Since cerebrovascular diseases and dementia are responsible for a huge economic burden, the early detection of patients at high risk for them, and the implementation of preventive measures as soon as possible, might be of great interest and profit.
The general aims of our research are:
- To promote awareness and knowledge of stroke in the general population and enhance collaboration between primary care services and hospital departments.
- To accurately predict those patients at high-risk for first stroke by the determination of novel risk factors or markers (neuroimaging or biological markers), and therefore to improve stroke risk stratification.
- To incorporate a standardized assessment of cognition in stroke research.
- To determine why interventions may be or not widely applied by means of cost-effectiveness and cost-utility studies.
To study quantitative predictors of preventive treatment compliance.
1) Silent cerebrovascular disease detection in a hypertensive cohort and its relationship with the risk of stroke and dementia (“ISSYS project: Investigating Silent Strokes in Hypertensives: a magnetic Resonance Imaging Study”)”. Silent cerebral infarctions (SCI) and other brain lesions (such as brain microbleeds, white matter changes or dilated perivascular spaces) detected with neuroimaging techniques, particularly with brain MRI, are common in aged healthy population and even more frequent in selected patients at risk, such as hypertensive patients. They might constitute a subclinical stage of cerebrovascular disease and might precede both overt stroke and cognitive decline; therefore we think that their identification in hypertensive patients would be an adequate and cost-effective tool, to prevent further strokes and dementia. Our current project includes 978 hypertensive patients, without known history of cerebrovascular disease or dementia, who have been prospectively collected from November 2010 to May 2012, among 14 Primary Care Teams in Barcelona. On baseline, a brain MRI has been performed in all of them to assess the presence of silent cerebrovascular lesions, together with the determination of several clinical and biological factors (plasma and genetic biomarkers). Assessment of cognition has been also performed in the entire cohort by means of a screening tool (Mattis Dementia Rating Scale-2) and a complete neuropsychological evaluation when necessary to determine the presence of MCI (Mild Cognitive Impairment). Participants are followed-up every year by phone to assess the presence of incident strokes, vascular events and/or cognitive impairment and will be re-evaluated three years after baseline.
Representative examples of subclinical/silent cerebrovascular lesions. From left to right: Brain infarct affecting caudate nuclei (FLAIR MRI), brain microbleed in left thalamus (GRE MRI), dilated perivascular spaces involving basal ganglia (T2 MRI) and extensive white matter changes (FLAIR MRI).
2) Hemodynamic changes associated with the risk of silent brain infarcts in hypertensive spanish population. Some circadian BP patterns (mainly non-dipping patterns) and several measures indicative of arterial stiffness (such as increased pulse pressure) have been linked with the presence of silent cerebrovascular lesions in other populations, mostly in Asian studies with non-treated hypertensives. Our aim in this project will be to assess the relationship of several BP measures obtained by 24 hours ambulatory blood pressure measurement with the type, severity and location of vascular lesions. This study follows a case-control design and participants have been chosen as a nested cohort within the ISSYS project.
3) Comparative study on the treatments, compliance and blood pressure control in a hypertensive cohort on Primary Care. This project is an observational study on the use of preventive treatments in hypertensives, including blood pressure lowering treatments, antiplatelets and lipid lowering drugs and how their use is on agreement with clinical guidelines. Also, the effect on BP control and adherence to treatments will be determined and related to the treatments (i.e. monotherapy vs combined pills).
- Pilar Delgado Martínez, MD, PhD
- Iolanda Riba Llena, MD, PhD student
- Andrea Vilar Bergua, MSc, PhD student
- Cristina Nafría Pérez, Clinical Neuropsychologist
- Antonio López Rueda, Neuroradiologist
- Juan Manuel Gómez Andrés, MSc
- Josefina Filomena Paci, MD, Primary Care Physician
- Anna Cartanyà, MD, Primary Care Physician in training
Collaborators from Primary Care and Hospital Departments:
- Primary Care (Institut Català de la Salut and IDIAP Jordi Gol): Xavier Mundet Tudurí, Francesc Orfila Pernàs, Carme Joana Jarca, Mar Domingo, Ernest Vinyole.
- Neurology department. Hospital Vall d’Hebron: Olga Maisterra, David Rodríguez Luna, Alan Flores Flores, Francesc Pujadas.
- Hypertension Unit and Nephrology Department: Jose Luis Tovar Méndez.
- Center for imaging diagnosis Dr Manchón: Jose L Fernández López-Lara, Merche García.
- IDIAP Jordi Gol and Sant Roc Primary Care Center in the project “Retino-ICS: Usefulness of the retinography by non-midriatic chamber as a diagnostic tool for the detection of silent cerebral ischemia”.
- Neurology and Pneumology Departments. Hospital Vall d’Hebron (Drs Sampol, Romero, Santamarina, Álvarez) on the project “Sleep Apnea Syndrome and silent brain infarction in hypertensives”.
Riba-Llena I, Nafría C, Giralt D, Fernández-Cortiñas I, Jarca CI, Mundet X,
Tovar JL, Orfila F, Castañé X, Álvarez-Sabín J, Maisterra O, Montaner J, Delgado
P. Dementia Rating Scale-2 normative data for middle-and older-aged Castilian
speaking Spaniards. Clin Neuropsychol. 2016 May 11:1-14. [Epub ahead of print]
PubMed PMID: 27168059.
Vilar-Bergua A, Riba-Llena I, Ramos N, Mundet X, Espinel E, López-Rueda A,
Ostos E, Seron D, Montaner J, Delgado P. Microalbuminuria and the Combination of
MRI Markers of Cerebral Small Vessel Disease. Cerebrovasc Dis.
2016;42(1-2):66-72. doi: 10.1159/000445168. Epub 2016 Apr 1. PubMed PMID:
Riba-Llena I, Nafría C, Mundet X, López-Rueda A, Fernández-Cortiñas I, Jarca
CI, Jiménez-Balado J, Domingo M, Tovar JL, Orfila F, Pujadas F, Álvarez-Sabín J,
Maisterra O, Montaner J, Delgado P. Assessment of enlarged perivascular spaces
and their relation to target organ damage and mild cognitive impairment in
patients with hypertension. Eur J Neurol. 2016 Jun;23(6):1044-50. doi:
10.1111/ene.12979. Epub 2016 Mar 10. PubMed PMID: 26968973.
Filomena J, Riba-Llena I, Vinyoles E, Tovar JL, Mundet X, Castañé X, Vilar A,
López-Rueda A, Jiménez-Baladó J, Cartanyà A, Montaner J, Delgado P; ISSYS
Investigators. Short-Term Blood Pressure Variability Relates to the Presence of
Subclinical Brain Small Vessel Disease in Primary Hypertension. Hypertension.
2015 Sep;66(3):634-40; discussion 445. doi: 10.1161/HYPERTENSIONAHA.115.05440.
Epub 2015 Jun 22. PubMed PMID: 26101344.
Riba-Llena I, Nafría C, Filomena J, Tovar JL, Vinyoles E, Mundet X, Jarca CI,
Vilar-Bergua A, Montaner J, Delgado P. High daytime and nighttime ambulatory
pulse pressure predict poor cognitive function and mild cognitive impairment in
hypertensive individuals. J Cereb Blood Flow Metab. 2016 Jan;36(1):253-63. PubMed
PMID: 25966945; PubMed Central PMCID: PMC4759685.
Vilar-Bergua A, Riba-Llena I, Nafría C, Bustamante A, Llombart V, Delgado P,
Montaner J. Blood and CSF biomarkers in brain subcortical ischemic vascular
disease: Involved pathways and clinical applicability. J Cereb Blood Flow Metab.
2016 Jan;36(1):55-71. Review. PubMed PMID: 25899297; PubMed Central PMCID:
Riba-Llena I, Penalba A, Pelegrí D, Vilar A, Jarca CI, Filomena J, Montaner J,
Delgado P; ISSYS Study Group. Role of lipoprotein-associated phospholipase A2
activity for the prediction of silent brain infarcts in women. Atherosclerosis.
2014 Dec;237(2):811-5. doi: 10.1016/j.atherosclerosis.2014.11.003. Epub 2014 Nov
10. PubMed PMID: 25463126.