International Registry for Ambulatory Blood Pressure and Arterial Stiffness Telemonitoring
Conditions: Hypertension
Sponsor: Italian Institute of Telemedicine

1.0 
TITLE PAGE 
 
INTERNATIONAL REGISTRY FOR AMBULATORY BLOOD PRESSURE AND ARTERIAL 
STIFFNESS TELEMONITORING 
 
VASOTENS (Vascular health ASsessment Of The hypertENSive patients) Registry 
 
 
STUDY PROTOCOL 
 
 
Final Version - 20/02/2015 
 
NCT Number: NCT02577835 
 
Project Coordinator: 
Dr. Stefano Omboni 
 
Clinical Research Unit 
 
Italian Institute of Telemedicine 
 
Via Colombera 29 
 
21048 Solbiate Arno (Varese) 
 
Italy 
 
Co-coordinator: 
Dr. Igor Posokhov 
 
Hemodynamic Laboratory 
 
PO Box 69  
 
603009 Nizhniy Novgorod 
 
Russia 
 
CONFIDENTIALITY STATEMENT 
 
The information in this document is privileged or confidential and may not be disclosed unless such disclosure is required by law. In 
any event, persons to whom the information is disclosed must be informed that the information is privileged or confidential and may 
not be further disclosed by them. These restrictions on disclosure will apply equally to all future information supplied to you which is 
indicated as privileged or confidential. 

2.0 
TABLE OF CONTENTS 
 
1.0 
TITLE PAGE ........................................................................................................................................................ 1 
2.0 
TABLE OF CONTENTS ..................................................................................................................................... 2 
3.0 
RESPONSIBILITIES ........................................................................................................................................... 3 
4.0 
SYNOPSIS ............................................................................................................................................................. 4 
5.0 
LIST OF ABBREVIATIONS .............................................................................................................................. 7 
6.0 
INTRODUCTION ................................................................................................................................................ 8 
7.0 
PROJECT OBJECTIVES ................................................................................................................................... 8 
8.0 
OVERALL PROJECT DESIGN AND PLAN ................................................................................................... 8 
9.0 
SELECTION OF PROJECT POPULATION.................................................................................................... 8 
9.1 
INCLUSION CRITERIA ........................................................................................................................................... 9 
9.2 
EXCLUSION CRITERIA .......................................................................................................................................... 9 
10.0 
PROJECT ACTIVITIES ..................................................................................................................................... 9 
10.1 
CREATION OF RESEARCH NETWORK AND DATA COLLECTION ............................................................................... 9 
10.2 
ABPM DATA ANALYSIS ..................................................................................................................................... 10 
10.3 
DISSEMINATION ACTIVITIES .............................................................................................................................. 10 
11.0 
STATISTICAL METHODS .............................................................................................................................. 10 
12.0 
INVESTIGATORS AND PROJECT ADMINISTRATIVE STRUCTURE .................................................. 11 
12.1 
PROJECT COORDINATORS .................................................................................................................................. 11 
12.2 
SCIENTIFIC COMMITTEE AND OTHER PROJECT STRUCTURES .............................................................................. 11 
12.2.1 
Steering Committee ................................................................................................................................... 11 
12.2.2 
Scientific Committee ................................................................................................................................. 11 
12.2.3 
National Coordinators .............................................................................................................................. 12 
12.2.4 
Scientific and Organizing Secretariat ....................................................................................................... 12 
12.3 
INVESTIGATORS ................................................................................................................................................. 12 
12.4 
CRO .................................................................................................................................................................. 12 
13.0 
ETHICS ............................................................................................................................................................... 12 
13.1 
INDEPENDENT ETHICS COMMITTEE OR INSTITUTIONAL REVIEW BOARD ........................................................... 12 
13.2 
SUBJECT INFORMATION AND CONSENT .............................................................................................................. 12 
14.0 
DATA MANAGEMENT .................................................................................................................................... 13 
14.1 
ELECTRONIC CASE REPORT FORM (E-CRF) ....................................................................................................... 13 
14.2 
PROJECT MONITORING ....................................................................................................................................... 14 
14.3 
DATA QUALITY CONTROL AND ASSURANCE ....................................................................................................... 14 
15.0 
INSURANCE ....................................................................................................................................................... 14 
16.0 
DISCONTINUATION OF THE PROJECT .................................................................................................... 14 
17.0 
STATEMENT OF CONFIDENTIALITY ........................................................................................................ 15 
18.0 
REPORTING ...................................................................................................................................................... 15 
19.0 
DATA ACCESS AND PUBLICATION POLICY ........................................................................................... 15 
20.0 
PROTOCOL AMENDMENTS ......................................................................................................................... 15 
21.0 
REFERENCE LIST ............................................................................................................................................ 16 
22.0 
APPENDICES ..................................................................................................................................................... 18 
 

3.0 
RESPONSIBILITIES 
Project Coordinator 
Stefano Omboni 
Clinical Research Unit 
Italian Institute of Telemedicine 
Via Colombera 29 
21048 Solbiate Arno (Varese) 
Italy 
 
Co-coordinator: 
 
Igor Posokhov 
Hemodynamic Laboratory 
PO Box 69  
603009 Nizhniy Novgorod 
Russia 
 
Steering Committee 
 
Stefano Omboni (Italy), Gianfranco Parati (Italy), Igor Posokhov (Russia), Anatoli Rogoza (Russia) 
 
Scientific Committee 
 
Stefano Omboni (Italy), Gianfranco Parati (Italy), Igor Posokhov (Russia), Anatoli Rogoza (Russia), Yulia 
Kotovskaya (Russia)  
 
Study centers: 
 
Italian centers (initially 10-15) 
Russian centers (initially 10-15) 

4.0 
SYNOPSIS 
 
Project title 
 
INTERNATIONAL REGISTRY FOR AMBULATORY BLOOD PRESSURE 
AND ARTERIAL STIFFNESS TELEMONITORING 
Project name 
VASOTENS (Vascular health ASsessment Of The hypertENSive patients) 
REGISTRY 
Scientific Coordinator 
Dr. Stefano Omboni (Italy) 
Clinical Research Unit 
Italian Institute of Telemedicine 
Via Colombera 29 
21048 Solbiate Arno (Varese) 
Italy 
Co-coordinator 
Dr. Igor Posokhov (Russia) 
PO Box 69  
603009 Hemodynamic Laboratory 
Nizhniy Novgorod 
Russia 
Project centers 
At least 30 Hypertension centers will be involved in the project, each one providing 
at least 100 patients, which will be followed-up over time. Centers will be selected in 
different countries, initially in Europe, starting from Italy and Russia. Mandatory 
criteria of a center to be included in the study are the availability in the facility of a 
BPLab ABPM monitor, the potential for providing and properly following-up the 
number of patients required by the protocol, the availability of Internet connection, 
regular access to the web and human resources to upload ABPM and clinical data. 
Date of starting of the project 
Launch of the project (first investigators’ meeting): 
June 2015 
First patient uploaded into the database: 
September 2015 
Objectives 
The project has several practical objectives and questions to be answered. These will 
be: 
• The evaluation of non-invasive ambulatory blood pressure and arterial stiffness 
estimates (through pulse wave analysis, PWA) in hypertensive subjects 
undergoing an ambulatory blood pressure monitoring (ABPM) for clinical reasons 
in the selected centers 
• The evaluation of the changes in blood pressure and arterial stiffness estimates 
following treatment initiation according to current guidelines 
• The assessment of the impact of non-invasive arterial stiffness estimation on 
target organ damage and patient’s cardiovascular (CV) prognosis 
• The definition of the normalcy thresholds for pulse wave velocity (PWV), 
augmentation index (AI), and other current and future indices derived from PWA 
in hypertensive subjects, according to outcome data 
• The definition of the relationship between arterial stiffness, blood pressure 
absolute level and blood pressure variability, and outcomes 
• The setup of a worldwide network of centers performing ambulatory PWA, and 
the validation and promotion of the use of such technique for hypertension 
screening and follow-up 
• The provision of evidence of the clinical relevance of non-invasive arterial 
stiffness assessment, in order to favor the inclusion of such evaluation in 
recommendations on hypertension management 
Methodology 
International, multicenter, observational, prospective project  
Population 
The registry will include data from subjects fulfilling the inclusion criteria and whose 
data are contained in existing databases collected by the participating centers and who 
are regularly followed-up at the center. New subjects can be enrolled for this project, 
but they must be submitted to ABPM because it is required for evaluating their 
hypertension status, according to current recommendations 
Inclusion criteria 
• Male and female subjects 
• Age ≥18 years 
• Subjects referred to routine diagnostic evaluation for hypertension or established 
hypertensive subjects 
• ABPM performed for clinical reasons with a BPLab device 
• The minimum validity requirements for inclusion of the ABPM in the study are: 
- Interval between measurements not exceeding 30 minutes 

- At least 70% of expected number of readings 
- At least 20 valid readings during the day-time and 7 during the nigh-time 
• Availability of individual measurements for ABPM on a .bpw file (BPLab format) 
or data directly downloaded on the telemedicine platform of the study (see below 
for details) 
• Availability of basic demographic and clinical information: 
- Age 
- Gender 
- Height 
- Weight  
- Ethnicity 
- Superficial distance between jugulum and symphysis (surrogate of aortic 
length) 
- Waist circumference 
- Smoking status 
- Alcohol drinking 
- Coffee or tea drinking 
- Dyslipidemia (yes/no and indication on treatment) 
- Diabetes (yes/no and indication on treatment) 
- Diagnosis of hypertension (yes/no and indication on treatment) 
- Family history of premature CV disease 
- Medical history, with particular regard to previous and/or concurrent CV 
diseases 
- Office blood pressure and heart rate obtained in the same treatment condition 
as ABPM 
- Left ventricular mass index (LVMI) at echocardiogram 
- When available, diameter of the aorta (aortic annulus, root and sinotubular 
junction ) and/or cardiac output, assessed by the echocardiogram 
- Intima-media thickness (IMT) at carotid ultrasonography 
- ECG (indication on left ventricular hypertrophy, Sokolow–Lyon and Cornell 
index) 
- When available, ankle-brachial index 
- Microalbuminuria and serum creatinine (calculation of estimated glomerular 
filtration rate - eGFR) 
- When available, pulse wave velocity (PWV), augmentation index (AI) and 
central blood pressure taken during the office visit with a validated device 
different for BPLab Vasotens (e.g. Sphygmocor or Complior) 
• Availability of a signed informed consent form 
Exclusion criteria 
• 
Age <18 years 
• 
Atrial fibrillation, frequent ectopic beats, second or third degree atrioventricular 
blocks, or other conditions which might make difficult or unreliable the 
automatic blood pressure measurement with the oscillometric technique 
• 
Upper arm circumference <22 cm 
• 
Pregnancy 
Data collection 
Data contained in existing electronic databases or data of newly enrolled subjects 
fulfilling the inclusion criteria will be uploaded/entered on the study website. These 
data will include ABPM measures (blood pressure and arterial stiffness) obtained 
with a BPLab device and clinical data. ABPM data will be provided as .bpw files or 
directly uploaded by linking the ABPM device to the website through a personal 
computer. 
Data collection will be ensured by a dedicated web-based telemedicine platform, 
including an electronic case report form (e-CRF). The e-CRF will allow collection of 
patient’s clinical data, such as family history, anthropometric data, habits, past and 
current diseases, therapies, office BP, and laboratory tests, including evaluation of 
target organ damage. 
The project does not involve any type of intervention related to the study and the 
physicians will manage the patients included in the Registry according to the 
requirements of clinical practice and current guidelines. However, 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). The 

physicians will also be free to use the ambulatory blood pressure data in the clinical 
management of the patients. 
The telemedicine system will allow a) standardized and centralized data collection, b) 
data validation by experts and counselling to remote centers, c) setup and 
maintenance of the Registry.  
Statistical methods 
Standard variables (systolic and diastolic blood pressure, pulse pressure and heart 
rate), central systolic and diastolic blood pressure, and arterial stiffness indices (PWV 
and AI) will be averaged for the whole 24-hour period, and separately for the day-
time and night-time subperiods. Additionally, hourly averages will be computed, and 
in case of blood pressure, variability will be evaluated by calculation of weighted 
standard deviation and average real variability. 
Other variables of interest will be defined in the course of the study and calculated 
subsequently according to the procedures defined in a specific statistical analysis 
plan. 
The occurrence of any CV event (death or hospitalization for congestive heart failure, 
myocardial infarction, angina, stroke or cerebrovascular accident, renal failure, etc.) 
during the study will be evaluated by the Kaplan-Meier method. Time-to-event 
curves will be drawn and the survival analysis will be performed according to the 
Cox proportional hazard model, which will allow to analyze predictors of outcomes.  
Relationship between blood pressure and arterial stiffness estimates and organ 
damage and prognosis will be evaluated.  

5.0 
LIST OF ABBREVIATIONS 
 
ABPM 
= 
Ambulatory Blood Pressure Monitoring 
AI 
= 
Augmentation Index 
CRO 
= 
Contract Research Organization 
CV 
= 
Cardiovascular 
ECG 
= 
Electrocardiogram 
e-CRF 
= 
electronic CRF 
eGFR 
= 
Estimated Glomerular Filtration Rate 
IMT 
= 
Intima Media Tickness 
LVMI 
= 
Left Ventricular Mass Index 
PWA 
= 
Pulse Wave Analysis 
PWV 
= 
Pulse Wave Velocity 

6.0 
INTRODUCTION 
 
In recent years, great emphasis has been placed on the role of arterial stiffness and central blood pressure as 
independent predictors for the development of cardiovascular (CV) diseases [1-3]. Consequently, the 
assessment of arterial stiffness and central hemodynamics is recommended as additional tests for the clinical 
evaluation of hypertensive patients (based on history, physical examination and findings from routine 
laboratory tests), particularly for those at risk for CV complications [4]. 
Regional and local arterial stiffness may be measured directly, and non-invasively, at various sites along the 
arterial tree, by assessing Pulse Wave Velocity (PWV) and Augmentation Index (AI) [1]. Central BPs are 
derived from non-invasive techniques of measurement of radial or carotid pulses [5]. 
The most widely employed methods for evaluating pulse waveforms are those based on applanation 
tonometry and transfer functions, although recently oscillometric ambulatory blood pressure monitoring 
(ABPM) devices using specific algorithms for pulse wave analyses (PWA) have been proposed for assessing 
arterial stiffness [6-9]. At present, oscillometry is an affordable technique, and may allow a comfortable, 
accurate, repeated and prolonged estimation of arterial stiffness and central hemodynamics over the 24-hours 
in daily life conditions [9]. The most recent studies seem to indicate reliability and feasibility of ambulatory 
arterial stiffness evaluation based on analysis of brachial oscillograms [10-12]. 
However, very few information is available on the prognostic value of ambulatory central blood pressure 
[13,14], and no information at all is provided by any study on the clinical value of 24-hour arterial stiffness 
estimation (PWV and AI). For this reason, we decided to create a large database (registry) of ABPM 
recordings obtained with a non-invasive device, able to determine central BP and various indices of arterial 
stiffness (mainly PWV and AI) over the 24-hours, based on a clinically validated technology of PWA of 
oscillometric BP measurements, integrated in the ambulatory BP monitor [10,12,13]. Specifically, this project 
aims at creating an international network of centers performing ABPM and arterial stiffness monitoring, in 
order to evaluate the impact of such estimates on the clinical outcome of hypertensive patients. The results of 
the data collected at baseline and during regular follow-up of hypertensive patients will help to provide 
evidence on the clinical usefulness of such technologies for the screening and follow-up of the hypertensive 
patients. 
 
7.0 
PROJECT OBJECTIVES 
 
The specific project objectives are: 
 
• The evaluation of non-invasive ambulatory blood pressure and arterial stiffness estimates (through PWA) 
in hypertensive subjects undergoing an ABPM for clinical reasons in the selected centers 
• The evaluation of the changes in blood pressure and arterial stiffness estimates following treatment 
initiation according to current guidelines 
• The assessment of the impact of non-invasive arterial stiffness estimation on target organ damage and 
patient’s CV prognosis 
• The definition of the normalcy thresholds for PWV, AI and other current and future indices derived from 
PWA, in hypertensive subjects, according to outcome data 
• The definition of the relationship between arterial stiffness, blood pressure absolute level and blood 
pressure variability, and outcomes 
• The setup of a worldwide network of centers performing ambulatory PWA, and the validation and 
promotion of the use of such technique for hypertension screening and follow-up 
• The provision of evidence on the clinical relevance of non-invasive arterial stiffness assessment, in order 
to favor the inclusion of such evaluation in recommendations on hypertension management 
 
8.0 
OVERALL PROJECT DESIGN AND PLAN 
 
International, multicenter, observational, prospective project 
 
9.0 
SELECTION OF PROJECT POPULATION 
 
The registry will include data from subjects fulfilling the inclusion criteria and whose data are contained in 

existing databases collected by the participating centers and who are regularly followed-up at the center. New 
subjects can be enrolled for this project, but they must be submitted to ABPM because it is required for 
evaluating their hypertension status, according to current recommendations. 
While the present document contains the initial list of participating countries (Italy and Russia) and centers, 
other centers willing to participate in the project and able to provide a significant contribution may be 
accepted also after the project has initiated. 
 
9.1 
Inclusion criteria 
 
• Male and female subjects 
• Age ≥18 years 
• Subjects referred to routine diagnostic evaluation for hypertension or established hypertensive subjects 
• ABPM performed for clinical reasons with a BPLab device 
• The minimum validity requirements for inclusion of the ABPM in the study are: 
- Interval between measurements not exceeding 30 minutes 
- At least 70% of expected number of readings 
- At least 20 valid readings during the day-time and 7 during the nigh-time 
• Availability of individual measurements for ABPM on a .bpw file (BPLab format) or data directly 
downloaded on the telemedicine platform of the study (see below) 
• Availability of basic clinical information (as detailed in Section 14.1): 
• Availability of a signed informed consent form 
 
9.2 
Exclusion criteria 
 
• Age <18 years 
• Atrial fibrillation, frequent ectopic beats, second or third degree atrioventricular blocks, or other 
conditions which might make difficult or unreliable the automatic blood pressure measurement with the 
oscillometric technique 
• Upper arm circumference <22 cm 
• Pregnancy 
 
10.0 
PROJECT ACTIVITIES 
 
10.1 
Creation of research network and data collection 
 
Data contained in existing electronic databases or data of newly enrolled subjects fulfilling the inclusion 
criteria will be uploaded/entered on the study website. These data will include ABPM measures (blood 
pressure and arterial stiffness) obtained with a BPLab device and clinical data. ABPM data will be provided 
as .bpw files or directly uploaded by linking the ABPM device to the website through a personal computer. 
24-hour ambulatory blood pressure recordings will be done in accordance with the procedures described in 
the Appendix 1. 
Data collection will be ensured by a dedicated web-based telemedicine platform, including an electronic case 
report form (e-CRF). ABPM data will be transmitted to the project website and analyzed in real-time with 
production of an electronic report sent by e-mail to the Investigator and available on the website. Only 
ambulatory blood pressure data collected with a BPLab monitor will be included in the system. The e-CRF 
will allow collection of patient’s clinical data, such as family history, anthropometric data, habits, past and 
current diseases, therapies, office BP, and laboratory tests, including evaluation of target organ damage. 
More than one ABPM recording may be performed in the same patient if deemed necessary by the physician 
in charge. They will be uploaded in the telemedicine system and complemented by an update of clinical 
information, as mentioned above. The project does not involve any type of intervention related to the study 
and the physicians will manage the patients included in the registry according to the requirements of clinical 
practice and current guidelines. However, 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). 
The physicians will also be free to use the ambulatory blood pressure data in the clinical management of the 
patients. 

The telemedicine system will allow a) standardized and centralized data collection, b) data validation by 
experts and counselling to remote centers, c) setup and maintenance of the Registry. 
 
10.2 
ABPM data analysis 
 
Principal derived ABPM variables and arterial stiffness measures will be calculated immediately once the 
data are input in the database and their adequate quality is verified. Mean blood pressure and heart rate 
values, PWV and AI will be computed for 24-hour, day-time and night-time by averaging the all the 
individual readings for the subperiod in question. Measures of blood pressure variabilities (weighted 
standard deviation and average real variability) will also be computed based on individual readings. 
Other variables of interest (e.g. nocturnal blood pressure fall, morning surge, etc.) will be subsequently 
defined in the framework of sub-analyses based on the registry data and calculated according to the 
procedures specifically defined. 
 
10.3 
Dissemination activities 
 
An important part of activities in this project will be aimed at disseminating the knowledge on correct use of 
ambulatory blood pressure and arterial stiffness estimation in clinical practice and in research and thus at 
achieving a possibly standardized and widespread use of this integrated technology in the participating 
centers. In order to achieve these aims the project, apart from data collection, will involve the following 
activities: 
 
• Exchange of knowledge between participating centers already expert in ABPM use and in arterial 
stiffness measurement. This will be mainly achieved by cooperation of investigators in preparing a 
possibly unified methodology of ABPM data collection and analysis and by jointly addressing 
methodological issues that may arise during the project. 
• Performance of studies aimed at optimizing a possible clinical application of non-invasive ambulatory 
arterial stiffness estimation, based on data collected in the Registry 
• Providing instructions on appropriate ambulatory arterial stiffness monitoring methodology to other 
physicians. Indeed, an important feature of the project will be to actively involve intermediate level 
centers, not necessarily expert in ABPM use and arterial stiffness determination. A major task of the 
consortium will be to provide these participants with an accurate information on correct methodology and 
interpretation of such data, in order to support them in case of difficulties and to monitor the correctness 
of the use of the methodology in these centers during the project 
• Preparation of specific recommendations on the use and clinical application of ABPM integrated with 
arterial stiffness evaluation 
• Cooperation with international and national scientific societies in the area related to ABPM and arterial 
stiffness monitoring. The majority of the VASOTENS Scientific Committee members will be selected 
among active members of international and national hypertension societies, including the membership in 
the bodies specifically dedicated to blood pressure and arterial stiffness measurement. This will facilitate 
the dissemination of information on the project and its findings and will also allow an interaction with 
writing committees involved in the preparation of guidelines pertinent to this area 
 
11.0 
STATISTICAL METHODS 
 
Basic descriptive statistics of the entire registry with calculation of absolute and relative frequencies for 
categorical variables and calculation of average value, standard deviation, minimum and maximum for 
continuous variables will be calculated. 
Standard variables (systolic and diastolic blood pressure, pulse pressure and heart rate), central systolic and 
diastolic blood pressure, and arterial stiffness indices (PWV and AI) will be averaged for the whole 24-hour 
period, and separately for the day-time and night-time subperiods. Additionally, hourly averages will be 
computed, and in case of blood pressure, variability will be evaluated by calculation of weighted standard 
deviation and average real variability. 
Relationship between blood pressure and arterial stiffness estimates and organ damage and prognosis will be 
evaluated. 

Other variables of interest will be defined in the course of the study and calculated subsequently according to 
the procedures defined in a specific statistical analysis plan. 
The occurrence of any cardiovascular event (death or hospitalization for congestive heart failure, myocardial 
infarction, angina, stroke or cerebrovascular accident, renal failure, etc.) during the study will be evaluated 
by the Kaplan-Meier method. Time-to-event curves will be drawn and the survival analysis will be 
performed according to the Cox proportional hazard model, which will allow to analyze predictors of 
outcomes.  
Analysis will be performed periodically: the first will be done at the end of the first year of follow-up of all 
the recruited subjects. 
 
12.0 
INVESTIGATORS AND PROJECT ADMINISTRATIVE STRUCTURE 
 
12.1 
Project Coordinators 
 
The Promoter of the project and Scientific Coordinator is: 
 
Dr. Stefano Omboni 
Clinical Research Unit 
Italian Institute of Telemedicine 
Via Colombera 29 
21048 Solbiate Arno (Varese) 
Italy 
Tel +39 0331 984529 
Fax +39 0331 984530 
stefano.omboni@iitelemed.org 
 
Study co-coordinator is: 
 
Dr. Igor Posokhov 
Hemodynamic Laboratory 
PO Box 69  
603009 Nizhniy Novgorod 
Russia 
Tel  +7 831 2961414 
Fax +7 831 2961415 
igor@posohov.ru 
 
12.2 
Scientific Committee and other project structures 
 
The Project Coordinators will be supported by the following structures. 
 
12.2.1 Steering Committee 
 
The Steering Committee will directly coordinate the project activities and prepare the preliminary versions of 
the project documents to be subsequently presented to the Scientific Committee. The Steering Committee 
will be formed by the Project Coordinators and by the individual coordinator of each country (National 
Coordinator). Members of the Steering Committee are: 
 
Stefano Omboni (Italy), Gianfranco Parati (Italy), Igor Posokhov (Russia), Anatoli Rogoza (Russia). 
 
12.2.2 Scientific Committee 
 
The main tasks of the Scientific Committee will be the design of the project, the selection of participating 
doctors, check and approval of the protocol, of its appendices and possible amendments, supervision of and 
support to Investigators, evaluation of the results and preparation of manuscripts based on project results. 
The Scientific Committee will be formed by the Project Coordinators, the National Coordinators and by no 

more than one major local investigator. 
 
Stefano Omboni (Italy), Gianfranco Parati (Italy), Igor Posokhov (Russia), Anatoli Rogoza (Russia), Yulia 
Kotovskaya (Russia)  
 
12.2.3 National Coordinators 
 
The National Coordinators will coordinate local investigators and stimulate recruitment and data collection 
in each country. They will also organize, when feasible, local investigators’ meeting. 
 
12.2.4 Scientific and Organizing Secretariat 
 
The Contract Research Organization (CRO) of the study will be Docleader Ltd. located in Solbiate Arno 
(Varese), Italy. When requested, this company will assist the Promoter and Coordinators in all the scientific 
and practical aspects related to the study, e.g. protocol and appendices definition, organization of investigators’ 
meeting, contacts with the investigators, data management and analysis, reporting, etc. (see Section 12.4) 
 
12.3 
Investigators 
 
This multicenter international project will involve investigators from Hypertension Centers worldwide. 
Initially two countries will be involved in the studies (Italy and Russia). 
Basic technical requirements for the inclusion of a center in the project will be: 
 
• The availability in the facility of a BPLab ABPM monitor  
• The ability to perform proper 24-hour ABPM  
• The potential for providing and properly following-up the number of patients required by the protocol  
• The availability of Internet connection, regular access to the web and human resources to upload ABPM 
and clinical data 
 
The investigator will need to have a medium-high level of expertise in informatics. 
Given the observational nature of the project, it will not foresee any costs for the doctors and health 
insurance system and will not cause implementation of additional diagnostic examinations or changes in the 
use of any specific class of antihypertensive drugs.  
 
12.4 
CRO 
 
Upon request, the CRO of the project will assist the Promoter in some of the activities related to the study 
(e.g. protocol finalization and formatting, training of the investigators in the project procedures, data 
management and analysis, preparation of statistical reports, etc.)  
The CRO will have the responsibility to take all the necessary measures to ensure proper conduct of the 
project regarding the ethical aspects, adherence to the protocol, and the integrity and validity of data 
recorded in the e-CRF. 
 
13.0 
ETHICS 
 
13.1 
Independent Ethics Committee or Institutional Review Board 
 
The data collection can be started in each center only after approval or notification (depending on local laws) 
of the project protocol Independent Ethics Committees. 
 
13.2 
Subject information and consent 
 
The investigator must obtain written informed consent from each patient (Appendix 2), before submitting 
him or her to any procedure of the project. 
Each patient must provide written informed consent after receiving information and explanations about the 

objectives, commitments, rights and responsibilities faced by his/her participation in the project. In 
particular, the patient must be informed: 
 
• That this is a research project 
• About the objectives of the project 
• About the project procedures 
• About the free and voluntary participation in the project, and the possibility to get more information on 
the project from the investigator in charge of the project 
• That anonymity of the patient will be kept on the official documentation of the project 
• About the methods for the processing of personal data 
 
The information will be provided to the patient through an information sheet (Appendix 2) and verbally by 
the investigator. 
The written informed consent of the patient should be documented on the appropriate form, which must be 
dated and signed by the subject. According to local laws, the patient might also be asked to sign a separate 
form for the processing of personal data. The patient who will not provide the written authorization will not 
participate in the project. In case of subjects legally incapable or with restriction, consent must be provided 
by the legal representative. 
The original signed informed consent obtained from the patient will be retained by the investigator in the 
patient’s file at the project center, while one copy will be delivered to the patient. 
 
14.0 
DATA MANAGEMENT 
 
14.1 
Electronic Case Report Form (e-CRF) 
 
Data will be collected for each patient by an e-CRF located on a website. The e-CRF will allow the 
collection of the main demographic and clinical data including the patient's medical history and concomitant 
therapies. All data must accurately reflect the patients’ view, or be an expression of their knowledge about 
their health. 
The following data will be entered fin the e-CRF, for each subject and visit: 
 
• Age 
• Gender 
• Height 
• Weight 
• Ethnicity 
• Superficial distance between jugulum and symphysis (surrogate of aortic length) 
• Waist circumference 
• Smoking status 
• Alcohol drinking 
• Coffee or tea drinking 
• Dyslipidemia (yes/no and indication on treatment) 
• Diabetes (yes/no and indication on treatment) 
• Diagnosis of hypertension (yes/no and indication on treatment) 
• Family history of premature CV disease 
• Medical history, with particular regard to previous and/or concurrent CV diseases 
• Office blood pressure and heart rate obtained in the same treatment condition as ABPM 
• Left ventricular mass index (LVMI) at echocardiogram 
• When available, diameter of the aorta (aortic annulus, root and sinotubular junction ) and/or cardiac 
output, assessed by the echocardiogram 
• Intima-media thickness (IMT) at carotid ultrasonography 
• ECG (indication on left ventricular hypertrophy, Sokolow–Lyon and Cornell index) 
• When available, ankle-brachial index 

• Microalbuminuria and serum creatinine (calculation of estimated glomerular filtration rate - eGFR) 
• When available, pulse wave velocity (PWV) augmentation index (AI) and central blood pressure taken 
during the office visit with a validated device different for BPLab Vasotens (e.g. Sphygmocor or 
Complior) 
 
Access to the e-CRF will be granted through authentication with ID and password. The investigator will be 
responsible for the faithful transcription of the results of any laboratory or instrumental diagnostic tests. If 
changes have to be made to data, they will be overwritten with the correct ones. The system will keep record 
of the date and time of the corrections. 
The data entered in the e-CRF will be stored in a database residing on a webserver. When entering data in the 
e-CRF the system will automatically check their congruence. A further data check will be made on the 
database in order to highlight missing data, or compilation errors, inconsistencies, protocol violations. The 
list of these errors will be discussed with the investigator, and appropriate changes agreed with him/her. 
The blood pressure and arterial stiffness measurements made with the BPLab blood pressure monitor will be 
uploaded electronically by the telemedicine system onto the e-CRF. 
 
14.2 
Project monitoring 
 
Given its observational nature, no formal monitoring is foreseen for this project. However, electronic data 
verification could be done by the monitor and data manager, who will get in touch with the investigators, via 
e-mail, fax or phone, and when needed may ask the investigator to correct the erroneous data or complete 
missing data on the e-CRF. 
Each investigator will be required to keep records of the project in a file located at the project center. The 
investigator is asked to keep a paper or computer file of the patients enrolled in the project, but also of those 
assessed but not included in the project. 
The Promoter might eventually ask the CRO to visit the center and will thus have free access to the 
documentation of the project in order to: 
 
• Check the progress of the project 
• Verify adherence to the protocol procedures 
• Discuss any problems 
• Review the adequacy of the completion of the e-CRF and that its content complies with the source data 
(in this case the patient's personal data will still be kept confidential) 
 
The verification of source documentation may also be made in the course of an audit by the Promoter in 
order to ensure the validity of the data, or during the inspection by the competent authorities, depending on 
local rules. Personal data of the patient will still be kept confidential. 
 
14.3 
Data quality control and assurance 
 
The investigator agrees to participate in the project in full adherence to the present protocol and to verify and 
check that the information provided on the e-CRF is as precise and accurate as possible. 
The procedures for data monitoring and verification will be ensured by the presence of logical checks and 
range (defined a priori) for the different variables and by automatic identification of inconsistencies by the 
software used to manage the database. The controls and related corrections can be made on the e-CRF 
directly by the investigator on the website. 
 
15.0 
INSURANCE 
 
Because of its observational nature, this project does not require insurance, apart from that already required 
for normal clinical practice and available at each general practice’s or specialist’ office. 
 
16.0 
DISCONTINUATION OF THE PROJECT 
 

The Promoter reserves the right to discontinue the project at any time. This decision will be communicated in 
writing to the investigator. Similarly, if the investigator decides to withdraw from the project he/she must 
give immediate written notice to the Promoter. 
 
17.0 
STATEMENT OF CONFIDENTIALITY 
 
All documentation related to the project will be provided to the investigator and his coworkers by the 
Promoter under conditions of confidentiality. None of these documents may be disclosed to third parties not 
directly involved in the project without the written permission of the Promoter. 
The investigator must ensure the anonymity of individual patients. 
All materials, information (verbal or written) and unpublished documents provided to the investigators, 
including this protocol are the exclusive property of the Promoter. This material or information (either global 
or partial) cannot be delivered or disclosed by the investigator or any other person of his or her group to any 
unauthorized person without a formal written consent of the Promoter. 
The investigator will consider confidential all information received, acquired or derived during the project 
and take all necessary measures to ensure their confidentiality in accordance with the privacy requirements 
and local privacy laws. 
 
18.0 
REPORTING 
 
Detailed reports of the study results will be published, starting form the end of the first year of follow-up. 
The investigator agrees that the results of this study can be verified by national and/or international quality 
control authorities. To do so, if requested, the investigator must provide to these authorities all the 
information requested. 
 
19.0 
DATA ACCESS AND PUBLICATION POLICY 
 
All unpublished material (for example the protocol and the e-CRF) provided to the investigator is 
confidential and cannot be disclosed in any way without the written approval of the Scientific Coordinators. 
All data and results and all intellectual property rights derived from the project are the property of the 
Promoter. 
Any publication or oral presentation concerning the project, even when regarding partial results, must be 
approved and authorized by the Promoter. 
At each point of the project each member of the Scientific Committee can propose the performance of an 
analysis based on the data contained in the registry. The draft of the analysis plan will be discussed among 
the Scientific Committee members and undergo the final approval by the Scientific Coordinators and the 
Steering Committee. The author of the proposal will coordinate the data analysis, which will be performed 
centrally. 
The authors’ list for each publication will include the proponent(s) (as the first authors), all members of the 
Steering Committee, and up to three people most directly involved in the performance of the study. The 
authors list will include the statement “on behalf of VASOTENS Investigators” and the complete list of 
Scientific Committee members and Investigators will be provided at the end of the paper. This policy may be 
modified in individual cases upon agreement of all interested sides. 
 
20.0 
PROTOCOL AMENDMENTS 
 
This protocol and appendices form an integral part of this document. 
After the protocol is negotiated and signed by the parties no modification can be made by the Promoter, nor 
by the Coordinators or by the investigators, without agreement among the parties. Any agreed changes will 
be ratified in writing by the Promoter and Coordinator and annexed to this protocol. 
Any amendment will be reported to the Ethics Committee. 

21.0 
REFERENCE LIST 
1 
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos 
C, Wilkinson I, Struijker-Boudier H; European Network for Non-invasive Investigation of Large 
Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical 
applications. Eur Heart J 2006; 27: 2588-2605. 
2 
Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause 
mortality with arterial stiffness: a systematic review and meta-analysis. J Am College Cardiol 2010; 55: 
1318-1327. 
3 
McEniery CM, Cockcroft JR, Roman MJ, Franklin SS, Wilkinson IB. Central blood  pressure: current 
evidence and clinical importance. Eur Heart J 2014; 35: 1719-1725. 
4 
ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the 
management of arterial hypertension of the European Society of Hypertension (ESH) and the European 
Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J 
Hypertens 2013; 31: 1925-1938. 
5 
O'Rourke MF, Adji A. Noninvasive studies of central aortic pressure. Curr Hypertens Rep 2012;14:8-
20. 
6 
Baulmann J, Schillings U, Rickert S, Uen S, Düsing R, Illyes M, Cziraki A,Nickering G, Mengden T. A 
new oscillometric method for assessment of arterial stiffness: comparison with tonometric and piezo-
electronic methods. J Hypertens 2008; 26: 523-528. 
7 
Trachet B, Reymond P, Kips J, Swillens A, De Buyzere M, Suys B, Stergiopulos N, Segers P. 
Numerical validation of a new method to assess aortic pulse wave velocity from a single recording of a 
brachial artery waveform with an occluding cuff. Ann Biomed Eng 2010; 38: 876-888. 
8 
Hametner B, Wassertheurer S, Kropf J, Mayer C, Eber B, Weber T. Oscillometric estimation of aortic 
pulse wave velocity: comparison with intra-aortic catheter measurements. Blood Press Monit 2013; 18: 
173-176. 
9 
Posokhov IN. Pulse wave velocity 24-hour monitoring with one-site measurements by oscillometry. 
Med Devices (Auckl) 2013; 6: 11-15. 
10 Ageenkova OA, Purygina MA. Central aortic blood pressure, augmentation index, and reflected wave 
transit time: reproducibility and repeatability of data obtained by oscillometry. Vasc Health Risk Manag 
2011; 7: 649-656. 
11 Luzardo L, Lujambio I, Sottolano M, da Rosa A, Thijs L, Noboa O, Staessen JA, Boggia J. 24-h 
ambulatory recording of aortic pulse wave velocity and central systolic augmentation: a feasibility 
study. Hypertens Res 2012; 35: 980-987. 
12 Omboni S, Posokhov IN, Rogoza AN. Evaluation of 24-Hour Arterial Stiffness Indices and Central 
Hemodynamics in Healthy Normotensive Subjects versus Treated or Untreated Hypertensive Patients: 
A Feasibility StudyVolume. Int J Hypertens 2015:601812. 
13 Zhang Y, Kollias G, Argyris AA, Papaioannou TG, Tountas C, Konstantonis GD, Achimastos A, 
Blacher J, Safar ME, Sfikakis PP, Protogerou AD. Association of left ventricular diastolic dysfunction 
with 24-h aortic ambulatory blood pressure: the SAFAR study. J Hum Hypertens 2014 Nov 13 [Epub 
ahead of print]. 
14 Protogerou AD, Argyris AA, Papaioannou TG, Kollias GE, Konstantonis GD, Nasothimiou E, 
Achimastos A, Blacher J, Safar ME, Sfikakis PP. Left-ventricular hypertrophy is associated better with 

24-h aortic pressure than 24-h brachial pressure in hypertensive patients: the SAFAR study. J Hypertens 
2014;32:1805-1814. 

22.0 
APPENDICES 
 
Appendices to the protocol are provided apart. 
 
Appendix 1 - Ambulatory blood pressure monitoring procedures 
 
Appendix 2 - Patient information sheet and informed consent form 
 
Appendix 3 - Investigator’s approval page