title: Elevated levels of D-dimers increase the risk of ischaemic and haemorrhagic stroke. Findings from the EPICOR Study.
abstract: Elevated D-dimer levels are reportedly associated with coronary artery disease. It was the study objective to investigate the association of baseline D-dimer levels with strokes that occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Using a nested case-cohort design, a centre--stratified sample of 832 subjects (66 % women, age 35-71) was selected as subcohort and compared with 289 strokes in a mean follow-up of nine years. D-dimers were measured by an automated latex-enhanced immunoassay (HemosIL-IL). The multivariable hazard ratios were estimated by a Cox regression model using Prentice method. Individuals with elevated D-dimer levels had significantly higher risk of incident stroke. It was evident from the second quartile (D-dimers > 100 ng/ml) and persisted almost unchanged for higher D-dimers (hazard ratio [HR] 2.10, 95 % confidence interval [CI]: 1.28-3.47; 2.42, 95 %CI: 1.44-4.09 and 2.10, 95 %CI: 1.27-3.48 for the second, third or fourth quartile compared with the lowest quartile, respectively). The association was independent of several confounders, including triglycerides and C-reactive protein. No differences were observed in men and women (P for interaction=0.46), in hypertensive or non-hypertensive subjects (P for interaction=0.88) or in subjects with low (< 1 mg/l) or elevated (≥ 1 mg/l) C-reactive protein (P for interaction=0.35). After stratification for stroke type, the hazard ratio for every standard deviation increase was statistically significant both for ischaemic (1.21; 95 %CI: 1.01 to 1.45) and haemorrhagic (1.24; 95 %CI: 1.00 to 1.65) strokes. In conclusion, our data provide clear evidence that elevated levels of D-dimers are potential risk factors not only for ischaemic but also for haemorrhagic strokes.
authors.forename: Augusto
authors.initials: A
authors.lastname: Di Castelnuovo
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.forename: Amalia
authors.initials: A
authors.lastname: de Curtis
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Giurdanella
authors.forename: Sabina
authors.initials: S
authors.lastname: Sieri
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Giovanni
authors.initials: G
authors.lastname: de Gaetano
authors.forename: Maria Benedetta
authors.initials: MB
authors.lastname: Donati
authors.affiliation: Licia Iacoviello, Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS-Istituto Neurologico Mediterraneo Neuromed, Via dell'Elettronica. 86077-Pozzilli (IS), Italy, Tel.: +39 0 3485108779, E-mail: licia.iacoviello@neuromed.it.
authors.forename: Licia
authors.initials: L
authors.lastname: Iacoviello
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D002545:Brain Ischemia / Q000097:blood / Q000453:epidemiology*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000097:blood / Q000453:epidemiology*; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000453:epidemiology; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D014280:Triglycerides; C036309:fibrin fragment D; D002097:C-Reactive Protein
keywords: Stroke / prevention; cerebrovascular disease; coagulation factors; epidemiological studies; risk factors