Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure

Koki Nakanishi; Marco R. Di Tullio; Min Qian; John L.P. Thompson; Arthur J. Labovitz; Douglas L. Mann; Ralph L. Sacco; Patrick M. Pullicino; Ronald S. Freudenberger; John R. Teerlink; Susan Graham; Gregory Y.H. Lip; Bruce Levin; Jay P. Mohr; Richard Buchsbaum; Conrado J. Estol; Dirk J. Lok; Piotr Ponikowski; Stefan D. Anker; Shunichi Homma

doi:10.1159/000474958

Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure

Koki Nakanishi, Marco R. Di Tullio, Min Qian, John L.P. Thompson, Arthur J. Labovitz, Douglas L. Mann, Ralph L. Sacco, Patrick M. Pullicino, Ronald S. Freudenberger, John R. Teerlink, Susan Graham, Gregory Y.H. Lip, Bruce Levin, Jay P. Mohr, Richard Buchsbaum, Conrado J. Estol, Dirk J. Lok, Piotr Ponikowski, Stefan D. Anker, Shunichi Homma

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5 Scopus citations

Abstract

Background: Although high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm. Methods: We examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review. Results: During 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups; 22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and 21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR <64/beats/min; p = 0.038), along with a history of stroke or transient ischemic attack and left ventricular ejection fraction. Conclusions: In contrast to its beneficial effect on mortality and hospital re-admissions, lower RHR may increase the risk of ischemic stroke in patients with systolic heart failure in sinus rhythm.

Original language	English
Pages (from-to)	43-50
Number of pages	8
Journal	Cerebrovascular Diseases
Volume	44
Issue number	1-2
DOIs	https://doi.org/10.1159/000474958
State	Published - Jul 1 2017

Keywords

Beta-blocker
Heart failure
Ischemic stroke
Resting heart rate
Sinus rhythm
Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial

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10.1159/000474958

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Nakanishi, K., Di Tullio, M. R., Qian, M., Thompson, J. L. P., Labovitz, A. J., Mann, D. L., Sacco, R. L., Pullicino, P. M., Freudenberger, R. S., Teerlink, J. R., Graham, S., Lip, G. Y. H., Levin, B., Mohr, J. P., Buchsbaum, R., Estol, C. J., Lok, D. J., Ponikowski, P., Anker, S. D., & Homma, S. (2017). Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure. Cerebrovascular Diseases, 44(1-2), 43-50. https://doi.org/10.1159/000474958

@article{b0d99a57eb0a4584a9a34581bb812ee4,

title = "Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure",

abstract = "Background: Although high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm. Methods: We examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review. Results: During 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups; 22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and 21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR <64/beats/min; p = 0.038), along with a history of stroke or transient ischemic attack and left ventricular ejection fraction. Conclusions: In contrast to its beneficial effect on mortality and hospital re-admissions, lower RHR may increase the risk of ischemic stroke in patients with systolic heart failure in sinus rhythm.",

keywords = "Beta-blocker, Heart failure, Ischemic stroke, Resting heart rate, Sinus rhythm, Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial",

author = "Koki Nakanishi and {Di Tullio}, {Marco R.} and Min Qian and Thompson, {John L.P.} and Labovitz, {Arthur J.} and Mann, {Douglas L.} and Sacco, {Ralph L.} and Pullicino, {Patrick M.} and Freudenberger, {Ronald S.} and Teerlink, {John R.} and Susan Graham and Lip, {Gregory Y.H.} and Bruce Levin and Mohr, {Jay P.} and Richard Buchsbaum and Estol, {Conrado J.} and Lok, {Dirk J.} and Piotr Ponikowski and Anker, {Stefan D.} and Shunichi Homma",

note = "Funding Information: The study was funded by U01-NS-043975 (Dr. Shunichi Homma) and U01-NS-039143 (Dr. John L.P. Thompson) from the National Institute of Neurological Disorders and Stroke. Publisher Copyright: {\textcopyright} 2017 S. Karger AG, Basel.",

year = "2017",

month = jul,

day = "1",

doi = "10.1159/000474958",

language = "English",

volume = "44",

pages = "43--50",

journal = "Cerebrovascular Diseases",

issn = "1015-9770",

number = "1-2",

}

Nakanishi, K, Di Tullio, MR, Qian, M, Thompson, JLP, Labovitz, AJ, Mann, DL, Sacco, RL, Pullicino, PM, Freudenberger, RS, Teerlink, JR, Graham, S, Lip, GYH, Levin, B, Mohr, JP, Buchsbaum, R, Estol, CJ, Lok, DJ, Ponikowski, P, Anker, SD & Homma, S 2017, 'Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure', Cerebrovascular Diseases, vol. 44, no. 1-2, pp. 43-50. https://doi.org/10.1159/000474958

TY - JOUR

T1 - Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure

AU - Nakanishi, Koki

AU - Di Tullio, Marco R.

AU - Qian, Min

AU - Thompson, John L.P.

AU - Labovitz, Arthur J.

AU - Mann, Douglas L.

AU - Sacco, Ralph L.

AU - Pullicino, Patrick M.

AU - Freudenberger, Ronald S.

AU - Teerlink, John R.

AU - Graham, Susan

AU - Lip, Gregory Y.H.

AU - Levin, Bruce

AU - Mohr, Jay P.

AU - Buchsbaum, Richard

AU - Estol, Conrado J.

AU - Lok, Dirk J.

AU - Ponikowski, Piotr

AU - Anker, Stefan D.

AU - Homma, Shunichi

N1 - Funding Information: The study was funded by U01-NS-043975 (Dr. Shunichi Homma) and U01-NS-039143 (Dr. John L.P. Thompson) from the National Institute of Neurological Disorders and Stroke. Publisher Copyright: © 2017 S. Karger AG, Basel.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Background: Although high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm. Methods: We examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review. Results: During 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups; 22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and 21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR <64/beats/min; p = 0.038), along with a history of stroke or transient ischemic attack and left ventricular ejection fraction. Conclusions: In contrast to its beneficial effect on mortality and hospital re-admissions, lower RHR may increase the risk of ischemic stroke in patients with systolic heart failure in sinus rhythm.

AB - Background: Although high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm. Methods: We examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review. Results: During 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups; 22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and 21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR <64/beats/min; p = 0.038), along with a history of stroke or transient ischemic attack and left ventricular ejection fraction. Conclusions: In contrast to its beneficial effect on mortality and hospital re-admissions, lower RHR may increase the risk of ischemic stroke in patients with systolic heart failure in sinus rhythm.

KW - Beta-blocker

KW - Heart failure

KW - Ischemic stroke

KW - Resting heart rate

KW - Sinus rhythm

KW - Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial

UR - http://www.scopus.com/inward/record.url?scp=85018528014&partnerID=8YFLogxK

U2 - 10.1159/000474958

DO - 10.1159/000474958

M3 - Article

C2 - 28419982

AN - SCOPUS:85018528014

SN - 1015-9770

VL - 44

SP - 43

EP - 50

JO - Cerebrovascular Diseases

JF - Cerebrovascular Diseases

IS - 1-2

ER -

Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure

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Keywords

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