Etiologic diagnosis of ischemic stroke subtypes with plasma biomarkers.
OBJECTIVE
Because there is no biologic marker offering precise information about stroke etiology, many patients receive a diagnosis of undetermined stroke even after all available diagnostic tests are done, precluding correct treatment.


METHODS
To examine the diagnostic value of a panel of biochemical markers to differentiate stroke etiologies, consecutive acute stroke patients were prospectively evaluated. Brain computed tomography, ultrasonography, cardiac evaluations, and other tests were done to identify an etiologic diagnosis according to TOAST classification. Blood samples were drawn on Emergency Department arrival (<24 hours) to test selected biomarkers: C-reactive protein, D-dimer, soluble receptor for advanced glycation end products, matrix metalloproteinase-9, S-100b, brain natriuretic peptide (BNP), neurotrophin-3, caspase-3, chimerin, and secretagogin (assayed by ELISA).


RESULTS
Of 707 ischemic stroke patients included, 36.6% were cardioembolic, 21.4% atherothrombotic, 18.1% lacunar, and 23.9% of undetermined origin. High levels of BNP, soluble receptor for advanced glycation end products, and D-dimer (P<0.0001) were observed in patients with cardioembolic stroke. Independent predictors (odds ratios with CIs are given) of cardioembolic stroke were as follows: atrial fibrillation 15.3 (8.4-27.7, P<0.001); other embolic cardiopathies 14.7 (4.7-46, P<0.001); total anterior circulation infarction 4 (2.3-6.8, P<0.001); BNP >76 pg/mL 2.3 (1.4-3.7, P=0.001); and D-dimer >0.96 microg/mL 2.2 (1.4-3.7, P=0.001). Even among patients with transient symptoms (n=155), a high BNP level identified cardioembolic etiology (6.7, 2.4-18.9; P<0.001). A model combining clinical and biochemical data had a sensitivity of 66.5% and a specificity of 91.3% for predicting cardioembolism.


CONCLUSIONS
Using a combination of biomarkers may be a feasible strategy to improve the diagnosis of cardioembolic stroke in the acute phase, thus rapidly guiding other diagnostic tests and accelerating the start of optimal secondary prevention.
Montaner
Joan
J
Neurovascular Research Laboratory, Neurovascular Unit, Neurology Department, Vall d'Hebron Hospital, Barcelona, Spain. 31862jmv@comb.es
Perea-Gainza
Mila
M
Delgado
Pilar
P
Ribó
Marc
M
Chacón
Pilar
P
Rosell
Anna
A
Quintana
Manolo
M
Palacios
Mauricio E
ME
Molina
Carlos A
CA
Alvarez-Sabín
José
J
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology; D002097:C-Reactive Protein / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000097:blood; D053148:Caspase 3 / Q000097:blood; D020740:Chimerin Proteins / Q000097:blood; D003331:Coronary Vessels; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D020766:Intracranial Embolism / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D020933:Neurotrophin 3 / Q000097:blood; D011237:Predictive Value of Tests; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D012307:Risk Factors; D064046:Secretagogins; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D020740:Chimerin Proteins; D005338:Fibrin Fibrinogen Degradation Products; D020933:Neurotrophin 3; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C576556:SCGN protein, human; D064046:Secretagogins; C036309:fibrin fragment D; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9