Spanish scientists discover a new method for


image: Enrique Calvo, Jesús Vázquez, Álvaro Alfayate, Estefanía Núñez and José Luis Martín Ventura.
to see Continued

Credit: CNIC

A study published in the journal eBiomedicine identifies new biomarkers that predict the presence of subclinical atherosclerosis. The study was carried out by scientists from the Spanish Cardiovascular Research Network (CIBERCV) working at CNIC and the Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma de Madrid (IIS-FJD-UAM), in partnership with other institutions. “Atherosclerosis is one of the main causes of cardiovascular disease, which is one of the main health problems in the world and which places an enormous burden on health care systems. It is therefore a major goal to identify the disease in its earliest stages, so that interventions can halt its progression before it reaches an advanced stage,” said study coordinator Jesús Vázquez, principal investigator of CIBERCV and head of the cardiovascular proteomics laboratory at CNIC.

Early prevention is the best approach to combat the cardiovascular disease pandemic. Atherosclerosis has a long preclinical phase and is usually not diagnosed until advanced stages, often after a cardiovascular event. The use of non-invasive imaging techniques to detect atherosclerosis allows for more accurate risk stratification than with conventional methods, and current clinical guidelines recommend the use of imaging techniques to assess individual risk in combination with scales based on traditional risk factors, especially in individuals. low to moderate risk according to these scales.

Nevertheless, cardiovascular imaging techniques are not universally available, and the extent of atherosclerosis varies considerably between individuals in the same traditional risk category. There is therefore much interest in developing alternative rapid and non-invasive methods to estimate the burden of atherosclerosis.

Plasma biomarkers that track subclinical atherosclerosis, such as those described in the eBiomedicine circumvent the limitations of imaging approaches and improve the prediction of cardiovascular risk.


The new study is part of the PESA CNIC-SANTANDER (Progression and Early Detection of Subclinical Atherosclerosis) study, a large-scale project carried out in partnership between CNIC and Santander Bank. PESA analyzes the development of atherosclerotic plaques in an asymptomatic population of bank employees aged 40 to 54 at the start of the study. The PESA results clearly demonstrate that atherosclerosis is prevalent in the general population, firmly establishing the value of early detection.

In the new study, the research team analyzed a collection of 880 blood plasma samples obtained from participants in the PESA study. The samples were examined by proteomic techniques with the aim of identifying circulating biomarkers of atherosclerosis in its early asymptomatic phase.

From an initial panel of candidate biomarkers detected in this analysis, the team selected three proteins for validation from a collection of over 3000 plasma samples from the ILERVAS cohort. These samples were examined using rapid and widely available techniques through a partnership with Binding Site Ltd. and Quirónsalud Hospital Madrid.

Summarizing the results, José Luis Martín Ventura, CIBERCV scientist at IIS-FJD-UAM and one of the study coordinators, said that “the main contribution of this study is the development of a panel of biomarkers which can identify the presence of atherosclerosis in healthy patients. , asymptomatic people, including people with none of the classic cardiovascular risk factors.

The study’s first author and CNIC scientist, Estefanía Núñez, asserted that “biomarkers can be measured in blood samples using standard methods widely available in hospitals and clinical laboratories.”

“The CNIC group has extensive experience in the use of proteomic techniques for the bulk analysis of samples from patients with different cardiovascular conditions, and we have worked for several years with our colleagues at IIS-FJD on the identification and validation of cardiovascular biomarkers”, explained Jesús Vázquez.

Several studies have shown that detection of coronary calcifications or carotid plaques with non-invasive imaging techniques improves risk prediction and reclassification compared to conventional risk factors. However, these imaging techniques have their limitations.

“Imaging techniques allow the effective detection of atherosclerosis, but these methods are expensive and require highly trained personnel and specialized devices, which are not available in some regions and countries,” Vázquez said.

“Traditionally, the risk of developing cardiovascular disease has been assessed from a combination of factors such as smoking, body weight and high blood pressure. However, many people with none of these risk factors develop atherosclerotic plaques, which has sparked interest in the early detection of the disease. The new discovery offers an alternative method to detect the presence of atherosclerosis that is both rapid and readily available,” explained Martín Ventura.

This is the largest study to date to explore the association between plasma protein concentrations and subclinical atherosclerosis using high-performance, unbiased quantitative proteomics. The study demonstrates the potential of proteomics linked to mass spectrometry for the discovery of biomarkers of human diseases.

The PESA study is co-financed in equal parts by the Center National de Investigaciones Cardiovasculares (CNIC), Madrid, Spain and Banco Santander. The ILERVAS study was funded by the Provincial Council of Lleida.

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