September 2010 | Vol 7 | N.º 9 | CNIC-24 [ PDF (864 KB)]

Progress of the Spanish National Cardiovascular Research Centre (CNIC)

Ginés Sanz, Juliana Redondo and Valentín Fuster*
Correspondence to:
V. Fuster, The Zena and Michael A Wiener Cardiovascular Institute, Mount Sinai Hospital, 1190 Fifth Avenue, New York, NY 10029, USA.
Email valentin.fuster@mssm.edu

LOOKING BACK
With the publication of this final article in the CNIC edition of Nature Reviews Cardiology, it seems appropriate to reflect on the progress made at the Centre over the two years of collaboration with Nature Publishing Group.

The CNIC (National Cardiovascular Research Centre) was created to be the nexus of an expanded Spanish contribution to cardiovascular research and to play a leading role in the application of research results in clinical practice, both nationally and internationally. This prioritisation of translational research is reflected in the Centre’s organisation in which three basic research departments (Vascular Biology and Inflammation, Cardiovascular Developmental Biology and Regenerative Cardiology) are complemented by two departments that have a more directly clinical orientation (Epidemiology, Atherothrombosis and Imaging). During the last two years, these departments have seen the recruitment of new staff (Figure 1), including at the most senior level, thereby doubling the number of researchers and laying the foundation for the Centre’s future growth and the development of new research lines.

In terms of core facilities, the CNIC has made an extraordinary effort to consolidate its infrastructure, with the creation of new core facilities in cellomics and microscopy imaging. A completely new platform for cardiovascular imaging is at an advanced stage, and in December 2009 the CNIC signed a contract with Philips for the installation of this imaging equipment. The equipment will be used to establish innovative non-invasive imaging protocols for animal research and diagnosis in human patients and will thus facilitate the interface between basic and translational research.

The CNIC Applied Departments are developing an ambitious program that includes several research projects ranging from the molecular basis of atherothrombosis in various animal models to large epidemiological studies. Potential applications of new biomarkers and advanced imaging techniques are being investigated in two large cohorts of young individuals in Aragón and Madrid. In accordance with the CNIC’s mission of improving health and preventing cardiovascular disease, the development of a polypill, through a joint venture with FERRER International, is reaching its clinical stage.

Many of these research lines, at both the basic and clinical levels, have been presented in this section over the past two years. More than 20 articles have covered key aspects of state-of-the-art cardiovascular research, including cell signalling, atherosclerosis pathogenesis, vascular inflammation, and genetics and epigenetics. In addition, we have presented 8 translational projects funded by the CNIC, which are being carried out in more than 20 national and international institutions.

Other key strategic objectives at the CNIC during 2008 and 2009 were the discovery and professional training of new researchers. We have devised tailored programmes for young investigators and more experienced research staff at each stage of their careers. Two new programmes—CardioJoven and Cardio-Image—launched in 2008 focus primarily on translational research, and the CNIC also cemented its relationship with the university sector through its participation in the Master’s–PhD programme (2008) and the Campus de Excelencia (2009), run by the Universidad Autónoma de Madrid and the Spanish Research Council (CSIC).

The last two years were also landmark years for science education, with the inaugural CNIC symposium in July 2008 and the consolidation of the CNIC international seminar cycle, which hosted prestigious cardiovascular research figures as invited speakers. In addition, we saw rapid growth in the CNIC’s scientific production, with a significant increase in the volume and quality of published articles, including several in leading journals in basic and clinical cardiovascular research.

Looking back, it is very satisfying to see the progress made across the full range of the CNIC’s activities. As this progress continues in the coming years, we are confident that the CNIC will rapidly establish itself as a reference centre for basic and applied cardiovascular research.

PROGRESS IN FIGURES

Publications
Table 1 summarises the cumulative and average impact factors (IF) in each area according to CNIC Department, calculated according to the ISI Journal Citation Reports (JCR) for 2008 and 2009 publications. Publications with no IF—for example, chapters in book series and articles published in journals not currently listed by the JCR—are not included in the table. Note that the publications from the Atherothrombosis and Imaging Department related to imaging research were conducted at institutions other than CNIC, since the full imaging equipment installation at the CNIC will not be completed until December 2010.

Technology Transfer
The CNIC pursues an active exploitation strategy, in line with the strong focus of the Centre on translational and applied research. Considering the high potential for exploitation of several of the results protected. It is expected that CNIC (Figure 2) will begin to acquire important income from royalties during the next two years or so. Moreover, it is foreseen that during the next three years the CNIC will spin off its first company.
Four new patent applications were presented during 2009, and four previously presented applications were extended into international patent applications. In total, there were 12 patents with CNIC participation at various stages of the application process.

Competitive funding
A total of 47 applications for competitive funding were approved last year, providing a total of about €6.8 million external funding to the CNIC for the upcoming three years. Of this, approximately €0.8 million came from international sources, and approximately €6 million came from national sources. Most of the funding obtained was for research projects (€4.8 million), and most of the rest (€1.8 million) was funding for contracts and fellowships, with about €60,000 for other types of awards. This was double the amount of competitive funding obtained in 2008. Funding obtained for research projects increased by about 160%, whereas funding for contracts and fellowships increased by about 40% as compared to 2008. Regarding the origin of funds, as compared with 2008, the amounts of funding obtained from international sources increased by a factor of three and the funds obtained from national funding sources doubled.

FUTURE PROSPECTS
In the coming years, the CNIC will further its efforts on development of basic research, translational medicine and training of excellence in the cardiovascular area in order to reach its general mission, “From research to health”.

Infrastructure
At the level of infrastructure, biomedical research is an extremely demanding area, in which significant investments are necessary to carry out leading cardiovascular research on a global scale. For that reason, the CNIC is currently investing in the creation of a new imaging facility, within the Atherothrombosis and Cardiovascular Imaging Department, devoted to the latest multimode cardiovascular imaging techniques for precise anatomic and functional cardiovascular studies. This new unit will provide echocardiography (including three-dimensional, stress, contrast and transeophageal imaging), vascular ultrasound, nuclear perfusion and metabolic imaging, cardiovascular computed tomography, and cardiovascular magnetic resonance. The facility will also be equipped with new imaging technology based on magnetic particle imaging (MPI), an innovative system for acquiring images that is distinct from the current magnetic resonance imaging techniques. An image analysis core laboratory will be developed during the next year, including new medical staff and technicians specifically trained in vascular three-dimensional echography, magnetic resonance and positron emission tomography techniques. The creation of this unit will provide an exceptional opportunity to develop cutting-edge cardiovascular research in small and large animal models as well as humans.

The laboratory for cardiovascular imaging, in both small and large animal models, will be located in the CNIC building and will be equipped to perform nanoPET/CT, 7 tesla microMR, optical imaging, intravascular optical coherence tomography (OCT), small-animal echocardiography, intravital microscopy, development of contrast agents, 3 Tesla MRI, PET/CT (multidetector CT) for large animals, and mobile Rx catheterisation.

The studies on advanced imaging in humans will be developed at Hospital Carlos III pursuant to a collaboration agreement signed between the CNIC and the Health Advisory Board of the Autonomous Community of Madrid (CAM), which creates a Human Cardiovascular Imaging Scientific Research Laboratory in the hospital. The imaging research lines with humans will be developed in cooperation with Phillips Healthcare (Andover, Minnesota, and Aachen, Germany), a division of Phillips Electronics North America Corporation.

The Human Cardiovascular Imaging Scientific Research Laboratory equipment located in Hospital Carlos III consists of 3 Tesla PET/MRI, multidetector CT, echocardiography equipment, and exercise and stress tests.

In the coming months, the CNIC will also make a significant effort toward the renewal of the Animal Facility to meet the needs of the new research groups that are being incorporated into the centre. The CNIC Animal Facility, which is a Comparative Medicine Unit, is one of the most modern facilities in Europe for housing animal models. The Unit currently has areas for housing mice (Mus musculus), rats (Rattus norvegicus), and zebrafish (Danio rerio). The housing capacity in the rodent area is currently 6,400 cages, to be increased this year to approximately 16,000 cages.

The new installation will be designed and equipped to house additional animal models, such as pigs (Sus scrofa) and rabbits (Oryctolagus cuniculus), as well as the necessary imaging equipment. This facility will also have an area in which to carry out cardiovascular surgery and recovery of the animals, a necropsy room for collecting samples, a radiology room for imaging follow-up of certain experimental procedures, a clinical pathology laboratory and a microbiology laboratory to support the animal models and the imaging laboratories.

Prevention and Translational Research
Since the origin of the CNIC project, we have been very conscious of the need for translational research and other research projects to promote the prevention of cardiovascular disease. So far, the prevention of cardiovascular disease has been hampered by the limited predictive power of screening procedures for detecting people at high risk. With the installation of the new imaging facility, the CNIC will be able to undertake ambitious multi-departmental clinical projects to apply these technologies to improve diagnostics and to test the efficacy of new treatments.

Within this type of translational-prevention research project, the CNIC is carrying out two large studies: the Aragon Workers Health Study (AWHS) and the Progression of Early Subclinical Atherosclerosis (PESA) study (CNIC2-Santander). In cooperation with the Instituto Aragonés de Ciencias de la Salud, the AWHS has already enrolled more than 5000 healthy workers. Clinical, laboratory and psychosocial data are being obtained from these workers, and a large biobank of blood, urine and DNA samples is being assembled. The volunteers will be followed-up for 6 years. In addition, the PESA project, a 9-year longitudinal study, has recently started. This study was designed to detect the prevalence and rate of progression of subclinical vascular lesions in a population of 4000 workers of both sexes, aged 40 to 54 years. The study examines the association of these clinical parameters with the presence of genetic, epigenetic, metabolomic, proteomic and environmental factors, including dietary habits, physical activity, biorhythms, psychosocial characteristics and exposure to environmental pollutants.

Participants are first assessed with basic techniques, including CT imaging to estimate coronary calcium, three-dimensional ultrasound of the carotid artery and two-dimensional ultrasound measurement of the abdominal aorta and the rate of ankle-brachial pressure. These techniques are used for early diagnosis of individuals with subclinical atherosclerosis; participants are then studied with advanced imaging techniques in order to determine the atherosclerotic burden and its progression and the presence and progression of inflammation in atherosclerotic plaques. The study will also provide important data on the prevalence of unrecognised myocardial infarction in this population and will assess the prevalence and progression of subclinical atherosclerosis in women during peri-menopause and its relationship to cardiovascular risk factors and hormonal changes.

The CNIC is also involved in an European project funded by the European Union, called the HYPERImge Project, whose main aim is to develop new protocols for the detection of unrecognised myocardial infarction and for the substitution of PET/CET technology with PET/MR, the latter of which is a hybrid system that will be used in the future for the previously mentioned large studies.

Regarding the prevention of cardiovascular disease, the CNIC has also joined in a private-public partnership with Ferrer International to develop a new polypill to improve accessibility and adherence to treatment for secondary cardiovascular prevention. After a 4-year process of galenic developing and preclinical testing, the CNIC-Ferrer polypill has undergone extensive clinical testing, including pharmacokinetics and pharmacodynamic studies. At the present time, we are in the final process of registering the polypill in several countries. In addition, the FOCUS project, designed and coordinated by the CNIC, will evaluate the polypill strategy in cardiovascular secondary prevention. This is an international multicentre project aimed at identifying factors that contribute to inadequate cardiovascular prevention in different social and economic settings as well as the role of a polypill in improving cardiovascular prevention. Eighty sites in Argentina, Brasil, Italy, Paraguay and Spain will provide 4000 patients. The project is funded by the 7th EC Programme.

Another field of interest for the CNIC in the coming years will be the development of cardiovascular projects to study population sectors that have traditionally been ignored. One of these sectors is the female population, specifically young women. Although heart disease causes many deaths in younger women, this phenomenon has been virtually ignored by the medical profession because it represents only a small fraction of the total incidence of atherosclerotic heart disease. However, young women who suffer an acute myocardial infarction (AMI) have a mortality risk markedly higher than that of young men, and the limited data on young women from minority groups in the ISA suggest that this population may have the highest risk of any young subgroup. The CNIC has recently started a new project, called IMJOVEN, to identify key demographic, clinical, metabolic, psychosocial, healthcare delivery, and biological determinants of prognosis in 300 women with a previous history of AMI. This project is being coordinated by the CNIC Translational Department, the Spanish Society of Cardiology and the Spanish RECAVA (Red Cardiovascular) and HERACLES networks.

Training and Education
One of the main objectives of the CNIC is the training and education of future investigators. To accomplish this aim, the Centre has developed a comprehensive training plan (the CNIC-JOVEN Training Plan; Table 2) that covers all levels from secondary education through the training of postdoctoral researchers and other young professionals.

In the coming months, the CNIC intends to reinforce its international visibility by promoting international postgraduate education through the establishment of collaboration agreements with prominent Spanish universities. The CNIC will collaborate with these universities to design a master’s course devoted to the cardiovascular area, in English and adapted to the new European Higher Education Area (EHEA).

CONCLUDING REMARKS
Looking back, the team of talented scientists, technicians and support personnel at the CNIC can be justifiably satisfied with the progress made over the past two years. We look forward to seeing the CNIC’s progress continue in the future, and we are confident that the Centre will rapidly establish itself as a reference centre for basic and applied cardiovascular research.

*Ginés Sanz. Centro Nacional de Investigaciones Cardiovasculares (CNIC), C/ Melchor Fernández Almagro, 3, 28029 Madrid, Spain (G. Sanz, J. Redondo, V. Fuster). The Zena and Michael A Wiener Cardiovascular Institute, Mount Sinai Hospital, 1190 Fifth Avenue, New York, NY 10029, USA (V. Fuster). The Marie-Josée and Henry R Kravis Center for Cardiovascular Health and the Richard Gorlin, MD/Heart Research Foundation, Mount Sinai School of Medicine, New York, USA (V. Fuster).