Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04353232 |
| Other study ID # |
AIRCARD |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 2, 2020 |
| Est. completion date |
September 1, 2026 |
Study information
| Verified date |
October 2023 |
| Source |
Odense University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The purpose of this study is to determine the impact of individually lifetime accumulated
exposure to air and noise pollution on the incidence and prevalence of cardiovascular
diseases (CVD) and mortality.
Air as well as noise pollution have harmful effects on human health. Experimental and
clinical studies have shown a strong impact between particulate matter (PM2.5) and
cardiovascular disease (CVD). Prolonged exposure to PM2.5 has been associated with the
development of atherosclerosis and adverse cardiovascular events. However, also short-term
exposure has been linked to acute coronary events. PM2.5 is, however, a combination of many
components of specific pollutants that have a size of two and a half microns or less in
width. However, there is a knowledge gap, as investigation into which specific components of
air pollutants that contribute the most to the development of CVD is lacking. There is a need
to adopt and encourage preventive measures but also put in place environmental policies that
are effective in promoting the reduction of exposure to pollutants. We want to aid in this
shift by showing which specific pollutants contribute the most to the development of CVD so
that we can better target these specific air pollutants for better prevention initiatives.
Description:
The purpose of this study is to determine the impact of individually accumulated exposure to
air and noise pollution, as well as exposure fluctuations (peaks), on the incidence and
prevalence of CVD. Noise pollution can be a significant confounder for the relation
investigated and we will therefore include accumulated data for noise over time together with
air pollution data.
The ICD or SKS disease classification code system will be used to identify clinical events
for patients from the two trials (described below). CVD mortality and total mortality as well
as clinical events from myocardial infarctions, percutaneous coronary interventions, coronary
artery bypass grafts, heart failure, apoplexies, and bypass will be examined. The analysis
will be stratified by socioeconomic status to determine if there is a social inequality in
the air and noise pollution impact.
We will examine the individual air pollution exposure as well as noise exposure to understand
each pollutants' contribution to the accumulated risk and demonstrate the impact of air and
noise pollution on CVD morbidity and mortality. We hypothesize that:
1. the amount of accumulated air as well as noise pollution is a highly independent
significant risk factor for clinical CVD, when accounting for all traditional
cardiovascular risk factors.
2. certain subdivisions of the air pollution exposure carry the highest contribution for
development of clinical CVD. This will provide novel and valuable information as this
has never been investigated with the precision we can deliver.
3. accumulated air and noise pollution from both individual home addresses and work
addresses together better predicts clinical CVD than models based solely on home
addresses. No study has evaluated this before.
Furthermore, the impact on the result of social inequality will be thoroughly examined.
This study is designed as a prospective registry-based observational study using modelled
air/noise pollution data. The population is predominantly males from two Danish clinical
trials (DANCAVAS and VIVA trials)
DANCAVAS I and II are two similar population-based randomized, multicentered, clinically
controlled studies designed to evaluate the benefits of 7-step multiple cardiovascular
screening and modern vascular prophylaxis in a population of men and a small subpopulation of
females, aged 60-74 years, living in the southern part of Denmark. For each participant, all
relevant CVD risk factors were measured or determined.
The screening included: 1) low-dose non-contrast CT scan to detect CAC and aortic/iliac
aneurysms, 2) ankle-brachial blood pressure index (ABI) to detect peripheral arterial disease
(PAD) and hypertension, 3) a telemetric assessment of the heart rhythm, and 4) a measurement
of the cholesterol and plasma glucose levels.
The Viborg Vascular (VIVA) screening trial (44) is a randomized, multicentered,
population-based clinically controlled study designed to evaluate the benefits of vascular
screening and modern vascular prophylaxis in men between 65-74 years of age living in the
region of Mid Denmark (Viborg County). For each participant, abdominal ultrasound scanning of
the infrarenal aorta were performed to detect abdominal aortic aneurism (AAA), and ABI were
measured to detect PAD and hypertension. In all, 18,749 men were screened.
A total of 33,723 participants in the age of 60-74 are included from the two cohorts. In both
trials, an AAA was defined as maximal infrarenal diameter of 30 mm or more, and PAD was
defined as an ABI < 0.90 or >=1.40 using the same validated hand held Doppler-based
methodology (46). We have accounted for traditional CVD confounders in all participants. This
is unique for our study. Previous studies on air pollution and CVD burden have not been able
to prospectively consider these confounding variables to the same extent.
In Denmark a validated and reliable air pollution model system is available. The system is
named DEHM/UBM/AirGIS and consists of three coupled models; the Danish Eulerian Hemispheric
Model (DEHM), the Urban Background Model (UBM) and the Operational Street Pollution Model
(OSPM) and a GIS system (AirGIS) that couples the modelled concentrations with the address
level of the population. The system calculates air pollution concentrations of 80 chemical
species as well as air pollution levels in cities, in streets and on address level even on
both side of the street. These pollution levels can be calculated back to 1979 giving
retrospectively data 40 years back. The model system is validated in relation to air
pollution measurements throughout Denmark back to 1990 with high correlation between model
estimated values and measured values. This multi-scale model system is unique, capable of
running on very high temporal (hourly) and spatial (address level) resolutions. The
development of the models and the calculation of air pollution and measurements is performed
at Aarhus University, Department of Environmental Science (ENVS). The model is robust; taking
all necessary factors into account that could contribute to the individual life-long air
pollution exposure and the model is one of the best in the world.
Noise is calculated using state-of-the-art algorithms implemented in a well-known software,
the SoundPLAN. The algorithms, reflecting advanced physics and mathematics-based knowledge,
consider the propagation of sound in the atmosphere as well as the sound originating from the
source, e.g., road transport, railway. Here, information from various national registers,
such as the national traffic database, including traffic counts, travel speeds, the building
register, the address register, and the Danish surface and elevation model, to name a few. In
addition, advanced weather classes reflecting all meteorological conditions in Denmark are
used in noise calculations. The model output is a noise estimate at the address location or
any location of interest in Denmark, which can be subsequently used to investigate the health
impacts of short-term and/or long-term noise exposure.
The entire study population is monitored until December 31. 2022, in the Danish national
registers.
Primarily, a multivariate Cox proportional hazards regression model will be used to examine
the associations between air- and noise pollution and all-cause mortality and CVD morbidity
and mortality when adjusting for inclusion date, sex, and other potential confounding factors
at baseline.
Descriptive statistics of the main study variables to examine noise pollution will be
presented in tables, frequencies with percentages of dichotomous/ordinal variables and
medians with quartiles for numeric variables. Outcomes will be analyzed both as dichotomized
variables, present CAC, severe CAC (CAC score above 400), AAA and PAD, and as the underlying
continuous variables, CAC score, aortic diameter, and lowest measured ankle-brachial blood
pressure index. Confounding CVD variables will be considered and adjusted for (e.g.,
lifestyle, medical history, QoL, weight, height, waist circumference, blood pressure, ABI,
calcium score for coronary arteries, aortic dimensions, HbA1c and lipid parameters).
To investigate hypothesis about noise we will, for each dichotomized outcome, estimate
adjusted odds ratios using multivariable logistic regression, with cumulated noise pollution
as exposure and the Framingham risk factors as confounders. The continuous variables will be
analyzed in multivariable linear regression models and the cardiovascular risk factors as
confounders.
To investigate the impact of work versus home address, we will compare regression models with
accumulated air pollution from both work and home addresses with models with air pollution
only from home addresses. ROC curves from both models will be compared to evaluate the
hypothesis.
