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Mechanisms behind the protective effects of aerobic exercise on brain health remain elusive but may be vascular in origin and relate to cerebral pulsatility. This pilot study investigated the effects of 12-wk aerobic exercise training on cerebral pulsatility and its vascular contributors (large artery stiffness, characteristic impedance) in at-risk middle-aged adults. Twenty-eight inactive middle-aged adults with elevated blood pressure or stage 1 hypertension were assigned to either moderate/vigorous aerobic exercise training (AET) for 3 days/wk or no-exercise control (CON) group. Middle cerebral artery (MCA) pulsatility index (PI), large artery (i.e., aorta, carotid) stiffness, and characteristic impedance were assessed via Doppler and tonometry at baseline, 6, and 12 wk, whereas cardiorespiratory fitness (V̇o 2peak ) was assessed via incremental exercise test and cognitive function via computerized battery at baseline and 12 wk. V̇o 2peak increased 6% in AET and decreased 4% in CON ( P < 0.05). Proximal aortic compliance increased ( P = 0.04, partial η 2 = 0.14) and aortic characteristic impedance decreased ( P = 0.02, partial η 2  = 0.17) with AET but not CON. Cerebral pulsatility showed a medium-to-large effect size increase with AET, although not statistically significant ( P = 0.07, partial η 2  = 0.11) compared with CON. Working memory reaction time improved with AET but not CON ( P = 0.02, partial η 2  = 0.20). Our data suggest 12-wk AET elicited improvements in central vascular hemodynamics (e.g., proximal aortic compliance and characteristic impedance) along with apparent, paradoxical increases in cerebral pulsatile hemodynamics. NEW & NOTEWORTHY We identify differential central versus cerebrovascular responses to 12 wk of aerobic exercise training in middle-aged adults. Although proximal aortic compliance and characteristic impedance improved after 12 wk of exercise, cerebral pulsatility tended to unexpectedly increase. These data suggest short-term aerobic exercise training may lead to more immediate benefits in the central vasculature, whereas longer duration exercise training may be required for beneficial changes in pulsatility within the cerebrovasculature.

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Purpose of Review: Concepts of pulsatile arterial haemodynamics, including relationships between oscillatory blood pressure and flow in systemic arteries, arterial stiffness and wave propagation phenomena have provided basic understanding of underlying haemodynamic mechanisms associated with elevated arterial blood pressure as a major factor of cardiovascular risk, particularly the deleterious effects of isolated systolic hypertension in the elderly. This topical review assesses the effects of pulsatility of blood pressure and flow in the systemic arteries on the brain. The review builds on the emerging notion of the "pulsating brain", taking into account the high throughput of blood flow in the cerebral circulation in the presence of mechanisms involved in ensuring efficient and regulated cerebral perfusion., Recent Findings: Recent studies have provided evidence of the relevance of pulsatility and hypertension in the following areas: (i) pressure and flow pulsatility and regulation of cerebral blood flow, (ii) cerebral and systemic haemodynamics, hypertension and brain pathologies (cognitive impairment, dementia, Alzheimer's disease), (iii) stroke and cerebral small vessel disease, (iv) cerebral haemodynamics and noninvasive estimation of cerebral vascular impedance, (v) cerebral and systemic pulsatile haemodynamics and intracranial pressure, (iv) response of brain endothelial cells to cyclic mechanical stretch and increase in amyloid burden. Studies to date, producing increasing epidemiological, clinical and experimental evidence, suggest a potentially significant role of systemic haemodynamic pulsatility on structure and function of the brain.

An increasing number of end-stage heart failure patients are now implanted with continuous-flow left ventricular assist devices (CF-LVADs). Although this therapeutic approach is associated with improved clinical outcomes, continuous flow physiology reduces arterial pulse pressure and pulsatility to an extent that is unique to this population. Recent data suggest that high blood pressure (BP) contributes to life-threatening complications such as pump thrombosis and stroke of CF-LVAD patients. However, limited understanding of the distinct hemodynamics of these pumps makes measurement and, consequently, medical management of BP quite challenging. Here, we review the evolution of LVAD design, the impact of CF-LVAD flow, and "artificial pulse" technology on hemodynamics and BP measurement, as well as suggest new approaches for the assessment and interpretation of the unique physiology of modern LVADs.

Objective: To compare the degree of impaired placentation in women with and those without chronic hypertension (CH) who develop pre-eclampsia (PE) in pregnancy., Methods: Data were derived from prospective screening for adverse pregnancy outcomes in women with singleton pregnancy attending their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation. This visit included recording of maternal characteristics and medical history and measurement of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A). The measured biomarkers were converted to multiples of the median (MoM) after adjustment for pregnancy characteristics. MoM values in women with CH who developed PE (n = 283) were compared to those of women without CH who developed PE (n = 2236)., Results: In both groups with and without CH, measurements of MAP and UtA-PI were increased, whereas those of PlGF and PAPP-A were decreased and the deviation from normal in all biomarkers decreased with advancing gestational age at delivery with PE. There was no significant difference between women with and those without CH in the slope of the regression line of log 10 MoM biomarker values against gestational age at delivery with PE for any of the biomarkers. However, there was a significant difference in the intercepts and coefficients of biomarkers in the two groups; compared to those without CH, MAP MoM, PlGF MoM and PAPP-A MoM were higher and UtA-PI MoM was lower in the CH group (all P < 0.01)., Conclusion: In pregnancies that develop PE, the degree of impaired placentation, reflected in high UtA-PI and low PlGF and PAPP-A at 11-13 weeks' gestation, is less in women with CH than in those without CH. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

It remains uncertain whether intensive antihypertensive therapy can normalize pulsatile hemodynamics resulting in minimized residual cardiovascular risks. In this study, office and 24-hour ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, carotid-femoral pulse wave velocity (PWV), and forward (Pf) and reflected (Pb) pressure wave from a decomposed carotid pressure wave were measured in hypertensive participants. Among them, 57 patients whose 24-hour SBP and DBP were normalized by three or more classes of antihypertensive medications were included. Another 57 age- and sex-matched normotensive participants were randomly selected from a community survey. The well-treated hypertensive patients had similar 24-hour SBP, lower DBP, and higher PP values. The treated patients had higher PWV (11.7±0.3 vs 8.3±0.2 m/s, P<.001), Pf, Pb, Pb/Pf, and left ventricular mass index values. After adjustment for age, sex, body mass index, and office SBP, the differences for PWV, Pb, and Pb/Pf remained significant. Hypertensive patients whose 24-hour SBP and DBP are normalized may still have markedly increased arterial stiffness and wave reflection., (© 2015 Wiley Periodicals, Inc.)

Aim: To investigate the specific features of arterial wall endothelial dysfunction and stiffness in patients with hypertension concurrent with gout., Subjects and Methods: A total of 54 patients were examined and divided into 2 groups. A study group consisted of 33 hypertensive patients with gout and a comparison group included 21 hypertensive patients without hyperuricemia. The patients did not differ in blood pressure (BP) readings. Uric acid was determined by the reaction with tungstophosphoric solution AT (Reagent, Dnepropetrovsk, Ukraine). The validity of results was checked using the control sera (Biocont C, Russia). Enzyme immunoassays and Doppler studies were used to investigate peripheral vasoregulation. Body mass index, intima-media thickness (IMT), pulse wave velocity (PWV), cardio-ankle vascular index (CAVI), endothelin-1 (ET-1), and endothelium-dependent vasodilation (EDVD) were determined., Results: All the studied indicators have directly or indirectly a negative impact, by deteriorating the function of the vessel wall. The found arterial structural changes suggest that there is an early atheromatous process in the arterial wall of hypertensive patients with gout. Addition of gout promotes endothelial dysfunction and worsens the course of hypertension. An elevation of indicators, such as PWV, CAVI, and ET-1 levels, has the poorest prognosis for the course of hypertension., Conclusion: The determination of CAVI, PWV, ET-1 levels, arterial stiffness index along with additional criteria, such as EDVD and IMT, may be used as criteria for a cardiovascular risk in hypertensive patients.

Background: Increased arterial stiffness leads to increased pulsatile load on the heart. We investigated associations of components of pulsatile load with a measure of left ventricular (LV) systolic function-global longitudinal strain (GLS), in a community-based cohort ascertained based on family history of hypertension., Methods: Arterial tonometry and echocardiography with speckle tracking were performed in 520 adults with normal LV ejection fraction (EF) (age 67±9 years, 70% hypertensive) to quantify measures of pulsatile load (characteristic aortic impedance (Zc), total arterial compliance (TAC), and augmentation index (AI)) and GLS. The associations of log-Zc, log-TAC, and AI with GLS were assessed using sex-specific z-scores for each measure of arterial load., Results: In univariable analyses, higher Zc was associated with worse GLS (less negative) and higher TAC and AI were associated with better GLS (all P < 0.001). In a multivariable model including age, sex, heart rate (HR), LVEF, mean arterial load (systemic vascular resistance), and measures of pulsatile load, Zc remained associated with GLS (β = 0.28, P < 0.001), while the associations of TAC and AI were no longer significant (P > 0.5). Additional adjustment for cardiovascular risk factors and history of coronary heart disease and stroke did not attenuate the association of Zc with GLS; Zc, sex, HR, LVEF remained associated with GLS after stepwise elimination (all P < 0.001)., Conclusions: Greater proximal aortic stiffness, as manifested by a higher Zc, is independently associated with worse LV longitudinal function., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Arterial stiffness is typical feature of vascular remodeling in chronic kidney disease (CKD). Increased arterial stiffness raises flow and pressure pulsatility and is considered the principle pathogenic mechanism of isolated systolic hypertension, left ventricular hypertrophy, and congestive heart failure. Apart from the impact of arterial stiffness on left ventricular afterload, downstream transmission of pressure pulsatility to the level of microcirculation is suggested to promote injury of other susceptible organs. This may be of particular importance for kidney injury progression, since passive renal perfusion along with low resistance and input impedance in renal microvessels make kidneys particularly vulnerable to the damaging effect of systemic pulsatile pressure. Recent studies have provided evidence that arterial stiffness culminates in elevated pulsatility and resistance in renal microvasculature, promoting structural damage of small intra-renal arterioles. Further, prospective observational studies have shown that reduced aortic compliance is closely associated with the annual rate of renal function decline and represents independent predictor of kidney injury progression to end-stage renal disease among patients with CKD. This article provides insights into the cross-talk between macrocirculation and renal microcirculation and summarizes the currently available clinical evidence linking increased arterial stiffness with kidney disease progression., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The use of pulse wave analysis may guide the provider in making choices about blood pressure treatment in prehypertensive or hypertensive patients. However, there is little clinical guidance on how to interpret and use pulse wave analysis data in the management of these patients. A panel of clinical researchers and clinicians who study and clinically use pulse wave analysis was assembled to discuss strategies for using pulse wave analysis in the clinical encounter. This manuscript presents an approach to the clinical application of pulse waveform analysis, how to interpret central pressure waveforms, and how to use existing knowledge about the pharmacodynamic effect of antihypertensive drug classes in combination with brachial and central pressure profiles in clinical practice. The discussion was supplemented by case-based examples provided by panel members, which the authors hope will provoke discussion on how to understand and incorporate pulse wave analysis into clinical practice., (© 2015 Wiley Periodicals, Inc.)

Although the profibrotic inflammatory substance galectin-3 predicts outcomes in the general population, the mechanisms responsible for this effect are uncertain. We aimed to determine whether circulating galectin-3 concentrations are associated with carotid femoral (aortic) pulse wave velocity and aortic reflective wave index (applanation tonometry and SphygmoCor software) in 966 randomly selected participants from a community sample. Galectin-3 concentrations were not independently associated with office (n=966) or 24-hour (n=661) systolic (P=0.88-0.92) or diastolic (P=0.65-0.94) blood pressure. In contrast, with adjustments for age, sex (in all participants), office or 24-hour mean arterial pressure (or systolic blood pressure and pulse pressure), pulse rate, body mass index, regular smoking, regular alcohol intake, total cholesterol concentrations, diabetes mellitus or an glycohemoglobin >6.1%, treatment for hypertension, and estimated glomerular filtration rate, galectin-3 was independently associated with aortic pulse wave velocity in all participants (partial r=0.15, P<0.0001) and reflective wave index in men (partial r=0.13, P<0.02). In 745 participants who had never received antihypertensive therapy, galectin-3 concentrations were similarly independently associated with pulse wave velocity in all participants (partial=0.16, P<0.0001) and reflective wave index in men (partial r=0.15, P<0.02). The blood pressure-independent relations between galectin-3 concentrations and aortic hemodynamics persisted with further adjustments for C-reactive protein concentrations (pulse wave velocity in all participants: partial r=0.14, P<0.0001; reflective wave index in men: partial r=0.12, P<0.05). In conclusion, despite a lack of independent association with brachial blood pressure, the profibrotic inflammatory substance galectin-3 may contribute toward adverse outcomes through an effect on aortic stiffness, an effect that cannot be attributed to general inflammatory changes., (© 2015 American Heart Association, Inc.)

Pulsatile components of blood pressure may arise from forward (ventricular generated) or backward wave travel in the arterial tree. The objective of this study was to determine the relative contributions of forward and backward waves to pulsatility. We used wave intensity and wave separation analysis to determine pulsatile components of blood pressure during inotropic and vasopressor stimulation by dobutamine and norepinephrine in normotensive subjects and compared pulse pressure components in hypertensive (mean±SD, 48.8±11.3 years; 165±26.6/99±14.2 mm Hg) and normotensive subjects (52.2±12.6 years; 120±14.2/71±8.2 mm Hg). Dobutamine (7.5 μg/kg per minute) increased the forward compression wave generated by the ventricle and increased pulse pressure from 36.8±3.7 to 59.0±3.4 mm Hg (mean±SE) but had no significant effect on mean arterial pressure or the midsystolic backward compression wave. By contrast, norepinephrine (50 ng/kg per minute) had no significant effect on the forward compression wave but increased the midsystolic backward compression wave. Despite this increase in the backward compression wave, and an increase in mean arterial pressure, norepinephrine increased central pulse pressure less than dobutamine (increases of 22.1±3.8 and 7.2±2.8 mm Hg for dobutamine and norepinephrine, respectively; P<0.02). An elevated forward wave component (mean±SE, 50.4±3.4 versus 35.2±1.8 mm Hg, in hypertensive and normotensive subjects, respectively; P<0.001) accounted for approximately two thirds of the total difference in central pulse pressures between hypertensive and normotensive subjects. Increased central pulse pressure during inotropic stimulation and in essential hypertension results primarily from the forward compression wave., (© 2014 American Heart Association, Inc.)

No longitudinal study addressed whether systolic blood pressure level (SBPL) or within-visit variability (SBPV) predict arterial properties or vice versa. In families randomly recruited from a Flemish population, we determined SBPL and SBPV from five consecutive blood pressure readings. The indexes of SBPV were variability independent of the mean, the difference between maximum and minimum SBPL, and average real variability. We measured carotid intima-media thickness and distensibility by ultrasound and carotid-femoral pulse wave velocity by tonometry (SphygmoCor, version 8.2). Effect sizes were computed for 1-s.d. increments in the predictors, while accounting for covariables and family clusters. Among 1087 participants (50.4% women; mean age, 41.8 years), followed up for 2.55 years (median), higher SBPL predicted (P < or = 0.019) higher carotid intima-media thickness (+15 μm), lower carotid distensibility (-1.53 10(-3) kPa(-1)) and faster carotid-femoral pulse wave velocity (+0.285 m s(-1)) at follow-up, whereas none of the SBPV indexes predicted the arterial traits at follow-up (P> or = 0.11). In a subset of 713 participants, followed up for another 3.14 years, lower carotid distensibility predicted (P<0.01) higher SBPL (+2.57 mm Hg), variability independent of the mean (+0.531 units), difference between maximum and minimum SBPL (+1.75 mm Hg) and average real variability (+0.654 mm Hg). Higher carotid-femoral pulse wave velocity predicted a 1.11 mm Hg increase SBPL (P=0.031). In conclusion, temporality and effect size suggest that SBPL but not within-visit SBPV cause arterial stiffness and carotid intima-media thickness. Carotid stiffness, independent of SBPL, predicts within-visit SBPV, possibly because baroreflexes originating from a stiff carotid artery wall are impaired. Finally, stiffness of the aorta contributes to the age-related SBPL possibly, because faster returning reflected waves augments SBPL.

Brachial-ankle pulse wave velocity (baPWV) is a non-invasive measure of arterial stiffness obtained using an automated system. Although baPWVs have been widely used as a non-invasive marker for evaluation of arterial stiffness, evidence for the prognostic value of baPWV in the general population is scarce. In this study, we assessed the association between baPWV and future cardiovascular disease (CVD) incidence in a Japanese population. From 2002 to 2009, baPWV was measured in a total of 4164 men and women without a history of CVD, and they were followed up until the end of 2009 with a median follow-up period of 6.5 years. Hazard ratios (HRs) for CVD incidence according to baPWV levels were calculated using a Cox proportional hazards model adjusted for potential confounding factors, including seated or supine blood pressure (BP). During the follow-up period, we observed 40 incident cases of CVD. In multivariable-adjusted model, baPWV as a continuous variable was not significantly associated with future CVD risk after adjustment for supine BP. However, compared with lower baPWV category (<18 m s(-1)), higher baPWV (< or = 18.0 m s(-1)) was significantly associated with an increased CVD risk (HR: 2.70, 95% confidence interval: 1.18-6.19). Higher baPWV (< or = 18.0 m s(-1)) would be an independent predictor of future CVD event in the general Japanese population.

There is limited evidence on the effect of potassium supplementation on the vasculature in patients at increased cardiovascular risk. Potassium increases aldosterone and there is a strong association of hyperaldosteronism with poor cardiac outcomes. We aimed to determine whether potassium supplementation has a significant medium-term effect on aldosterone levels and, if so, what the overall effect of this is on vascular function in patients at moderate cardiovascular disease risk. Forty patients at moderate cardiovascular disease risk were included in a randomised placebo-controlled crossover study. Patients were assigned to 64 mmol potassium chloride or placebo for 6 weeks. Vascular function was assessed using pulse-wave analysis including the detection of a change in augmentation index to salbutamol and nitroglycerine-induced vasodilation. There was no change in augmentation index with potassium vs placebo (25.2±1.4 vs. 26.0±1.3%, respectively). Potassium improved brachial systolic blood pressure (131.8±2.2 vs. 137.1±2.4 mm Hg; P=0.013), central systolic blood pressure (123.2±2.3 vs. 128.4±2.3 mm Hg; P=0.011) and central diastolic blood pressure (80.3±1.3 vs. 83.7±1.4 mm Hg; P=0.019). Plasma renin activity and serum aldosterone both increased with potassium (P=0.001 and P=0.048 respectively). We found that potassium supplementation had no effect on endothelial function or pulse-wave analysis. It lowered brachial systolic and central blood pressure. It was associated with increased plasma renin activity and serum aldosterone.

The measurement of central blood pressure has generated interest as a tool in predicting cardiovascular events. The purpose of this article is to review the meaning and measurement of the central blood pressure and consider its potential value as an index of the antihypertensive response. Indirect estimation of central aortic pressures is obtained by the study of the radial pulse wave compared with a central pulse wave contour measured at the carotid or femoral artery level. The sum of the forward pressure wave created by ventricular contraction and of the reflected pressure wave from the peripheral arterial system produce the peak systolic blood pressure in the aorta. Measurement of the peripheral reflected-wave contribution to aortic blood pressure can be quantified as the augmentation index. Also, the increase in the rapidity of this travelling wave can be measured as the pulse wave velocity. These 2 parameters are considered to be valid indices of the peripheral arterial stiffness. Along with the calculation of systolic and diastolic aortic pressures, these measurements can give a better understanding of the actual central blood pressure to which core organs like heart, brain, and kidneys are submitted. There is tantalizing evidence for the potential value of central blood pressure as a useful index of antihypertensive action, but until clear evidence is obtained, its use should continue to be considered exploratory., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The impact of country of birth (Africa, Asia, or France) on variations of hemodynamic, clinical, and biological parameters of a French general population was evaluated. The study included 2743 subjects (1641 men, 1102 women; mean age 45.4 ± 13.5 years) with at least two health checkups at the Centre d'Investigations Préventives et Cliniques, Paris, between 2008 and 2011. The interval between the two visits (V1, V2) was 1.74 ± 0.66 years. Changes of hemodynamic, biological and clinical markers were calculated using the V2-V1 absolute difference or percent variation. African- and Asian-born were compared separately to French-born subjects using variance analysis and χ² tests. In men, country of birth was not associated with any significant mean hemodynamic parameter variation. In women, mean brachial and central pulse pressures, heart rate (HR), and central augmentation index (CAI) varied significantly more among African- than Asian-born women, when compared with French-born women. For each hemodynamic parameter, V1 values were the first predictive of this change. Country of birth was a significant predictor of HR and CAI changes. Evaluation of interactions showed that a gender × birth country interaction was significant with CAI variation and, to a lesser extent, HR. Finally, country of birth impacted changes in CAI differently in men and women, suggesting that wave reflections play an important role in cardiovascular risk mainly in women. Their effects act predominantly on pulse pressure level and its amplification, indicating an increasing contribution of CAI with age., (Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Uric acid may be involved in the pathogenesis of hypertension. We investigated the roles of four major hemodynamic parameters of blood pressure, including arterial stiffness, wave reflections, cardiac output (CO), and total peripheral resistance (TPR), in the association between uric acid and central systolic blood pressure (SBP-c)., Methods: A sample of 1303 normotensive and untreated hypertensive Taiwanese participants (595 women, aged 30-79 years) was drawn from a community-based survey. Study subjects' baseline characteristics, biochemical parameters, carotid-femoral pulse wave velocity (cf-PWV), amplitude of the backward pressure wave decomposed from a calibrated tonometry-derived carotid pressure waveform (Pb), CO, TPR, and SBP-c were analyzed., Results: In multi-variate analyses adjusted for age, waist circumference, body mass index, creatinine, total cholesterol, smoking, and heart rate, uric acid significantly correlated with Pb and cf-PWV in men, and Pb and TPR in women. The correlation between uric acid and Pb remained significant in men and women when cf-PWV was further adjusted. In the final multi-variate prediction model (model r(2)=0.839) for SBP-c, the significant independent variables included uric acid (partial r(2)=0.005), Pb (partial r(2)=0.651), cf-PWV (partial r(2)=0.005), CO (partial r(2)=0.062), TPR (partial r(2)=0.021), with adjustment for age, sex, waist circumference, body mass index, creatinine, total cholesterol, smoking, and heart rate., Conclusions: Uric acid was significantly independently associated with wave reflections, which is the dominant determinant of SBP-c. Uric acid was also significantly associated with SBP-c independently of the major hemodynamic parameters., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aortic stiffening often precedes cardiovascular diseases, including stroke, but the underlying pathophysiological mechanisms remain obscure. We hypothesized that such abnormalities could be attributable to altered central blood flow dynamics. In 296 patients with uncomplicated hypertension, Doppler velocity pulse waveforms were recorded at the proximal descending aorta and carotid artery to calculate the reverse/forward flow ratio and diastolic/systolic flow index, respectively. Tonometric waveforms were recorded on the radial artery to estimate aortic pressure and characteristic impedance (Z0) and to determine carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocities. In all subjects, the aortic flow waveform was bidirectional, comprising systolic forward and diastolic reverse flows. The aortic reverse/forward flow ratio (35 ± 10%) was positively associated with parameters of aortic stiffness (including pulse wave velocity, Z0, and aortic/peripheral pulse wave velocity ratio), independent of age, body mass index, aortic diameter, and aortic pressure. The carotid flow waveform was unidirectional and bimodal with systolic and diastolic maximal peaks. There was a positive relationship between the carotid diastolic/systolic flow index (28 ± 9%) and aortic reverse/forward flow ratio, which remained significant after adjustment for aortic stiffness and other related parameters. The Bland-Altman plots showed a close time correspondence between aortic reverse and carotid diastolic flow peaks. In conclusion, aortic stiffness determines the extent of flow reversal from the descending aorta to the aortic arch, which contributes to the diastolic antegrade flow into the carotid artery. This hemodynamic relationship constitutes a potential mechanism linking increased aortic stiffness, altered flow dynamics, and increased stroke risk in hypertension.

Background: Accumulation of advanced glycation end products (AGEs) in the human body might engender arterial stiffening. We investigated the relationship of plasma AGE concentration with arterial stiffness and wave reflections in a Chinese population., Methods: The study subjects were recruited from a newly established residential area in the suburb of Shanghai in 2009. Using the SphygmoCor system, we measured carotid-femoral pulse wave velocity (cfPWV) and central augmentation indices (cAI) and peripheral augmentation indices (pAI). Plasma AGE concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis., Results: The 1,051 study participants (mean age = 55.1±13.1 years) included 663 (63.1%) women, 390 (37.1%) hypertensive patients, and 90 (8.6%) diabetic or prediabetic subjects. Plasma AGE concentration was higher in men than women (5.62 vs. 5.07 μg/ml; P = 0.02) and with older age (r = 0.13 in both sexes; P ≤ 0.01) and higher serum total/high-density lipoprotein cholesterol ratio (r = 0.20 in men and r = 0.15 in women; P < 0.0001). In multiple regression analyses, plasma AGE concentration was significantly associated with cAI and pAI (1.9% and 4.0% increase per 10-time increase in plasma AGE concentration, respectively; P ≤ 0.02) but not with cfPWV (P = 0.62). However, there was significant (P = 0.001) interaction between plasma AGE concentration and age in relation to cfPWV. Only in subjects aged ≥70 years, cfPWV increased with higher levels of plasma AGE concentration (bottom vs. top quintile distributions = 8.10 vs. 8.90 m/s; P = 0.02)., Conclusions: AGEs accumulate with aging and high cholesterol and are associated with arterial wave reflections and, in an age-dependent manner, with arterial stiffness.

Central blood pressure is more closely associated with cardiovascular events and target organ damage than peripheral blood pressure measured over the brachium using a conventional method. This study was designed to investigate the distribution of central systolic blood pressure values estimated by Omron HEM-9000AI in the Japanese general population. A cross-sectional study were performed in 10,756 subjects without overt cardiovascular disease (male=6574; mean age 55.3±12.5 years, range 20-91 years). Of these, 7348 subjects received no antihypertensive, antidiabetic or lipid-lowering drug treatment, and were used for the present analysis. Estimated central systolic blood pressure was higher than brachial systolic blood pressure and was significantly correlated with age and brachial blood pressure. The central systolic blood pressure values obtained from subjects without cardiovascular risk factors other than hypertension were 125.8±37.2 (mean±2 s.d., n=3760) mm Hg. The values obtained from subjects with no cardiovascular risk factors were 112.6±19.2 (n=1975) mm Hg for optimal and 129.2±14.9 mm Hg for normal brachial blood pressure categories (n=697). This study is the first to show the distribution of central systolic blood pressure values estimated using the Omron HEM-9000AI, marking an important step toward implementing the clinical use of central blood pressure in the diagnosis and management of hypertension.

We examined whether the central aortic systolic blood pressure, a marker of the function of the systemic arterial tree, might be a more powerful predictor of the development of hypertension than the brachial-ankle pulse wave velocity, a marker of the stiffness of the large- to middle-sized arteries, independent of the conventional risk factors for the development of hypertension. In 1268 Japanese men without hypertension (43±8 years old), the relationships between three variables (the second peak of the radial pressure waveform (SP2), brachial-ankle pulse wave velocity and conventional risk factors measured at the first examination) with the presence of hypertension at the second examination (after 3 years' follow-up) were examined. Hypertension was detected at the second examination in 154 men. The best cutoff points of the brachial-ankle pulse wave velocity and SP2, for predicting the development of hypertension, were 12.7 m/s and 109 mm Hg, respectively. The results of a logistic regression analysis confirmed that an SP2 of ≥109 mm Hg (odds ratio=8.493, P<0.001) was a more powerful predictor of the development of hypertension than a brachial-ankle pulse wave velocity of ≥12.7 m/s, independent of the conventional risk factors. The net reclassification index of SP2 (at the best cutoff point) to brachial-ankle pulse wave velocity was 0.211 (P<0.001), indicating that SP2 is a better predictor of the development of hypertension than brachial-ankle pulse wave velocity. In middle-aged Japanese men without hypertension, SP2 may be a more powerful predictor of the development of hypertension than the assessment of stiffness in large to middle-sized arteries independent of the conventional risk factors.

The possible relationships between indicators of small resistance artery structure and of arterial stiffness and central hemodynamics have not yet been evaluated. Aim of this study was to assess the relationship between indicators of large arteries stiffness, including carotido-femoral pulse wave velocity and of vascular alterations in small resistance arteries (media/lumen ratio, M/L) in patients with primary and secondary hypertension. In 73 patients (mean age, 53±14 years, 34 females, 25 with type 2 diabetes mellitus, 18 never treated) with essential (n=37) and secondary (n=36) hypertension, carotido-femoral pulse wave velocity was measured. In all patients, small resistance arteries were dissected from subcutaneous fat biopsies and mounted on an isometric myograph, for the measurement of the M/L. Pulse wave analysis was performed in 67 patients. M/L ratio was significantly related to brachial systolic blood pressure and pulse pressure (r=0.36 and 0.31, P<0.001, respectively) and to central systolic and pulse pressure (r=0.44 and 0.42, P<0.001, respectively). A positive correlation was observed between M/L ratio and carotido-femoral pulse wave velocity (r=0.45; P<0.001); this correlation remained statistically significant after adjustment for age and mean blood pressure. M/L ratio was also associated to aortic augmentation index (r=0.33; P=0.008), and this correlations remained statistically significant after adjustment for potential confounders. In hypertensive patients, the presence of structural alterations of small resistance arteries may be associated with the increase in large arteries stiffness and possibly contribute to an increase in central pressure by increasing the magnitude of wave reflections.

Once considered an inconsequential part of the aging process, the development of isolated systolic hypertension represents a late manifestation of increased elastic artery stiffness and is the predominant hypertensive subtype in the middle-aged and elderly populations. Its inherent increased risk for vascular events, such as coronary heart disease, stroke, heart failure, peripheral artery disease, chronic kidney disease, and dementia, highlights the importance of its control. The purpose of this short review is to summarize how hypertension is different in the elderly when compared with "essential hypertension" in younger adults. The emphasis will be on the multiple ways that increased artery stiffness affects the natural history and clinical manifestations of hypertension in the elderly., (© 2012 Wiley Periodicals, Inc.)

Although the circadian variation of catecholamine has been reported, that of the pulse wave velocity (PWV) has not. Brachial ankle (ba) PWV is associated with well-established indices of central stiffness. It is not known whether arterial stiffness is associated with catecholamine. The aim of the present study was to evaluate the changes in baPWV and those on the plasma epinephrine and norepinephrine levels in the morning and evening in hypertensive patients (HPs) and normotensive subjects (NSs). The baPWV and blood pressure (BP) were measured in 14 NSs (14 males, 39 ± 5 years) and 10 HPs (9 males and 1 female, 55 ± 13 years) at 06:00 h, noon, 18:00 h, and midnight, respectively. The plasma epinephrine and norepinephrine levels were measured in 14 NSs and 5 HPs at 06:00 h and 18:00 h, respectively. There was no significant difference in BPs at 06:00 h, noon, 18:00 h, and midnight in either NSs or HPs. The baPWV at 06:00 h was significantly lower than that at noon, 18:00 h, and midnight in NSs (P = 0.01, 0.04, and 0.0008, respectively). The plasma epinephrine and norepinephrine levels at 06:00 h were markedly lower than those at 18:00 h in NSs (P = 0.002 and 0.003, respectively). There were no significant changes in the baPWV of HPs at 06:00 h, noon, 18:00 h, or midnight. The plasma epinephrine and norepinephrine levels at 06:00 h were notably lower than those at 18:00 h in HPs (P = 0.004 and 0.01, respectively). Only NSs showed a significant reduction in the baPWV with a decrease in the plasma catecholamine levels in the morning, suggesting that the baPWV of NSs may be correlated with the variation of the plasma catecholamine levels.

The objective was to analyze pulse wave velocity (PWV) in normotensive, high-normal, and hypertensive youths by using aortic-derived parameters from peripheral recordings. The impact of obesity on vascular phenotypes was also analyzed. A total of 501 whites from 8 to 18 years of age were included. The subjects were divided according to BP criteria: 424 (85%) were normotensive, 56 (11%) high-normal, and 21 (4%) hypertensive. Obesity was present in 284 (56%) and overweight in 138 (28%). Pulse wave analysis using a SphygmoCor device was performed to determine central blood pressure (BP), augmentation index, and measurement of PWV. Among the BP groups, differences appeared in age, sex, and height but not in body mass index. Significant differences in peripheral and central systolic and diastolic BPs and pulse pressures were observed within groups. A graded increase in PWV was present across the BP strata without differences in augmentation index. Using a multiple regression analysis, age, BP groups, and obesity status were independently associated with PWV. Older and hypertensive subjects had the highest PWV, whereas, from normal weight status to obesity, PWV decreased. Likewise, PWV was positively related to peripheral or central systolic BP and negatively related to body mass index z score. For 1 SD of peripheral systolic BP, PWV increased 0.329 m/s, and for 1 SD of body mass index z score PWV decreased 0.129 m/s. In conclusion, PWV is increased in hypertensive and even in high-normal children and adolescents. Furthermore, obesity, the factor most frequently related to essential hypertension in adolescents, blunted the expected increment in PWV of hypertensive and high-normal subjects.

Objective: Input impedance is the frequency-dependent afterload to pulsatile blood flow. Studies of input impedance have been performed as early as the 1960s and have been applied to hypertension (HTN). However, to date, these studies have not been systematically evaluated. This systematic review aims to summarize the literature, interpret existing data from the perspective of impedance theory, and to discuss their potential for generating physiological insights into HTN., Methods: We identified 11 studies wherein computed impedance moduli from both HTN and control (CNT) groups were reported. In addition, we performed bivariate analyses of raw data from three of these studies., Results: Major findings include HTN groups had consistently elevated impedance moduli at 0 Hz (Z(0)) and at heart rate frequency (Z(1)), an increased frequency wherein impedance phase first crosses 0 (f(0)), but no consistent pattern in characteristic impedance (Z(c)), when compared to CNT groups; SBP and DBP are highly correlated with Z(0) and Z(1), moderately correlated with f(0), less correlated with Z(c); the measurement and calculation methods for Z(c) are varied and inconsistent; and a not insignificant proportion of hypertensive individuals have 'normal' Z(0), Z(1) and Z(c) values. These findings are limited by the heterogeneous study populations and small sample sizes., Conclusion: These findings suggest that Z(0), Z(1) and f(0) are significantly associated with HTN, whereas the role of Z(c) is less clear. Additional studies are needed to evaluate these input impedance variables in order to generate substantial implications in clinic settings.

We recently developed a novel method for assessment of arterial wave reflections (ARCSolver method): based on adopted Windkessel methods, flow curves are estimated from pressure waveforms, and wave separation analysis is performed, yielding the amplitudes of the forward and backward waves. The aim of this study was to investigate their clinical correlates and prognostic impact. In 725 patients (417 men; mean age, 64 years) undergoing coronary angiography, we determined wave reflections from radial tonometry and transfer function-derived aortic waveforms using pulse wave analysis, as well as wave separation analysis. Measures of pulsatile arterial function were statistically significant, although moderately associated with markers of cardiac load and subclinic cardiac, renal, and aortic end-organ damage. After a median follow-up duration of 1399 days, 139 patients reached the combined cardiovascular end point (death, myocardial infarction, stroke, coronary, cerebrovascular, and peripheral revascularization). In univariate analysis, the relative risk of the combined end point increased with increasing levels of incident pressure wave height, augmented pressure, and forward and backward wave amplitude (hazard ratio for 1 SD was 1.302, 1.236, 1.226, and 1.276; P<0.01 for all, respectively). In multivariate analysis, backward wave amplitude was the most consistent predictor of the combined end point. Of note, its predictive value was independent of brachial systolic, diastolic, and mean blood pressures and was superior to brachial pulse pressure. In conclusion, the amplitude of the reflected wave, as assessed with a novel method for wave separation, is associated with hypertensive end organ damage and is an independent predictor of cardiovascular events in high-risk patients.

Background: We sought to clarify, using functional and biological approaches, the role of epoxyeicosatrienoic acids, nitric oxide (NO)/reactive oxygen species balance, and endothelin-1 in conduit artery endothelial dysfunction during essential hypertension., Methods and Results: Radial artery diameter and mean wall shear stress were determined in 28 untreated patients with essential hypertension and 30 normotensive control subjects during endothelium-dependent flow-mediated dilatation induced by hand skin heating. The role of epoxyeicosatrienoic acids and NO was assessed with the brachial infusion of inhibitors of cytochrome P450 epoxygenases (fluconazole) and NO synthase (N(G)-monomethyl-l-arginine [L-NMMA]). Compared with controls, hypertensive patients exhibited a decreased flow-mediated dilatation in response to postischemic hyperemia as well as to heating, as shown by the lesser slope of their diameter-shear stress relationship. In controls, heating-induced flow-mediated dilatation was reduced by fluconazole, L-NMMA, and, to a larger extent, by L-NMMA+fluconazole. In patients, flow-mediated dilatation was not affected by fluconazole and was reduced by L-NMMA and L-NMMA+fluconazole to a lesser extent than in controls. Furthermore, local plasma epoxyeicosatrienoic acids increased during heating in controls (an effect diminished by fluconazole) but not in patients. Plasma nitrite, an indicator of NO availability, increased during heating in controls (an effect abolished by L-NMMA) and, to a lesser extent, in patients, whereas, inversely, reactive oxygen species increased more in patients (an effect diminished by L-NMMA). Plasma endothelin-1 decreased during heating in controls but not in patients., Conclusions: These results show that an impaired role of epoxyeicosatrienoic acids contributes, together with an alteration in NO/reactive oxygen species balance and endothelin-1 pathway, to conduit artery endothelial dysfunction in essential hypertension., Clinical Trial Registration: https://www.eudract.ema.europa.eu. Unique identifier: RCB2007-A001-10-53.

Background: Arterial hypertension affects endothelial function and arterial stiffness. The angiotensin (AT1) receptor antagonist irbesartan improves endothelial function and arterial stiffness in hypertensive patients. Nebivolol, a beta(1)-selective beta blocker, reduces systemic vascular resistance and stimulates nitric oxide release thus exerting positive effects on vascular function. However, comparative studies on the vascular effects of third generation beta-blockers and AT1 receptor blockers are lacking. Aim of this randomized, double-blind study was to test the hypothesis of non-inferiority of nebivolol to irbesartan, both in association with hydrochlorothiazide, on endothelial function, arterial stiffness and central hemodynamic parameters in patients with arterial hypertension naïve on therapy., Methods: Sixty-five patients were randomized to receive irbesartan/hydrochlorothiazide (150 mg/12.5 mg day) or nebivolol/hydrochlorothiazide (5mg/12.5 mg day) for 8-weeks. Endothelial function, pulse wave velocity, augmentation index, central and brachial blood pressures were measured at baseline and at the end of the study., Results: Systolic and diastolic central blood pressure, as well as brachial arterial pressure, decreased to a similar extent after both treatments. Similar changes in endothelial function between groups were detected at the end of the study. A significant reduction in pulse wave velocity, central blood pressure, and augmentation index adjusted for heart rate, was found in both the treatment groups at the end of the study, without significant differences between groups., Conclusions: The results of this study confirm the hypothesis of non-inferiority of short-term treatment with nebivolol compared to irbesartan, both in association with hydrochlorothiazide, on endothelial function, arterial stiffness and central hemodynamic parameters in hypertensive patients naïve on therapy., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Pulse wave velocity (PWV), a direct marker of arterial stiffness, is an independent cardiovascular risk factor. Although the angiotensin II type 1 receptor blockade belongs to major antihypertensive and cardioprotective therapies, less is known about the effects of long-term stimulation of the angiotensin II type 2 receptor. Previously, compound 21, a selective nonpeptide angiotensin II type 2 receptor agonist improved the outcome of myocardial infarction in rats along with anti-inflammatory properties. We investigated whether compound 21 alone or in combination with angiotensin II type 1 receptor blockade by olmesartan medoxomil could prevent PWV increase and aortic remodeling in N(ω)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension. Male adult Wistar rats (n=65) were randomly assigned to control, L-NAME, L-NAME+compound-21, L-NAME+olmesartan, and L-NAME+olmesartan+compound-21 groups and treated for 6 weeks. We observed that L-NAME hypertension was accompanied by enhanced PWV, increased wall thickness, and stiffness of the aorta, along with elevated hydroxyproline concentration. Olmesartan completely prevented hypertension, PWV and wall thickness increase, and the increase of aortic stiffness and partly prevented hydroxyproline accumulation. Compound 21 partly prevented all of these alterations, yet without concomitant prevention of blood pressure rise. Although the combination therapy with olmesartan and compound 21 led to blood pressure levels, PWV, and wall thickness comparable to olmesartan-alone-treated rats, only in the combination group was complete prevention of increased hydroxyproline deposition achieved, resulting in even more pronounced stiffness reduction. We conclude that chronic angiotensin II type 2 receptor stimulation prevented aortic stiffening and collagen accumulation without preventing hypertension in rats with inhibited NO synthase. These effects were additive to angiotensin II type 1 receptor blockade, yet without additional blood pressure-lowering effect, and they seem to be NO and blood pressure independent.

Previous studies suggest that ANG II-induced hypertension in rats fed a high-salt (HS) diet (ANG II-salt hypertension) has a neurogenic component dependent on an enhanced sympathetic tone to the splanchnic veins and independent from changes in sympathetic nerve activity to the kidney or hind limb. The purpose of this study was to extend these findings and test whether altered autonomic control of splanchnic resistance arteries and the heart also contributes to the neurogenic component. Mean arterial pressure (MAP), heart rate (HR), superior mesenteric artery blood flow, and mesenteric vascular resistance (MVR) were measured during 4 control days, 14 days of ANG II delivered subcutaneously (150 ng·kg(-1)·min(-1)), and 4 days of recovery in conscious rats fed a HS (2% NaCl) or low-salt (LS; 0.1% NaCl) diet. Autonomic effects on MAP, HR, and MVR were assessed by acute ganglionic blockade with hexamethonium (20 mg/kg iv) on day 3 of control, days 1, 3, 5, 7, 10, and 13 of ANG II, and day 4 of recovery. MVR increased during ANG II infusion in HS and LS rats but remained elevated only in HS rats. Additionally, the MVR response to hexamethonium was enhanced on days 10 and 13 of ANG II selectively in HS rats. Compared with LS rats, HR in HS rats was higher during the 2nd wk of ANG II, and its response to hexamethonium was greater on days 7, 10, and 13 of ANG II. These results suggest that ANG II-salt hypertension is associated with delayed changes in autonomic control of splanchnic resistance arteries and the heart.

Objectives: With growing awareness of arterial stiffness (AS) in the past 10 years, it was realized that resistant hypertension (RH) and AS share the same associated conditions such as older age, isolated systolic hypertension (HT), obesity, chronic kidney disease (CKD), and so on. Until now, there is no study investigating the role of AS in RH. In our study we aimed to determine whether there is an association between RH and AS., Methods: Among 87 patients enrolled in this study, 30 were resistant hypertensives (Group 1), 29 were controlled hypertensives (Group 2), and 28 were normotensives (Group 3). Arterial stiffness was measured by both applanation tonometry and echocardiography; augmentation index, pulse wave velocity (PWV), aortic strain, and aortic distensibility were recorded in each patient. Diastolic function parameters were also assessed., Results: In resistant hypertensive group, augmentation index and PWV were significantly higher than Group 2 and Group 3 (P = .03 and P < .01). Aortic strain and aortic distensibility parameters were significantly lower in RH group (P < .01 and P < .01). Arterial stiffness parameters were similar among Group 2 and Group 3. Among diastolic function parameters, left atrial volume index and left ventricular mass index significantly differ between groups. These two parameters were significantly lower in control group (P < .01 and P = .02) whereas similar in Group 1 and Group 2. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were significantly different between groups as expected. When the correlation between two methods of AS was analyzed, a significant strong inverse correlation was found between echocardiographic and tonometric parameters., Conclusion: Arterial stiffness was found to be associated with RH. The inconsistency of this association in controlled hypertensives suggests a possible role of AS in RH pathogenesis. This study also showed that aortic strain and distensibility correlate well with the PWV which is the gold standard in the assessment of AS. This finding is important for the evaluation of AS more commonly in daily practice as echocardiography is a more feasible device than applanation tonometry.

A three-dimensional computer model of human aortic arch with three branches is reproduced to study the pulsatile blood flow with Finite Element Method. In specific, the focus is on variation of wall shear stress, which plays an important role in the localization and development of atherosclerotic plaques. Pulsatile pressure pulse is used as boundary condition to avoid flow entry development, and the aorta walls are considered rigid. The aorta model along with boundary conditions is altered to study the effect of hypotension and hypertension. The results illustrated low and fluctuating shear stress at outer and inner wall of aortic arch, proximal wall of branches, and entry region. Despite the simplification of aorta model, rigid walls and other assumptions results displayed that hypertension causes lowered local wall shear stresses. It is the sign of an increased risk of atherosclerosis. The assessment of hemodynamics shows that under the flow regimes of hypotension and hypertension, the risk of atherosclerosis localization in human aorta may increase.

Background: Augmentation pressure has emerged as a surrogate marker for cardiovascular disease, and endothelial dysfunction has been proposed as related factor. However, the relationship between augmentation pressure and digital endothelial function has not yet been well defined. We investigated the relationship between augmentation pressure and digital reactive hyperemia (RH) in patients with hypertension using peripheral arterial tonometry (PAT), which is regarded as being representative of endothelial function., Methods: One hundred hypertensive patients (64 males; mean age, 49 ± 12 years) without a history of taking antihypertensive medication were enrolled in this study., Results: The mean augmentation pressure and augmentation index (AIx) normalized for a heart rate of 75 beats/min (AIx75) were 15 ± 8 mm Hg and 26 ± 11%, respectively. The mean RH-PAT index and log transformed PAT ratio were 2.24 ± 0.55 and 0.62 ± 0.30. There was an inverse relationship between the RH-PAT index and age, male sex, and body mass index. The log transformed PAT ratio also showed inverse relationship with age and male sex. The RH-PAT index and the log transformed PAT ratio showed no relationship with augmentation pressure or AIx75. In a multiple linear regression analysis, age, height, and central systolic BP demonstrated an independent association with augmentation pressure and AIx75., Conclusion: In patients with hypertension, the RH-PAT index determined using PAT was not associated with augmentation pressure or AIx75. Digital vascular function may be a less important factor for pressure augmentation in patients with hypertension.

A significant link has been reported between aortic stiffening and renal microvascular damage, but the underlying mechanism remains poorly understood. We hypothesized that alterations in central and renal hemodynamics are responsible for this link. In 133 patients with hypertension, pressure waveforms were recorded on the radial, carotid, femoral, and dorsalis pedis arteries with applanation tonometry to estimate the aortic pressures and aortic (carotid-femoral) and peripheral (carotid-radial and femoral-dorsalis pedis) pulse wave velocities. Flow-velocity waveforms were recorded on the renal segmental arteries with duplex ultrasound to calculate the resistive index (RI) as [1 - (end-diastolic velocity/peak systolic velocity)] and on the femoral arteries to calculate the reverse/forward flow index and diastolic/systolic forward-flow ratio. Albuminuria was defined as urinary albumin/creatinine ratio ≥30 mg/g of creatinine. The renal RI (mean: 0.65±0.07) was strongly correlated (P<0.001) with the aortic pulse pressure (r=0.62), incident pressure wave (r=0.55), augmented pressure (r=0.49), and aortic pulse wave velocity (r=0.51), although not with the mean arterial pressure or peripheral pulse wave velocities. The correlations remained highly significant after consideration of confounders including age, cholesterol, hemoglobin A(1c), and glomerular filtration rate. The renal RI was inversely correlated with the femoral reverse and diastolic forward flow indices. Both aortic pulse pressure and renal RI correlated with the urinary albumin/creatinine ratio independent of confounders. Each 0.1 increase in renal RI was associated with a 5.4-fold increase in the adjusted relative risk of albuminuria. In conclusion, increased aortic pulse pressure causes renal microvascular damage through altered renal hemodynamics resulting from increased peripheral resistance and/or increased flow pulsation.

Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides (LTPs) derived from enzymatic treatment of casein hydrolysate. Our aim was to evaluate this effect on a large number of hemodynamic parameters. We conducted a prospective double-blind randomized clinical trial, which included 52 patients affected by high-normal blood pressure (BP) or first-degree hypertension. We investigated the effect of a 6-week treatment with the LTPs isoleucine-proline-proline and valine-proline-proline at 3 mg per day, assumed to be functional food, on office BP, 24-h ambulatory BP monitoring (ABPM) values, stress-induced BP increase and cardiac output-related parameters. In the LTP-treated subjects, we observed a significant reduction in office systolic BP (SBP; -5±8 mm Hg, P=0.013) and a significant improvement in pulse wave velocity (PWV; -0.66±0.81 m s(-1), P=0.001; an instrumental biomarker of vascular rigidity). No effect on 24-h ABPM parameters and BP reaction to stress was observed from treatment with the combined LTPs. LTPs, but not placebo, were associated with a mild but significant change in the stroke volume (SV), SV index (markers of cardiac flow), the acceleration index (ACI) and velocity index (VI) (markers of cardiac contractility). No effect was observed on parameters related to fluid dynamics or vascular resistance. LTPs positively influenced the office SBP, PWV, SV, SV index, ACI and VI in patients with high-normal BP or first-degree hypertension.

Recent evidence suggests that low-grade urinary albumin excretion is a marker of early general attenuation of vascular function, but studies are limited to Caucasian population groups. We compared low-grade urinary albumin excretion (<3.5 mg mmol(-1) or 30 μg mg(-1)) between non-diabetic African (aged, 41.7 years; n=70) and Caucasian (aged, 44.6 years; n=91) men and ethnic-specific associations thereof with arterial stiffness and ambulatory blood pressure. The albumin-to-creatinine ratio (ACR) was determined from an 8 h overnight urine collection. We recorded ambulatory blood pressure over 24 h during a typical workday and the carotid-dorsalis pedis pulse wave velocity measured the next morning after a controlled overnight stay. ACR was higher in Africans compared with Caucasians (P < 0.001), also after adjusting for 24 h systolic blood pressure, diastolic blood pressure and hypertension prevalence (P < 0.001) or when grouped by similar 24 h mean arterial pressures (P < 0.01 for all categories). Daytime (P=0.002) and night time (P < 0.001) systolic and daytime (P < 0.001) and night time (P < 0.001) diastolic blood pressures were higher in Africans compared with Caucasians, but no differences existed for daytime and night time pulse pressure and pulse wave velocity. In African men only, after adjustment for covariates, night time systolic blood pressure (β=0.347; P=0.003), diastolic blood pressure (β=0.298; P=0.010) and mean arterial pressure (β=0.331; P=0.004) correlated positively with ACR. In addition, daytime (β=0.265; P=0.032) and night time (β=0.258; P=0.038) pulse pressure as well as pulse wave velocity (β=0.271; P=0.032) correlated positively with ACR. In conclusion, arterial stiffness and ambulatory blood pressure are already associated with low-grade albuminuria in non-diabetic African men with normal kidney function.

Background: The present study was designed to test the hypothesis that brachial-ankle pulse wave velocity (baPWV) predicts longitudinal increases in blood pressure (BP) and new onset of hypertension in individuals with normal BP., Methods: baPWV was measured using a semiautomated device in 2,496 participants (27-84 years) without hypertension who visited our hospital for a yearly health check-up. They were followed up for 4 years with the endpoint being development of hypertension., Results: During the follow-up period (median, 733 days; actual follow-up, 5,215 person-years), hypertension developed in 698 participants (133.8/1,000 person-years). Kaplan-Meier analysis revealed that risk for hypertension was increased across the tertiles of baseline baPWV. The hazard ratio (first tertile as reference) was 2.02 (95% confidence interval (CI) 1.55-2.64) and 3.49 (95% CI 2.66-4.57) in the second and third tertiles, respectively, after adjustment for possible risk factors. Multivariate Cox proportional hazard regression analysis adjusted for known risk factors, where baPWV was used as a continuous variable, also indicated that the baseline value of baPWV independently predicted new onset of hypertension (P < 0.001). Furthermore, baseline baPWV was significantly associated with a longitudinal increase in BP after adjustment for known risk factors in multiple regression analysis (P < 0.001)., Conclusion: This study provides the first evidence that baPWV is an independent predictor of longitudinal increases in BP as well as of new onset of hypertension.

Objective: To evaluate wave intensity (WI) on left ventricular (LV) performance in the different hypertensive remolding hearts., Methods: 105 hypertensive and 98 control subjects were underwent noninvasive evaluation of carotid arterial wave intensity, LV structure and function., Results: (1) There were increasing trends in the levels of blood pressure, LV end-diastolic diameter and LV mass index in the control, normal geometry group, concentric remodeling group, concentric and eccentric hypertrophy group. LV ejection fraction increased in the concentric hypertrophy group and decreased in the eccentric hypertrophy group in which mid-wall fractional shortening showed a decreasing trend. LV diastolic filling pressure presented increased progression accompanied by LV remodeling (P < 0.05). (2) Transient acceleration wave intensity (W1) in hypertensive subjects were higher than that in the control (P < 0.05). Transient deceleration wave intensity (W2) was lower than that in the control (P < 0.05). (3) W1 in the concentric hypertrophy group was higher and lower in the eccentric hypertrophy, compared with that in the control group, normal geometry group and concentric remodeling group (P < 0.05). W2 was lower in concentric hypertrophy group and eccentric hypertrophy group than that in the control, normal geometry group and concentric remodeling group (P < 0.05)., Conclusion: WI is a noninvasively obtained, clinically useful parameter for evaluation of LV performance.

The objective of this study was to compare home blood pressure (HBP) vs. ambulatory (ABP) and clinic (CBP) measurements in terms of their association with target-organ damage in children and adolescents. A total of 81 children and adolescents (mean age 13 ± 3 years, 53 boys) referred for elevated CBP had measurements of CBP (1 visit), HBP (6 days) and ABP (24-h). Seventy-six participants were also assessed with carotid-femoral pulse wave velocity (PWV) and 54 with echocardiography. Average CBP was 122.1 ± 15.1/71 ± 12.9 mm Hg (systolic/diastolic), HBP 121.3 ± 11.5/69.4 ± 6.6 mm Hg and 24-h ABP 118.9 ± 12/66.6 ± 6.1 mm Hg. Left ventricular mass (LVM) was correlated with systolic blood pressure (BP) (coefficient r = 0.55/0.54/0.45 for 24-h/daytime/nighttime ABP, 0.53 for HBP and 0.41 for CBP; all P< 0.01). No significant correlations were found for diastolic BP. PWV was also significantly correlated with systolic BP (r = 0.52/0.50/0.48 for 24-h/daytime/nighttime ABP, 0.50 for HBP and 0.47 for CBP; all P < 0.01). Only diastolic ABP and HBP were significantly correlated with PWV (r = 0.30 and 0.28, respectively, P<0.05). In multivariate stepwise regression analysis (with age, gender, body mass index [BMI], clinic, home and 24-h ambulatory systolic/diastolic BP and pulse pressure, clinic, home and 24-h heart rate as independent variables), PWV was best predicted by systolic HBP (R(2) = 0.22, beta ± s.e. = 0.06 ± 0.01), whereas LVM was determined (R(2) = 0.67) by 24-h pulse pressure (beta = 1.21 ± 0.41), age (beta = 2.93 ± 1.32), 24-h heart rate (beta = -1.27 ± 0.41) and BMI (beta = 1.78 ± 0.70). These data suggest that, in children and adolescents, ABP as well as HBP measurements appear to be superior to the conventional CBP measurements in predicting the presence of subclinical end-organ damage.

Aim: To ascertain whether high arterial rigidity is obligatory in arterial hypertension (AH) and the presence of AH is obligatory in patients with rigid arteries., Material and Methods: Volume sphygmography (VS) was made in 153 patients aged 60-86 years: 96 patients with untreated AH of degree 1-3 (40 males aged 71.0 +/- 7.6 years) and 57 normotensive subjects without cardiovascular symptoms (31 males aged 66.6 +/- 6.2 years). VS measured ankle-shoulder velocity of the pulse wave (PWVas) and cardiac-ankle vascular index (CAVI). PWVas > M+STD and CAVI > M+2STD (STD is deviation from mean value) were considered above normal for the age., Results: Hypertensive patients had significantly higher arterial rigidity than normotensives (PWVas 178 +/- 3.0 and 15.6 +/- 2.3 m/s, respectively, p = 0.00001); CAVI--9.7 +/- 2.1 and 8.6 +/- 1.1, respectively, p = 0.0003). Arterial rigidity in hypertensive patients occurred significantly more frequently than in normotensive subjects: by PWVas in 46 and 25% cases (p = 0.01), by CAVI--in 41 and 5% cases (p < 0.0001), respectively. It is essential that arterial rigidity was not increased in 54% hypertensive patients by PWVas and in 75% by CAVI., Conclusion: PWVas and CAVI were higher in elderly hypertensives than in elderly normotensives but elevated arterial rigidity was not obligatory in hypertensives while 25% elderly normotensives had it. Thus, elevated arterial rigidity is an essential but not obligatory mechanism of AH development in the elderly.

We measured the brachial-ankle pulse wave velocity (baPWV) in 491 normotensives and determined the "PWV index" (measured baPWV-theoretical baPWV) in 491 normotensives and 83 controlled hypertensives. Linear regression analysis revealed that the theoretical baPWV (cm/sec) was 0.21 × age(2) (years(2))-13.73 × age (years) + 0.05 × mean arterial pressure(2) (mmHg(2)) + 3.95 × heart rate (bpm) + 36.49 × gender (1 male; 0 female) + 733 (R(2) = 0.53). The calculated PWV index was significantly higher in 13 smokers than 70 nonsmokers among controlled hypertensives. The calculated PWV index might provide more precise information about inherent arterial stiffness.

In Africans, arterial stiffness progression seems more pronounced compared to Caucasians. We compared the arterial stiffness profiles of different age groups and focused on muscular arteries and two more central arterial segments in African and Caucasian people from South Africa. In African (N = 374) and Caucasian (N = 376) participants (20-70 years), we measured carotid-radial (C-R) and carotid-dorsalis pedis (C-DP) pulse wave velocity (PWV) and aortic characteristic impedance (Zao). Major findings were that normotensive and high-normal/hypertensive (HT) Caucasians indicated increased trends of C-R PWV with aging (P = .029 and P = .067), not seen in the African groups (P = .122 and P = .526). Both ethnic groups showed significant increases of C-DP PWV and Zao with aging. High-normal/hypertensive Africans had significantly stiffer arteries than hypertensive Caucasians for almost all age groups, and for all stiffness measures. African C-R PWV correlated significantly with blood pressure (BP), but not with age. Opposite results were observed for Caucasians. In conclusion, the stiffness of muscular arteries is already elevated in young Africans, in both those with normal or elevated BP. This is possibly due to an earlier deterioration during childhood, or perhaps already present from birth. Also, in Caucasians stiffness seems more age-related, while in Africans it seems to be more pressure-related.

We analyzed the possibility of using the radial pulse wave morphology, obtained by a movement transducer, to evaluate the aortic pulse wave velocity. The radial pulse wave signals were obtained by using a transducer, located on the pulse palpation area, in 167 healthy normotensive male volunteers, ages 20 to 70. The reflected wave was identified in every case. Also, a speed coefficient was defined as the ratio between the individual's height and the time between the maximum systolic wave and the arrival time of the reflected wave. We found that the specified coefficient in normotensive individuals increased linearly with age, in a similar way to the increase in aortic propagation velocity measured by other methods. The procedure was repeated on another set of 125 individuals with hypertension, without other risk factors, aged between the 3rd and 7th decade. This time we found similar values to normotensive individuals only on the 3th decade, and a pronounced increase on the velocity coefficient at advanced ages was observed. These findings support the feasibility of using this type of signals to indirectly evaluate the propagation velocity together with the increase index, a parameter commonly used in pulse wave analysis.

Aortic stiffness, peripheral wave reflection, and aorta-to-peripheral pulse pressure amplification all predict cardiovascular risk. However, the pathophysiological mechanism behind it is unknown. Tonometric pressure waveforms were recorded on the radial, carotid, and femoral arteries in 138 hypertensive patients (age: 56±13 years) to estimate aorta-to-peripheral amplifications, aortic augmentation index, and aortic (carotid-femoral) pulse wave velocity. The femoral Doppler velocity waveform was recorded to calculate the reverse/forward flow index and diastolic/systolic forward flow ratio. The aorta-to-femoral and aorta-to-radial amplifications correlated inversely with the aortic augmentation index and pulse wave velocity. The femoral flow waveform was triphasic, composed of systolic forward, subsequent reverse, and diastolic forward phases in 129 patients, whereas it was biphasic and lacked a diastolic forward flow in 9 patients. Both the femoral reverse index (30±10%) and diastolic forward ratio (12±4%) correlated positively with the aorta-to-femoral amplification and inversely with the aortic augmentation index and pulse wave velocity; these correlations were independent of age, sex, diastolic pressure, and femoral artery diameter. Patients with biphasic (versus triphasic) flow were older, shorter, included more diabetics, had smaller femoral diameters, and showed greater aortic pulse wave velocity even when adjusted for all of these covariates. In conclusion, because of the inverse (peripheral-to-aortic) pressure gradient, pulse pressure amplification normally produces a substantial reversal of the femoral flow, the degree of which is determined by the aortic distensibility and peripheral wave reflection. Arteriosclerosis (increased stiffness, increased augmentation, and reduced amplification) decreases both the reverse and diastolic forward flows, potentially causing circulatory disturbance of truncal organs and lower extremities.

Background: The effect of prolonged hypoxemia in early life on systemic arterial blood pressure at maturity was assessed in Sprague-Dawley rats., Methods: Animals hypoxic in early life (12 males, 10 females) were raised in hypoxia (FiO₂ = 0.12) for the first 10 days of life and subsequently raised in normoxia, along with age-matched controls (11 males, 9 females). At 2 months of age, arterial blood pressure was recorded intravascularly using telemetry in awake and unrestrained animals over two 12-h night-time (active) and daytime (resting) periods. Aortic pulse wave velocity was assessed in six additional hypoxic pretreated and five control anesthetized 2-month-old male rats., Results: Systolic, mean, and pulse pressures were significantly greater in the hypoxic pretreated group compared to the control group during resting and active periods in both sexes (P ≤ 0.05). Diastolic pressure and heart rate did not differ between the two groups. Hypoxic pretreated males displayed significantly increased blood pressure variability during the resting period. Aortic pulse wave velocity was also found to be elevated in the hypoxic pretreated rats., Conclusions: Prolonged hypoxic stress in early life in the rat is associated with increased systolic arterial pressure at maturity very likely due to decreased arterial compliance. These findings suggest that a nutrient-independent, postnatal stress may lead to long-lasting vascular alterations predisposing to increased arterial pressure at maturity. This raises the possibility that adult survivors of congenital cyanotic cardiac disease may be at risk for secondary cardiovascular morbidity unrelated to surgical repair or residual cardiac defects.