Clinical trial NCT01410318: Progression of Early Subclinical Atherosclerosis
Official title: Early Detection and Progression of Subclinical Atherosclerosis and Its Relationship to Coronary Risk Factors
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Atherosclerosis
Keywords: Atherosclerosis
PESA
Subclinical
Cardiovascular diseases
Coronary disease
Heart diseases
Heart Failure
Myocardial Infarction
Stroke
Arteriosclerosis
Lead sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Sponsor class: OTHER
Collaborators: name: Grupo Santander
First posted: 2011-08-05
Enrollment: 4184
Sex: ALL
Minimum age (years): 40
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target population of the study consists of employees (N= 4,184) of the Banco de Santander Group in the Madrid region (65% males and 35% females, aged 40-54 years).

Brief summary: The overall objective of this study is to characterize the prevalence and progression rate of subclinical atherosclerotic lesions and to study their association to the imaging characteristics of atheroma plaques and to the presence of genetic, epigenetic, metabolomic, and environmental factors, including dietary habits, physical activity, biorhythms, psychosocial characteristics, and exposure to environmental pollutants

Detailed description: Atherosclerosis is the most common cardiovascular disease and accounts for the greatest number of deaths. Atherosclerotic disease starts at an early age and follows a subclinical course for decades, becoming apparent in the fifth or sixth decades of life in men and approximately 10 years later in women. Its main clinical signs include myocardial infarction, angina pectoris, sudden death, or stroke. Disease occurrence and progression are conditioned by the presence of the so-called risk factors: smoking, dyslipidemia, hypertension, and diabetes, among others. From these factors, a number of equations have been developed for predicting the risk of an individual to suffer the disease, in order to apply adequate prevention measures such as lifestyle changes or drug treatment. However, despite the proven efficacy of such interventions, cardiovascular prevention has many limitations due to three significant problems:

1. The ability to predict risk from current equations is very limited because other genetic or environmental factors that may influence the course of disease are still unknown.
2. The ability for early prediction of cardiovascular risk from current equations is even more limited in individuals under 55 years of age.
3. Atherosclerotic disease is diagnosed too late, usually when the condition is very advanced and lesions are already irreversible, or when it has caused clinical signs or events in organs or territories vascularized by the diseased arteries. Clinical procedures currently used for detection of myocardial ischemia are however poorly sensitive and specific in the asymptomatic general population.

Technological advances made in the past decade in both laboratory tests and medical imaging have opened up new expectations for detection and treatment of atherosclerotic disease. Current research is focused on two aspects:

1. To improve the ability to predict the disease by incorporating risk factors obtained from the laboratory such as C-reactive protein, homocysteine, fibrinogen, myeloperoxidase, or lipoprotein-associated phospholipase A2. At the same time, development of genetics and the new so-called "omics" techniques allows for exploring the genetic variability of individuals and its contribution to development of the disease and its complications. Such technologies include genomics, epigenetics, transcriptomics, proteomics, and metabolomics.
2. To detect the disease at an early stage using the advanced imaging techniques, which may be used with no or minimal risks in large population groups. Use of magnetic resonance imaging (MRI) with and without contrast, computed tomography (CT), and positron emission tomography (PET) allows not only for identifying subclinical lesions, but also for studying the mechanisms of disease and for monitoring its course.

Very few population studies making combined use of some of these procedures are available. The actual potential of this approach and the impact it may have on early diagnosis of subclinical atherosclerosis, its progression, and its relationship to risk factors have not been assessed to date.

Eligibility criteria: Inclusion Criteria:

* Employees of the Banco de Santander Group
* Age between 40-54 years.

Exclusion Criteria:

* Myocardial Infarction
* Angina pectoris
* Stroke, either transient or with sequelae
* Peripheral vascular disease
* Prior angioplasty or heart surgery
* Atrial fibrillation
* Other heart diseases

Subjects with the following conditions will also be excluded:

* Pregnancy
* Active treatment for any cancer
* Morbid obesity (BMI ≥40)
* Renal failure with creatinine clearance \<60 mL/min, as estimated by the Cockcroft and Gault formula
* Any disease that decreases life expectation to ≤6 years
* Pacemaker, implantable automatic defibrillator, or any implanted device that contraindicates MRI
* A chest CT in the previous year

Primary outcomes:
measure: To assess the prevalence and 6-year progression rate of subclinical atherosclerotic disease in a population aged 40-54 years using basic and advanced cardiovascular imaging techniques.
timeFrame: 20 years
Secondary outcomes:
measure: To assess the association of both emerging and traditional cardiovascular risk factors with progression of subclinical atherosclerotic disease.
timeFrame: 20 years
Other outcomes:
measure: To characterize the composition and evolution of atherosclerotic lesions using MRI and 18FDG PET to determine their relationship to risk factors and genetic, epigenetic, metabolomic, and environmental factors.
timeFrame: 20 years
measure: To assess the prevalence and progression of subclinical atherosclerosis in perimenopausal women and its relationship to cardiovascular risk factors and hormonal changes.
timeFrame: 20 years
Locations:
city: Boadilla del Monte
country: Spain
facility: Ciudad Financiera del Grupo Santander
state: Madrid
Study officials:
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Valentín Fuster, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Antonio I Fernández Ortiz, PhD
role: STUDY_DIRECTOR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Borja Ibañez, PhD
role: STUDY_CHAIR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Ginés Sanz, PhD
role: STUDY_CHAIR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Jose María Ordovás, PhD
role: STUDY_CHAIR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Luis Jesús Jiménez Borreguero, MD
role: STUDY_CHAIR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Jose Luis Peñalvo, PhD
role: STUDY_CHAIR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Martín Laclaustra, PhD
role: STUDY_CHAIR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Ana Dopazo, PhD
role: STUDY_CHAIR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Leticia Fernández Friera, PhD
role: STUDY_CHAIR
affiliation: Banco Santander
name: Agustin Mocoroa, MD
role: STUDY_CHAIR
affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III
name: Beatriz Lopez Melgar, MD
role: STUDY_CHAIR
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