Elevated Pulse Pressure and Recurrent Hemorrhagic Stroke Risk in Stroke With Cerebral Microbleeds or Intracerebral Hemorrhage

Jong-Ho Park, Juneyoung Lee, Sun U Kwon, Hyuk Sung Kwon, Min Hwan Lee, Dong-Wha Kang, Jong-Ho Park, Juneyoung Lee, Sun U Kwon, Hyuk Sung Kwon, Min Hwan Lee, Dong-Wha Kang

Abstract

Background Which type of recurrent stroke is associated with pulse pressure (PP) remains uncertain in ischemic stroke with cerebral microbleeds or intracerebral hemorrhage. Methods and Results The PICASSO (Prevention of Cardiovascular Events in Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage) database involving 1454 subjects was analyzed. Subjects were stratified into quartiles according to the distribution of mean PP (mm Hg) during follow-up (mean, 1.9 years): <47 (first quartile), 48 to 53 (second quartile), 54 to 59 (third quartile), and ≥60 mm Hg (fourth quartile). The primary end point was hemorrhagic stroke, and the secondary end points were ischemic stroke, stroke of any type, and major adverse cardiovascular events. Adjusted time-dependent area under the receiver operating characteristic curve analysis was performed to assess the prediction accuracy of mean PP. The mean frequency of visit for blood pressure checkup was 9.4±5.5 times. The stroke incidence rate per 100 person-years was 3.14, 2.24, 5.52, and 6.22, respectively in increasing quartile of mean PP, and the rate of major adverse cardiovascular events was 3.82, 2.84, 6.37, and 7.14, respectively. In the presence of mean arterial pressure, hemorrhagic stroke risk was higher in the highest quartile (adjusted hazard ratio, 6.03; 95% CI, 1.04-34.99) versus the lowest quartile, which was evident at higher mean systolic blood pressure. Higher mean PP as a continuous variable was also a predictor of hemorrhagic stroke (1.09, 1.03-1.15). The time-dependent area under the receiver operating characteristic curve for hemorrhagic stroke was 0.79. Conclusions Long-term elevated PP with higher systolic blood pressure confers a greater risk of subsequent hemorrhagic stroke among stroke patients with cerebral microbleeds or intracerebral hemorrhage. Registration URL: https://www.clinicaltrials.gov; Unique identifier, NCT01013532.

Keywords: blood pressure; intracranial hemorrhage; risk; stroke; vascular stiffness.

Figures

Figure 1. Multivariable effect of mean PP…
Figure 1. Multivariable effect of mean PP on (A) hemorrhagic stroke, (B) stroke of any type (B), and (C) MACE by 10 mm Hg strata of mean SBP.
HR indicates hazard ratio; MACE, major adverse cardiovascular event; PP, pulse pressure; and SBP, systolic blood pressure.
Figure 2. Kaplan‐Meier curves for the end…
Figure 2. Kaplan‐Meier curves for the end points of (A) hemorrhagic stroke, (B) ischemic stroke, (C) stroke of any type, and (D) MACE.
MACE indicates major adverse cardiovascular event; and PP, pulse pressure.
Figure 3. Subgroup analysis of key endpoints
Figure 3. Subgroup analysis of key endpoints
CMBs indicates cerebral microbleeds; HR, hazard ratio; ICH, intracerebral hemorrhage; MACE, major adverse cardiovascular event; MAP, mean arterial pressure; NIHSS, National Institutes of Health Stroke Scale; PP, pulse pressure; and SBP, systolic blood pressure.

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