Risk of ischemic stroke in patients with ovarian cancer: a nationwide population-based study

BMC Medicine

Chia-Jen Liu⁹  Cheng-Hwai Tzeng⁹  Tzeng-Ji Chen³  Li-Yu Hu⁴  Chiu-Mei Yeh¹  Sheng-Hsuan Chien⁹  Yung-Tai Chen⁸  Vincent Yi-Fong Su²  Hua-Hsi Wu⁷  Chung-Jen Teng⁵  Ai-Seon Kuan⁶ 

[1] Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;Institute of Public Health, National Yang-Ming University, Taipei, Taiwan;Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan;Division of Oncology and Hematology, Department of Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan;School of Medicine, National Yang-Ming University, Taipei, Taiwan;Department of Obstetrics & Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan;Department of Medicine, Taipei City Hospital Heping Fuyou Branch, Taipei, Taiwan;Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

关键词: Population-based study;    Platinum;    Ovarian cancer;    Ischemic stroke;    Chemotherapy;   

Others  :  854932
DOI  :  10.1186/1741-7015-12-53

 received in 2014-01-10, accepted in 2014-02-25,  发布年份 2014

【 摘 要 】

Background

Cancer patients are at risk of thromboembolism. However, studies investigating the relationship between ovarian cancer and ischemic stroke are lacking. The objectives of this study were to assess the association between ovarian cancer and ischemic stroke, and to determine the predictive risk factors.

Methods

Ovarian cancer patients aged 20 years and older without antecedent cerebrovascular events and who were followed up for more than 1 year between 1 January 2003 and 31 December 2011 were recruited from the Taiwan National Health Insurance database. Hazard ratios (HRs) of stroke risk for ovarian cancer patients compared with an age- and comorbidity-matched cohort were calculated by Cox proportional regression analysis. The difference in cumulative ischemic stroke incidence between ovarian cancer patients and the matched cohort was analyzed with the Kaplan-Meier method and tested with the log-rank test.

Results

Each cohort (ovarian cancer and matched cohort) consisted of 8,810 individuals, with a median age of 49 years. After a median follow-up of 2.68 and 3.85 years, respectively, the ischemic stroke incidence was 1.38-fold higher in the ovarian cancer cohort than in the comparison cohort (9.4 versus 6.8 per 1,000 person-years), with an age- and comorbidity-adjusted HR of 1.49 (P <0.001). The ischemic stroke risk imposed by ovarian cancer was more prominent in patients under 50 years old (HR 2.28; P <0.001) compared with patients 50 years and older (HR 1.33; P = 0.005). Significant risk factors predicting stroke development were age 50 years and older (HR 2.21; P <0.001), hypertension (HR 1.84; P <0.001), diabetes mellitus (HR 1.71; P <0.001), and treatment with chemotherapy (HR 1.45; P = 0.017), especially platinum-based regimens.

Conclusions

Ovarian cancer patients were at an increased risk of developing ischemic stroke. Age, hypertension, diabetes, and chemotherapy treatment were independent risk factors.

【 授权许可】

   
2014 Kuan et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]1999–2010 cancer incidence and mortality data apps.nccd.cdc.gov/uscs/
• [2]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69-90.
• [3]Landrum LM, Java J, Mathews CA, Lanneau GS Jr, Copeland LJ, Armstrong DK, Walker JL: Prognostic factors for stage III epithelial ovarian cancer treated with intraperitoneal chemotherapy: a gynecologic oncology group study. Gynecol Oncol 2013, 130:12-18.
• [4]Cestari DM, Weine DM, Panageas KS, Segal AZ, DeAngelis LM: Stroke in patients with cancer: incidence and etiology. Neurology 2004, 62:2025-2030.
• [5]Graus F, Rogers LR, Posner JB: Cerebrovascular complications in patients with cancer. Medicine (Baltimore) 1985, 64:16-35.
• [6]Borowski A, Ghodsizad A, Gams E: Stroke as a first manifestation of ovarian cancer. J Neurooncol 2005, 71:267-269.
• [7]Sanderson A, Bonington SC, Carrington BM, Alison DL, Spencer JA: Cerebral metastasis and other cerebral events in women with ovarian cancer. Clin Radiol 2002, 57:815-819.
• [8]Universal health coverage in Taiwan http://www.nhi.gov.tw/Resource/webdata/21717_1_20120808UniversalHealthCoverage.pdf webcite
• [9]Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML: Validation of the national health insurance research database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf 2011, 20:236-242.
• [10]Kim SG, Hong JM, Kim HY, Lee J, Chung PW, Park KY, Kim GM, Lee KH, Chung CS, Bang OY: Ischemic stroke in cancer patients with and without conventional mechanisms: a multicenter study in Korea. Stroke 2010, 41:798-801.
• [11]Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC: Epidemiology of cancer-associated venous thrombosis. Blood 2013, 122:1712-1723.
• [12]Walker AJ, Card TR, West J, Crooks C, Grainge MJ: Incidence of venous thromboembolism in patients with cancer - a cohort study using linked United Kingdom databases. Eur J Cancer 2013, 49:1404-1413.
• [13]Matsushita H, Kurabayashi T, Tomita M, Yamamoto Y, Aoki Y, Tanaka K: Disseminated intravascular coagulation associated with intratumoral hemorrhage of ovarian cancer. Gynecol Obstet Invest 2001, 51:274-276.
• [14]Yokota N, Koizume S, Miyagi E, Hirahara F, Nakamura Y, Kikuchi K, Ruf W, Sakuma Y, Tsuchiya E, Miyagi Y: Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells. Br J Cancer 2009, 101:2023-2029.
• [15]Wang X, Wang E, Kavanagh JJ, Freedman RS: Ovarian cancer, the coagulation pathway, and inflammation. J Transl Med 2005, 3:25. BioMed Central Full Text
• [16]von Tempelhoff GF, Dietrich M, Niemann F, Schneider D, Hommel G, Heilmann L: Blood coagulation and thrombosis in patients with ovarian malignancy. Thromb Haemost 1997, 77:456-461.
• [17]Jovin TG, Boosupalli V, Zivkovic SA, Wechsler LR, Gebel JM: High titers of CA-125 may be associated with recurrent ischemic strokes in patients with cancer. Neurology 2005, 64:1944-1945.
• [18]Harmsen P, Lappas G, Rosengren A, Wilhelmsen L: Long-term risk factors for stroke: twenty-eight years of follow-up of 7457 middle-aged men in Goteborg, Sweden. Stroke 2006, 37:1663-1667.
• [19]Chu CN, Chen SW, Bai LY, Mou CH, Hsu CY, Sung FC: Increase in stroke risk in patients with head and neck cancer: a retrospective cohort study. Br J Cancer 2011, 105:1419-1423.
• [20]Chen PC, Muo CH, Lee YT, Yu YH, Sung FC: Lung cancer and incidence of stroke: a population-based cohort study. Stroke 2011, 42:3034-3039.
• [21]Huang YS, Lee CC, Chang TS, Ho HC, Su YC, Hung SK, Lee MS, Chou P, Chang YH, Lee CC: Increased risk of stroke in young head and neck cancer patients treated with radiotherapy or chemotherapy. Oral Oncol 2011, 47:1092-1097.
• [22]Nilsson G, Holmberg L, Garmo H, Terent A, Blomqvist C: Increased incidence of stroke in women with breast cancer. Eur J Cancer 2005, 41:423-429.
• [23]Czaykowski PM, Moore MJ, Tannock IF: High risk of vascular events in patients with urothelial transitional cell carcinoma treated with cisplatin based chemotherapy. J Urol 1998, 160:2021-2024.
• [24]Ruiz MA, Marugan I, Estelles A, Navarro I, Espana F, Alberola V, San Juan L, Aznar J, Garcia-Conde J: The influence of chemotherapy on plasma coagulation and fibrinolytic systems in lung cancer patients. Cancer 1989, 63:643-648.
• [25]Licciardello JT, Moake JL, Rudy CK, Karp DD, Hong WK: Elevated plasma von Willebrand factor levels and arterial occlusive complications associated with cisplatin-based chemotherapy. Oncology 1985, 42:296-300.
• [26]Schilsky RL, Anderson T: Hypomagnesemia and renal magnesium wasting in patients receiving cisplatin. Ann Intern Med 1979, 90:929-931.
• [27]Manno EM: Magnesium sulphate and cerebral vasospasm. Lancet Neurol 2005, 4:329-330.
• [28]Eguchi R, Fujimori Y, Ohta T, Kunimasa K, Nakano T: Calpain is involved in cisplatin-induced endothelial injury in an in vitro three-dimensional blood vessel model. Int J Oncol 2010, 37:1289-1296.
• [29]Periard D, Boulanger CM, Eyer S, Amabile N, Pugin P, Gerschheimer C, Hayoz D: Are circulating endothelial-derived and platelet-derived microparticles a pathogenic factor in the cisplatin-induced stroke? Stroke 2007, 38:1636-1638.
• [30]Yen T, Walsh JD, Pejler G, Berndt MC, Geczy CL: Cisplatin-induced platelet activation requires mononuclear cells: role of GMP-140 and modulation of procoagulant activity. Br J Haematol 1993, 83:259-269.
• [31]Li SH, Chen WH, Tang Y, Rau KM, Chen YY, Huang TL, Liu JS, Huang CH: Incidence of ischemic stroke post-chemotherapy: a retrospective review of 10,963 patients. Clin Neurol Neurosurg 2006, 108:150-156.
• [32]Martin GG, Fernandez SP, Castro VS, Cueto OH, Acebal MR: Vertebral artery occlusion after chemotherapy. Stroke 2008, 39:e38. Author reply e39
• [33]Provencio M, Bonilla F, Lacasta A, Espana P: Cerebral infarction after cisplatin-based chemotherapy. Postgrad Med J 1994, 70:525-526.
• [34]Seng S, Liu Z, Chiu SK, Proverbs-Singh T, Sonpavde G, Choueiri TK, Tsao CK, Yu M, Hahn NM, Oh WK, Galsky MD: Risk of venous thromboembolism in patients with cancer treated with cisplatin: a systematic review and meta-analysis. J Clin Oncol 2012, 30:4416-4426.
• [35]Tsai SJ, Huang YS, Tung CH, Lee CC, Lee MS, Chiou WY, Lin HY, Hsu FC, Tsai CH, Su YC, Hung SK: Increased risk of ischemic stroke in cervical cancer patients: a nationwide population-based study. Radiat Oncol 2013, 8:41. BioMed Central Full Text
• [36]Jagsi R, Griffith KA, Koelling T, Roberts R, Pierce LJ: Stroke rates and risk factors in patients treated with radiation therapy for early-stage breast cancer. J Clin Oncol 2006, 24:2779-2785.
• [37]De Bruin ML, Dorresteijn LD, van’t Veer MB, Krol AD, van der Pal HJ, Kappelle AC, Boogerd W, Aleman BM, van Leeuwen FE: Increased risk of stroke and transient ischemic attack in 5-year survivors of Hodgkin lymphoma. J Natl Cancer Inst 2009, 101:928-937.