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Published in: BMC Nephrology 1/2016

Open Access 01-12-2016 | Research article

Association of multiple ischemic strokes with mortality in incident hemodialysis patients: an application of multistate model to determine transition probabilities in a retrospective observational cohort

Authors: James B. Wetmore, Jonathan D. Mahnken, Milind A. Phadnis

Published in: BMC Nephrology | Issue 1/2016

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Abstract

Background

Little is known about the effect of multiple, or subsequent, ischemic strokes in patients receiving hemodialysis.

Methods

We undertook a retrospective cohort study of incident hemodialysis patients with Medicare coverage who had experienced a first ischemic stroke. Factors associated with either a subsequent ischemic stroke or death following a first new stroke were modeled. A multistate model with Cox proportional hazards was used to predict transition probabilities from first ischemic stroke to either subsequent stroke or to death, and the demographic and clinical factors associated with the respective transition probabilities were determined. Effect of a subsequent ischemic stroke on survival was quantified.

Results

Overall, 12,054 individuals (mean age 69.7 years, 41.3 % male, 53.0 % Caucasian and 34.0 % African-American) experienced a first new ischemic stroke. Female sex was associated with an increased risk of having a subsequent ischemic stroke (adjusted hazard ratio 1.37, 95 % confidence intervals 1.20 – 1.56, P < 0.0001); African-Americans, as compared to Caucasians, had lower likelihood of dying after a first new ischemic stroke (0.81, 0.77 – 0.85, P < 0.0001). A subsequent stroke trended towards having a higher likelihood of transitioning to death compared to a first new ischemic stroke on dialysis (1.72, 0.96 – 3.09, P = 0.071). When a subsequent ischemic stroke occurs at 24 months, probability of survival dropped >15 %, in absolute terms, from 0.254 to 0.096, with substantial drops observed at subsequent time points such that the probability of survival was more than halved.

Conclusions

Likelihood of subsequent ischemic stroke and of survival in hemodialysis patients appears to vary by sex and race: females are more likely than males to experience a subsequent ischemic stroke, and Caucasians are more likely than African-Americans to die after a first new ischemic stroke. The risk of a transitioning to a subsequent stroke (after having had a first) increases until about 1 year, then decreases. Subsequent strokes are associated with decreased probability of survival, an effect which increases as time since first stroke elapses. This information may be of assistance to clinicians when counseling hemodialysis patients about the implications of recurrent ischemic stroke.
Literature
1.
go back to reference Berry JD, Dyer A, Cai X, Garside DB, Ning H, Thomas A, Greenland P, Van Horn L, Tracy RP, Lloyd-Jones DM. Lifetime risks of cardiovascular disease. N Engl J Med. 2012;366(4):321–9.CrossRefPubMedPubMedCentral Berry JD, Dyer A, Cai X, Garside DB, Ning H, Thomas A, Greenland P, Van Horn L, Tracy RP, Lloyd-Jones DM. Lifetime risks of cardiovascular disease. N Engl J Med. 2012;366(4):321–9.CrossRefPubMedPubMedCentral
2.
go back to reference United States Renal Data System. USRDS 2012 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. In: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. 2012. United States Renal Data System. USRDS 2012 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. In: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. 2012.
3.
go back to reference Wiesholzer M, Harm F, Tomasec G, Barbieri G, Putz D, Balcke P. Incidence of stroke among chronic hemodialysis patients with nonrheumatic atrial fibrillation. Am J Nephrol. 2001;21(1):35–9.CrossRefPubMed Wiesholzer M, Harm F, Tomasec G, Barbieri G, Putz D, Balcke P. Incidence of stroke among chronic hemodialysis patients with nonrheumatic atrial fibrillation. Am J Nephrol. 2001;21(1):35–9.CrossRefPubMed
4.
go back to reference Seliger SL, Gillen DL, Longstreth Jr WT, Kestenbaum B, Stehman-Breen CO. Elevated risk of stroke among patients with end-stage renal disease. Kidney Int. 2003;64(2):603–9.CrossRefPubMed Seliger SL, Gillen DL, Longstreth Jr WT, Kestenbaum B, Stehman-Breen CO. Elevated risk of stroke among patients with end-stage renal disease. Kidney Int. 2003;64(2):603–9.CrossRefPubMed
5.
go back to reference Seliger SL, Gillen DL, Tirschwell D, Wasse H, Kestenbaum BR, Stehman-Breen CO. Risk factors for incident stroke among patients with end-stage renal disease. J Am Soc Nephrol. 2003;14(10):2623–31.CrossRefPubMed Seliger SL, Gillen DL, Tirschwell D, Wasse H, Kestenbaum BR, Stehman-Breen CO. Risk factors for incident stroke among patients with end-stage renal disease. J Am Soc Nephrol. 2003;14(10):2623–31.CrossRefPubMed
6.
go back to reference Sozio SM, Armstrong PA, Coresh J, Jaar BG, Fink NE, Plantinga LC, Powe NR, Parekh RS. Cerebrovascular disease incidence, characteristics, and outcomes in patients initiating dialysis: the choices for healthy outcomes in caring for ESRD (CHOICE) study. Am J Kidney Dis. 2009;54(3):468–77.CrossRefPubMedPubMedCentral Sozio SM, Armstrong PA, Coresh J, Jaar BG, Fink NE, Plantinga LC, Powe NR, Parekh RS. Cerebrovascular disease incidence, characteristics, and outcomes in patients initiating dialysis: the choices for healthy outcomes in caring for ESRD (CHOICE) study. Am J Kidney Dis. 2009;54(3):468–77.CrossRefPubMedPubMedCentral
7.
go back to reference Sanchez-Perales C, Vazquez E, Garcia-Cortes MJ, Borrego J, Polaina M, Gutierrez CP, Lozano C, Liebana A. Ischaemic stroke in incident dialysis patients. Nephrol Dial Transplant. 2010;25(10):3343–8.CrossRefPubMed Sanchez-Perales C, Vazquez E, Garcia-Cortes MJ, Borrego J, Polaina M, Gutierrez CP, Lozano C, Liebana A. Ischaemic stroke in incident dialysis patients. Nephrol Dial Transplant. 2010;25(10):3343–8.CrossRefPubMed
8.
go back to reference Power A, Chan K, Singh SK, Taube D, Duncan N. Appraising stroke risk in maintenance hemodialysis patients: a large single-center cohort study. Am J Kidney Dis. 2012;59(2):249–57.CrossRefPubMed Power A, Chan K, Singh SK, Taube D, Duncan N. Appraising stroke risk in maintenance hemodialysis patients: a large single-center cohort study. Am J Kidney Dis. 2012;59(2):249–57.CrossRefPubMed
9.
go back to reference Wetmore JB, Ellerbeck EF, Mahnken JD, Phadnis MA, Rigler SK, Spertus JA, Zhou X, Mukhopadhyay P, Shireman TI. Stroke and the “Stroke Belt” in Dialysis: Contribution of Patient Characteristics to Ischemic Stroke Rate and Its Geographic Variation. J Am Soc Nephrol. 2013;24(12):2053–61.CrossRefPubMedPubMedCentral Wetmore JB, Ellerbeck EF, Mahnken JD, Phadnis MA, Rigler SK, Spertus JA, Zhou X, Mukhopadhyay P, Shireman TI. Stroke and the “Stroke Belt” in Dialysis: Contribution of Patient Characteristics to Ischemic Stroke Rate and Its Geographic Variation. J Am Soc Nephrol. 2013;24(12):2053–61.CrossRefPubMedPubMedCentral
10.
go back to reference Wetmore JB, Phadnis MA, Ellerbeck EF, Shireman TI, Rigler SK, Mahnken JD. Relationship between stroke and mortality in dialysis patients. Clin J Am Soc Nephrol. 2015;10(1):80–9.CrossRefPubMed Wetmore JB, Phadnis MA, Ellerbeck EF, Shireman TI, Rigler SK, Mahnken JD. Relationship between stroke and mortality in dialysis patients. Clin J Am Soc Nephrol. 2015;10(1):80–9.CrossRefPubMed
11.
go back to reference Wetmore JB, Rigler SK, Mahnken JD, Mukhopadhyay P, Shireman TI. Considering health insurance: how do dialysis initiates with Medicaid coverage differ from persons without Medicaid coverage? Nephrol Dial Transplant. 2010;25(1):198–205.CrossRefPubMed Wetmore JB, Rigler SK, Mahnken JD, Mukhopadhyay P, Shireman TI. Considering health insurance: how do dialysis initiates with Medicaid coverage differ from persons without Medicaid coverage? Nephrol Dial Transplant. 2010;25(1):198–205.CrossRefPubMed
12.
go back to reference Volkova N, McClellan W, Soucie JM, Schoolwerth A. Racial disparities in the prevalence of cardiovascular disease among incident end-stage renal disease patients. Nephrol Dial Transplant. 2006;21(8):2202–9.CrossRefPubMed Volkova N, McClellan W, Soucie JM, Schoolwerth A. Racial disparities in the prevalence of cardiovascular disease among incident end-stage renal disease patients. Nephrol Dial Transplant. 2006;21(8):2202–9.CrossRefPubMed
13.
go back to reference Andrade SE, Harrold LR, Tjia J, Cutrona SL, Saczynski JS, Dodd KS, Goldberg RJ, Gurwitz JH. A systematic review of validated methods for identifying cerebrovascular accident or transient ischemic attack using administrative data. Pharmacoepidemiol Drug Saf. 2012;21 Suppl 1:100–28.CrossRefPubMedPubMedCentral Andrade SE, Harrold LR, Tjia J, Cutrona SL, Saczynski JS, Dodd KS, Goldberg RJ, Gurwitz JH. A systematic review of validated methods for identifying cerebrovascular accident or transient ischemic attack using administrative data. Pharmacoepidemiol Drug Saf. 2012;21 Suppl 1:100–28.CrossRefPubMedPubMedCentral
14.
go back to reference Go AS, Hylek EM, Chang Y, Phillips KA, Henault LE, Capra AM, Jensvold NG, Selby JV, Singer DE. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? Jama. 2003;290(20):2685–92.CrossRefPubMed Go AS, Hylek EM, Chang Y, Phillips KA, Henault LE, Capra AM, Jensvold NG, Selby JV, Singer DE. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? Jama. 2003;290(20):2685–92.CrossRefPubMed
15.
go back to reference Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med. 2007;26(11):2389–430.CrossRefPubMed Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med. 2007;26(11):2389–430.CrossRefPubMed
16.
go back to reference Klein JP, Shu Y. Multi-state models for bone marrow transplantation studies. Stat Methods Med Res. 2002;11(2):117–39.CrossRefPubMed Klein JP, Shu Y. Multi-state models for bone marrow transplantation studies. Stat Methods Med Res. 2002;11(2):117–39.CrossRefPubMed
17.
go back to reference de Wreede LC, Fiocco M, Putter H. The mstate package for estimation and prediction in non- and semi-parametric multi-state and competing risks models. Comput Methods Programs Biomed. 2010;99(3):261–74.CrossRefPubMed de Wreede LC, Fiocco M, Putter H. The mstate package for estimation and prediction in non- and semi-parametric multi-state and competing risks models. Comput Methods Programs Biomed. 2010;99(3):261–74.CrossRefPubMed
18.
go back to reference Klein JP, Keiding N, Copelan EA. Plotting summary predictions in multistate survival models: probabilities of relapse and death in remission for bone marrow transplantation patients. Stat Med. 1993;12(24):2315–32.CrossRefPubMed Klein JP, Keiding N, Copelan EA. Plotting summary predictions in multistate survival models: probabilities of relapse and death in remission for bone marrow transplantation patients. Stat Med. 1993;12(24):2315–32.CrossRefPubMed
19.
go back to reference Kamel H, Johnson DR, Hegde M, Go AS, Sidney S, Sorel M, Hills NK, Johnston SC. Detection of atrial fibrillation after stroke and the risk of recurrent stroke. J Stroke Cerebrovasc Dis. 2012;21(8):726–31.CrossRefPubMed Kamel H, Johnson DR, Hegde M, Go AS, Sidney S, Sorel M, Hills NK, Johnston SC. Detection of atrial fibrillation after stroke and the risk of recurrent stroke. J Stroke Cerebrovasc Dis. 2012;21(8):726–31.CrossRefPubMed
20.
go back to reference Wetmore JB, Phadnis MA, Mahnken JD, Ellerbeck EF, Rigler SK, Zhou X, Shireman TI. Race, Ethnicity, and State-by-State Geographic Variation in Hemorrhagic Stroke in Dialysis Patients. Clin J Am Soc Nephrol. 2014;9(4):756–63.CrossRefPubMedPubMedCentral Wetmore JB, Phadnis MA, Mahnken JD, Ellerbeck EF, Rigler SK, Zhou X, Shireman TI. Race, Ethnicity, and State-by-State Geographic Variation in Hemorrhagic Stroke in Dialysis Patients. Clin J Am Soc Nephrol. 2014;9(4):756–63.CrossRefPubMedPubMedCentral
21.
go back to reference Toyoda K, Fujii K, Fujimi S, Kumai Y, Tsuchimochi H, Ibayashi S, Iida M. Stroke in patients on maintenance hemodialysis: a 22-year single-center study. Am J Kidney Dis. 2005;45(6):1058–66.CrossRefPubMed Toyoda K, Fujii K, Fujimi S, Kumai Y, Tsuchimochi H, Ibayashi S, Iida M. Stroke in patients on maintenance hemodialysis: a 22-year single-center study. Am J Kidney Dis. 2005;45(6):1058–66.CrossRefPubMed
22.
go back to reference Iseki K, Fukiyama K. Predictors of stroke in patients receiving chronic hemodialysis. Kidney Int. 1996;50(5):1672–5.CrossRefPubMed Iseki K, Fukiyama K. Predictors of stroke in patients receiving chronic hemodialysis. Kidney Int. 1996;50(5):1672–5.CrossRefPubMed
23.
go back to reference Iseki K, Fukiyama K. Clinical demographics and long-term prognosis after stroke in patients on chronic haemodialysis. The Okinawa Dialysis Study (OKIDS) Group. Nephrol Dial Transplant. 2000;15(11):1808–13.CrossRefPubMed Iseki K, Fukiyama K. Clinical demographics and long-term prognosis after stroke in patients on chronic haemodialysis. The Okinawa Dialysis Study (OKIDS) Group. Nephrol Dial Transplant. 2000;15(11):1808–13.CrossRefPubMed
24.
go back to reference Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler III ER, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB. American Heart Association Statistics C, Stroke Statistics S: Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29–322.CrossRefPubMed Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler III ER, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB. American Heart Association Statistics C, Stroke Statistics S: Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29–322.CrossRefPubMed
25.
go back to reference Paulus JK, Lai LY, Lundquist C, Daneshmand A, Buettner H, Lutz JS, Raman G, Wessler BS, Kent DM. Field Synopsis of the Role of Sex in Stroke Prediction Models. J Am Heart Assoc. 2016;5(5). [epub ahead of print]. Paulus JK, Lai LY, Lundquist C, Daneshmand A, Buettner H, Lutz JS, Raman G, Wessler BS, Kent DM. Field Synopsis of the Role of Sex in Stroke Prediction Models. J Am Heart Assoc. 2016;5(5). [epub ahead of print].
26.
go back to reference Kucirka LM, Grams ME, Lessler J, Hall EC, James N, Massie AB, Montgomery RA, Segev DL. Association of race and age with survival among patients undergoing dialysis. JAMA. 2011;306(6):620–6.CrossRefPubMedPubMedCentral Kucirka LM, Grams ME, Lessler J, Hall EC, James N, Massie AB, Montgomery RA, Segev DL. Association of race and age with survival among patients undergoing dialysis. JAMA. 2011;306(6):620–6.CrossRefPubMedPubMedCentral
27.
go back to reference Roderick P, Byrne C, Casula A, Steenkamp R, Ansell D, Burden R, Nitsch D, Feest T. Survival of patients from South Asian and Black populations starting renal replacement therapy in England and Wales. Nephrol Dial Transplant. 2009;24(12):3774–82.CrossRefPubMedPubMedCentral Roderick P, Byrne C, Casula A, Steenkamp R, Ansell D, Burden R, Nitsch D, Feest T. Survival of patients from South Asian and Black populations starting renal replacement therapy in England and Wales. Nephrol Dial Transplant. 2009;24(12):3774–82.CrossRefPubMedPubMedCentral
28.
go back to reference Wagner M, Ansell D, Kent DM, Griffith JL, Naimark D, Wanner C, Tangri N. Predicting mortality in incident dialysis patients: an analysis of the United Kingdom Renal Registry. Am J Kidney Dis. 2011;57(6):894–902.CrossRefPubMedPubMedCentral Wagner M, Ansell D, Kent DM, Griffith JL, Naimark D, Wanner C, Tangri N. Predicting mortality in incident dialysis patients: an analysis of the United Kingdom Renal Registry. Am J Kidney Dis. 2011;57(6):894–902.CrossRefPubMedPubMedCentral
29.
go back to reference Udayaraj U, Pruthi R, Casula A, Roderick P. UK Renal Registry 16th annual report: chapter 6 demographics and outcomes of patients from different ethnic groups on renal replacement therapy in the UK. Nephron Clin Pract. 2013;125(1–4):111–25.CrossRefPubMed Udayaraj U, Pruthi R, Casula A, Roderick P. UK Renal Registry 16th annual report: chapter 6 demographics and outcomes of patients from different ethnic groups on renal replacement therapy in the UK. Nephron Clin Pract. 2013;125(1–4):111–25.CrossRefPubMed
Metadata
Title
Association of multiple ischemic strokes with mortality in incident hemodialysis patients: an application of multistate model to determine transition probabilities in a retrospective observational cohort
Authors
James B. Wetmore
Jonathan D. Mahnken
Milind A. Phadnis
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2016
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-016-0350-3

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