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Antikoagülan Tedavi Alan Non-valvüler Atriyal Fibrilasyon Hastalarında Nöron Spesifik Enolaz ile Tespit Edilen Sessiz Serebral İnfarkt

Yıl 2018, Cilt: 71 Sayı: 2, 130 - 134, 10.10.2018

Öz

Amaç: Atriyal fibrilasyonu (AF) olan hastalarda serebral infarkt, klinik olarak sessiz infarkttan katastrofik sonuçları olan duruma kadar, geniş bir yelpazede görülebilir. Klinik olarak belirgin inme veya geçici iskemik atak (GİA) yokluğunda, nöron spesifik enolazın (NSE) yükselmesi, sessiz serebral infarkt (SSİ) olarak adlandırılır ve nörolojik defisitler, kognitif fonksiyonlarda bozulma ve hatta mortalite artışı ile ilişkili olabilir. Oral antikoagülan almakta olan non-valvüler AF’li hastalarda SSİ prevalansını değerlendirmeyi amaçladık.

Gereç ve Yöntem: Kan örnekleri, polikliniğe başvuran non-valvüler AF’li ardışık 100 hastadan toplandı. NSE seviyesinde 12 ng/mL’den fazla artış olması SSİ olarak kabul edildi.

Bulgular: Hastaların yaş ortalaması 70 idi ve çoğunlukla kadındı. Kırk dokuz hasta (%49) warfarin kullanıyordu. Ortalama uluslararası normalleştirilmiş oran düzeyi 2,3±1,1 idi. Elli bir hasta (%51) direkt oral antikoagülan (DOAC) tedavisi [dabigatran (n=7), rivaroksaban (n=13) ve apiksaban (n=31)] alıyordu. Çalışma popülasyonunun ortalama CHA2DS2-VASc skoru 3,8±1,5 idi. Kırk üç hastada (%43) NSE yükselmesi saptandı. Bu hastalar daha yaşlıydılar, kronik kalp yetmezliği ve geçirilmiş inme/GİA öyküsü daha yüksekti. Artmış sol atriyum çapı, azalmış glomerüler filtrasyon hızı ve yüksek CHA2DS2-VASc skoru, SSİ ile ilişkili diğer faktörlerdi. DOAC alan hastalar ve oral antikoagülan tedaviye ilave aspirin alan hastalarda SSİ görülme prevalansı daha düşüktü. Çok değişkenli analiz, yüksek CHA2DS2-VASc skorunu [odds oranı (OR): 2,6; %95 güven aralığı (GA): 1,3-5,1; p=0,007] ve warfarinin kullanımını (OR: 3,8; %95 GA: 1,2-11,9; p=0,02) SSİ’nin bağımsız öngördürücüleri olarak göstermiştir.

Sonuç: Sessiz beyin hasarı, oral antikoagülan tedaviye rağmen nonvalvüler atriyal fibrilasyonu olan hastalarda oldukça yaygındır

Etik Beyan

Etik Kurul Onayı: Çalışmamız için Ankara Üniversitesi Etik Kurulu’ndan onay alınmıştır (onay numarası: 15-756-16). Hasta Onayı: Tüm hastalar yazılı onam formunu onaylamıştır.

Destekleyen Kurum

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Proje Numarası

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Teşekkür

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Kaynakça

  • 1. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-2375.
  • 2. Feinberg WM, Seeger JF, Carmody RF, et al. Epidemiologic features of asymptomatic cerebral infarction in patients with nonvalvular atrial fibrillation. Arch Intern Med 1990;150:2340-2344.
  • 3. Guidotti M, Tadeo G, Zanasi S, et al. Silent cerebral ischemia in patients with chronic atrial fibrillation--a case-control study. Ir J Med Sci 1990;159:96- 97.
  • 4. Petersen P, Pedersen F, Johnsen A, et al. Cerebral computed tomography innparoxysmal atrial fibrillation. Acta Neurol Scand 1989;79:482-486.
  • 5. Marfella R, Sasso FC, Siniscalchi M, et al. Brief episodes of silent atrial fibrillation predict clinical vascular brain disease in type 2 diabetic patients. J Am Coll Cardiol 2013;62:525-530.
  • 6. Kim MH, Moon JS, Park SY, et al. Different risk factor profiles between silent brain infarction and symptomatic lacunar infarction. Eur Neurol 2011;65:250-256.
  • 7. Bokura H, Kobayashi S, Yamaguchi S, et al. Silent brain infarction and subcortical white matter lesions increase the risk of stroke and mortality: a prospective cohort study. J Stroke Cerebrovasc Dis 2006;15:57-63.
  • 8. Kobayashi S, Okada K, Koide H, et al. Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke 1997;28:1932-1939.
  • 9. Liebetrau M, Steen B, Hamann GF, et al. Silent and symptomatic infarcts on cranial computerized tomography in relation to dementia and mortality: a population-based study in 85-year-old subjects. Stroke 2004;35:1816- 1820.
  • 10. Shmkawa A, Ueda K, Kiyohara Y, et al. Silent cerebral infarction in a community-based autopsy series in Japan. The Hisayama Study. Stroke 1995;26:380-385.
  • 11. Yamanouchi H, Nagura H, Mizutani T, et al. Embolic brain infarction in nonrheumatic atrial fibrillation: a clinicopathologic study in the elderly. Neurology 1997;48:1593-1597.
  • 12. Price TR, Manolio TA, Kronnal RA, et al. Silent brain infarction on magnetic resonance imaging and neurological abnormalities in community-dwelling older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Stroke 1997;28:1158-1164.
  • 13. Avdibegovic E, Becirovic E, Salimbasic Z, et al. Cerebral cortical atrophy and silent brain infarcts in psychiatric patients. Psychiatr Danub 2007;19:49-55.
  • 14. Wright CB, Festa JR, Paik MC, et al. White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility. Stroke 2008;39:800-805.
  • 15. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215-1222.
  • 16. Yamashita H, Fujikawa T, Yanai I, et al. Cognitive dysfunction in recovered depressive patients with silent cerebral infarction. Neuropsychobiology 2002;45:12-18.
  • 17. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-2962.
  • 18. Kelley RE, Minagar A. Cardioembolic stroke: an update. South Med J 2003;96:343-349.
  • 19. Friberg L, Hammar N, Rosenqvist M. Stroke in paroxysmal atrial fibrillation: report from the Stockholm Cohort of Atrial Fibrillation. Eur Heart Jn2010;31:967-975.
  • 20. Shinkawa A, Ueda K, Kiyohara Y, et al. Silent cerebral infarction in a community-based autopsy series in Japan: the Hisayama Study. Stroke 1995;26:380-385.
  • 21. Das RR, Seshadri S, Beiser AS, et al. Prevalence and correlates of silent cerebral infarcts in the Framingham Offspring Study. Stroke 2008;39:2929- 2935.
  • 22. Shea S, Di Tullio M. Atrial fibrillation, silent cerebral ischemia, and cognitive function. J Am Coll Cardiol 2013;62:1998-1999.
  • 23. Cao L, Pokorney SD, Hayden K, et al. Cognitive Function: Is There More to Anticoagulation in Atrial Fibrillation Than Stroke? J Am Heart Assoc 2015;4:001573.
  • 24. Sato H, Koretsune Y, Fukunami M, et al. Aspirin attenuates the incidence of silent brain lesions in patients with nonvalvular atrial fibrillation. Circ J 2004;68:410-416.
  • 25. Shin SY, Na JO, Lim HE, et al. Improved endothelial function in patients with atrial fibrillation through maintenance of sinus rhythm by successful catheter ablation. J Cardiovasc Electrophysiol 2011;22:376-382.
  • 26. Wieberdink RG, van Schie MC, Koudstaal PJ, et al. High von Willebrand factor levels increase the risk of stroke: The Rotterdam study. Stroke 2010;41:2151-2156.
  • 27. Lim HS, Willoughby SR, Schultz C, et al. Effect of atrial fibrillation on atrial thrombogenesis in humans: Impact of rate and rhythm. J Am Coll Cardiol 2013;61:852-860.
  • 28. Lim HS, Willoughby SR, Schultz C, et al. Successful catheter ablation decreases platelet activation and improves endothelial function in patients with atrial fibrillation. Heart Rhythm 2014;11:1912-1918.
  • 29. Kamiyama N, Koyama Y, Saito Y, et al. Pulse dispersion due to atrial fibrillation causes arterial thrombosis in a rabbit experimental model. Jpn Circ J 2000;64:516-519.
  • 30. Minamino T, Kitakaze M, Sanada S, et al. Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation: Role of nitric oxide. Circulation 1998;98:1721-1727.
  • 31. Kumagai K, Fukunami M, Kitabatake A, et al. Increased intracardiovasucular clotting in patients with chronic atrial fibrillation. J Am Coll Cardiol 1990;16:377-380.
  • 32. Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010;137:263-272.
  • 33. Singer DE, Chang Y, Borowsky LH, et al. A New Risk Scheme to Predict Ischemic Stroke and Other Thromboembolism in Atrial Fibrillation: The ATRIA Study Stroke Risk Score. J Am Heart Assoc 2013;2:e000250.

Silent Cerebral İnfarction in Anticoagulated Patients with Non-valvular Atrial Fibrillation as Detected with Neuron Specific Enolase

Yıl 2018, Cilt: 71 Sayı: 2, 130 - 134, 10.10.2018

Öz

Objectives: Cerebral infarction in patients with atrial fibrillation (AF) may vary from being clinically silent to catastrophic. Elevation of neuronspecific enolase (NSE) in the absence of any clinically apparent stroke or transient ischemic attack (TIA), so-called silent cerebral infarction (SCI), may be associated with neurologic deficits, cognitive decline and even increased mortality. We aim to evaluate the prevalence of SCI in patients with non-valvular AF who are taking oral anticoagulants.

Materials and Methods: Blood samples were collected from 100 consecutive patients with non-valvular AF admitted to outpatient clinic. NSE levels of greater than 12 ng/mL was considered as SCI.

Results: Patients were mainly female with a mean age of 70 years. Fourty-nine of them (49%) were taking warfarin. Mean international normalized rate level was 2.3±1.1. Fifty-one patients (51%) were on direct oral anticoagulant (DOAC) treatment [dabigatran (n=7), rivaroxaban (n=13) and apixaban (n=31)]. Mean CHA2DS2-VASc score of the study population was 3.8±1.5. Fourty-three patients (43%) were found to have NSE elevation. They were older and more likely to have history of chronic heart failure and previous stroke/TIA. Increased left atrial diameter, reduced glomeruler filtration rate, and higher CHA2DS2-VASc score were other factors associated with SCI. Patients taking DOACs and patients who were taking aspirin on top of oral anticoagulant treatment were less likely to have SCI. Multivariate analysis demonstrated higher CHA2DS2-VASc score [odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3-5.1; p=0.007] and use of warfarin (OR: 3.8; 95% CI: 1.2-11.9; p=0.02) as independent predictors of SCI.

Conclusion: Silent brain injury is highly prevalent among patients with non-valvular AF despite the use of oral anticoagulant therapy.

Etik Beyan

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Destekleyen Kurum

-

Proje Numarası

-

Teşekkür

-

Kaynakça

  • 1. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-2375.
  • 2. Feinberg WM, Seeger JF, Carmody RF, et al. Epidemiologic features of asymptomatic cerebral infarction in patients with nonvalvular atrial fibrillation. Arch Intern Med 1990;150:2340-2344.
  • 3. Guidotti M, Tadeo G, Zanasi S, et al. Silent cerebral ischemia in patients with chronic atrial fibrillation--a case-control study. Ir J Med Sci 1990;159:96- 97.
  • 4. Petersen P, Pedersen F, Johnsen A, et al. Cerebral computed tomography innparoxysmal atrial fibrillation. Acta Neurol Scand 1989;79:482-486.
  • 5. Marfella R, Sasso FC, Siniscalchi M, et al. Brief episodes of silent atrial fibrillation predict clinical vascular brain disease in type 2 diabetic patients. J Am Coll Cardiol 2013;62:525-530.
  • 6. Kim MH, Moon JS, Park SY, et al. Different risk factor profiles between silent brain infarction and symptomatic lacunar infarction. Eur Neurol 2011;65:250-256.
  • 7. Bokura H, Kobayashi S, Yamaguchi S, et al. Silent brain infarction and subcortical white matter lesions increase the risk of stroke and mortality: a prospective cohort study. J Stroke Cerebrovasc Dis 2006;15:57-63.
  • 8. Kobayashi S, Okada K, Koide H, et al. Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke 1997;28:1932-1939.
  • 9. Liebetrau M, Steen B, Hamann GF, et al. Silent and symptomatic infarcts on cranial computerized tomography in relation to dementia and mortality: a population-based study in 85-year-old subjects. Stroke 2004;35:1816- 1820.
  • 10. Shmkawa A, Ueda K, Kiyohara Y, et al. Silent cerebral infarction in a community-based autopsy series in Japan. The Hisayama Study. Stroke 1995;26:380-385.
  • 11. Yamanouchi H, Nagura H, Mizutani T, et al. Embolic brain infarction in nonrheumatic atrial fibrillation: a clinicopathologic study in the elderly. Neurology 1997;48:1593-1597.
  • 12. Price TR, Manolio TA, Kronnal RA, et al. Silent brain infarction on magnetic resonance imaging and neurological abnormalities in community-dwelling older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Stroke 1997;28:1158-1164.
  • 13. Avdibegovic E, Becirovic E, Salimbasic Z, et al. Cerebral cortical atrophy and silent brain infarcts in psychiatric patients. Psychiatr Danub 2007;19:49-55.
  • 14. Wright CB, Festa JR, Paik MC, et al. White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility. Stroke 2008;39:800-805.
  • 15. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215-1222.
  • 16. Yamashita H, Fujikawa T, Yanai I, et al. Cognitive dysfunction in recovered depressive patients with silent cerebral infarction. Neuropsychobiology 2002;45:12-18.
  • 17. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-2962.
  • 18. Kelley RE, Minagar A. Cardioembolic stroke: an update. South Med J 2003;96:343-349.
  • 19. Friberg L, Hammar N, Rosenqvist M. Stroke in paroxysmal atrial fibrillation: report from the Stockholm Cohort of Atrial Fibrillation. Eur Heart Jn2010;31:967-975.
  • 20. Shinkawa A, Ueda K, Kiyohara Y, et al. Silent cerebral infarction in a community-based autopsy series in Japan: the Hisayama Study. Stroke 1995;26:380-385.
  • 21. Das RR, Seshadri S, Beiser AS, et al. Prevalence and correlates of silent cerebral infarcts in the Framingham Offspring Study. Stroke 2008;39:2929- 2935.
  • 22. Shea S, Di Tullio M. Atrial fibrillation, silent cerebral ischemia, and cognitive function. J Am Coll Cardiol 2013;62:1998-1999.
  • 23. Cao L, Pokorney SD, Hayden K, et al. Cognitive Function: Is There More to Anticoagulation in Atrial Fibrillation Than Stroke? J Am Heart Assoc 2015;4:001573.
  • 24. Sato H, Koretsune Y, Fukunami M, et al. Aspirin attenuates the incidence of silent brain lesions in patients with nonvalvular atrial fibrillation. Circ J 2004;68:410-416.
  • 25. Shin SY, Na JO, Lim HE, et al. Improved endothelial function in patients with atrial fibrillation through maintenance of sinus rhythm by successful catheter ablation. J Cardiovasc Electrophysiol 2011;22:376-382.
  • 26. Wieberdink RG, van Schie MC, Koudstaal PJ, et al. High von Willebrand factor levels increase the risk of stroke: The Rotterdam study. Stroke 2010;41:2151-2156.
  • 27. Lim HS, Willoughby SR, Schultz C, et al. Effect of atrial fibrillation on atrial thrombogenesis in humans: Impact of rate and rhythm. J Am Coll Cardiol 2013;61:852-860.
  • 28. Lim HS, Willoughby SR, Schultz C, et al. Successful catheter ablation decreases platelet activation and improves endothelial function in patients with atrial fibrillation. Heart Rhythm 2014;11:1912-1918.
  • 29. Kamiyama N, Koyama Y, Saito Y, et al. Pulse dispersion due to atrial fibrillation causes arterial thrombosis in a rabbit experimental model. Jpn Circ J 2000;64:516-519.
  • 30. Minamino T, Kitakaze M, Sanada S, et al. Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation: Role of nitric oxide. Circulation 1998;98:1721-1727.
  • 31. Kumagai K, Fukunami M, Kitabatake A, et al. Increased intracardiovasucular clotting in patients with chronic atrial fibrillation. J Am Coll Cardiol 1990;16:377-380.
  • 32. Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010;137:263-272.
  • 33. Singer DE, Chang Y, Borowsky LH, et al. A New Risk Scheme to Predict Ischemic Stroke and Other Thromboembolism in Atrial Fibrillation: The ATRIA Study Stroke Risk Score. J Am Heart Assoc 2013;2:e000250.
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Kardiyoloji
Bölüm Makaleler
Yazarlar

Hüseyin Göksülük 0000-0003-0700-8155

Proje Numarası -
Yayımlanma Tarihi 10 Ekim 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 71 Sayı: 2

Kaynak Göster

APA Göksülük, H. (2018). Silent Cerebral İnfarction in Anticoagulated Patients with Non-valvular Atrial Fibrillation as Detected with Neuron Specific Enolase. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 71(2), 130-134. https://doi.org/10.4274/atfm.16362
AMA Göksülük H. Silent Cerebral İnfarction in Anticoagulated Patients with Non-valvular Atrial Fibrillation as Detected with Neuron Specific Enolase. Ankara Üniversitesi Tıp Fakültesi Mecmuası. Ekim 2018;71(2):130-134. doi:10.4274/atfm.16362
Chicago Göksülük, Hüseyin. “Silent Cerebral İnfarction in Anticoagulated Patients With Non-Valvular Atrial Fibrillation As Detected With Neuron Specific Enolase”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 71, sy. 2 (Ekim 2018): 130-34. https://doi.org/10.4274/atfm.16362.
EndNote Göksülük H (01 Ekim 2018) Silent Cerebral İnfarction in Anticoagulated Patients with Non-valvular Atrial Fibrillation as Detected with Neuron Specific Enolase. Ankara Üniversitesi Tıp Fakültesi Mecmuası 71 2 130–134.
IEEE H. Göksülük, “Silent Cerebral İnfarction in Anticoagulated Patients with Non-valvular Atrial Fibrillation as Detected with Neuron Specific Enolase”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, c. 71, sy. 2, ss. 130–134, 2018, doi: 10.4274/atfm.16362.
ISNAD Göksülük, Hüseyin. “Silent Cerebral İnfarction in Anticoagulated Patients With Non-Valvular Atrial Fibrillation As Detected With Neuron Specific Enolase”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 71/2 (Ekim 2018), 130-134. https://doi.org/10.4274/atfm.16362.
JAMA Göksülük H. Silent Cerebral İnfarction in Anticoagulated Patients with Non-valvular Atrial Fibrillation as Detected with Neuron Specific Enolase. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2018;71:130–134.
MLA Göksülük, Hüseyin. “Silent Cerebral İnfarction in Anticoagulated Patients With Non-Valvular Atrial Fibrillation As Detected With Neuron Specific Enolase”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, c. 71, sy. 2, 2018, ss. 130-4, doi:10.4274/atfm.16362.
Vancouver Göksülük H. Silent Cerebral İnfarction in Anticoagulated Patients with Non-valvular Atrial Fibrillation as Detected with Neuron Specific Enolase. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2018;71(2):130-4.