Ambulatory Arterial Pressure Research Articles

Dietary Cinnamaldehyde Activation of TRPA1 Antagonizes High-Salt-Induced Hypertension Through Restoring Renal Tubular Mitochondrial Dysfunction.

The renal proximal tubule (RPT) plays a pivotal role in regulating sodium reabsorption and thus blood pressure (BP). Transient receptor potential ankyrin 1 (TRPA1) has been reported to protect against renal injury by modulating mitochondrial function. We hypothesize that the activation of TRPA1 by its agonist cinnamaldehyde may mitigate high-salt intake-induced hypertension by inhibiting urinary sodium reabsorption through restoration of renal tubular epithelial mitochondrial function. Trpa1-deficient (Trpa1-/-) mice and wild-type (WT) mice were fed standard laboratory chow [normal diet (ND) group, 0.4% salt], standard laboratory chow with 8% salt [high-salt diet (HS) group], or standard laboratory chow with 8% salt plus 0.015% cinnamaldehyde [high-salt plus cinnamaldehyde diet (HSC) group] for 6 months. Urinary sodium excretion, reactive oxygen species (ROS) production, mitochondrial function, and the expression of sodium hydrogen exchanger isoform 3 (NHE3) and Na+/K+-ATPase of RPTs were determined. Chronic dietary cinnamaldehyde supplementation reduced tail systolic BP and 24-hour ambulatory arterial pressure in HS-fed WT mice. Compared with the mice fed HS, cinnamaldehyde supplementation significantly increased urinary sodium excretion, inhibited excess ROS production, and alleviated mitochondrial dysfunction of RPTs in WT mice. However, these effects of cinnamaldehyde were absent in Trpa1-/- mice. Furthermore, chronic dietary cinnamaldehyde supplementation blunted HS-induced upregulation of NHE3 and Na+/K+-ATPase in WT mice but not Trpa1-/- mice. The present study demonstrated that chronic activation of Trpa1 attenuates HS-induced hypertension by inhibiting urinary sodium reabsorption through restoring renal tubular epithelial mitochondrial function. Renal TRPA1 may be a potential target for the management of excessive dietary salt intake-associated hypertension.

Odnos varijabilnosti arterijskog pritiska iz ambulatornog 24-časovnog monitoringa arterijskog pritiska sa ehokardiografskim parametrima u bolesnika pod antihipertenzivnom terapijom

Introduction: Variability of systolic daytime arterial pressure was until recently a controversial parameter but is now recognized as an independent prognostic risk factor for stroke in hypertensive patients. Blood pressure variability is a quantitative index of spontaneous daily and nocturnal variations in systolic and diastolic arterial blood pressure and has been proposed as a risk factor for inducing subclinical damage to target organs in arterial hypertension. Besides varying degrees of left ventricular myocardial hypertrophy (LVH), patients with hypertension also exhibit accompanying diastolic dysfunction of the left ventricle as an early sign of hypertensive damage, even when myocardial hypertrophy does not develop. The variability of pressure over 24 hours in Ambulatory Blood Pressure Monitoring (ABPM) has not been sufficiently studied in terms of correlation with echocardiographic parameters in controlled hypertension. Methods: A total of 196 adequately treated patients with stage 2 hypertension, with a target of achieving normotension less than 140/90, were examined. The total of 196 patients, 109 males and 87 females, with a mean age of 49.3 ± 8.4 years, untreated or inadequately treated patients with stage 2 hypertension (mean BP before treatment 167/106 mmHg) were divided into three groups according to blood pressure variability parameters. Alongside standard methods: medical history, clinical examination, and electrocardiogram (ECG), 24-hour ambulatory arterial pressure monitoring (ABPM, so-called blood pressure holter) was performed with 24-hour, daytime, and nighttime variability of systolic and diastolic blood pressure as well as Color and Tissue Doppler echocardiography after adequate treatment. Results: Elevated blood pressure variability was observed in 66/196 patients (34%) in group V despite good pressure regulation, while 130/169 (66%) had normal variability - group C (control). A subgroup ExtV was particularly highlighted within group V with extreme variability of daytime systolic BP (SD>20 mmHg) - 15/66 patients (8%). Evaluation of left ventricular myocardial mass index (LVMI) showed no difference in the degree of LVH between groups C and V. In the subgroup ExtV (from group V with extreme blood pressure variability), comprising 15/66 patients (8%), a significant difference in the degree of left ventricular myocardial hypertrophy was found between groups C and V regarding extreme variability (p<0.01). There was no difference concerning gender and age structure. Statistical analysis of investigated 24-hour blood pressure parameters and echocardiographic parameters did not show significant correlation through calculation of the linear correlation coefficient between mean arterial pressure measured by 24-hour ambulatory pressure monitoring and standard deviations of daytime and nighttime pressure and the degree of left ventricular myocardial hypertrophy (linear correlation coefficients r <0.20), as expected. However, there is a moderate but significant correlation between the best echocardiographic parameter of diastolic function, E/E' ratio, and variability of daytime systolic pressure: r= 0.41. Only the subgroup with extreme variability ExtV in terms of daytime systolic pressure has a statistically significant correlation with the degree of LVMI myocardial hypertrophy, r=0.51. Conclusion: One-third of the examined patients, 66/196 patients (34%) in group V, had elevated blood pressure variability despite good pressure regulation. There was no significant difference in the degree of left ventricular myocardial hypertrophy between the investigated parameters of 24-hour blood pressure and echocardiographic indices, except in extreme variability ExtV (P<0.01). However, there is a moderate but significant correlation between the best echocardiographic parameter of diastolic function, E/E' ratio, and variability of daytime systolic pressure: r= 0.41. Only the subgroup with extreme variability ExtV in terms of daytime systolic pressure has a statistically significant correlation with the degree of LVMI myocardial hypertrophy, r=0.51.

Influence of an acute fast on ambulatory blood pressure and autonomic cardiovascular control.

Evidence suggests that intermittent fasting improves cardiovascular health by reducing arterial blood pressure, but contributing mechanisms are unclear. The purpose of this study was to determine the influence of an acute fast on hemodynamics, muscle sympathetic nerve activity (MSNA), and autonomic control at rest and during an arterial pressure challenge. Twenty-five young normotensive volunteers were tested twice, in the fed and fasted (24 h) states (randomized). Twenty-four hour ambulatory blood pressure was measured before an autonomic function test, which consisted of a 10-min period of controlled breathing (CB) at 0.25 Hz followed by 3, 15-s Valsalva maneuvers (VMs). We recorded the ECG, beat-to-beat arterial pressure, and MSNA throughout the autonomic test. Vagal-cardiac modulation via heart rate variability (HRV) was assessed in both time and frequency domains, cardiovagal baroreflex sensitivity (cvBRS) was assessed with linear regression, and stroke volume was estimated from pulse contour. All fed versus fasted comparisons presented are different at P < 0.05. Fasting reduced ambulatory mean arterial pressure (81 ± 1 vs. 78 ± 1 mmHg) and heart rate (69 ± 2 vs. 65 ± 2 beats/min). CB revealed enhanced HRV through increased R-R intervals (992 ± 30 vs. 1,059 ± 37 ms) and normalized high frequency (HFnu) R-R interval spectral power (55 ± 3 vs. 62 ± 3%). Estimated stroke volume was higher after fasting (by 13%) as was cvBRS (20 ± 2 vs. 26 ± 5 ms/mmHg) and cvBRS during phase IV of the VM (9 ± 1 vs. 12 ± 1 ms/mmHg). MSNA (n = 12) did not change (16 ± 11 vs. 15 ± 8 bursts/min; P = 0.18). Our results show that acute fasting is consistent with improved cardiovascular health: such improvements are driven by reduced ambulatory arterial pressure and enhanced vagal-cardiac modulation.

Acute Fasting Increases Vagal Tone and Reduces Ambulatory Arterial Pressure

Obesity is a chronic metabolic disorder associated with increased risk of cardiovascular disease, and intermittent fasting might mitigate risk. Intermittent fasting creates a negative energy balance that results in weight loss, but the cardiovascular benefits of fasting have not been studied thoroughly. The purpose of this study was to investigate the influences of an acute 24-hr fast on cardiovascular control and hemodynamics. Ours was a randomized, crossover design with autonomic testing occurring 3-hrs postprandial (fed) and 24-hrs postprandial (fast). A standardized meal was provided for both conditions. 24-hrs before autonomic testing participants wore an ambulatory blood pressure (ABP) cuff which recorded 3 brachial pressures per hr during the day and 2 pressures per hr at night. 24-hour ABP was averaged and compared via a paired t-test (N=17, 6 Female; fed vs. fasted). 3 participants did not meet inclusion criteria of at least 20 valid day and 7 valid night recordings. Twenty young (23±0.7 yrs), normotensive, non-obese (25±0.8 BMI), participants completed the autonomic test. We measured blood glucose (GLU), ketones (β-OHB), and triglycerides (TRG) to confirm a successful fast. With subjects in a supine position during the autonomic test, we recorded the ECG and beat-to-beat arterial pressure (finger plethysmography). Cardiovagal baroreflex sensitivity (cvBRS) was determined by beat-to-beat changes in R-R interval (RRI) and systolic pressure (SAP) using the sequence method. Only sequences with linear r values >0.7 were accepted (cvBRS-up N=18; cvBRS-down N=20). Spectral analysis was used to assess heart rate variability. The high frequency (HFnu; 0.15-0.40 Hz) and low frequency (Lfnu; 0.04-0.15 Hz) components were normalized to total power. Subjects rested quietly for 10 min while breathing in time to a computer display prompting them to breathe at a frequency of 15 breaths/min. The last 8 min of the autonomic test were averaged and compared via a paired t-test (N = 20, 7 Female; fed vs. fasted). Data are expressed as mean±SE. P-values ≤ 0.05 were considered significant and are indicated by an asterisk (*). Changes in TRG, GLU and β-OHB with fasting were consistent with expectations: TRG and GLU decreased (TRG; 114±11 fed vs. 68±6* mg/dL fast)(GLU; 99±3 fed vs. 80±2* mg/dL fast), and β-OHB increased (β-OHB; 0.13±.03 fed vs. 0.57±.12* mmol/L fast). Overall SAP and diastolic (DAP) ABP decreased in the fasted condition (SAP;111±1.5 fed vs. 109±1.5* mmHg fast) (DAP; 66±1.4 fed vs. 64±1.5* mmHg fast). During the autonomic test, RRI, cvBRS-up, cvBRS-down, and HFnu increased, and LFnu decreased in the fasted condition. (RRI; 991±35 fed vs. 1053±45* ms fast)(cvBRS-up 19.5±3 fed vs. 26.4±6* ms/mmHg fast) (cvBRs-down; 15.3±1 fed vs. 21.5±3* ms/mmHg fast) (HFnu; 54.4±3 fed vs. 61.4±4* a.u. fast) (LFnu; 45.6±3 fed vs. 38.6±3* a.u. fast). Our results suggest that acute fasting may convey cardioprotective benefits through enhanced vagal tone and reduced 24-hr ambulatory arterial pressure.

Mineralocorticoid Receptor-Dependent Impairment of Baroreflex Contributes to Hypertension in a Mouse Model of Primary Aldosteronism.

Primary aldosteronism (PA) is the most common cause of secondary hypertension. The paucity of good animal models hinders our understanding of the pathophysiology of PA and the hypertensive mechanism of PA remains incompletely known. It was recently reported that genetic deletion of TWIK-related acid-sensitive potassium-1 and potassium-3 channels from mice (TASK−/−) generates aldosterone excess and mild hypertension. We addressed the hypertensive mechanism by assessing autonomic regulation of cardiovascular activity in this TASK−/− mouse line that exhibits the hallmarks of PA. Here, we demonstrate that TASK−/− mice were hypertensive with 24-h ambulatory arterial pressure. Either systemic or central blockade of the mineralocorticoid receptor (MR) markedly reduced elevated arterial pressure to normal level in TASK−/− mice. The response of heart rate to the muscarinic cholinergic receptor blocker atropine was similar between TASK−/− and wild-type mice. However, the responses of heart rate to the β-adrenergic receptor blocker propranolol and of arterial pressure to the ganglion blocker hexamethonium were enhanced in TASK−/− mice relative to the counterparts. Moreover, the bradycardiac rather than tachycardiac gain of the arterial baroreflex was significantly attenuated and blockade of MRs to a large degree rescued the dysautonomia and baroreflex gain in TASK−/− mice. Overall, the present study suggests that the MR-dependent dysautonomia and reduced baroreflex gain contribute to the development of hyperaldosteronism-related hypertension.

A3299 TRPV1 activation by dietary capsaicin improves high salt diet-induced hypertension

Objectives: High-salt intake contributes to the development of hypertension. We have reported that transient receptor potential vanilloid type 1 (TRPV1) activation by dietary capsaicin improves endothelial function in genetically hypertensive rats. We investigate whether TRPV1 activation also antagonizes high-salt induced hypertension. Methods: C57BL/6J (WT) and TRPV1−/− mice were randomized into three groups (n = 8) and were fed with normal diet (ND), high-salt diet (8% salt, HS) or high-salt plus 0.01% capsaicin diet (HSC). Mouse systolic blood pressure (SBP) was measured by tail-cuff plethysmography and 24-hour ambulatory arterial pressure was measured with telemetric transmitters. Results: The study showed that TRPV1 activation inhibited the increased αENaC activity, and increased urinary sodium excretion through reducing sodium reabsorption in WT mice on a HS but not in TRPV1−/− mice. TRPV1 activation significantly lowered tail SBP in WT mice on a HS after the 8 month. TRPV1 activation also lowered 24-hour ambulatory arterial pressure in WT HS group mice after 10-month treatment. Importantly, the hypotensive effect of capsaicin was absent in TRPV1−/− mice. Plasma aldosterone levels were lower in mice on a HS compared with mice on a ND in WT and TRPV1−/−mice. The urinary sodium excretion and volume of water intake were higher in mice on a HS compared with in WT and TRPV1−/−mice on ND. However, the plasma sodium, potassium and chloride, urinary potassium, and food intake were not different among each group of WT and TRPV1−/− mice. Conclusion: TRPV1 activation by capsaicin increases urinary sodium excretion and prevents high-salt diet induced hypertension through antagonizing αENaC-mediated urinary sodium reabsorption.

Abstract P247: Non-dipping Ambulatory Blood Pressure in Non-hypertensive Individuals

Non-dipping predicts increased cardiovascular risk in hypertension. However, the mechanisms leading to non-dipping remain unknown. Also, non-dipping in normotension and prehypertension is less well-described. The study objective was to determine the prevalence of non-dipping, and the association of non-dipping with other cardiovascular risk factors, in non-hypertensive young adults. The study cohort included 176 non-hypertensive, non-diabetic individuals, mean age 27 ( Table 1 ). Office and 24-hour ambulatory BP were measured, along with fasting adipokine levels, insulin sensitivity (QUICKI) and measures of vascular stiffness: Ambulatory arterial stiffness index (AASI) and pulse pressure. The distribution of dipping patterns was 58% dippers, 35% non-dippers, 5% extreme dipping, and 2% reverse dipping. CRP, IL6, and AASI are significantly associated with non-dipping ( Table 2 ). Non-dipping in common in young non-hypertensive adults. Inflammation and vascular stiffness may be potential mechanisms explaining the increased cardiovascular risk associated with non-dipping.

PP.29.26] AMBULATORY ARTERIAL STIFFNESS INDEX IN PATIENTS WITH METABOLIC SYNDROME AND NEWLY DIAGNOSED HYPERTENSION BEFORE AND AFTER ONE YEAR OF TREATMENT WITH LOSARTANE AND TELMISARTANE

Objective: To measure the ambulatory arterial stiffness index (AASI) and pulse pressure (PP) in patients with newly diagnosed hypertension and metabolic syndrome before and after 1 year of treatment with losartane or telmisartane once daily. Design and method: Blood pressure (BP) measurement using 24-hour ambulatory BP monitoring (ABPM, SpaceLabs 90207) according to the ESH criteria. Metabolic syndrome and hypertension defined by ATP III criteria. Fifty seven patients in two groups; 30 patients treated with telmisartane and 27 patients with losartane. PP pressure calculated as systolic minus diastolic BP, AASI defined as 1-regression slope of diastolic on systolic BP computed from 24-hour recording for each patient. Statistic evaluation before and after treatment using paired Students T-test. Results: Telmisartane (N = 30), before treatment: mean 24-hour ABPM 135/84 mmHg, PP 50,8 ± 8,7 mmHg, AASI 0,37 ± 0,01, after treatment: mean 24-hour ABPM 126/79 mmHg, difference −9/5 mmHg, P < 0,01, PP 47,4 ± 6,0 mmHg, difference −3,4 mmHg, P < 0,01, AASI 0,38 ± 0,04, difference + 0,01, P = 0,642. Losartane (N = 27), before treatment: mean 24-hour ABPM 135/84 mmHg, PP 51,2 ± 7 mmHg, AASI 0,38 ± 0,05, after treatment: mean 24-hour ABPM 124/77 mmHg, difference 11/7 mmHg, P < 0,01, PP 46,9 ± 5,8 mmHg, difference −4,3 mmHg, P < 0,01, AASI 0,38 ± 0,04, difference 0, P = 0,68. Conclusions: After treatment significantly decreased the value of 24-hour ABPM, and PP, AASI values were not significantly affected.

Baroreflex failure increases the risk of pulmonary edema in conscious rats with normal left ventricular function.

In heart failure with preserved ejection fraction (HFpEF), the complex pathogenesis hinders development of effective therapies. Since HFpEF and arteriosclerosis share common risk factors, it is conceivable that stiffened arterial wall in HFpEF impairs baroreflex function. Previous investigations have indicated that the baroreflex regulates intravascular stressed volume and arterial resistance in addition to cardiac contractility and heart rate. We hypothesized that baroreflex dysfunction impairs regulation of left atrial pressure (LAP) and increases the risk of pulmonary edema in freely moving rats. In 15-wk Sprague-Dawley male rats, we conducted sinoaortic denervation (SAD, n = 6) or sham surgery (Sham, n = 9), and telemetrically monitored ambulatory arterial pressure (AP) and LAP. We compared the mean and SD (lability) of AP and LAP between SAD and Sham under normal-salt diet (NS) or high-salt diet (HS). SAD did not increase mean AP but significantly increased AP lability under both NS (P = 0.001) and HS (P = 0.001). SAD did not change mean LAP but significantly increased LAP lability under both NS (SAD: 2.57 ± 0.43 vs. Sham: 1.73 ± 0.30 mmHg, P = 0.01) and HS (4.13 ± 1.18 vs. 2.45 ± 0.33 mmHg, P = 0.02). SAD markedly increased the frequency of high LAP, and SAD with HS prolonged the duration of LAP > 18 mmHg by nearly 20-fold compared with Sham (SAD + HS: 2,831 ± 2,366 vs. Sham + HS: 148 ± 248 s, P = 0.01). We conclude that baroreflex failure impairs volume tolerance and together with salt loading increases the risk of pulmonary edema even in the absence of left ventricular dysfunction. Baroreflex failure may contribute in part to the pathogenesis of HFpEF.

Relationship between objectively measured physical activity and cardiovascular aging in the general population – The EVIDENT trial

BackgroundAging has been associated with an increase in arterial stiffness. We analyzed the relationship between regular physical activity and cardiovascular aging evaluated by the radial augmentation index (rAIx), ambulatory arterial stiffness index (AASI), pulse pressure (PP) and heart age in subjects without atherosclerotic disease. MethodsA cross-sectional study was performed including 1365 subjects from the EVIDENT trial (mean age 54.9 ± 13.7 years; 60.3% women). As a measure of total volume of physical activity we used counts/minute recorded in an accelerometer (Actigraph GT3X) that participants wore for seven days, collecting data in 60-sec epochs, and respondents with ≥4 valid days were retained for the analysis. Arterial stiffness was evaluated using measures of rAIx, AASI, and central and peripheral PP on the B-pro device. rAIx was adjusted to 75 heart rate(rAIx75). Cardiovascular risk and heart age was estimated by the Framingham Risk Score. ResultsThe median (IQR) of counts/min was 236.9 (176.3–307.8), rAIx75 90 (77–100), sleep PP 40 mmHg (33–47), central PP 39 mmHg (32–47) and heart age 57 years (45–73) and the mean ± SD of the ASSI was 0.44 ± 0.07. We found an inverse correlation between counts/minute and rAIx75 (r = −0.086; p < 0.01), AASI (r = −0.146; p < 0.001), heart age (r = −0.163; p < 0.001) and peripherals PP. These associations were remained after controlling for potential confounders, except for rAIx75. In the multiple regression analysis, after adjustment, an inverse association persisted between counts/minute and AASI, sleep PP and heart age, but not with rAIx75. Accordingly, for every 100 higher counts/minute of accelerometer measures, both AASI and sleep PP would be lower by one measurement unit (beta = −0.979 and −1.031 respectively, p < 0.001) and the estimated heart age by half year (beta = −0.525, p = 0.023). ConclusionsRegular physical activity was inversely associated with parameters related to advanced cardiovascular aging after adjustment for potentially influencing variables.Trial registration: Clinical Trials.gov Identifier: NCT01083082.

Ambulatory arterial stiffness index in type 1 diabetes mellitus: any different during pregnancy?

ObjectiveTo analyze the ambulatory arterial stiffness index (AASI) and pulse pressure (PP) during pregnancy and 3 months after delivery in type 1 diabetes mellitus (T1DM) and compare it to healthy pregnant controls. Study designProspective, descriptive study of 59 women with T1DM and 42 non-diabetic women. Blood pressure was measured using a portable oscillometry monitor and AASI was calculated as 1 minus the regression slope of diastolic on systolic blood pressure obtained from 24-h monitoring. Main outcome measures were comparisons of the AASI and PP between T1DM women and controls examined during pregnancy, and of the AASI and PP during and after pregnancy in T1DM women. ResultsPP and AASI were higher at all times during pregnancy in T1DM compared to postpartum (p<0.01). AASI and PP were significantly associated with albumin excretion rate when adjusting for retinopathy, preeclampsia, duration of diabetes, HbA1c, age, and BMI. The AASI was positively correlated with night–day ratio in the 1st and 3rd trimesters during pregnancy. No difference was found in AASI compared with non-diabetic controls during pregnancy. ConclusionsAASI and PP increased during diabetic pregnancy and were associated with the women's albuminuria grade.

Abstract 199: Renin-angiotensin-aldosterone System Polymorphisms-based Risk Score In Resistant Arterial Hypertension And Adverse Cardiovascular Events: The Genhart-rio SubStudy

Introduction: Renin-angiotensin-aldosterone system (RAAS) determines arterial pressure fluctuation. Resistant arterial hypertension (RAH) has increased risk for end organ damage. The aim of this study was to prospectively investigate, in subjects with RAH in a South American city: 1) Adverse cardiovascular events defined as fatal and non-fatal stroke or acute myocardial infarction (AMI); and 2) the association between RAAS polymorphisms and adverse cardiovascular events. Methods: Two hundred and twelve subjects under investigation for RAH were admitted. All subjects received standard drug therapy aiming at achieving &lt;140/90mmHg, and were re-evaluated four weeks later, including 24h ambulatory arterial pressure monitoring. Subjects with secondary causes of RAH were excluded. Eighty eight subjects (age 57±10 y.o, 58 women) underwent genotyping to RAAS polymorphisms: renin (G1051A), angiotensinogen (M235T), angiotensin II type 1 receptor (A1166C) and aldosterone synthase (C344T). In this group, 65% were found RAH and 35% pseudo-RAH. Subjects were actively followed at scheduled clinical visits and phone contact. During follow-up, a composite of fatal and nonfatal stroke and/or AMI was assessed. A genetic score (GEN) based on allele risk was composed for each polymorphism (zero [low risk homozygosis], 1 [heterozygosis] to 2 [high risk homozygosis]), and summed up. Cox proportional-hazard model assessed both RAH and RAAS polymorphisms hazards for adverse events. (α&lt;0.05) Results: During a median follow-up of 26 years, 40 subjects reached composite endpoint (median 22 years of follow-up). Hardy-Weinberg equilibrium was observed in all polymorphism. Optimal cutoff for GEN was &gt;3 (AUC=0.66; p=0.006). In Cox proportional-hazard model, RAH and GEN&gt;3 were independently associated with composite endpoint (RAH Hazard ratio [HR] 2.3; 95%CI [1.1-5.0]; p=0.027; and GEN&gt;3 HR 3.4; 95%CI [1.2-9.6]; p=0.020). No significant differences according to age, gender, hypertension time were found. Conclusion: RAH determines an increased risk for a composite of stroke and AMI. A RAAS stratified genetic score identifies hypertensive subjects at increased risk for adverse cardiovascular events. ( NCT01173029 )

Symmetric ambulatory arterial stiffness index and 24-h pulse pressure in HIV infection

HIV infection has been associated with increased cardiovascular risk. Twenty-four-hour ambulatory blood pressure (BP) is a more accurate and prognostically relevant measure of an individual's BP load than office BP, and the ambulatory BP-derived ambulatory arterial stiffness index (AASI) and symmetric AASI (s-AASI) are established cardiovascular risk factors. In the setting of the HIV and HYpertension (HIV-HY) study, an Italian nationwide survey on high BP in HIV infection, 100 HIV-infected patients with high-normal BP or untreated hypertension (72% men, age 48 ± 10 years, BP 142/91 ± 12/7 mmHg) and 325 HIV-negative individuals with comparable age, sex distribution, and office BP (68% men, age 48 ± 10 years, BP 141/90 ± 11/8 mmHg) underwent 24-h ambulatory BP monitoring. Despite having similar office BP, HIV-infected individuals had higher 24-h SBP (130.6 ± 14 vs. 126.4 ± 10 mmHg) and pulse pressure (49.1 ± 9 vs. 45.9 ± 7 mmHg, both P < 0.001), and a lower day-night reduction of mean arterial pressure (14.3 ± 9 vs. 16.3 ± 7%, P = 0.025). Both s-AASI and AASI were significantly higher in HIV patients (s-AASI, 0.22 ± 0.18 vs. 0.11 ± 0.15; AASI, 0.46 ± 0.22 vs. 0.29 ± 0.17; both P <0.001). In a multivariate regression, s-AASI was independently predicted by HIV infection (β = 0.252, P <0.001), age, female sex, and 24-h SBP. In HIV patients, s-AASI had an inverse relation with CD4 cell count (Spearman's ρ -0.24, P = 0.027). Individuals with HIV infection and borderline or definite hypertension have higher symmetric AASI and 24-h systolic and pulse pressures than HIV-uninfected controls matched by office BP. High ambulatory BP may play a role in the HIV-related increase in cardiovascular risk.

Association of renal function with the ambulatory arterial stiffness index and pulse pressure in hypertensive patients

Arterial stiffness exemplified by the ambulatory arterial stiffness index (AASI) and pulse pressure (PP) predicts cardiovascular morbidity and mortality. The present cross-sectional study assessed the association of renal function with AASI and 24-h PP in hypertensive inpatients. Subjects included 948 hypertensive inpatients with drug treatment (mean age, 53.3 years; male, 67.1%). The AASI was defined as 1 minus the regression slope of diastolic over systolic blood pressure readings obtained from 24-h recordings. Renal function was evaluated by serum creatinine and urinary albumin excretion was expressed by the urinary albumin-to-urinary creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease formula and chronic kidney disease-epidemiology collaboration formula. As AASI and 24-h PP increased, serum creatinine concentrations and ACR increased, and eGFR decreased. Multiple linear regression showed that AASI and 24-h PP were associated with eGFR-EPI (B=-12.00, P=0.001 vs. B=-0.14, P=0.002) and ACR (B=0.56, P=0.004 vs. B=0.01, P=0.017) independent of other cardiovascular risk factors. After additional adjustment for 24-h PP, the association of AASI with eGFR-EPI had borderline significance (P=0.053), whereas the significant associations of 24-h PP with serum creatinine and ACR persisted (P=0.009 and P=0.006) after adjusting for confounding factors and AASI. Multiple logistic regression analysis showed that each s.d. increase in 24-h PP (that is, 13 mm Hg) was associated with a higher risk of suffering from microalbuminuria (MA) by 39% (P=0.038) after additional adjustment for AASI. In conclusion, AASI is more closely associated with eGFR compared with 24-h PP in hypertensive inpatients. However, for MA 24-h PP is a better predictor.

Associations between reactive oxygen species, blood pressure and arterial stiffness in black South Africans: the SABPA study

Many mechanisms, including oxidative stress, contribute to hypertension. This study investigated the possible associations between oxidative stress, blood pressure and arterial stiffness in black South Africans. Ambulatory blood pressure measurements were taken for 101 black South African men and 99 women. The stiffness indices included ambulatory arterial stiffness index (AASI) and pulse pressure (PP). Reactive oxygen species (ROS) levels (P<0.0001) were higher in the African women compared with men. ROS levels were also higher in hypertensive compared with normotensive men. The 24 h systolic blood pressure (SBP; P<0.01), 24 h diastolic blood pressure (DBP; P<0.0001) and pulse wave velocity (PWV; P<0.01) were significantly higher in African men compared with women. There were unadjusted positive associations of 24 h SBP (r=0.33; P=0.001), 24 h DBP (r=0.26; P=0.008) and 24 h PP (r=0.29; P=0.003) with ROS in African men only. A positive association between AASI and ROS existed only in hypertensive men (r=0.27; P=0.035), but became nonsignificant (B=0.0014; P=0.14) after adjustments. Adjusted, positive associations of 24 h SBP (B=0.181; P=0.018) and 24 h PP (B=0.086; P=0.050) with ROS were again only evident in African men. ROS is positively associated with SBP and PP in African men, suggesting that increased ROS levels may contribute to hypertension in this population group.

How many measurements are needed to provide reliable information in terms of the ambulatory arterial stiffness index? the Ohasama study

The aim of this study was to investigate how frequent ambulatory blood pressure (ABP) readings need to be obtained to reproduce the ambulatory arterial stiffness index (AASI) and pulse pressure (PP) without loss of information. We compared concordance from full and reduced ABP recordings. We recorded 24-h ABP at 30-min intervals in 1542 residents of Ohasama, Japan (baseline age, 40-93 years; 63.4% women). We randomly excluded up to 16 readings per recording or we selected readings at fixed 1- or 2-h intervals. Using full recordings as reference, we computed for the reduced recordings repeatability coefficient by Bland and Altman's approach. By Cox regression, we also calculated multivariate-adjusted hazard ratios for cardiovascular mortality. The median number of ABP readings per recording was 46. Randomly excluding more readings reduced the concordance of AASI, but not PP. Selecting blood pressure readings at 1- or 2-h intervals produced mean values of AASI and PP, which significantly differed from those in full recordings. During follow-up (median, 13.3 years) 126 cardiovascular deaths occurred. Across quartiles, AASI significantly predicted cardiovascular mortality in a U-shaped manner. AASI lost its prognostic significance when the number of randomly excluded readings increased from 8 to 16 or when the interval between readings was 1 h or longer. Compared with PP, AASI is less reproducible when the number of readings in ABP decreases, but this does not affect the predictive accuracy of AASI for cardiovascular mortality, until the median number of readings per ABP recording is less than ∼35.

Ambulatory arterial stiffness index, pulse pressure and pulse wave velocity in children and adolescents

Arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV) or indirectly by pulse pressure (PP) or ambulatory arterial stiffness index (AASI), is an independent predictor of cardiovascular disease in adults. However, in children limited evidence is available. This study investigated the usefulness of AASI and PP as indices of arterial stiffness in children and adolescents, by taking PWV as the reference method. Eighty-two children and adolescents (mean age 13.1±2.9 years) had 24-h ambulatory blood pressure (ABP) monitoring, PWV measurement and echocardiography. Compared with normotensives, subjects with hypertension (n=16) had higher 24-h ABP, 24-h PP and PWV, but not AASI. 24-h, PP was strongly correlated with age, weight, height, 24-h systolic ABP, PWV, left ventricular mass (LVM), LVM index, stroke volume and inversely with 24-h heart rate. AASI was also correlated with weight, height, systolic ABP and LVM, yet these associations were weaker than those of PP, and no significant correlations were found with PWV or LVM index. Moreover, closer agreement of PWV was observed with 24-h PP (71%, kappa 0.21) than with 24-h AASI (61%, kappa -0.06) in detecting subjects at the top quartile of the respective distributions. In children and adolescents, 24-h PP compared with AASI appears to be more closely associated with: (i) arterial stiffness assessed by PWV; (ii) target organ damage assessed by LVM index; and (iii) the presence of essential hypertension. These data suggest that the usefulness of AASI as an index of arterial stiffness in the pediatric population is questionable.

Increased Ambulatory Arterial Stiffness Index and Pulse Pressure in Microalbuminuric Patients With Type 1 Diabetes

Ambulatory arterial stiffness index (AASI) has been proposed as an indirect measure of arterial stiffness. The aims of this study were (i) to analyze AASI and pulse pressure (PP) in micro- and normoalbuminuric type 1 diabetes mellitus (T1DM) patients and healthy controls and (ii) to explore the relation between nocturnal blood pressure (BP) reduction, BP variability, and AASI. Ambulatory BP monitoring was performed in 34 micro- and 34 normoalbuminuric T1DM patients matched for gender, age, and diabetes duration and in 34 nondiabetic controls matched for gender and age. AASI and PP were calculated based on 24-h, day, and night BP recordings. AASI increased from the control group (0.30 +/- 0.14) to the normo- (0.35 +/- 0.15) and microalbuminuric group (0.41 +/- 0.19; P < 0.05). After adjustment for nightly systolic BP reduction and systolic daytime BP variability (s.d.) in multivariate analysis, the association weakened and became nonsignificant (P = 0.078). No significant intergroup differences were found when AASI was calculated separately from day and night BP data. There was no significant difference between day and night AASI. The 24-h PP increased from the control group (48 +/- 7 mm Hg) to the normo- (50 +/- 6 mm Hg) and microalbuminuric group (54 +/- 9 mm Hg; P < 0.01). The association remained in the multivariate analysis. Day and night PPs were higher in microalbuminuric patients compared to healthy controls. AASI and PP are higher in microalbuminuric T1DM patients compared to healthy controls. The nocturnal BP reduction and systolic daytime BP variability are determinants of AASI. We propose these associations to reflect biological characteristics of arterial stiffness.

Dissociation Between Sympathetic Nerve Traffic and Sympathetically Mediated Vascular Tone in Normotensive Human Obesity

Obesity increases the risk of hypertension and its cardiovascular complications. This has been partly attributed to increased sympathetic nerve activity, as assessed by microneurography and catecholamine assays. However, increased vasoconstriction in response to obesity-induced sympathoactivation has not been unequivocally demonstrated in obese subjects without hypertension. We evaluated sympathetic alpha-adrenergic vascular tone in the forearm by brachial arterial infusion of the alpha-adrenoreceptor antagonist phentolamine (120 microg/min) in normotensive obese (daytime ambulatory arterial pressure: 123+/-1/77+/-1 mm Hg; body mass index: 35+/-1 kg/m(2)) and lean (daytime ambulatory arterial pressure: 123+/-2/77+/-2 mm Hg; body mass index: 22+/-1 kg/m(2)) subjects (n=25 per group) matched by blood pressure, age, and gender. Microneurographic sympathetic nerve activity to skeletal muscle was significantly higher in obese subjects (30+/-3 versus 22+/-1 bursts per minute; P=0.02). Surprisingly, complete alpha-adrenergic receptor blockade by phentolamine (at concentrations sufficient to completely inhibit norepinephrine and phenylephrine-induced vasoconstriction) caused equivalent vasodilatation in obese (-57+/-2%) and lean subjects (-57+/-3%; P=0.9). In conclusion, sympathetic vascular tone in the forearm circulation is not increased in obese normotensive subjects despite increased sympathetic outflow. Vasodilator factors or mechanisms occurring in obese normotensive subjects could oppose the vasoconstrictor actions of increased sympathoactivation. Our findings may help to explain why some obese subjects are protected from the development of hypertension.

Ambulatory Arterial Stiffness Index or Pulse Pressure: Which Correlates Better with Arterial Stiffness in Resistant Hypertension?

The ambulatory arterial stiffness index (AASI) is a recently proposed index derived from 24-h ambulatory blood pressure monitoring (ABPM) for the evaluation of arterial stiffness. In this cross-sectional study we investigated whether AASI reflects arterial stiffness in patients with resistant hypertension by comparing AASI and ambulatory pulse pressure (PP) with aortic pulse wave velocity (PWV), a measure of arterial stiffness, in 391 resistant hypertensives. Clinical, laboratory and echocardiographic variables, 24-h ABPM and aortic PWV (measured using the Complior device) were obtained. AASI was calculated as 1--the regression slope of 24-h diastolic on systolic blood pressure (BP). Statistical analysis involved single and multiple linear regressions to assess the correlations between the two ABPM variables and PWV, both unadjusted and adjusted for potential confounders (age, gender, body height, presence of diabetes, 24-h mean arterial pressure [MAP], heart rate, and nocturnal BP reduction). Ambulatory PP and aortic PWV were independently associated with age, gender, presence of diabetes, and 24-h MAP, whereas AASI was associated with age, diabetes, and nocturnal diastolic BP reduction. PP showed stronger unadjusted (r=0.39, p<0.001) and adjusted (r=0.22, p<0.001) correlations with aortic PWV than AASI (r=0.12, p=0.032 and r= -0.04, p=0.47, respectively). In the analysis of subgroups stratified by gender, age, presence of atherosclerotic diseases and diabetes, dipping pattern, and ambulatory BP control, the superiority of PP over AASI was apparent in all subgroups. In conclusion, 24-h ambulatory PP was better correlated to arterial stiffness, as evaluated by aortic PWV, than the novel AASI, in patients with resistant hypertension.