.001 for all, respectively). CONCLUSIONS: These results suggest that pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, may predict BP response to RDN.

Feasibility of Dialysate Bolus-Based Absolute Blood Volume Estimation in Maintenance Hemodialysis Patients.

BACKGROUND: Absolute blood volume (ABV) is a critical component of fluid status, which may inform target weight prescriptions and hemodynamic vulnerability of dialysis patients. Here, we utilized the changes in relative blood volume (RBV), monitored by ultrasound (BVM) upon intradialytic 240 mL dialysate fluid bolus-infusion 1 h after hemodialysis start, to calculate the session-specific ABV. With the main goal of assessing clinical feasibility, our sub-aims were to (i) standardize the BVM-data read-out; (ii) determine optimal time-points for ABV-calculation, "before-" and "after-bolus"; (iii) assess ABV-variation. METHODS: We used high-level programming language and basic descriptive statistics in a retrospective study of routinely measured BVM-data from 274 hemodialysis sessions in 98 patients. RESULTS: Regarding (i) and (ii), we automatized the processing of RBV-data, and determined an algorithm to select the adequate RBV-data points for ABV-calculations. Regarding (iii), we found in 144 BVM-curves from 75 patients, that the average ABV ± standard deviation was 5.2 ± 1.5 L and that among those 51 patients who still had ≥2 valid estimates, the average intra-patient standard deviation in ABV was 0.8 L. Twenty-seven of these patients had an average intra-patient standard deviation in ABV <0.5 L. CONCLUSIONS: We demonstrate feasibility of ABV-calculation by an automated algorithm after dialysate bolus-administration, based on the BVM-curve. Based on our results from this simple "abridged" calculation approach with routine clinical measurements, we encourage the use of multi-compartment modeling and comparison with reference methods of ABV-determination. Hopes are high that clinicians will be able to use ABV to inform target weight prescription, improving hemodynamic stability.

Electrocardiographic parameters of left ventricular hypertrophy and prediction of mortality in hemodialysis patients.

BACKGROUND: In hemodialysis patients, left ventricular hypertrophy (LVH) contributes to high cardiovascular mortality. We examined cardiovascular mortality prediction by the recently proposed Peguero-Lo Presti voltage since it identifies more patients with electrocardiographic (ECG) LVH than Cornell or Sokolow-Lyon voltages. METHODS: A total of 308 patients on hemodialysis underwent 24 h ECG recordings. LVH parameters were measured before and after dialysis. The primary endpoint of cardiovascular mortality was recorded during a median 3-year follow up. Risk prediction was assessed by Cox regression, both unadjusted and adjusted for the Charlson Comorbidity Index and the Cardiovascular Mortality Risk Score. RESULTS: The Peguero-Lo Presti voltage identified with 21% the most patients with positive LVH criteria. All voltages significantly increased during dialysis. Factors such as ultrafiltration rate, Kt/V, body mass index, sex, and phosphate were the most relevant for these changes. During follow-up, 26 cardiovascular deaths occurred. Post-dialysis Peguero-Lo Presti cut-off as well as the Peguero-Lo Presti and Cornell voltages were independently associated with cardiovascular mortality in unadjusted and adjusted analysis. The Sokolow-Lyon voltage was not significantly associated with mortality. An optimal cut-off for the prediction of cardiovascular mortality was estimated at 1.38 mV for the Peguero-Lo Presti. CONCLUSIONS: The post-dialysis Peguero-Lo Presti cut-off as well as the Peguero-Lo Presti and Cornell voltages allowed independent risk prediction of cardiovascular mortality in hemodialysis patients. Measuring the ECG LVH parameters after dialysis might allow a standardized interpretation as dialysis-specific factors influence the voltages.

Increased Excess Pressure After Creation of an Arteriovenous Fistula in End-Stage Renal Disease.

BACKGROUND: Reservoir-wave analysis (RWA) separates the arterial waveform into reservoir and excess pressure (XSP) components, where XSP is analogous to flow and related to left ventricular workload. RWA provides more detailed information about the arterial tree than traditional blood pressure (BP) parameters. In end-stage renal disease (ESRD), we have previously shown that XSP is associated with increased mortality and is higher in patients with arteriovenous fistula (AVF). In this study, we examined whether XSP increases after creation of an AVF in ESRD. METHODS: Before and after a mean of 3.9 ± 1.2 months following creation of AVF, carotid pressure waves were recorded using arterial tonometry. XSP and its integral (XSPI) were derived using RWA through pressure wave analysis alone. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (CF-PWV). RESURLTS: In 38 patients (63% male, age 59 ± 15 years), after AVF creation, brachial diastolic BP decreased (79 ± 10 vs. 72 ± 12 mm Hg, P = 0.002), but the reduction in systolic BP, was not statistically significant (133 ± 20 vs. 127 ± 26 mm Hg, P = 0.137). However, carotid XSP (14 [12-19] to 17 [12-22] mm Hg, P = 0.031) and XSPI increased significantly (275 [212-335] to 334 [241-439] kPa∙s, P = 0.015), despite a reduction in CF-PWV (13 ± 3.6 vs. 12 ± 3.5 m/s, P = 0.025). CONCLUSIONS: Creation of an AVF resulted in increased XSP in this population, despite improvement in diastolic BP and aortic stiffness. These findings underline the complex hemodynamic impact of AVF on the cardiovascular system.

Twenty-Four-Hour Central (Aortic) Systolic Blood Pressure: Reference Values and Dipping Patterns in Untreated Individuals.

Central (aortic) systolic blood pressure (cSBP) is the pressure seen by the heart, the brain, and the kidneys. If properly measured, cSBP is closer associated with hypertension-mediated organ damage and prognosis, as compared with brachial SBP (bSBP). We investigated 24-hour profiles of bSBP and cSBP, measured simultaneously using Mobilograph devices, in 2423 untreated adults (1275 women; age, 18-94 years), free from overt cardiovascular disease, aiming to develop reference values and to analyze daytime-nighttime variability. Central SBP was assessed, using brachial waveforms, calibrated with mean arterial pressure (MAP)/diastolic BP (cSBPMAP/DBPcal), or bSBP/diastolic blood pressure (cSBPSBP/DBPcal), and a validated transfer function, resulting in 144 509 valid brachial and 130 804 valid central measurements. Averaged 24-hour, daytime, and nighttime brachial BP across all individuals was 124/79, 126/81, and 116/72 mm Hg, respectively. Averaged 24-hour, daytime, and nighttime values for cSBPMAP/DBPcal were 128, 128, and 125 mm Hg and 115, 117, and 107 mm Hg for cSBPSBP/DBPcal, respectively. We pragmatically propose as upper normal limit for 24-hour cSBPMAP/DBPcal 135 mm Hg and for 24-hour cSBPSBP/DBPcal 120 mm Hg. bSBP dipping (nighttime-daytime/daytime SBP) was -10.6 % in young participants and decreased with increasing age. Central SBPSBP/DBPcal dipping was less pronounced (-8.7% in young participants). In contrast, cSBPMAP/DBPcal dipping was completely absent in the youngest age group and less pronounced in all other participants. These data may serve for comparison in various diseases and have potential implications for refining hypertension diagnosis and management. The different dipping behavior of bSBP versus cSBP requires further investigation.

A comparison between left ventricular ejection time measurement methods during physiological changes induced by simulated microgravity.

NEW FINDINGS: What is the central question of this study? First, we validated easy-to-use oscillometric left ventricular ejection time (LVET) against echocardiographic LVET. Second, we investigated progression of left ventricular ejection time index (LVETI), pre-ejection period index (PEPI), total electromechanical systole index (QS2I) and PEP/LVET ratio during 60 days of head-down tilt (HDT). What is the main finding and its importance? The LVETosci and LVETecho showed good agreement in effect direction. Hence, LVETosci might be useful to evaluate cardiovascular responses during space flight. Moreover, the approach might be useful for individual follow-up of patients with altered ejection times. Furthermore, significant effects of 60 days of HDT were captured by measurements of LVETI, PEPI, QS2I and PEP/LVET ratio. ABSTRACT: Systolic time intervals that are easy to detect might be used as parameters reflecting cardiovascular deconditioning. We compared left ventricular ejection time (LVET) measured via ultrasound Doppler on the left ventricular outflow tract with oscillometrically measured LVET, measured at the brachialis. Furthermore, we assessed the progression of the left ventricular ejection time index (LVETI), the pre-ejection period index (PEPI), the Weissler index (PEP/LVET) and the total electromechanical systole index (QS2I) during prolonged strict head-down tilt (HDT) bed rest, including 16 male and eight female subjects. Simultaneous oscillometric and echocardiographic LVET measurements showed significant correlation (r = 0.53 with P = 0.0084 before bed rest and r = 0.73 with P < 0.05 on the last day of bed rest). The shortening of LVET during HDT bed rest measured with both approaches was highly concordant in their effect direction, with a concordance rate of 0.96. Our results also demonstrated a significant decrease of LVETI (P < 0.0001) and QS2I (P = 0.0992) and a prolongation of PEPI (P = 0.0049) and PEP/LVET (P = 0.0003) during HDT bed rest over 60 days. Four days after bed rest, LVETI recovered completely to its baseline value. Owing to the relationship between shortening of LVETI and heart failure progression, the easy-to-use oscillometric method might not only be a useful way to evaluate the cardiovascular system during space flights, but could also be of high value in a clinical setting.

U-Shaped Association of the Heart Rate Variability Triangular Index and Mortality in Hemodialysis Patients With Atrial Fibrillation.

Background: Atrial fibrillation (AF) is common in hemodialysis patients and contributes to increased mortality. We aimed to examine heart rate variability triangular index (HRVI) in hemodialysis patients with AF as it has recently been reported to predict mortality in AF patients without kidney disease. Methods: A total of 88 patients on hemodialysis with a medical history of AF or newly diagnosed AF underwent 24-h electrocardiography recordings. The primary endpoint of cardiovascular mortality was recorded during a median follow up of 3.0 years. Risk prediction was assessed by Cox regression, both unadjusted and adjusted for the Charlson Comorbidity Index and the Cardiovascular Mortality Risk Score. Results: Median age was 76 years, median dialysis vintage was 27 months. Altogether, 22 and 44 patients died due to cardiovascular and non-cardiovascular causes. In 55% of patients AF was present during the recording. Kaplan-Meier plots of HRVI quartiles suggested a non-linear association between HRVI, cardiovascular, and all-cause mortality which was confirmed in non-linear Cox regression analysis. Adjusted linear Cox regression revealed a hazard ratio of 6.2 (95% CI: 2.1-17.7, p = 0.001) and 2.2 (95% CI: 1.3-3.8, p = 0.002) for the outer quartiles (combined first and fourth quartile) for cardiovascular and all-cause mortality, respectively. Patients in the first quartile were more likely to have sinus rhythm whereas patients in the fourth quartile were more likely to have AF. Conclusions: We found a U-shaped association between HRVI and mortality in hemodialysis AF patients. The results might contribute to risk stratification independent of known risk scores in hemodialysis AF patients.

Limited Effect of 60-Days Strict Head Down Tilt Bed Rest on Vascular Aging.

BACKGROUND: Cardiovascular risk may be increased in astronauts after long term space flights based on biomarkers indicating premature vascular aging. We tested the hypothesis that 60 days of strict 6° head down tilt bed rest (HDTBR), an established space analog, promotes vascular stiffening and that artificial gravity training ameliorates the response. METHODS: We studied 24 healthy participants (8 women, 24-55 years, BMI = 24.3 ± 2.1 kg/m2) before and at the end of 60 days HDTBR. 16 subjects were assigned to daily artificial gravity. We applied echocardiography to measure stroke volume and isovolumetric contraction time (ICT), calculated aortic compliance (stroke volume/aortic pulse pressure), and assessed aortic distensibility by MRI. Furthermore, we measured brachial-femoral pulse wave velocity (bfPWV) and pulse wave arrival times (PAT) in different vascular beds by blood pressure cuffs and photoplethysmography. We corrected PAT for ICT (cPAT). RESULTS: In the pooled sample, diastolic blood pressure (+8 ± 7 mmHg, p < 0.001), heart rate (+7 ± 9 bpm, p = 0.002) and ICT (+8 ± 13 ms, p = 0.036) increased during HDTBR. Stroke volume decreased by 14 ± 15 ml (p = 0.001). bfPWV, aortic compliance, aortic distensibility and all cPAT remained unchanged. Aortic area tended to increase (p = 0.05). None of the parameters showed significant interaction between HDTBR and artificial gravity training. CONCLUSION: 60 days HDTBR, while producing cardiovascular deconditioning and cephalad fluid shifts akin to weightlessness, did not worsen vascular stiffness. Artificial gravity training did not modulate the response.