Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study.
OBJECTIVE
Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis.


METHODS
The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index.


RESULTS
After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease.


CONCLUSIONS
Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular pathway involved in the development of ICAD from its asymptomatic stage.
Department of Neurosciences, Hospital Universitari Germans Trias I Pujol, Universitat Auto`noma de Barcelona, Badalona, Barcelona, Spain.elenacancio@gmail.com
Elena
E
López-Cancio
Amparo
A
Galán
Laura
L
Dorado
Marta
M
Jiménez
María
M
Hernández
Mónica
M
Millán
Silvia
S
Reverté
Anna
A
Suñol
Jaume
J
Barallat
Anna
A
Massuet
Maria Teresa
MT
Alzamora
Antonio
A
Dávalos
Juan Francisco
JF
Arenillas
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000097:blood* / Q000453:epidemiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000150:complications*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D002537:Intracranial Arteriosclerosis / Q000097:blood* / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012044:Regression Analysis; D052243:Resistin / Q000097:blood*; D012307:Risk Factors; D013030:Spain
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D052243:Resistin; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine