Progression of Early Subclinical Atherosclerosis

Atherosclerosis Clinical Trial

— PESA  

Official title:

Early Detection and Progression of Subclinical Atherosclerosis and Its Relationship to Coronary Risk Factors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01410318
• Other study ID #: PESA CNIC-SANTANDER
• Status: Active, not recruiting
• Start date: June 14, 2010
• Est. completion date: June 2030

Study information

• Verified date: April 2021
• Source: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4184
• Est. completion date: June 2030
• Est. primary completion date: June 2030
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 54 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis

Locations

Country	Name	City	State
Spain	Ciudad Financiera del Grupo Santander	Boadilla del Monte	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III	Grupo Santander

Country where clinical trial is conducted

Spain, 

References & Publications (23)

Coffeng JK, van der Ploeg HP, Castellano JM, Fernández-Alvira JM, Ibáñez B, García-Lunar I, van der Beek AJ, Fernández-Ortiz A, Mocoroa A, García-Leal L, Cárdenas E, Rojas C, Martínez-Castro MI, Santiago-Sacristán S, Fernández-Gallardo M, Mendiguren JM, B — View Citation

Cortes-Canteli M, Gispert JD, Salvadó G, Toribio-Fernandez R, Tristão-Pereira C, Falcon C, Oliva B, Mendiguren J, Fernandez-Friera L, Sanz J, Garcia-Ruiz JM, Fernandez-Ortiz A, Sanchez-Gonzalez J, Ibanez B, Molinuevo JL, Fuster V. Subclinical Atherosclero — View Citation

de la Chica JA, Gómez-Talavera S, García-Ruiz JM, García-Lunar I, Oliva B, Fernández-Alvira JM, López-Melgar B, Sánchez-González J, de la Pompa JL, Mendiguren JM, Martínez de Vega V, Fernández-Ortiz A, Sanz J, Fernández-Friera L, Ibáñez B, Fuster V. Assoc — View Citation

Domínguez F, Fuster V, Fernández-Alvira JM, Fernández-Friera L, López-Melgar B, Blanco-Rojo R, Fernández-Ortiz A, García-Pavía P, Sanz J, Mendiguren JM, Ibañez B, Bueno H, Lara-Pezzi E, Ordovás JM. Association of Sleep Duration and Quality With Subclinica — View Citation

Fernández-Alvira JM, Fuster V, Dorado B, Soberón N, Flores I, Gallardo M, Pocock S, Blasco MA, Andrés V. Short Telomere Load, Telomere Length, and Subclinical Atherosclerosis: The PESA Study. J Am Coll Cardiol. 2016 May 31;67(21):2467-76. doi: 10.1016/j.j — View Citation

Fernández-Alvira JM, Fuster V, Pocock S, Sanz J, Fernández-Friera L, Laclaustra M, Fernández-Jiménez R, Mendiguren J, Fernández-Ortiz A, Ibáñez B, Bueno H. Predicting Subclinical Atherosclerosis in Low-Risk Individuals: Ideal Cardiovascular Health Score a — View Citation

Fernández-Friera L, Fuster V, López-Melgar B, Oliva B, García-Ruiz JM, Mendiguren J, Bueno H, Pocock S, Ibáñez B, Fernández-Ortiz A, Sanz J. Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors. J Am — View Citation

Fernández-Friera L, Fuster V, López-Melgar B, Oliva B, Sánchez-González J, Macías A, Pérez-Asenjo B, Zamudio D, Alonso-Farto JC, España S, Mendiguren J, Bueno H, García-Ruiz JM, Ibañez B, Fernández-Ortiz A, Sanz J. Vascular Inflammation in Subclinical Ath — View Citation

Fernández-Friera L, Ibáñez B, Fuster V. Imaging subclinical atherosclerosis: is it ready for prime time? A review. J Cardiovasc Transl Res. 2014 Oct;7(7):623-34. doi: 10.1007/s12265-014-9582-4. Epub 2014 Aug 14. Review. — View Citation

Fernández-Friera L, Peñalvo JL, Fernández-Ortiz A, Ibañez B, López-Melgar B, Laclaustra M, Oliva B, Mocoroa A, Mendiguren J, Martínez de Vega V, García L, Molina J, Sánchez-González J, Guzmán G, Alonso-Farto JC, Guallar E, Civeira F, Sillesen H, Pocock S, — View Citation

Fernández-Ortiz A, Jiménez-Borreguero LJ, Peñalvo JL, Ordovás JM, Mocoroa A, Fernández-Friera L, Laclaustra M, García L, Molina J, Mendiguren JM, López-Melgar B, de Vega VM, Alonso-Farto JC, Guallar E, Sillesen H, Rudd JH, Fayad ZA, Ibañez B, Sanz G, Fuster V. The Progression and Early detection of Subclinical Atherosclerosis (PESA) study: rationale and design. Am Heart J. 2013 Dec;166(6):990-8. doi: 10.1016/j.ahj.2013.08.024. Epub 2013 Oct 10. — View Citation

Hurtado-Roca Y, Bueno H, Fernandez-Ortiz A, Ordovas JM, Ibañez B, Fuster V, Rodriguez-Artalejo F, Laclaustra M. Oxidized LDL Is Associated With Metabolic Syndrome Traits Independently of Central Obesity and Insulin Resistance. Diabetes. 2017 Feb;66(2):474 — View Citation

López-Melgar B, Fernández-Friera L, Oliva B, García-Ruiz JM, Peñalvo JL, Gómez-Talavera S, Sánchez-González J, Mendiguren JM, Ibáñez B, Fernández-Ortiz A, Sanz J, Fuster V. Subclinical Atherosclerosis Burden by 3D Ultrasound in Mid-Life: The PESA Study. J — View Citation

López-Melgar B, Fernández-Friera L, Oliva B, García-Ruiz JM, Sánchez-Cabo F, Bueno H, Mendiguren JM, Lara-Pezzi E, Andrés V, Ibáñez B, Fernández-Ortiz A, Sanz J, Fuster V. Short-Term Progression of Multiterritorial Subclinical Atherosclerosis. J Am Coll C — View Citation

López-Melgar B, Fernández-Friera L, Sánchez-González J, Vilchez JP, Cecconi A, Mateo J, Peñalvo JL, Oliva B, García-Ruiz JM, Kauffman S, Jiménez-Borreguero LJ, Ruiz-Cabello J, Fernández-Ortiz A, Ibáñez B, Fuster V. Accurate quantification of atherosclerot — View Citation

Martínez-López D, Roldan-Montero R, García-Marqués F, Nuñez E, Jorge I, Camafeita E, Minguez P, Rodriguez de Cordoba S, López-Melgar B, Lara-Pezzi E, Fernández-Ortiz A, Ibáñez B, Valdivielso JM, Fuster V, Michel JB, Blanco-Colio LM, Vázquez J, Martin-Vent — View Citation

Peñalvo JL, Fernández-Friera L, López-Melgar B, Uzhova I, Oliva B, Fernández-Alvira JM, Laclaustra M, Pocock S, Mocoroa A, Mendiguren JM, Sanz G, Guallar E, Bansilal S, Vedanthan R, Jiménez-Borreguero LJ, Ibañez B, Ordovás JM, Fernández-Ortiz A, Bueno H, — View Citation

Redondo-Bravo L, Fernández-Alvira JM, Górriz J, Mendiguren JM, Sanz J, Fernández-Friera L, García-Ruiz JM, Fernández-Ortiz A, Ibáñez B, Bueno H, Fuster V. Does Socioeconomic Status Influence the Risk of Subclinical Atherosclerosis?: A Mediation Model. J A — View Citation

Rossello X, Fuster V, Oliva B, Sanz J, Fernández Friera LA, López-Melgar B, Mendiguren JM, Lara-Pezzi E, Bueno H, Fernández-Ortiz A, Ibanez B, Ordovás JM. Association Between Body Size Phenotypes and Subclinical Atherosclerosis. J Clin Endocrinol Metab. 2 — View Citation

Sánchez-Cabo F, Rossello X, Fuster V, Benito F, Manzano JP, Silla JC, Fernández-Alvira JM, Oliva B, Fernández-Friera L, López-Melgar B, Mendiguren JM, Sanz J, Ordovás JM, Andrés V, Fernández-Ortiz A, Bueno H, Ibáñez B, García-Ruiz JM, Lara-Pezzi E. Machin — View Citation

Tsilingiri K, de la Fuente H, Relaño M, Sánchez-Díaz R, Rodríguez C, Crespo J, Sánchez-Cabo F, Dopazo A, Alonso-Lebrero JL, Vara A, Vázquez J, Casasnovas JM, Alfonso F, Ibáñez B, Fuster V, Martínez-González J, Martín P, Sánchez-Madrid F. Oxidized Low-Dens — View Citation

Uzhova I, Fuster V, Fernández-Ortiz A, Ordovás JM, Sanz J, Fernández-Friera L, López-Melgar B, Mendiguren JM, Ibáñez B, Bueno H, Peñalvo JL. The Importance of Breakfast in Atherosclerosis Disease: Insights From the PESA Study. J Am Coll Cardiol. 2017 Oct — View Citation

Yin X, Willinger CM, Keefe J, Liu J, Fernández-Ortiz A, Ibáñez B, Peñalvo J, Adourian A, Chen G, Corella D, Pamplona R, Portero-Otin M, Jove M, Courchesne P, van Duijn CM, Fuster V, Ordovás JM, Demirkan A, Larson MG, Levy D. Lipidomic profiling identifies — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.		20 years
Other	To assess the prevalence and progression of subclinical atherosclerosis in perimenopausal women and its relationship to cardiovascular risk factors and hormonal changes.		20 years
Primary	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.	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.	20 years
Secondary	To assess the association of both emerging and traditional cardiovascular risk factors with progression of subclinical atherosclerotic disease.	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.	20 years

External Links

•   Estudio Pesa