Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03385122 |
| Other study ID # |
Corinthia |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
November 20, 2017 |
| Last updated |
December 26, 2017 |
| Start date |
October 20, 2015 |
| Est. completion date |
December 31, 2030 |
Study information
| Verified date |
December 2017 |
| Source |
University of Athens |
| Contact |
Evangelos Oikonomou |
| Phone |
00306947701299 |
| Email |
boikono[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Environmental factors constitute an important but underappreciated risk factor towards the
development and progression of cardiovascular disease (CVD). Environmental exposure in
variable pollutants is implicated in the derangement or propagation of adverse
pathophysiological processes linked with atherosclerosis, including genetic, hemodynamic,
metabolic, oxidative and inflammation parameters. However no data exists concerning
environmental pollution in rural or semi-rural areas. Therefore the purpose of the
"Corinthia" study is to examine the impact of environmental pollution in indices of
cardiovascular morbidity and mortality in a cross-sectional and longitudinal design.
Corinthia study began in October 2015 and is planned to recruit 2400 individuals from
different regions of Corinthia country with different environmental exposure to pollutants
and different patterns of soil-ground and/or air pollution until September 2018. Baseline
measurements will include lifestyle measurements, anthropometric characteristics and a
comprehensive cardiovascular examination. The follow-up is planned to extent, prospectively,
up to 10 years and this study is anticipated to provide valuable data on the distinct impact
of soil and air pollution in early markers of atherosclerosis and cardiovascular disease and
in the overall impact of environment pollution to cardiovascular morbidity and mortality.
Description:
Introduction
Despite major advances in cardiovascular (CV) medicine during the last decades, deaths and
morbidity from cardiovascular diseases (CVD) are increasing globally [1, 2]. It seems that
population aging and population growth balances out the decline in age-specific death rates
from CVD that could be attributed to more effective prevention and treatment strategies [2].
Interestingly, the progress in confronting CVD is evident around the world but notably
heterogeneous. Regions with the fastest growing population dynamics experienced relative
increase in CV deaths in line with global trends. In contrast, developed regions reported no
detectable change or little decrease in CV mortality as rapid aging of the population offsets
the declines in age-specific death rates [3]. Residual CV risk beyond traditional risk
factors should be reassessed and further explored in the quest of new underlying mechanisms
that could provide the substrate for innovative preventive interventions and therapeutic
goals.
Under this prism, environmental factors constitute an important but underappreciated risk
factor towards the development and progression of CVD [4]. Environmental exposure in variable
pollutants is implicated in the derangement or propagation of adverse pathophysiological
processes linked with atherosclerosis, including genetic, hemodynamic, metabolic, oxidative
and inflammation parameters [4]. Recent studies suggest that chronic environmental stress is
an important determinant of CVD risk, even below current regulatory standards for exposure
levels [4, 5].
One of the most important studies in the field of environmental cardiology, the Multi-Ethnic
Study of Atherosclerosis and Air Pollution (MESA Air) investigated the association between
long-term air pollution exposure and the progression of subclinical atherosclerosis and the
incidence of CVD at an urban dwelling population [6]. However no data exists concerning
environmental pollution in rural or semi-rural areas. Therefore the purpose of the
"Corinthia" study is to examine the impact of environmental pollution in indices of CV
morbidity and mortality in a cross-sectional and longitudinal design.
Rational of the study National-based data for Greece concerning environment pollution and CVD
morbidity and mortality are markedly scarce. Research activity has focused on soil and
groundwater anthropogenic contamination in river basin of heavy polluted industrialized areas
but without reporting associations with CVD [7]. Moreover, certain prospective or
retrospective studies have examined the association of long-term exposure to air pollution
with CVD morbidity in urban population [8, 9]. The region of Corinth has rural or semi-rural
areas with high exposure to soil and air contamination in distinct territories-patterns. The
investigators hypothesized that long term exposure to environmental pollutants mediates
detrimental epigenetic, oxidative, inflammatory and pro-atherogenic effects that could
accelerate the progress and the severity of CVD as well as the quality of life and the
overall morbidity and mortality. Therefore, the investigators sought to investigate in a
cross sectional and longitudinal design the impact of different type of environmental
pollution in indices of subclinical atherosclerosis, on rates of CV morbidity and mortality
and on CVD risk.
Hypothesis of the study I. The primary hypothesis of the study is that individual exposed to
different environmental pollutants have increased rate of all-cause mortality.
II. The secondary hypothesis of the study is that individuals exposed to different
environmental pollutants have increased rate of CV mortality and increased incidence of
non-fatal CVD (i.e. acute coronary syndromes, peripheral aortic disease, cerebrovascular
disease).
III. Additional hypothesis of the study is that:
1. Individuals exposed to different environmental pollutants present an adverse
cardiometabolic profile in terms of surrogate markers of early atherosclerosis and
oxidative stress
2. Environmental pollution affects adversely the quality of life in exposed subjects
3. Environmental pollution confers epigenetic alterations (telomere shortening, microRNAs
mobilization and circulation) in subjects exposed to different pollutants
Experimental details and design of the Corinthia study The present study began at October
2015 and is planned to recruit 1500 individuals from different regions of Corinth with
different environmental exposure to pollutants and different patterns of soil-ground and/or
air pollution until December 2016.
The investigators plan to recruit individuals living in three different areas according to
environmental pollution (Figure 1):
i. Subjects living in areas with no evidence of soil/ground or air pollution ii. Subjects
living in areas with air pollution iii. Subjects living in areas with soil/ground pollution
Residents of the selected regions who are not planning to move within the next 10 years will
be approached. An acceptance rate of participation of approximately 80% of those eligible
subjects is anticipated. Exclusion criteria for the study would be
1. Inability and unwillingness to obtain informed consent
2. Individuals less than 40 years of age The recruitment into Corinthia study will be
community-based, with an emphasis on balancing recruitment across the three areas,
census blocks, age categories (per decades) and gender. The sampling frame will
implement information from the latest national Census and will proceed along geographic
boundaries. As sampling unit we will use each household, with a goal of including no
more than 2 eligible participants from different households per census block. Initial
contact will be performed by telephone or door-to-door. Telephone recruitment will be
based on a list built from the specified geographic boundaries. Initial contact included
a screening questionnaire and household enumeration of all eligible persons. The
recruitment goal is 500 participants from each of the three areas of interest. During
this period the research team will communicate with the local authorities and with
health services in the areas of research in order to organize the volunteering selection
of the participants in each area. Responsibility of the research team is also the
organization of the places where field research will take place. Pilot measurements will
take place and accordingly the research team will estimate the validity of the tests,
and will calculate variability coefficients of the tests.
The first 24 months will be devoted to recruitment (October 2015- September 2018).
Quality Control and repeatability of measures The research fellow recruited for the study
will perform all vascular and anthropometric measurements. The research fellow will undergo a
2 month training and accreditation for these measurements. Echocardiographic measurements
will be performed by the same trained cardiac physiologist.
Study Measurements Baseline measurements for participants in the "Corinthia" Study will
include parameters affecting the everyday lifestyle such as smoking habits, physical activity
and diet. Anthropometric (height, weight, waist circumference) socio-economic and lifestyle
characteristics (marital status, educational level, economic and professional status), as
well as, family history and history of cardiovascular risk factors and diseases will be
recorded. The investigators also planning to identify the psychological state of individuals
(using a valid Depression Scale ZUNG) and participants mental status (MMSE-Mini Mental State
Examination). We will record the presence and the treatment in use, if any, of hypertension,
diabetes mellitus and hypercholesterolemia. Subjects will be submitted to a full cardiac
examination, including physical examination, electrocardiography, echocardiography
(Evaluation of left ventricle ejection fraction, of left ventricle dimensions, evaluation of
valvular function, of transmittal flow pattern, of right ventricle systolic pressure, of
aortic distensibility etc.), blood pressure measurements, arterial wall properties
measurement with non-invasive estimation of pulse wave velocity and estimation of
atherosclerotic burden with evaluation of carotid intima media thickens and of
atherosclerotic plaques in carotid arteries. Peripheral blood samples will be gathered for
DNA analysis, routine biochemical tests and measurement of inflammatory markers and markers
of oxidative stress. Subsequent examinations, which will include repetitions of certain
baseline measurements as well as new measures, will be scheduled at approximately adjacent
2-year intervals.
Selection of regions-Environmental measurements Data on soil/ground contamination with
pollutants (pesticides, fertilizers etc) and of air pollution from industrial gasses and
exposures will be provided from records and measurements of the Faculty of Geology and
Geoenvironment and the faculty of Environmental Physics of the National and Kapodistrian
University of Athens.
Follow-up The study investigators will prospectively perform the 5 and 10-year follow-up
about participants': (a) Vital status (death from any cause or due to CVD), (b) development
of coronary heart disease (CHD) (i.e., myocardial infarction, angina pectoris, other
identified forms of ischemia, heart failure of different types, and chronic arrhythmias) and
(c) development of cerebrovascular disease.
With an anticipated loss to follow-up of approximately~15% [10] the ten year follow up data
are expected to decipher the effect of long term exposure to pollution on overall and
cardiovascular mortality and morbidity as well as on interim endpoints of surrogate markers
of subclinical atherosclerosis. Respectively, with a type I error predefined to 0.05 and all
considered to be 2-tailed, a sample size of 1500 subjects would yield adequate power (>80%)
to detect a 1.5- fold change in Hazzard ratio per area-group change in the aforementioned
index variable towards the secondary endpoint (all-cause mortality) taking into account an
event rate of 6%, a follow up period of minimum 60 months and an anticipated loss to follow
up of less than 15%. Type I error was predefined at 0.05 and all tests were considered to be
2-tailed.
Conclusion The Corinthia study is an epidemiological study of Environmental importance with a
cross-sectional and prospective longitudinal design planning to provide data on the distinct
impact of soil and air pollution in indices of cardiovascular morbidity and mortality and in
the overall health status of a rural or semi-rural population of the Greek country.
