D-dimer for prediction of long-term outcome in cryptogenic stroke patients with patent foramen ovale
Young Dae Kim
1
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
,
Dongbeom Song
1
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
,
Hyo Suk Nam
1
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
,
Kijeong Lee
1
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
,
Joonsang Yoo
1
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
,
Geu-Ru Hong
2
Division of Cardiology, Severance Cardiovascular Hosptial, Younsei University Health System, Seoul, Korea
,
Hye Sun Lee
3
Department of Biostatistics, Yonsei University College of Medicine, Seoul, Korea
,
Chung Mo Nam
4
Department of Preventive medicine, Yonsei University College of Medicine, Seoul, Korea
,
Ji Hoe Heo
1
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
› Author AffiliationsFinancial support: This work was supported by a grant of the Korea Healthcare Technology R&D Project through the Korean Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI10C2020).
Patent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648–17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.
3
Hagen PT,
Scholz DG,
Edwards WD.
Incidence and Size of Patent Foramen Ovale During the First 10 Decades of Life: An Autopsy Study of 965 Normal Hearts. Mayo Clinic Proc 1984; 59: 17-20.
4
Khairy P,
O’Donnell CP,
Landzberg MJ.
Transcatheter closure versus medical therapy of patent foramen ovale and presumed paradoxical thromboemboli: a systematic review. Ann Intern Med 2003; 139: 753-760.
6
Carroll JD,
Saver JL,
Thaler DE.
et al.
Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 2013; 368: 1092-1100.
8
Furlan AJ,
Reisman M,
Massaro J.
et al.
Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012; 366: 991-999.
9
Wahl A,
Juni P,
Mono ML.
et al.
Long-term propensity score-matched comparison of percutaneous closure of patent foramen ovale with medical treatment after paradoxical embolism. Circulation 2012; 125: 803-812.
11
Lethen H,
Flachskampf FA,
Schneider R.
et al.
Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack. Am J Cardiol 1997; 80: 1066-1069.
12
Guyatt GH,
Akl EA,
Crowther M.
et al.
Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: 7S-47S.
13
Lee BI,
Nam HS,
Heo JH.
et al.
Yonsei Stroke Registry. Analysis of 1,000 patients with acute cerebral infarctions. Cerebrovasc Dis 2001; 12: 145-151.
14
Cho HJ,
Choi HY,
Kim YD.
et al.
Transoesophageal echocardiography in patients with acute stroke with sinus rhythm and no cardiac disease history. J Neurol Neurosurg Psychiatry 2010; 81: 412-415.
15
Lippi G,
Bonfanti L,
Saccenti C.
et al.
Causes of elevated D-dimer in patients admitted to a large urban emergency department. Eur J Intern Med 2014; 25: 45-48.
18
Agarwal S,
Bajaj NS,
Kumbhani DJ.
et al.
Meta-analysis of transcatheter closure versus medical therapy for patent foramen ovale in prevention of recurrent neurological events after presumed paradoxical embolism. JACC Cardiovasc Interv 2012; 05: 777-789.
20
Lamy C,
Giannesini C,
Zuber M.
et al.
Clinical and Imaging Findings in Cryptogenic Stroke Patients With and Without Patent Foramen Ovale: The PFO-ASA Study. Stroke 2002; 33: 706-711.
21
Arauz A,
Murillo L,
Marquez JM.
et al.
Long-term risk of recurrent stroke in young cryptogenic stroke patients with and without patent foramen ovale. Int J Stroke 2012; 07: 631-634.
22
Rengifo-Moreno P,
Palacios IF,
Junpaparp P.
et al.
Patent foramen ovale transcatheter closure vs medical therapy on recurrent vascular events: a systematic review and meta-analysis of randomized controlled trials. Eur Heart J 2013; 34: 3342-3352.
23
Mas JL,
Arquizan C,
Lamy C.
et al.
Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001; 345: 1740-1746.
24
Berthet K,
Lavergne T,
Cohen A.
et al.
Significant association of atrial vulnerability with atrial septal abnormalities in young patients with ischemic stroke of unknown cause. Stroke 2000; 31: 398-403.
25
Sorensen HT,
Horvath-Puho E,
Pedersen L.
et al.
Venous thromboembolism and subsequent hospitalisation due to acute arterial cardiovascular events: a 20-year cohort study. Lancet 2007; 370: 1773-1779.
26
Konstantinides S,
Geibel A,
Kasper W.
et al.
Patent foramen ovale is an important predictor of adverse outcome in patients with major pulmonary embolism. Circulation 1998; 97: 1946-1951.
27
Giardini A,
Donti A,
Formigari R.
et al.
Comparison of results of percutaneous closure of patent foramen ovale for paradoxical embolism in patients with versus without thrombophilia. Am J Cardiol 2004; 94: 1012-1016.
28
Pezzini A,
Del Zotto E,
Magoni M.
et al.
Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke 2003; 34: 28-33.
32
Goldhaber SZ,
Hennekens CH,
Evans DA.
et al.
Factors associated with correct antemortem diagnosis of major pulmonary embolism. Am J Med 1982; 73: 822-826.
34
Anderson Jr. FA,
Wheeler HB,
Goldberg RJ.
et al.
A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991; 151: 933-938.
36
Cosmi B,
Legnani C,
Tosetto A.
et al.
Use of D-dimer testing to determine duration of anticoagulation, risk of cardiovascular events and occult cancer after a first episode of idiopathic venous thromboembolism: the extended follow-up of the PROLONG study. J Thromb Thrombolysis 2009; 28: 381-388.
37
Kleinegris MC,
ten Cate H,
ten Cate-Hoek AJ.
D-dimer as a marker for cardiovascular and arterial thrombotic events in patients with peripheral arterial disease. A systematic review. Thromb Haemost 2013; 110: 233-243.
38
Ridker PM,
Hennekens CH,
Cerskus A.
et al.
Plasma concentration of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men. Circulation 1994; 90: 2236-2240.
