Progression of Early Subclinical Atherosclerosis (PESA)

• 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. [ Time Frame: 6 years ]

  The basic imaging tests consist of vascular 2D and 3D ultrasound in carotid, aorta and ilio-femoral arteries and computed tomography (CT) for coronary artery calcification. The advanced imaging test consist of magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose-positron emission tomography (18FDG PET) in carotid and ilio-femoral territories.

  These imaging techniques enable early detection of subclinical atherosclerosis, characterization of the atherosclerotic burden, and monitoring of disease progression.

  
  

• To assess the association of both emerging and traditional cardiovascular risk factors with progression of subclinical atherosclerotic disease. [ Time Frame: 6 years ]
  The main emerging risk factors to be investigated will be genetic markers (using genome-wide association scans), epigenetic markers (by genome-wide analysis of DNA methylation), and metabolomic markers (metabolomic profile in serum). Conventional factors are defined as those included in the prediction equations (European SCORE equation for Mediterranean countries and REGICOR), dietary habits, physical activity, and psychosocial characteristics.
  
  

• 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. [ Time Frame: 6 years ]
  
• To assess the prevalence and progression of subclinical atherosclerosis in perimenopausal women and its relationship to cardiovascular risk factors and hormonal changes. [ Time Frame: 6 years ]
  

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.