Characteristics of functional state of arteriolar and venular skin microvessels in patients with essential arterial hypertension.

The aim of the study was to evaluate the vasomotor activity of skin precapillary arterioles, depending on the condition of blood outflow from the capillary bed in patients with essential arterial hypertension (AH). The study included 30 normotensive subjects (NT) and 63 patients with AH, who were tested with a laser Doppler flowmetry with wavelet analysis of blood flow oscillations on the right forearm and ambulatory blood pressure monitoring (ABPM) on the left shoulder. Antihypertensive therapy was stopped for all patients 14 days prior to the experiment or AH was diagnosed for the first time. The hypertensive patients were divided into 2 groups, depending on the amplitude of the respiratory blood flow oscillations in skin microvessels. The first group included 30 patients without blood outflow violations of the capillary bed (AHVN), the second group consisted of 33 patients with various intensity of functional disorders in venular sector of microvasculature (AHVS). If the value of the amplitude of blood flow oscillations can be related to the tone" definition, then AHVN patients have a significant increase in neurogenic component of vascular tone (p<0.002) and violation of microvessel vasomotor endothelial function (p=0.065) in regard to NT, and AHVS patients to NT have a significant reduction of myogenic component tone of precapillary arterioles (p<0.05). AHVN patients compared to AHVS patients have a higher precapillary arteriolar tone due to endothelial (p<0.01), neurogenic (p<0.01) and myogenic (p<0.01) components of the vascular tone. Despite the lower values of the precapillary arteriolar tone, AHVS patients have higher BP values both at daytime (p<0.0005), and in nocturnal hours (p<0.05), and the functional state of venular sector is connected with nocturnal BP reduction. Obtained results indicate that hypertensive patients can have significant differences in the functional state of microvessels. The assessment of the initial skin microvasculatory regulatory mechanism status could potentially be useful for individual choice of antihypertensive therapy.

Cardio-ankle vascular index for predicting cardiovascular morbimortality and determinants for its progression in the prospective advanced approach to arterial stiffness (TRIPLE-A-Stiffness) study.

BACKGROUND: The cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value for cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression. METHODS: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years. FINDINGS: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI. INTERPRETATION: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments. FUNDING: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan.

Ambulatory blood pressure and arterial stiffness web-based telemonitoring in patients at cardiovascular risk. First results of the VASOTENS (Vascular health ASsessment Of The hypertENSive patients) Registry.

The VASOTENS Registry is an international telehealth-based repository of 24-hour ambulatory blood pressure monitorings (ABPM) obtained through an oscillometric upper-arm BP monitor allowing combined estimation of some vascular biomarkers. The present paper reports the results obtained in 1200 participants according to different categories of CV risk. Individual readings were averaged for each recording and 24-hour mean of brachial and aortic systolic (SBP) and diastolic blood pressure (DBP), pulse wave velocity (PWV), and augmentation index (AIx) obtained. Peripheral and central BP, PWV and AIx values were increased in older participants (SBP only) and in case of hypertension (SBP and DBP). BP was lower and PWV and AIx higher in females. PWV was increased and BP unchanged in case of metabolic syndrome. Our results suggest that ambulatory pulse wave analysis in a daily life setting may help evaluate vascular health of individuals at risk for CV disease.

Effects of metabolic syndrome on arterial function in different age groups: the Advanced Approach to Arterial Stiffness study.

OBJECTIVE: The aim of the Advanced Approach to Arterial Stiffness study was to compare arterial stiffness measured simultaneously with two different methods in different age groups of middle-aged and older adults with or without metabolic syndrome (MetS). The specific effects of the different MetS components on arterial stiffness were also studied. METHODS: This prospective, multicentre, international study included 2224 patients aged 40 years and older, 1664 with and 560 without MetS. Patients were enrolled in 32 centres from 18 European countries affiliated to the International Society of Vascular Health & Aging. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the carotid-femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40-49, 50-59, 60-74, 75-90 years. In this report, we present the baseline data of this study. RESULTS: Both CF-PWV and CAVI increased with age, with a higher correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age-adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated (r = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not CAVI were higher in presence of MetS (CF-PWV: 9.57 ±â€Š0.06 vs. 8.65 ±â€Š0.10, P < 0.001; CAVI: 8.34 ±â€Š0.03 vs. 8.29 ±â€Š0.04, P = 0.40; mean ±â€ŠSEM; MetS vs. no MetS). The absence of an overall effect of MetS on CAVI was related to the heterogeneous effects of the components of MetS on this parameter: CAVI was positively associated with the high glycaemia and high blood pressure components, whereas lacked significant associations with the HDL and triglycerides components while exhibiting a negative association with the overweight component. In contrast, all five MetS components showed positive associations with CF-PWV. CONCLUSION: This large European multicentre study reveals a differential impact of MetS and age on CAVI and CF-PWV and suggests that age may have a more pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This important finding may be due to heterogeneous effects of MetS components on CAVI. The clinical significance of these original results will be assessed during the longitudinal phase of the study.

Relationships between 24-h blood pressure variability and 24-h central arterial pressure, pulse wave velocity and augmentation index in hypertensive patients.

Twenty-four-h blood pressure variability (BPV) predicts cardiovascular complications in hypertension, but its association with pulse wave indices (central arterial pressure, pulse wave velocity (PWV) and augmentation index (AIx)) is poorly understood. In the present study, we assessed the degree of the effect of 24-h BPV on 24-h pulse wave indices. Brachial blood pressure was measured non-invasively over the 24 h with an electronic, oscillometric, automated device (BPLab) in 661 uncomplicated treated or untreated hypertensive patients. Digitalized oscillometric waveforms were analyzed with a validated algorithm to obtain pulse wave indices. Twenty-four-h BPV was calculated as the unweighted (SDu) or weighted s.d. (SDw) of the mean blood pressure or as the average real variability (ARV). Twenty-four-h systolic BPV showed a direct and significant relationship with the central arterial systolic pressure (r=0.28 SDu, r=0.40 SDw, r=0.34 ARV), PWV (r=0.10 SDu, r=0.21 SDw, r=0.19 ARV) and AIx (r=0.17 SDu, r=0.27 SDw, r=0.23 ARV). After adjustment for age, sex, body mass index, antihypertensive treatment and 24-h systolic blood pressure, the relationship lost some power but was still significant for all measures, except for the AIx. Pulse wave indices were higher in patients with high BPV than in those with low BPV: after adjustment, these differences were abolished for the AIx. The diastolic BPV showed a weak association with the pulse wave indices. In conclusion, in hypertensive patients, 24-h systolic BPV is moderately and independently associated with 24-h central arterial pressure and stiffness.

Vascular Health Assessment of The Hypertensive Patients (VASOTENS) Registry: Study Protocol of an International, Web-Based Telemonitoring Registry for Ambulatory Blood Pressure and Arterial Stiffness.

BACKGROUND: Hypertension guidelines recommend ambulatory blood pressure (ABP), central aortic pressure (CAP), and pulse wave velocity (PWV) as parameters for estimating blood pressure (BP) control and vascular impairment. Recent advances in technology have enabled devices to combine non-invasive estimation of these parameters over the 24-hour ABP monitoring. However, currently there is limited evidence on the usefulness of such an approach for routine hypertension management. OBJECTIVE: We recently launched an investigator-initiated, international, multicenter, observational, prospective study, the Vascular health Assessment Of The Hypertensive patients (VASOTENS) Registry, aimed at (1) evaluating non-invasive 24-hour ABP and arterial stiffness estimates (through 24-hour pulse wave analysis, PWA) in hypertensive subjects undergoing ambulatory blood pressure monitoring (ABPM) for clinical reasons; (2) assessing the changes in estimates following treatment; (3) weighing the impact of 24-hour PWA on target organ damage and cardiovascular prognosis; (4) assessing the relationship between arterial stiffness, BP absolute mean level and variability, and prognosis; and (5) validating the use of a 24-hour PWA electronic health (e-health) solution for hypertension screening. METHODS: Approximately 2000 subjects, referred to 20 hypertension clinics for routine diagnostic evaluation and follow-up of hypertension of any severity or stage, will be recruited. Data collection will include ABPM, performed with a device allowing simultaneous non-invasive assessment of 24-hour CAP and arterial stiffness (BPLab), and clinical data (including cardiovascular outcomes). As recommended by current guidelines, each patient will be followed-up with visits occurring at regular intervals (ideally every 6 months, and not less than once a year depending on disease severity). A Web-based telemedicine platform (THOLOMEUS) will be used for data collection. The use of the telemedicine system will allow standardized and centralized data collection, data validation by experts and counseling to remote centers, setup and maintenance of the Registry, and prompt data analysis. RESULTS: First follow-up results are expected to be available in the next 2 years. CONCLUSIONS: The results of the VASOTENS Registry will help define the normalcy thresholds for current and future indices derived from 24-hour PWA, according to outcome data, and will also provide supporting evidence for the inclusion of this type of evaluation in hypertension management. TRIAL REGISTRATION: Clinicaltrials.gov NCT02577835; https://clinicaltrials.gov/ct2/show/NCT02577835 (Archived by WebCite at http://www.Webcitation.org/6hzZBKY2Q).

Evaluation of 24-Hour Arterial Stiffness Indices and Central Hemodynamics in Healthy Normotensive Subjects versus Treated or Untreated Hypertensive Patients: A Feasibility Study.

Objective. Central blood pressure (BP) and vascular indices estimated noninvasively over the 24 hours were compared between normotensive volunteers and hypertensive patients by a pulse wave analysis of ambulatory blood pressure recordings. Methods. Digitalized waveforms obtained during each brachial oscillometric BP measurement were stored in the device memory and analyzed by the validated Vasotens technology. Averages for the 24 hours and for the awake and asleep subperiods were computed. Results. 142 normotensives and 661 hypertensives were evaluated. 24-hour central BP, pulse wave velocity (PWV), and augmentation index (AI) were significantly higher in the hypertensive group than in the normotensive group (119.3 versus 105.6 mmHg for systolic BP, 75.6 versus 72.3 mmHg for diastolic BP, 10.3 versus 10.0 m/sec for aortic PWV, -9.7 versus -40.7% for peripheral AI, and 24.7 versus 11.0% for aortic AI), whereas reflected wave transit time (RWTT) was significantly lower in hypertensive patients (126.6 versus 139.0 ms). After adjusting for confounding factors a statistically significant between-group difference was still observed for central BP, RWTT, and peripheral AI. All estimates displayed a typical circadian rhythm. Conclusions. Noninvasive assessment of 24-hour arterial stiffness and central hemodynamics in daily life dynamic conditions may help in assessing the arterial function impairment in hypertensive patients.

Day-to-day repeatability of the Pulse Time Index of Norm.

The pulse wave velocity (PWV) threshold for hypertensive target organ damage is presently set at 10 meters per second. New 24-hour monitors (eg, BPLab® and Vasotens®) provide several PWV measurements over a period of 24-72 hours. A new parameter, ie, the Pulse Time Index of Norm (PTIN), can be calculated from these data. The PTIN is defined as the percentage of a 24-hour period during which the PWV does not exceed 10 meters per second. The aim of the present study was to test the new PTIN for clinical feasibility using day-to-day repeatability analysis. Oscillometrically generated waveform files (n=85), which were previously used for research studies, were reanalyzed using the new 2013 version software of the Vasotens technology program, which enables calculation of PTIN. The intraclass correlation coefficient was 0.98 and Cronbach's alpha was 0.97, indicating that the PTIN has excellent day-to-day repeatability and internal consistency. The present results show adequate repeatability, and PTIN assessment using the Vasotens technology appears to be feasible.

The 24-hour pulse wave velocity, aortic augmentation index, and central blood pressure in normotensive volunteers.

The purpose of this study was to examine the pulse wave velocity, aortic augmentation index corrected for heart rate 75 (AIx@75), and central systolic and diastolic blood pressure during 24-hour monitoring in normotensive volunteers. Overall, 467 subjects (206 men and 261 women) were recruited in this study. Participants were excluded from the study if they were less than 19 years of age, had blood test abnormalities, had a body mass index greater than 2 7.5 kg/m(2), had impaired glucose tolerance, or had hypotension or hypertension. Ambulatory blood pressure monitoring (ABPM) with the BPLab(®) device was performed in each subject. ABPM waveforms were analyzed using the special automatic Vasotens(®) algorithm, which allows the calculation of pulse wave velocity, AIx@75, central systolic and diastolic blood pressure for "24-hour", "awake", and "asleep" periods. Circadian rhythms and sex differences in these indexes were identified. Pending further validation in prospective outcome-based studies, our data may be used as preliminary diagnostic values for the BPLab ABPM additional index in adult subjects.

The "Pulse Time Index of Norm" highly correlates with the left ventricular mass index in patients with arterial hypertension.

BACKGROUND: Arterial stiffness, as measured by the pulse wave velocity (PWV), is recommended for routine use in clinical practice as an important parameter for the evaluation of cardiovascular risk.1 New 24-hour monitors (eg, with Vasotens technology; Petr Telegin Company, Nizhny Novgorod, Russian Federation) provide single PWV measurements as well as several PWV measurements over a period of 24 hours.2 Such 24-hour pulse wave analysis led to the development of the novel Pulse Time Index of Norm (PTIN), which is defined as the percentage of a 24-hour period during which the PWV does not exceed the 10 m/second PWV threshold. The aim of this study is to test the new PTIN for correlation with the left ventricular mass index (LVMI). METHODS: Oscillometrically generated waveform files (n=137) used for clinical research studies were reanalyzed using the new 2013 version of the Vasotens technology program, which enables PTIN calculations. RESULTS: A good correlation (r=-0.72) between the PTIN and the LVMI was shown, which was significantly above the blood pressure load (r=0.41). CONCLUSION: The PTIN generated by the Vasotens technology can be recommended as an indicator of end organ damage via hypertension.

Carotid atherosclerosis, endothelial disfunction, and arterial stiffness in young and middle-aged men with coronary artery disease.

Background. To assess structural and functional status of the arteries in young and middle-aged men with recently developed CAD. Methods and Results. A total of 78 men aged 28 to 50 years underwent carotid ultrasound, endothelial function, and arterial stiffness measurements. Angiographically proven CAD was present in 49 patients. Carotid plaques were present in 45 (91.8%) patients with CAD and in 8 (27.6%) men without CAD (P < 0.001). Patients with CAD more often had multiple plaques (86.7% versus 13.8%, P < 0.001). The prevalence of carotid intima-media thickness (IMT) ≥0.9 mm and of abnormal brachial artery flow-mediated dilatation (FMD) was not differing in both groups. The mean aortic pulse wave velocity (PWV) was 6.8 ± 1.3 m/s for patients with CAD and 5.8 ± 0.9 m/s for subjects without CAD (P < 0.001). Aortic PWV above the 75th percentile of the "normal" samples was found in 26 (53.1%) patients with CAD and in 7 (24.1%) subjects without CAD (P = 0.02). Aortic PWV was related to the severity of CAD. Conclusions. Carotid plaques and increased aortic PWV may be more powerful predictors of the occurrence of CAD in young and middle-aged men, than the presence of increased carotid IMT and abnormal brachial artery FMD.