Airflow Limitation in Cardiac Diseases in Europe (the ALICE study).

Airflow limitation (AL) occurs in a number of respiratory diseases including
asthma and COPD; in middle-aged and older patients it typically represents
COPD, and is associated with a high degree of co-morbidity which includes
cardiovascular diseases and risk factors such as hypertension and diabetes.

Chronic Obstructive Pulmonary Disease (COPD) is mainly related causally to
smoking and ageing. The prevalence estimates in the general adult population
are influenced by sampling methodologies and by methods used to identify COPD,
and underlying prevalence of risk factors that vary geographically. In reports
from studies of those aged 40 years or older, prevalence ranges from 4% to more
than 20% [Buist, 2007;
Menezes, 2005].

COPD often goes undiagnosed, especially in patients with established coronary
disease because COPD and cardiovascular diseases share a major etiological
factor: smoking. The WHO estimated that in 2000, 4.83 million premature deaths
in the world were attributable to smoking, the three leading causes of death
from smoking being CVD (1.69 million deaths), COPD (0.97 million deaths), and
lung cancer (0.85 million deaths) [Ezzati, 2003].

The association of COPD with increased morbidity, hospital admissions, worse
health status, increased inflammatory markers and cardiovascular disease has
been documented [Melbye, 2007; Sin, 2005]. Individuals with reduced lung
function have an increased risk
of cardiovascular disease which is independent of smoking [Sin, 2005], and
therefore establishing the prevalence of COPD in cardiovascular patients will
be important in identifying patients at risk.

The prevalence of cardiovascular conditions and other co-morbidities in COPD
patients, with a range of severities, has been reported extensively before for
example: [Soriano, 2005; Hansell, 2004; Rodríguez-Roisin, 2008]. On the other
hand, the prevalence of AL and/or COPD has yet to be fully determined in
patients with established cardiovascular disease.

One of the first studies to prospectively investigate the prevalence, severity
and treatment of COPD in patients with established cardiovascular disease (CVD)
concluded that 34% (95% confidence interval (CI): 25-42) of Spanish CVD
patients (one in three patients with coronary artery disease recruited from a
hospital clinic, and one in five patients with CVD in the general population)
suffered airflow limitation compatible with COPD [Soriano, 2010]. Importantly,
the majority of patients with coronary artery disease and AL (87.2%) were not
diagnosed for their AL, and remained mostly untreated.

Additionally, studies from Japan have examined the prevalence of COPD in
various comorbid populations [Yamasaki, 2010; Fukahori, 2009]; and of
particular interest, [Wada, 2010], examined 753 patients attending a
cardiovascular outpatient clinic and identified 79 (10.5%) as COPD (FEV1/FEV6
<0.70) with the PiKo-6. However, [Izquierdo, 2010], concluded that COPD was not
associated with Ischemic Heart Disease (IHD), and that the greater prevalence
of classical CV risk factors in COPD patients could explain the higher
occurrence of IHD in these patients.

Establishing the prevalence of AL in cardiovascular patients, and describing
the burden of these diseases, especially in those patients with undiagnosed AL,
will provide evidence supporting a pro-active approach for identification of
COPD among patients with established cardiac disease.

The primary objective is to establish the point prevalence of Airflow
Limitation (AL) compatible with COPD, in current/former smokers, with
established cardiac diseases, in Europe.

Secondary Objectives are:
• To establish the point prevalence of AL compatible with COPD stratified by
the major population characteristics;
• To establish the overall burden of AL in patients with cardiac diseases,
stratified by cardiac disease type (IHD only, co-morbid Congestive Heart
Failure (CHF) or comorbid with other cardiac diseases (other than CHF)):
• To compare health status in patients with cardiac diseases with and without
AL, and with or without prior COPD diagnosis (see Section 4.3, for definition),
• To compare healthcare resource utilisation in patients with cardiac diseases
with and without AL, and with or without prior COPD diagnosis;
• To explore the relationship between cardiac disease and risk factors with AL:
• To explore whether the type of cardiac disease diagnosis (IHD only, co-morbid
CHF, or co-morbid with other CV disease (other than CHF)) is related to the
presence and severity of AL, after adjustment for other risk factors of AL
(e.g. smoking),
• To explore whether the presence of airflow limitation is related to the
severity of cardiac disease;

A cross-sectional, observational cohort study.

Burden and risks are small.
There is no investigational product in this study, hence no adverse events are
to be expected in this regard.
Drawing a bloodsample can be painful and leave a bruise.
Measuring spirometry may lead to difficulty in breathing.
The brochodilator that will be adminisered during spirometry (Ventolin) will
have a small chance of temporary adverse events.

Participants only have 1 study visit, and no behavioural rules are imposed on
them.

There is a possible benefit if and when subjects are diagnosed with untreated
COPD. Referral, diagnosis and treatment may lead to a better health status.