Plain English Summary
Background and study aims
Diabetics often have silent heart disease which goes undetected. Despite controlling blood pressure (BP) and cholesterol, unexpected cardiac deaths still occur which means we need better ways of predicting those at high risk. A whole new possibility is to measure a substance in the bloodstream called brain natriuretic peptide (BNP), which should help identify silent heart disease which may otherwise progress to unexpected cardiac death. This work will see how good BNP is at identifying silent asymptomatic heart disease. The possibility is to use BNP for this purpose in the future so as to prevent unexpected cardiac deaths. The aim of this study is to examine if a blood sample measured for brain natriuretic peptide (BNP) might be a way of identifying those who have silent heart disease and its form.
Who can participate?
Adults aged 50 and older who have been treated for hypertensive of hypercholestromlemic.
What does the study involve?
Participants with no heart disease provide a blood sample taken and then undergo a full cardiac assessment. The blood sample results and the cardiac scan results are linked to look for whether BNP identifies those with silent heart disease
What are the possible benefits and risks of participating?
Participants may benefit from the BNP screening to identify if they have silent heart disease, enabling earlier treatment. There are no direct risks however participants may experience discomfort when providing blood samples.
Where is the study run from?
Ninewells Hospital and Medical School (UK)
When is the study starting and how long is it expected to run for?
February 2008 to December 2017
Who is funding the study?
British Heart Foundation (UK)
Who is the main contact?
Professor Allan Struthers
a.d.struthers@dundee.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Allan Struthers
ORCID ID
Contact details
Department of Clinical Pharmacology
Division of Medicine and Therapeutics
Ninewells Hospital and Medical School
University of Dundee
Dundee
DD19SY
United Kingdom
+44 (0)1382 632180
a.d.struthers@dundee.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
The potential to improve primary prevention by using brain natriuretic peptide (BNP) as an indicator of silent 'pancardiac' target organ damage
Acronym
The 5P Study
Study hypothesis
Despite controlling blood pressure (BP) and cholesterol, unexpected cardiac deaths still occur which means we need better ways of predicting those at high risk. A whole new possibility is to measure a substance in the bloodstream called brain natriuretic peptide (BNP), which should help identify silent heart disease which may otherwise progress to unexpected cardiac death. This work will see how good BNP is at identifying silent asymptomatic heart disease. The possibility is to use BNP for this purpose in the future so as to prevent unexpected cardiac deaths.
Study 1: What is the spectrum of cardiac target organ damage seen in those with an elevated BNP level?
Study 2: Does an elevated BNP in the absence of current ischaemia, left ventricular hypertrophy (LVH) or left atrial dilatation (LAD) identify those who will later develop LVH or LAD?
Ethics approval
Tayside Committee on Medical Research Ethics, 13/02/2008, ref: 08/S1402/15
Study design
Observational cohort study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Not specified
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use the contact details provided in the Interventions field to request a patient information sheet.
Condition
Cardiovascular diseases
Intervention
This is an observational cohort study where participants will undergo standard diagnostic tests but no pharmacological, surgical or lifestyle interventions will be made.
Study 1: What is the spectrum of cardiac target organ damage seen in those with an elevated BNP level?
The Participants will all undergo a full clinical assessment including 24 hour BP monitoring. In addition, blood samples will be taken for the following:
1. Total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides (fasting)
2. BNP, N-terminal BNP and N-terminal Atrial Natriuretic Peptide (ANP). BNP will be measured by a near patient BNP test (Biosite®) and by a standard radioimmunoassay (RIA) on a sample stored at -70 C° using the Peninsula® kit. N-terminal ANP and N-terminal BNP will also be measured by commercially available RIA kits.
3. Kidney function will be measured in three ways
4. Microalbuminuria. We will also be able to assess the value of measuring both BNP and microalbuminuria to identify cardiac target organ damage (TOD).
5. Electrocardiogram (ECG) and 24 hour ECG tape to identify paroxysmal arrhythmias, especially atrial fibrillation (AF)
6. Echocardiography for target organ damage. All measurements will be made according to the American Society of Echocardiography (ASE) recommendation.
7. Silent coronary disease. A non-invasive technique is obviously necessary. We have opted for a dual approach, i.e. dobutamine stress echocardiography (DE) with nuclear stress perfusion imaging (SPI) as a back-up. The recent ACC/AHA 2002 guidelines for chronic stable angina were our guide in choosing techniques.
8. Cardiac MRI. This will be done in suitable patients identified at this stage, i.e. 76 individuals without any target organ damage. This is mainly so that we have baseline data to be used later for Study 2.
Study 2: Does an elevated BNP in the absence of current ischaemia, LVH or LAD identify those who will later develop LVH or LAD?
Effectively, a similar study to Study 1 will be repeated in some of the same individuals four years later. The main analysis will be whether LVMI and LAD progress more over 4 years in those with high tercile BNPs than in those with low tercile BNPs when both groups are matched for their baseline LVMI and LAD. It is best when studying intraindividual changes in LVMI (or LAD) to use the more sensitive technique of MRI.
The prime aim of Study 2 is to see if a high BNP could identify those whose LV mass and/or whose LA volume will increase more in the next 4 years as detected by MRI. We shall also for completeness see if BNP also identifies those who will develop new (silent) coronary disease and stress echo will be undertaken. In addition, for completeness a delayed gadolinium enhancement on MRI will be added to the standard LV quantitative MRI assessment as a validated way of detecting old myocardial infarctions (MIs). These will be done in both the initial MR and the follow up MR but only in those patients taking part in Study 2.
Please use the following contact details to request a patient information sheet:
Dr Adnan Nadir MBBS, MRCP
British Heart Foundation Research Fellow
Division of Medicine & Therapeutics
Ninewells Hospital & Medical School
University of Dundee, Dundee DD19SY, UK
Tel: +44 (0)1382 632 180
Fax: +44 (0)1382 644 972
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
Study 1: The spectrum of cardiac target organ damage seen in those with an elevated BNP level
Study 2: Proportion of participants with elevated BNP in the absence of ischaemia, LVH or LAD who develop LVH or LAD at four years
Secondary outcome measures
No secondary outcome measures
Overall trial start date
18/02/2008
Overall trial end date
31/12/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Both males and females, age >50
2. Treated hypertensive and/or hypercholestrolemic
3. Primary prevention only i.e. no known ischaemic heart disease, cerebrovascular disease, heart failure or peripheral vascular disease
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
300
Participant exclusion criteria
1. Renal impairment
2. Obvious cause for raised BNP level e.g., valvular disease or arrhythmias
Recruitment start date
18/02/2008
Recruitment end date
17/02/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Ninewells Hospital and Medical School
Dundee
DD19SY
United Kingdom
Sponsor information
Organisation
University of Dundee (UK)
Sponsor details
Research and Innovation Services
11 Perth Road
Dundee
DD1 4HN
United Kingdom
+44 (0)1382 384664
a.j.ward@dundee.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
British Heart Foundation (UK)
Alternative name(s)
BHF
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a peer reviewed journal.
IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
31/12/2018
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN62172102_PIS_V4_4May16_Fife.pdf Uploaded 29/08/2017
- ISRCTN62172102_PIS_V4_4May16_Tayside.pdf Uploaded 29/08/2017