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Thromb Haemost 2014; 112(05): 941-946
DOI: 10.1160/th14-04-0297
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Elevated levels of D-dimers increase the risk of ischaemic and haemorrhagic stroke

Findings from the EPICOR Study
Augusto Di Castelnuovo
1   Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS-Istituto Neurologico Mediterraneo Neuromed-Pozzilli, Italy
,
Claudia Agnoli
2   Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
,
Amalia de Curtis
1   Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS-Istituto Neurologico Mediterraneo Neuromed-Pozzilli, Italy
,
Maria Concetta Giurdanella
3   Cancer Registry ASP Ragusa, Italy
,
Sabina Sieri
2   Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
,
Amalia Mattiello
4   Dipartimento di Medicina Clinica e Chirurgia, University of Naples “Federico II”, Italy
,
Giuseppe Matullo
5   Department of Medical Sciences, University of Torino, Italy
6   Human Genetics Foundation, Torino, Italy
,
Salvatore Panico
4   Dipartimento di Medicina Clinica e Chirurgia, University of Naples “Federico II”, Italy
,
Carlotta Sacerdote
6   Human Genetics Foundation, Torino, Italy
7   Unit of Cancer Epidemiology, AO Città della Salute e della Scienza-University of Torino and Center for Cancer Prevention, Torino, Italy
,
Rosario Tumino
3   Cancer Registry ASP Ragusa, Italy
,
Paolo Vineis
7   Unit of Cancer Epidemiology, AO Città della Salute e della Scienza-University of Torino and Center for Cancer Prevention, Torino, Italy
8   Department of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, London, UK
,
Giovanni de Gaetano
1   Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS-Istituto Neurologico Mediterraneo Neuromed-Pozzilli, Italy
,
Maria Benedetta Donati
1   Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS-Istituto Neurologico Mediterraneo Neuromed-Pozzilli, Italy
,
Licia Iacoviello
1   Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS-Istituto Neurologico Mediterraneo Neuromed-Pozzilli, Italy
› Author Affiliations Financial support: This work was supported by Compagnia di San Paolo for the EPIC, EPICOR and EPICOR2 projects and partially by Italian Ministry of Education, University and Research (MIUR) ex60% (2012).
Further Information

Publication History

Received: 03 April 2014

Accepted after minor revision: 30 May 2014

Publication Date:
20 November 2017 (online)

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Summary

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.

Keywords

Stroke / prevention - cerebrovascular disease - coagulation factors - epidemiological studies - risk factors
 

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