Chronic Stable AnginaNCT01864031
The Role of Alcohol Consumption in the Aetiology of Different Cardiovascular Disease Phenotypes: a CALIBER Study
An observational study of Chronic Stable Angina and Unstable Angina, run by University College, London at 1 site in United Kingdom.
Trial summary
The association between alcohol consumption and cardiovascular disease (CVD) has mostly been examined using broad endpoints or cause-specific mortality. The purpose of our study is to compare the effect of alcohol consumption in the aetiology of a range of cardiovascular disease phenotypes. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Chronic Stable Angina, Unstable Angina, Coronary Heart Disease Not Otherwise Specified
- How many people
- 2,240,000 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 1997to Dec 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The cohort used in the present study was drawn from patients registered with GPRD general practices in England that consented to data linkage (approx. 5% of the UK population). We used an open cohort design, where participants joined the cohort when they met the inclusion criteria at any point between 1st January 1997 and 25th March 2010 (the last GPRD data submission). Patients were included in cohort if they were aged ≥ 30 years, had at least one year of electronic health record data which met GPRD data quality standards, and had no record indicating any cardiovascular disease prior to study entry. Patients were followed up until the date of an initial presentation of one of our cardiovascular endpoints or were censored on the date of leaving the practice/last data submission from their practice. Patients who died before 1st January 2001 were excluded as cause-specific mortality data was not available for them (this approach is adopted in the Prospective Studies Collaboration).
Who may be able to join
- Aged ≥ 30 years.
- Patient in a GPRD registered practice that has consented to the linkage process (who also met data quality standards).
Who cannot join
- A recorded history of any cardiovascular disease phenotype prior to entering the study.
- Cause of death unknown.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Alcohol Consumption in the Aetiology of Different Cardiovascular Disease Phenotypes: a CALIBER Study Using Linked Electronic Health Records
The association between alcohol consumption and cardiovascular disease (CVD) has mostly been examined using broad endpoints or cause-specific mortality. The purpose of our study is to compare the effect of alcohol consumption in the aetiology of a range of cardiovascular disease phenotypes.
Read the detailed description
The relationship between cardiovascular diseases (CVDs) and alcohol consumption is complex. Moderate alcohol consumption has consistently been found to be associated with a reduced risk of commonly reported aggregates of CVD (e.g. coronary heart disease [CHD]) while heavy drinking (and abstaining from alcohol) is believed to be associated with an augmented risk. However, much remains to be clarified. For example, previous studies have typically been too small in size to adequately assess the impact of alcohol consumption on a range of major, pathologically distinct CVDs. Understanding the role of alcohol consumption in specific CVDs may provide novel insights into the mechanisms which give rise to the observed beneficial effects of moderate consumption for these aggregates.
As the focus of our research question is the effect of alcohol consumption on specific cardiovascular phenotypes we will not derive a single primary outcome. Utilising the strengths of the CALIBER data platform we will define multiple cardiovascular disease outcomes including: chronic stable angina (SA), unstable angina (UA), coronary heart disease not otherwise specified (CHD, NOS), acute myocardial infarction (MI), heart failure (HF), ventricular arrhythmias including cardiac arrest, abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD), ischaemic and haemorrhagic (subarachnoid and intracerebral) strokes, transient ischaemic attack (TIA), and sudden cardiac death (SCD) or unheralded coronary death (UCD). Additionally non-CVD mortality will be defined as a competing outcome. These outcomes are defined/validated using multiple sources; including a combination of symptoms, diagnoses (including the use of additional information from ECG findings and troponin values) and prescriptions.
For comparison purposes (to major studies/existing consortia) we will also estimate models for aggregated CHD (MI and unheralded coronary death), CVD (CHD and stroke of any type) and fatal CVD (combination of fatal CHD and fatal CVD) endpoints.
Secondary outcomes: To examine whether the association between drinking categories and specific MI phenotypes differ we will rerun our models in patients who remained in the cohort from January 2003, when information from MINAP became available. This will allow for the composite MI category to be decomposed into ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (nSTEMI) and myocardial infarction not otherwise specified (MI NOS).
In light of current debates on the U/J-shaped relationship observed between alcohol consumption and aggregated CVD outcomes five drinking categories have been defined including: (1) Never drinkers ("tee-total" and "non-drinkers"), former drinkers (those with codes for "stopped drinking alcohol" and/or "ex-drinker"), occasional drinkers (those with codes for "drinks rarely" and/or "drinks occasionally"), current moderate drinkers (those who had a code for current alcohol consumer and an indicator of whether they drank within daily [4/3 UK units of alcohol for men and women respectively] and weekly [21/14 UK units for men and women respectively] recommended sensible drinking limits) and current heavy drinkers (defined as those who exceeded daily or weekly sensible drinking limits). Unfortunately information on binge drinking was only available for a select minority of the cohort (~100 people) therefore a separate category for this drinking behaviour was not defined (but these patients were coded as heavy drinkers). Our referent category will be current moderate drinkers.
Competing-risk Cox proportional hazard models will be used to examine the association between drinking category and different cardiovascular disease phenotypes. Competing-risk regression takes into account the instantaneous failure rates of specific competing-causes (i.e. different cardiovascular phenotypes and death from non-coronary causes) - not doing so may overestimate the association between drinking categories and outcome. A detailed analytic protocol is available upon request.
This study is part of the CALIBER (Cardiovascular disease research using linked bespoke studies and electronic records) programme funded over 5 years from the NIHR and Wellcome Trust. The central theme of the CALIBER research is linkage of the Myocardial Ischaemia National Audit Project (MINAP) with primary care (GPRD), secondary care (HES) and other resources. The overarching aim of CALIBER is to better understand the aetiology and prognosis of specific coronary phenotypes across a range of causal domains, particularly where electronic records provide a contribution beyond traditional studies. CALIBER has received both Ethics approval (ref 09/H0810/16) and ECC approval (ref ECC 2-06(b)/2009 CALIBER dataset).
- Conditions
- Chronic Stable Angina, Unstable Angina, Coronary Heart Disease Not Otherwise Specified, Acute Myocardial Infarction, Heart Failure, Ventricular Arrhythmias
- Keywords
- Alcohol, Drinking, Abstainers, Former drinkers, Ex-drinkers, Aetiology, Initial presentation, Chronic Stable Angina, Unstable Angina, Coronary Heart Disease Not Otherwise Specified, Acute Myocardial Infarction, Heart Failure, ST elevation Myocardial Infarction (STEMI), non-ST elevation Myocardial Infarction (nSTEMI), Myocardial Infarction Not Otherwise Specified (MI NOS), Ventricular Arrhythmias, Cardiac Arrest, Abdominal Aortic Aneurysm, Peripheral Arterial Disease, Ischaemic Stroke
- Medical subject headings
- Angina, Stable, Angina, Unstable, Heart Failure, Heart Arrest, Aortic Aneurysm, Abdominal, Peripheral Arterial Disease, Ischemic Stroke, Death, Sudden, Cardiac
What is being measured
The primary outcome is the main question the study is designed to answer.
Initial presentation of cardiovascular disease
See "Conditions" and "Detailed Description" sections for further description of the endpoints used.
Measured: Study follow-up will commence on the earliest date that a patient fulfils the study inclusion criteria during the period between 1st January 1997 and 25th March 2010 (maximum of 13 years follow-up)
Secondary outcomes (1)
Non-CVD mortality
Death from non-CVD causes.
Measured: Same as for primary outcomes (maximum of 13 years follow-up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2013 (estimated)
- Study startJan 1997
- Primary completionDec 2013 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chronic Stable AnginaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,240,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Harry Hemingway, University College, London
- Investigators
- Steven Bell, PhD, Principal investigator, University College, LondonHarry Hemingway, FRCP, Study director, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01864031
- Sponsor's protocol ID
- CALIBER 12-02
- Other IDs
- 086091/Z/08/Z, RP-PG-0407-10314
- Status last verified
- May 2013
- First submitted
- 23 May 2013
- Last updated
- 29 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ. 2011 Feb 22;342:d671. doi: 10.1136/bmj.d671.
PubMed 21343207Roerecke M, Rehm J. The cardioprotective association of average alcohol consumption and ischaemic heart disease: a systematic review and meta-analysis. Addiction. 2012 Jul;107(7):1246-60. doi: 10.1111/j.1360-0443.2012.03780.x. Epub 2012 Mar 21.
PubMed 22229788Mukamal K. Alcohol intake and noncoronary cardiovascular diseases. Ann Epidemiol. 2007 May;17(5 Suppl):S8-S12. doi: 10.1016/j.annepidem.2007.01.003.
PubMed 17478332Stockwell T, Greer A, Fillmore K, Chikritzhs T, Zeisser C. How good is the science? BMJ. 2012 Mar 27;344:e2276; author reply e2294. doi: 10.1136/bmj.e2276. No abstract available.
PubMed 22453883Denaxas SC, George J, Herrett E, Shah AD, Kalra D, Hingorani AD, Kivimaki M, Timmis AD, Smeeth L, Hemingway H. Data resource profile: cardiovascular disease research using linked bespoke studies and electronic health records (CALIBER). Int J Epidemiol. 2012 Dec;41(6):1625-38. doi: 10.1093/ije/dys188. Epub 2012 Dec 5.
PubMed 23220717Bell S, Daskalopoulou M, Rapsomaniki E, George J, Britton A, Bobak M, Casas JP, Dale CE, Denaxas S, Shah AD, Hemingway H. Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records. BMJ. 2017 Mar 22;356:j909. doi: 10.1136/bmj.j909.
PubMed 28331015
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Alcohol Consumption in the Aetiology of Different Cardiovascular Disease Phenotypes: a CALIBER Study Using Linked Electronic Health Records
- ClinicalTrials.gov ID
- NCT01864031
- Acronym / sponsor ID
- CALIBER 12-02
- Conditions
- Chronic Stable Angina, Unstable Angina, Coronary Heart Disease Not Otherwise Specified, Acute Myocardial Infarction, Heart Failure, Ventricular Arrhythmias
- Keywords
- Alcohol, Drinking, Abstainers, Former drinkers, Ex-drinkers, Aetiology, Initial presentation, Chronic Stable Angina
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,240,000 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Jan 1997
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 29 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The association between alcohol consumption and cardiovascular disease (CVD) has mostly been examined using broad endpoints or cause-specific mortality. The purpose of our study is to compare the effect of alcohol consumption in the aetiology of a range of cardiovascular disease phenotypes.
Detailed description
The relationship between cardiovascular diseases (CVDs) and alcohol consumption is complex. Moderate alcohol consumption has consistently been found to be associated with a reduced risk of commonly reported aggregates of CVD (e.g. coronary heart disease [CHD]) while heavy drinking (and abstaining from alcohol) is believed to be associated with an augmented risk. However, much remains to be clarified. For example, previous studies have typically been too small in size to adequately assess the impact of alcohol consumption on a range of major, pathologically distinct CVDs. Understanding the role of alcohol consumption in specific CVDs may provide novel insights into the mechanisms which give rise to the observed beneficial effects of moderate consumption for these aggregates.
As the focus of our research question is the effect of alcohol consumption on specific cardiovascular phenotypes we will not derive a single primary outcome. Utilising the strengths of the CALIBER data platform we will define multiple cardiovascular disease outcomes including: chronic stable angina (SA), unstable angina (UA), coronary heart disease not otherwise specified (CHD, NOS), acute myocardial infarction (MI), heart failure (HF), ventricular arrhythmias including cardiac arrest, abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD), ischaemic and haemorrhagic (subarachnoid and intracerebral) strokes, transient ischaemic attack (TIA), and sudden cardiac death (SCD) or unheralded coronary death (UCD). Additionally non-CVD mortality will be defined as a competing outcome. These outcomes are defined/validated using multiple sources; including a combination of symptoms, diagnoses (including the use of additional information from ECG findings and troponin values) and prescriptions.
For comparison purposes (to major studies/existing consortia) we will also estimate models for aggregated CHD (MI and unheralded coronary death), CVD (CHD and stroke of any type) and fatal CVD (combination of fatal CHD and fatal CVD) endpoints.
Secondary outcomes: To examine whether the association between drinking categories and specific MI phenotypes differ we will rerun our models in patients who remained in the cohort from January 2003, when information from MINAP became available. This will allow for the composite MI category to be decomposed into ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (nSTEMI) and myocardial infarction not otherwise specified (MI NOS).
In light of current debates on the U/J-shaped relationship observed between alcohol consumption and aggregated CVD outcomes five drinking categories have been defined including: (1) Never drinkers ("tee-total" and "non-drinkers"), former drinkers (those with codes for "stopped drinking alcohol" and/or "ex-drinker"), occasional drinkers (those with codes for "drinks rarely" and/or "drinks occasionally"), current moderate drinkers (those who had a code for current alcohol consumer and an indicator of whether they drank within daily [4/3 UK units of alcohol for men and women respectively] and weekly [21/14 UK units for men and women respectively] recommended sensible drinking limits) and current heavy drinkers (defined as those who exceeded daily or weekly sensible drinking limits). Unfortunately information on binge drinking was only available for a select minority of the cohort (~100 people) therefore a separate category for this drinking behaviour was not defined (but these patients were coded as heavy drinkers). Our referent category will be current moderate drinkers.
Competing-risk Cox proportional hazard models will be used to examine the association between drinking category and different cardiovascular disease phenotypes. Competing-risk regression takes into account the instantaneous failure rates of specific competing-causes (i.e. different cardiovascular phenotypes and death from non-coronary causes) - not doing so may overestimate the association between drinking categories and outcome. A detailed analytic protocol is available upon request.
This study is part of the CALIBER (Cardiovascular disease research using linked bespoke studies and electronic records) programme funded over 5 years from the NIHR and Wellcome Trust. The central theme of the CALIBER research is linkage of the Myocardial Ischaemia National Audit Project (MINAP) with primary care (GPRD), secondary care (HES) and other resources. The overarching aim of CALIBER is to better understand the aetiology and prognosis of specific coronary phenotypes across a range of causal domains, particularly where electronic records provide a contribution beyond traditional studies. CALIBER has received both Ethics approval (ref 09/H0810/16) and ECC approval (ref ECC 2-06(b)/2009 CALIBER dataset).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The cohort used in the present study was drawn from patients registered with GPRD general practices in England that consented to data linkage (approx. 5% of the UK population). We used an open cohort design, where participants joined the cohort when they met the inclusion criteria at any point between 1st January 1997 and 25th March 2010 (the last GPRD data submission). Patients were included in cohort if they were aged ≥ 30 years, had at least one year of electronic health record data which met GPRD data quality standards, and had no record indicating any cardiovascular disease prior to study entry. Patients were followed up until the date of an initial presentation of one of our cardiovascular endpoints or were censored on the date of leaving the practice/last data submission from their practice. Patients who died before 1st January 2001 were excluded as cause-specific mortality data was not available for them (this approach is adopted in the Prospective Studies Collaboration).
Key inclusion criteria (2 listed)
- Aged ≥ 30 years.
- Patient in a GPRD registered practice that has consented to the linkage process (who also met data quality standards).
Key exclusion criteria (2 listed)
- A recorded history of any cardiovascular disease phenotype prior to entering the study.
- Cause of death unknown.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Initial presentation of cardiovascular disease
Time frame: Study follow-up will commence on the earliest date that a patient fulfils the study inclusion criteria during the period between 1st January 1997 and 25th March 2010 (maximum of 13 years follow-up)
See "Conditions" and "Detailed Description" sections for further description of the endpoints used.
1 secondary outcome
Non-CVD mortality
Time frame: Same as for primary outcomes (maximum of 13 years follow-up)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2013.
- Background: PubMed 21343207Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ. 2011 Feb 22;342:d671. doi: 10.1136/bmj.d671.
- Background: PubMed 22229788Roerecke M, Rehm J. The cardioprotective association of average alcohol consumption and ischaemic heart disease: a systematic review and meta-analysis. Addiction. 2012 Jul;107(7):1246-60. doi: 10.1111/j.1360-0443.2012.03780.x. Epub 2012 Mar 21.
- Background: PubMed 17478332Mukamal K. Alcohol intake and noncoronary cardiovascular diseases. Ann Epidemiol. 2007 May;17(5 Suppl):S8-S12. doi: 10.1016/j.annepidem.2007.01.003.
- Background: PubMed 22453883Stockwell T, Greer A, Fillmore K, Chikritzhs T, Zeisser C. How good is the science? BMJ. 2012 Mar 27;344:e2276; author reply e2294. doi: 10.1136/bmj.e2276. No abstract available.
- Background: PubMed 23220717Denaxas SC, George J, Herrett E, Shah AD, Kalra D, Hingorani AD, Kivimaki M, Timmis AD, Smeeth L, Hemingway H. Data resource profile: cardiovascular disease research using linked bespoke studies and electronic health records (CALIBER). Int J Epidemiol. 2012 Dec;41(6):1625-38. doi: 10.1093/ije/dys188. Epub 2012 Dec 5.
- Derived from this study: PubMed 28331015Bell S, Daskalopoulou M, Rapsomaniki E, George J, Britton A, Bobak M, Casas JP, Dale CE, Denaxas S, Shah AD, Hemingway H. Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records. BMJ. 2017 Mar 22;356:j909. doi: 10.1136/bmj.j909.
- CALIBER project websiteLink provided by the sponsor.
- UCL Research Department of Epidemiology and Public HealthLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Bell, PhD principal investigator
University College, London
Harry Hemingway, FRCP study director
University College, London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Stable Angina and Unstable Angina, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Initial presentation of cardiovascular disease (time frame: Study follow-up will commence on the earliest date that a patient fulfils the study inclusion criteria during the period between 1st January 1997 and 25th March 2010 (maximum of 13 years follow-up)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01864031, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2013.