Brief Title
The Role of Alcohol Consumption in the Aetiology of Different Cardiovascular Disease Phenotypes: a CALIBER Study
Official Title
The Role of Alcohol Consumption in the Aetiology of Different Cardiovascular Disease Phenotypes: a CALIBER Study Using Linked Electronic Health Records
Brief 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.
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 Type
Observational
Primary Outcome
Initial presentation of cardiovascular disease
Secondary Outcome
Non-CVD mortality
Condition
Chronic Stable Angina
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
2240000
Start Date
January 1997
Completion Date
December 2014
Primary Completion Date
December 2013
Eligibility Criteria
Inclusion Criteria:
- Aged ≥ 30 years.
- Patient in a GPRD registered practice that has consented to the linkage process (who
also met data quality standards).
Exclusion Criteria:
- A recorded history of any cardiovascular disease phenotype prior to entering the
study.
- Cause of death unknown.
Gender
All
Ages
30 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Steven Bell, PhD, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT01864031
Organization ID
CALIBER 12-02
Secondary IDs
086091/Z/08/Z
Responsible Party
Principal Investigator
Study Sponsor
University College, London
Study Sponsor
Steven Bell, PhD, Principal Investigator, University College, London
Verification Date
May 2013