Increased Pulse Pressure Research Articles

The role of illness burden in theory of mind performance among older adults

ABSTRACTBackground/Study Context: Theory of Mind (ToM) reflects the ability to reason about mental states in order to understand and predict behavior. Research has identified links between increased pulse pressure, a measure of vascular health, and reduced cognitive ToM in older adults. However, the relationships between other vascular and nonvascular conditions and reduced ToM are unknown. We examined (1) illnesses as predictors of cognitive and affective ToM and (2) neurocognitive mediators of illness burden and ToM. Methods: We used hierarchical regression and mediation to investigate the effects of vascular illness burden (hypertension, Type 2 diabetes, high cholesterol, and high pulse pressure) and nonvascular illness burden (osteoporosis, osteoarthritis, rheumatoid arthritis, and thyroid dysfunction) on cognitive and affective ToM in N = 86 community-dwelling older adults (59 females; 27 males, M age = 71.74 years). Results: Vascular illness burden emerged as a significant predictor of older adults’ cognitive ToM (R2 = .43, p < .001), and this relationship was mediated by executive functioning. Nonvascular illness burden did not predict cognitive nor affective ToM in this sample. Conclusion: Our findings highlight the specific importance of considering vascular health as a risk factor for declines in ToM in later life. Further elucidation of the associations between health, neurocognition, and ToM will be valuable in developing effective interventions for older adults given the high prevalence of vascular illness in later life.

A6144 Electrocardiographic left ventricular hypertrophy in relation to peripheral and central blood pressure indices in a Nigerian population

Objectives: Previous studies that addressed whether left ventricular hypertrophy is more closely associated with central than peripheral blood pressure (BP) have been inconsistent. Methods: Radial artery wave generated by applanation tonometry and calibrated with brachial BP in 162 adult Nigerians, were analysed by using generalized transfer function to derive central BP. We compared the associations of ECG voltages and left ventricular hypertrophy (ECG-LVH) as continuous and binary variables respectively with central and brachial BP indices. Results: In a multivariable adjusted analysis, 1 standard deviation (SD) increase in brachial systolic, diastolic, pulse and mean arterial pressures increased the Sokolow-Lyon QRS voltage by 0.34 (CI 0.21–0.48; p < 0.0001), 0.21 (CI, 0.07–0.36; p < 0.05); 0.22 (CI, 0.9–0.34 p < 0.001) and 0.29 (CI,0.14–0.43) similar to (p > 0.05) corresponding Sokolow-Lyon QRS increase of 0.26 (0.12–0.40, p < 0.001); 0.14 (0.00–0.28, p < 0.05); 0.24 (0.11–0.39; p < 0.001) and 0.19 (0.05–0.34, p < 0.05) respectively observed for 1 SD increment in central pressures. The odds ratio (OR) relating ECG-LVH to 1 SD increase in brachial systolic, pulse, and mean arterial pressures were 2.62 (CI, 1.49–4.65, p < 0.001); 1.88 (CI, 1.19–2.95, p < 0.01) and 2.16 (CI, 1.22–3.82, p < 0.01) was similar to (p > 0.05) corresponding OR of 2.41 (1.33–4.36, p < 0.01); 2.04 (1.23–3.37, p < 0.01); 2.00 (1.11–3.63, p < 0.001) observed for I SD increment in central pressures. Conclusion: Central and peripheral BP are similarly associated with Sokolow-Lyon ECG voltage and hypertrophy

Carotid artery wall mechanics in young males with high cardiorespiratory fitness.

What is the central question of this study? Common carotid artery (CCA) two-dimensional strain imaging detects intrinsic arterial wall properties beyond conventional measures of arterial stiffness, but the effect of cardiorespiratory fitness on two-dimensional strain-derived indices of CCA stiffness is unknown. What is the main finding and its importance? Two-dimensional strain imaging of the CCA revealed greater peak circumferential strain and systolic strain rate in highly fit men compared with their less fit counterparts. Altered CCA wall mechanics might reflect intrinsic training-induced adaptations that help to buffer the increase in pulse pressure and stroke volume during exercise. The influence of cardiorespiratory fitness on arterial stiffness in young adults remains equivocal. Beyond conventional measures of arterial stiffness, two-dimensional strain imaging of the common carotid artery (CCA) provides new information related to the intrinsic properties of the arterial wall. Therefore, the aim of this study was to assess the effect of cardiorespiratory fitness on both conventional indices of CCA stiffness and two-dimensional strain parameters, at rest and after a bout of aerobic exercise in young, healthy men. Short-axis ultrasound images of the CCA were recorded in 34 healthy men {22years old [95% confidence interval (CI), 19, 22]} before and immediately after 5min of aerobic exercise (40% of maximal oxygen consumption). Images were analysed for arterial diameter, peak circumferential strain (PCS) and peak systolic and diastolic strain rates (S-SR and D-SR). Heart rate, systolic and diastolic blood pressure were simultaneously assessed, and Peterson's elastic modulus (Ep ) and β-stiffness (β1 ) were calculated. Participants were separated post hoc into moderate- and high-fitness groups [maximal oxygen consumption, 48.9 (95% CI, 44.7, 53.2) versus 65.6mlkg-1 min-1 (95% CI, 63.1, 68.1), respectively; P<0.001]. The Ep and β1 were similar between groups at baseline (P>0.13) but were elevated in the moderate-fitness group postexercise (P<0.04). The PCS and S-SR were elevated in the high-fitness group at both time points [3.0% (95% CI,1.2, 4.9), P=0.002, and 0.401s-1 (95% CI,0.085, 0.72), P=0.02, respectively]. No group differences were observed in CCA heart rate, systolic or diastolic blood pressure or D-SR throughout the protocol (P>0.05). Highly fit individuals exhibit elevated CCA, PCS and S-SR, which might reflect training-induced adaptations that help to buffer the increase in pulse pressure and stroke volume during exercise.

Revisiting the Achilles Heel of Exercise Capacity in Continuous Flow LVAD Patients Using Invasive Exercise Hemodynamics

Background Continuous flow left ventricular assist devices (cfLVADs) have greatly improved survival and quality of life for patients with end-stage heart failure. However, exercise capacity remains poor and little is known about hemodynamics during exercise. We describe observations from invasive cardiopulmonary exercise (iCPEX) tests in 3 patients with continuous flow LVADs. Methods Three patients with cfLVADs (HeartMate II, HeartMate 3 and HeartWare HVAD) underwent iCPEX with a pulmonary artery catheter placed via the right internal jugular vein and using an exercise bicycle protocol with a 10 Watt ramp. Ventilatory measurements were made with a Sensormedics CPX testing unit (Sensormedics, VMAX Encore 29C). One subject also had a radial arterial line for blood pressure monitoring. Results The peak oxygen consumption averaged 1.03 ± 0.32 L/min (36.8% mean max. predicated) or 9.5± 1.7 mL/kg/min. Respiratory quotient averaged 1.2 ±0.1. With exercise, cardiac output increased modestly from 7.8 ± 2.8 to 10.8 ± 2.6 L/min. There was a progressive increase in pulmonary capillary wedge pressure (PCW) in all patients, from 25 ± 12 to 34 ± 13 mmHg. Right atrial pressure changed minimally in 2 subjects (20 to 24 mmHg and 6 to 10 mmHg), while there was a rise in RA pressure towards the end of exercise in one subject with known poor right ventricular function (14 to 28 mmHg). In the subject monitored with an arterial line, there was a rise in blood pressure from 94 to 106 mmHg mean and an increase in pulse pressure from 18 to 54 mmHg. Conclusion Hemodynamics during exercise in patients with cfLVADs demonstrates a modest increase in cardiac output that is associated with a non-physiologic increase PCW. Peak oxygen consumption was well below predicted. The rise in PCW with only a modest increase in exercise cardiac output raise the question of whether automated circulatory control to increase pump performance with exercise could lead to improved exercise capacity in cfLVAD patients. Figure 1

Aortic stiffness, central pulse pressure and cognitive function following acute resistance exercise.

While resistance exercise (RE) is known to be beneficial for overall health, one bout of RE acutely increases aortic stiffness and pulse pressure (PP). Increases in aortic stiffness and PP in a setting of aging has been shown to detrimentally impact cognitive function. This study examined whether increased aortic stiffness and PP from an acute bout of RE is associated with cognitive function. Thirty-five participants (21 ± 2years) underwent cognitive testing before and after either an acute bout of RE or a non-exercise time-control condition. Cognitive function was assessed as reaction time and accuracy during memory recognition, attention (Flanker) and working memory (N-back) tasks. Aortic stiffness and PP were measured via pulse wave velocity (PWV) and pulse wave analysis, respectively, using a brachial oscillometric device. There were significant increases in aortic PWV and aortic PP following RE (p < 0.05) with no change in PWV or PP following the non-exercise control condition (p > 0.05). There was no change in accuracy metrics (% hits) across conditions for any cognitive task (p > 0.05). There was a condition-by-time interaction for reaction time for the memory task (p < 0.05) driven by a significant decrease in reaction times following RE (p < 0.05) with no change in reaction time following the non-exercise control (p > 0.05). Functional increases in aortic stiffness and pulse pressure following acute RE occur in the absence of detrimental changes in cognitive function in young, healthy adults.

Ten‐year changes in ambulatory blood pressure: The prognostic value of ambulatory pulse pressure

Blood pressure (BP) changes and risk factors associated with pulse pressure (PP) increase in elderly people have rarely been studied using ambulatory blood pressure monitoring (ABPM). The aim is to evaluate 10-year ambulatory blood pressure (ABP) changes in older hypertensives, focusing on PP and its associations with mortality. An observational study was conducted on 119 consecutive older treated hypertensives evaluated at baseline (T0) and after 10years (T1). Treatment adherence was carefully assessed. The authors considered clinical parameters at T1 only in survivors (n=87). Patients with controlled ABP both at T0 and T1 were considered as having sustained BP control. Change in 24-hour PP between T0 and T1 (Δ24-hour PP) was considered for the analyses. Mean age at T0: 69.4±3.7years. Females: 57.5%. Significant decrease in 24-hour, daytime, and nighttime diastolic BP (all P<.05) coupled with an increase in 24-hour, daytime, and nighttime PP (all P<.05) were observed at T1. Sustained daytime BP control was associated with lower 24-hour PP increase than nonsustained daytime BP control (+2.23±9.36 vs +7.79±8.64mmHg; P=.037). The association between sustained daytime BP control and Δ24-hour PP remained significant even after adjusting for age, sex, and 24-hour PP at T0 (β=0.39; P=.035). Both 24-hour systolic BP and 24-hour PP at T0 predicted mortality (adjusted HR 1.07, P=.001; adjusted HR 1.25, P<.001, respectively). After ROC comparison (P=.001), 24-hour PP better predicted mortality than 24-hour systolic BP. The data confirm how ABP control affects vascular aging leading to PP increase. Both ambulatory PP and systolic BP rather than diastolic BP predict mortality in older treated hypertensives.

Individual and Joint Effects of Pulse Pressure and Blood Pressure Treatment Intensity on Serious Adverse Events in the SPRINT Trial

PurposeThe objective of this study was to determine individual and joint effects of pulse pressure and blood pressure treatment intensity on serious adverse events in the Systolic Blood Pressure Intervention Trial. MethodsPulse pressure was calculated by subtracting diastolic blood pressure from systolic blood pressure. Blood pressure treatment intensity goal was ≤140mm Hg in the control arm and ≤120mm Hg in the intensive arm. The primary outcome was a 5-point composite of hypotension, syncope, electrolyte abnormalities, acute renal insufficiency, or injurious falls. ResultsIn 9361 trial participants, the incident rate for the primary outcome per 1000 person-years increased with higher pulse pressure category: ≤49 mmHg: 20.4 (17.2-24.1), 50-59 mmHg: 24.5 (21.3-28.2), 60-69 mmHg: 31.7 (27.7-36.2), ≥70 mmHg: 44.6 (39.8-49.9; Ptrend < .0001; hazard ratio [HR] of pulse pressure [every 10mm Hg] 1.23; 95% confidence interval [CI], 1.18-1.28). The intensive treatment arm had a higher incidence rate of serious adverse events than the control arm (34.2, 95% CI, 31.2-37.3, vs 26.0, 95% CI, 23.4-28.8, P = .0001; HR 1.32; 95% CI, 1.15-1.51). The combined effect was not significant in the relative risk scale (HR 0.97, Pinteraction = .48) but was significant in the risk difference scale (P = .027), contributing 2.5 additional serious adverse events per 1000 person-years for every 10mm Hg increase in pulse pressure in excess of the individual effects of pulse pressure and treatment intensity. ConclusionsWider pulse pressure and intensive blood pressure treatment were individually associated with the composite adverse event outcome. A modest effect modification of pulse pressure and treatment intensity led to additional adverse events when both were present. Clinicians should use caution when treating older patients with elevated pulse pressure to an intensive blood pressure treatment target.

A randomized, double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design

ABSTRACTObjectives: The objective of this paper was to evaluate the efficacy, duration of effect, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adults with attention-deficit/hyperactivity disorder (ADHD).Methods: Adults with ADHD Rating Scale, Version IV (ADHD-RS-IV) scores ≥24 were randomized to SHP465 MAS (50 or 75 mg), placebo, or 25 mg MAS IR in a double-blind, three-period, crossover study using a simulated adult workplace environment. On the final day of each 7-day treatment period, efficacy was assessed for 16 h postdose. Primary efficacy analyses for Permanent Product Measure of Performance (PERMP) total score averaged across all postdose assessments and each postdose time point were conducted in the intent-to-treat population using a mixed linear model. Secondary end-points included PERMP problems attempted and answered correctly and ADHD-RS-IV scores based on clinician ratings of counselor observations using the Time Segment Rating System and participant self-report. Tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.Results: Least squares mean (95% CI) treatment differences (combined 50/75 mg SHP465 MAS–placebo) significantly favored SHP465 MAS over placebo for PERMP total score averaged across all postdose assessments (18.38 [11.28, 25.47]; P < .0001) and at each postdose assessment (all P < .02). Nominal superiority of MAS IR over placebo for PERMP total score averaged across all postdose assessments was observed (nominal P = .0001); treatment differences between SHP465 MAS and MAS IR were not significant (nominal P = .2443). The two most frequently reported TEAEs associated with SHP465 MAS were insomnia (36.5%) and anorexia (21.2%). Mean increases in pulse and blood pressure with SHP465 MAS exceeded those of placebo.Conclusions: SHP465 MAS (combined 50/75 mg) significantly improved PERMP total score versus placebo, with superiority observed from 2 to 16 h postdose. The tolerability profile of SHP465 MAS was similar to previous reports of SHP465 MAS in adults with ADHD.Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT00928148 identifier is NCT00928148.

DETERMINANTS OF LONG-TERM ALL-CAUSE AND CARDIOVASCULAR MORTALITY IN HYPERTENSIVE PATIENTS – FINDINGS FROM 16-YEAR FOLLOW-UP OF THE ASCOT LEGACY STUDY

Objective: To evaluate the baseline predictors of long-term all-cause- and cardiovascular (CV)-mortality amongst high-risk hypertensive patients, and to develop an integer-based risk score. Design and method: In the Anglo-Scandinavian Cardiovascular Outcomes Trial (ASCOT) legacy study, 8580 UK-based hypertensive patients were followed-up for mortality. All deaths (after the trial closure) were independently adjudicated by a team of 2 physicians. Cox-proportional hazards models were developed separately for 2 outcomes: all-cause- and CV- mortality using backwards stepwise-selection. All variables were considered for inclusion in the model; but, pre-specified covariates (age, sex, race, socio-economic status [SES], body-mass index [BMI], systolic blood pressure [SBP], total cholesterol, presence of diabetes, smoking history) were included even if statistically insignificant. Continuous variables were categorised if non-linear, or pre-specified based on clinical utility. Goodness-of-fit and C-statistics were calculated. Results: During median follow-up of 15.7 years, 3282 (38.3%) of 8580 hypertensive patients (mean age at baseline, 64.1 year) died with about a third (n, 1210) from CV-related causes. Figure 1 lists the baseline predictors significantly associated with all-cause- and CV-mortality. Aside from increasing age and smoking status, increasing baseline levels of fasting plasma glucose and serum creatinine, presence of atrial fibrillation and previous history of peripheral-or cerebrovascular- disease were significant risk factors for 2 outcomes. Notably, increase in pulse pressure (PP) (and not SBP) was an independent risk factor, with 47% and 53% significantly higher risk for all-cause and CV-mortality amongst those with PP> = 100 (vs. PP <60), respectively. BMI and alcohol intake were significantly associated with all-cause-(but not CV-) mortality: BMI < 20 kg/m2, and alcohol intake >28 units/week were associated with 79% and 20% increased risk respectively. Higher SES was associated with a significantly reduced risk for both outcomes. Both models had an excellent discriminative ability (c-statistics, 0.72 and 0.73, respectively).Conclusions: Our findings suggest that a few baseline determinants in our 2 models are different from those that are routinely used for CV-risk prediction. Particularly, increase in baseline PP (and not SBP) was found to be an independent and better predictor for both all-cause and CV-mortality in this high-risk hypertensive population.

Target Organ Damage and Cardiovascular Risk in a Hypertensive Roma Sample Population in Romania.

The largest European Roma community resides in Romania, but there is still little published data on cardiovascular (CV) risk factors and disease in this group. This study addresses the prevalence of arterial hypertension, associated CV disease risk, and target organ damage (TOD) in a Roma community from Bucharest, Romania. This is a cross-sectional community-based participatory research to assess for CV risk factors, TOD and CV disease, including 806 Roma ethnics (18-83 years) integrated in the local community, 36.16% males. Evaluation included physical examination with blood pressure, pulse wave velocity and anklebrachial measurements, laboratory tests, ECG, echocardiography and fundoscopy. Prevalence of hypertension was 33.62%, awareness 76.38%, higher in females (p>0.01), and control rate 44.39%. Compared to age-matched normotensives, hypertensives had more left ventricle hypertrophy and more frequently increased pulse pressure. Differences in TOD were attenuated between newly and previously diagnosed, controlled and uncontrolled, hypertensives. Cardiovascular disease was almost absent in normotensives. Ten-year risk for fatal CV disease followed an increasing trend from normotension to long standing hypertension. This is the first dedicated study to thoroughly assess TOD and risk for fatal CV disease in a Romanian Roma population. Hypertension was less prevalent than in the general population, with similar awareness, possibly as a consequence of integration in the surrounding community. Fatal CV disease risk followed the trend of increasing prevalence of risk factors, and hypertension played an important role in its modulation.

Compromised mechanical homeostasis in arterial aging and associated cardiovascular consequences.

Aging leads to central artery stiffening and associated hemodynamic sequelae. Because healthy arteries exhibit differential geometry, composition, and mechanical behaviors along the central vasculature, we sought to determine whether wall structure and mechanical function differ across five vascular regions-the ascending and descending thoracic aorta, suprarenal and infrarenal abdominal aorta, and common carotid artery-in 20 versus 100-week-old male wild-type mice. Notwithstanding generally consistent changes across these regions, including a marked thickening of the arterial wall, diminished in vivo axial stretch, and loss of elastic energy storage capacity, the degree of changes tended to be slightly greater in abdominal than in thoracic or carotid vessels. Likely due to the long half-life of vascular elastin, most mechanical changes in the arterial wall resulted largely from a distributed increase in collagen, including thicker fibers in the media, and localized increases in glycosaminoglycans. Changes within the central arteries associated with significant increases in central pulse pressure and adverse changes in the left ventricle, including increased cardiac mass and decreased diastolic function. Given the similar half-life of vascular elastin in mice and humans but very different life-spans, there are important differences in the aging of central vessels across these species. Nevertheless, the common finding of aberrant matrix remodeling contributing to a compromised mechanical homeostasis suggests that studies of central artery aging in the mouse can provide insight into mechanisms and treatment strategies for the many adverse effects of vascular aging in humans.

Midazolam increases preload dependency during endotoxic shock in rabbits by affecting venous vascular tone

BackgroundSeptic patients often require sedation in intensive care unit, and midazolam is one of the most frequently used sedatives among them. But the interaction between midazolam and septic shock is not known. The aim of this study is to investigate the effects of midazolam on preload dependency in an endotoxic shock model by evaluating systemic vascular tone and cardiac function.MethodsEighteen rabbits were randomly divided into three groups: Control group, MID1 group and MID2 group. Rabbits underwent ketamine anaesthesia and mechanical ventilation, and haemodynamic assessments were recorded in three groups (T0). Endotoxic shock was induced by lipopolysaccharide intravenously, and fluid resuscitation and norepinephrine were administered to obtain the baseline mean arterial pressure (MAP) (T1). Rabbits received equivalent normal saline (Control) and two consecutive dosages of midazolam: 0.3 mg kg−1 h−1 (MID1) and 3 mg kg−1 h−1 (MID2) (T2). Rabbits received another round of fluid challenge and norepinephrine infusion to return the MAP to normal (T3).ResultsNo significant differences in haemodynamic parameters were observed in three groups at T0, T1 or T3. Midazolam infusion significantly increased pulse pressure variation (PPV) and stroke volume variation (SVV) compared to the values in Control group, and MAP, central venous pressure (CVP), mean systemic filling pressure (Pmsf) and cardiac output (CO) decreased at T2. Same effects were observed with increasing doses of midazolam, and resistance for venous return (Rvr) decreased (MID1 vs. MID2) at T2. PPV and SVV increased significantly at T2 compared to the values at T1. MAP, CVP, Pmsf and CO decreased in MID1 and MID2 groups. Rvr also decreased in MID2 group (T2 vs. T1). Midazolam did not affect cardiac function index, systemic vascular resistance or artery resistance (T2 vs. T1).ConclusionsMidazolam administration promoted preload dependency in septic shock models via decreased venous vascular tone without affecting cardiac function.

Noninvasive Blood Pressure Monitoring and Prediction of Fluid Responsiveness to Passive Leg Raising.

Intravenous fluid boluses are administered to patients in shock to improve tissue hypoperfusion. However, fluid boluses result in clinically significant stroke volume increases in only about 50% of patients. Hemodynamic responses to passive leg raising measured with invasive and minimally invasive methods are accurate predictors of fluid responsiveness. However, few studies have used noninvasive blood pressure measurement to evaluate responses to passive leg raising. To determine if passive leg raising-induced increases in pulse pressure or systolic blood pressure can be used to predict clinically significant increases in stroke volume index in healthy volunteers. In a repeated-measures study, hemodynamic measurements were obtained in 30 healthy volunteers before, during, and after passive leg raising. Each participant underwent the procedure twice. In the first test, 20 participants (69%) were responders (stroke volume index increased by ≥ 15%); 9 (31%) were nonresponders. In the second test, 15 participants (50%) were responders and 15 (50%) were nonresponders. A passive leg raising-induced increase in pulse pressure of 9% or more predicted a 15% increase in stroke volume index (sensitivity, 50%; specificity, 44%). There was no association between passive leg raising-induced changes in systolic blood pressure and fluid responsiveness. A passive leg raising-induced change in stroke volume index measured by bioreactance differentiated fluid responders and nonresponders. Pulse pressure and systolic blood pressure measured by oscillometric noninvasive blood pressure monitoring were not sensitive or specific predictors of fluid responsiveness in healthy volunteers.

Experimental Weight Gain Increases Ambulatory Blood Pressure in Healthy Subjects: Implications of Visceral Fat Accumulation

ObjectiveTo examine whether experimentally induced weight gain raises ambulatory blood pressure (BP) in healthy subjects and identify any relationship between changes in BP and changes in regional fat distribution. Patients and MethodsTwenty-six normal weight subjects were randomized to 8 weeks of weight gain through overfeeding (n=16; age, 30.4±6.6 years) or to weight maintenance (controls; n=10; age, 27.1±7.7 years) between July 2004 and August 2010. Measures of body composition via dual energy X-ray absorptiometry and computed tomography, circulating biomarkers, and 24-hour ambulatory BP were obtained at baseline and after the 8-week experimental phase. ResultsOverfeeding resulted in 3.7 kg (95% CI, 2.9-4.5) increase in body weight in weight gainers, with increments in total (46.2 cm2; 95% CI, 27.6-64.9), visceral (13.8 cm2; 95% CI, 5.8-21.9), and subcutaneous fat (32.4 cm2; 95% CI, 13.5-51.3). No changes occurred in the maintenance group. Increases in 24-hour systolic BP (4 mm Hg; 95% CI, 1.6-6.3), mean BP (1.7 mm Hg; 95% CI, 0.3-3.3), and pulse pressure (2.8 mm Hg; 95% CI, 1.1-4.4) were evident after weight gain in the experimental group, whereas BP remained unchanged in controls. Changes in mean BP correlated only with changes in visceral fat (ρ=0.45; P=.02), but not with changes in other body composition measures. ConclusionModest weight gain causes elevation in 24-hour BP in healthy subjects. The association between increased BP and abdominal visceral fat accumulation suggests that visceral deposition of adipose tissue may contribute specifically to the enhanced risk of hypertension associated with weight gain.

Pulsatile operation of a continuous-flow right ventricular assist device (RVAD) to improve vascular pulsatility.

Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction. In addition, the performance of the speed modulation strategy has been assessed under different cardiovascular states, including variation in ventricular contractility and pulmonary arterial compliance. Our results indicated that the proposed pulse profile with optimised parameters (Apulse = 10000 rpm and ωmin = 3000 rpm) was able to generate pulmonary arterial pulse pressure within the physiological range (9–15 mmHg) while avoiding undesirable pump backflow under both co- and counter-pulsation modes. As compared to co-pulsation, stroke work was reduced by over 44% under counter-pulsation, suggesting that mechanical workload of the right ventricle can be efficiently mitigated through counter-pulsing the pump speed. Furthermore, our results showed that improved ventricular contractility could potentially lead to higher risk of ventricular suction and pump backflow, while stiffening of the pulmonary artery resulted in increased pulse pressure. In conclusion, the proposed speed modulation strategy produces pulsatile hemodynamics, which is more physiologic than continuous blood flow. The findings also provide valuable insight into the interaction between RVAD speed modulation and the pulmonary circulation under various cardiovascular states.

Pulse wave velocity and other indicators of arterial stiffness in hypertension comorbidity and chronic obstructive pulmonary disease.

The aim is to study pulse wave velocity (PWV) and other parameters of arterial stiffness in patients with comorbid arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD). 32 patients with a combination of AH and COPD (group 1), 30 patients with isolated hypertension (group 2), 18 patients with isolated COPD (group 3), 30 healthy subjects (control group) were examined. Applanation tonometry and pulse wave contour analysis at the carotid-femoral segment were made by SphygmoCor (AtCor Medical). Aortic systolic blood pressure in patients with the combination of hypertension and COPD was higher compared to the group of the patients with isolated hypertension by 9.83% (p=0.02), and the patients with COPD by 41.5% (p = 0.000042), respectively. Central pulse pressure in the first group was higher compared to the second group by 29.58% (p=0.00022), in the third group - by 53.4% (p=0.0029). The combination of hypertension and COPD (β=0.42, p=0.00019), age (β=0.39, p=0.0002) and the level of aortic pulse pressure (β=0.54, p=0.001) were marked as independent factors of PWV increasing according to the multiple regression analysis. In patients with a combination of hypertension and COPD the increase in PWV, systolic and pulse pressure in the ascending aorta was observed, compared to patients with isolated hypertension, isolated COPD and the control group during applanation tonometry.

INFLUENCE OF THE ACUTE HEMODYNAMIC INDEX ON INTRA-HOSPITAL MORTALITY OF HEART FAILURE PATIENTS: INSIGHTS FROM BREATHE REGISTRY

Although controlled heart rate (HR) and increased pulse pressure (PP) are related to better outcomes in stable heart failure (HF), the prognostic impact of hemodynamic response to acute stress is unknown. We hypothesized that higher HR and PP during HF decompensation would be related to better in-

Pulse pressure is associated with plasma amyloid-β transport dysfunction.

Increased pulse pressure (PP) has been implicated in the development and progression of Alzheimer's disease in middle-aged and elderly adults. Considering the close relationship between peripheral amyloid-β clearance and brain amyloid-β deposition, we investigated the potential association between PP and plasma amyloid-β transport function. In this cross-sectional study, a total of 1118 participants underwent a health assessment and quantification of plasma amyloid-β and amyloid-β transporter expression. Relationships between plasma levels of amyloid-β1-40, amyloid-β1-42, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), soluble receptor for advanced glycation end products (sRAGE), and PP were determined using multiple linear regressions. PP was a significant determinant of amyloid-β1-40 level (β = 0.059, P = 0.036) and log-transformed sRAGE (β = -0.002, P = 0.029) independent of age, sex, body mass index, pulse rate, mean arterial pressure, blood glucose, blood lipids, lifestyle, and medical history. Additionally, log-transformed soluble low-density lipoprotein receptor-related protein-1 and log-transformed sRAGE were positively associated with plasma amyloid-β1-40 level (β = 3.610, P < 0.001; β = 2.573, P = 0.001). Similar associations were observed between log-transformed sRAGE and plasma amyloid-β1-42 level (β = 1.350, P = 0.022). An elevation in PP is associated with increased plasma amyloid-β1-40 and decreased log-transformed sRAGE among individuals not taking antihypertensive medication. The underlying mechanism of this effect may be relevant to peripheral amyloid-β clearance.

Analyzing the association between aortic regurgitation and atherosclerosis: is pulse pressure a cause of atherosclerosis?

ABSTRACTIf pulse pressure, one of the mechanical stresses, is a risk factor for atherosclerotic cardiovascular disease, then atherosclerosis should be progressive in aortic regurgitation which is a representative disease with increased pulse pressure. This cross-sectional study included 1,149 patients. We examined the influence of aortic regurgitation on maximum intima-media thickness or brachial-ankle pulse wave velocity. The degree of aortic regurgitation was classified into 4 grades by color Doppler examination. There were 177 patients with aortic regurgitation. Pulse pressure was significantly higher in patients with aortic regurgitation than in those without it. On multiple regression analysis, aortic regurgitation was not found to be a significant independent variable for maximum intima-media thickness [standard partial regression coefficient: aortic regurgitation = grade 1, 0.011, P = 0.7635; aortic regurgitation ≥ grade 2, −0.034, P = 0.3289] and brachial-ankle pulse wave velocity [standard partial regression coefficient: aortic regurgitation = grade1, −0.043, P = 0.1197; aortic regurgitation ≥ grade2, 0.002, P = 0.9358] after adjusting for age, sex, body mass index, presence or absence of cardiovascular disease, antihypertensive treatment, diabetes, dyslipidemia, and smoking. These results found no causal association between aortic regurgitation and atherosclerosis, and were a contradiction to the opinion that pulse pressure was a risk factor of atherosclerosis.

Abstract WP169: Midlife to Late-Life Changes in Blood Pressure and Cerebral Blood Flow in Old Age: the AGES-Reykjavik Study

Introduction: Adverse changes in blood pressure (BP) over the life course can lead to adverse cerebrovascular outcomes, including reduced blood flow. In this life-course, longitudinal, population-based study, we investigated the link between midlife to late life changes in BP and cerebral blood flow (CBF) in old age. Methods: From the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study (2002-2011), 2491 individuals (mean age (SD): midlife 49.7 (6.1) and late-life 79.8 (4.7) years old) were included. BP was measured at three different time points: 1 in mid-life, and 2 in late-life measured 5 years apart (mean follow-up time 30.1 years). With linear mixed models, annual changes in BP were estimated for each participant (mmHg/year). Participants were categorized in tertiles of changes in systolic, pulse pressure and diastolic BP. Total CBF was measured in the last late-life visit with the Phase-Contrast MRI and standardized for brain parenchymal volume (mL/min/100mL). Results: Overall, each mmHg/year increase in systolic BP was associated with 3.2 mL/min/100 mL (95% CI: 0.7-5.7)) higher CBF. Mean (SE) CBF in low, middle and high tertiles of change in systolic BP were 56.0 (0.4), 56.6 (0.4) and 57.5 (0.4) mL/min/100mL respectively (P for trend: 0.01). A similar increase in total CBF was observed for an increase in pulse pressure: each mmHg/year increase in pulse pressure was associated with 6.3 mL/min/100mL (95% CI: 3.8-8.7) higher total CBF. In contrast, an increase in diastolic BP was linked with lower CBF: each mmHg/year increase in diastolic BP was associated with 6.3 mL/min/100mL (95% CI: 3.3-9.4) lower CBF. Mean (SE) CBF in low, middle and high tertiles of changes in diastolic BP were 57.3 (0.4), 57.3 (0.4) and 55.5 (0.4) mL/min/100mL respectively (P for trend: &lt;0.001). All these associations were independent of sociodemographic and cardiovascular factors and antihypertensive medications. Conclusion: In an over 30 years of midlife to late-life follow up, we observed that individuals with increasing systolic BP and pulse pressure have higher CBF in old age. Conversely, increase in diastolic BP is associated with lower CBF. The mechanisms behind the link between long-term BP alterations and CBF need to be elucidated.