Original Paper Received: January 10, 2014 Accepted: March 16, 2014 Published online: September 13, 2014
Eur Neurol 2014;72:203–208 DOI: 10.1159/000362269
Potential Blood Pressure Thresholds and Outcome in Acute Intracerebral Hemorrhage David Rodriguez-Luna a Marian Muchada a Socorro Piñeiro a Alan Flores a Marta Rubiera a Jorge Pagola a Pilar Coscojuela b Pilar Meler a Estela Sanjuan a Sandra Boned-Riera a Daniel A. Cárcamo a Alejandro Tomasello b Jose Alvarez-Sabin a Marc Ribo a Carlos A. Molina a
a Stroke Unit, Department of Neurology and b Department of Neuroradiology, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain
Key Words Intracerebral hemorrhage · Blood pressure · Hematoma growth · Outcome
were independently related to outcomes at 90 days. Conclusion: In patients with acute ICH, SBP lowering to at least less than 160 mm Hg threshold may be needed to minimize the deleterious effect of high SBP on 24-hour outcomes. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0014–3022/14/0724–0203$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
Elevated blood pressure (BP) is common in acute intracerebral hemorrhage (ICH) [1] and has been associated with hematoma growth (HG) [2–4], early neurological deterioration [4], and death or dependency [5]. That is why blood pressure is considered a major target for treatment in the acute period of ICH. Current European Stroke Organisation (ESO) [6] and American Heart Association (AHA) [7] guidelines for BP management in acute ICH have differing views about the optimal systolic BP (SBP) target. While AHA guidelines recommend maintaining SBP to values below 180 mm Hg, ESO guidelines recommend maintaining SBP below 180 or 160 mm Hg, with a target of 160 or 150 mm Hg, respectively, depending on the prior diagnosis of hypertension. However, these recommendations are based priDavid Rodriguez-Luna, MD, PhD Stroke Unit, Department of Neurology Vall d’Hebron University Hospital Ps. Vall d’Hebron, 119, 08035, Barcelona (Spain) E-Mail rodriguezlunad @ yahoo.es
Downloaded by: University of Tokyo 157.82.153.40 - 5/20/2015 11:56:21 PM
Abstract Background: Little is known about the relationships between different systolic blood pressure (SBP) thresholds and their outcomes in acute intracerebral hemorrhage (ICH). We aimed to determine the associations of potential systolic blood pressure (SBP) thresholds with hematoma growth (HG) and clinical outcome in patients with acute ICH. Methods: 117 patients with acute (50% (83.3–53.7%; AUC = 0.722), SBP 170-load >25.4% (83.3–58.3%; AUC = 0.714), and SBP 200-load >1.9% (66.7–73.1%; AUC = 0.693). Finally, 85 (72.6%) patients had poor outcome at 90 days, including the 35 (29.9%) patients who died. In adjusted multivariate analyses, none of the SBP loads were independently associated with poor outcome or 90-day mortality (table 5).
Discussion
olds, ROC curves identified SBP 170-load >18.7%, SBP 180-load >12.3% and SBP 190-load >2.1% as the cut-off points related to HG with the highest sensitivity–specificity (62.9–58%, 57.1–73.6% and 60–68.1%, respectively). The areas under the curve (AUC) were 0.633, 0.684 and 0.678, respectively. While none of the SBP loads were correlated with baseline or 24-hour ICH volumes, higher (170 to 200) but not lower (140 to 160) loads were correlated with the amount of both absolute and relative hematoma enlargement at 24 h (table 3). Furthermore, both SBP 170 and 180 loads were independently related to HG in multivariate analyses after adjusting by age, GCS score, baseline NIHSS score, hemoglobin, aPTT, baseline ICH volume, intraventricular extension, and the CTA spot sign (table 2). At 24 h, 25 (21.4%) patients experienced END, including the 7 (6%) patients who died. Similarly to HG analysis, both SBP 170 and 180 loads were independently related
Some studies have suggested that SBP reduction to lower thresholds than those recommended by guidelines may prevent the risk of HG in acute ICH. While INTERACT revealed a trend toward lower absolute and relative HG lowering SBP below 140 mm Hg as compared with target of 180 mm Hg [8], another study suggested that SBP lowering below 150 mm Hg may prevent the risk of HG [3]. Moreover, other studies have shown that SBP lowering below both 140 mm Hg [8–10] and 150 mm Hg [17] is safe in acute ICH. However, the optimal SBP treatment threshold remains uncertain. The present study expands previous observations on relationship between different potential SBP thresholds and outcome. This study shows that higher SBP 170 and 180 loads are independently related to HG and END. Further, higher SBP 160, 170 and 200 SBP loads were independently related to 24-hour mortality. However, we did not find a significant relationship between none of the SBP thresholds and clinical outcome at 90 days. These findings suggest a greater impact of the deleterious effect of high BP on outcome during the acute phase than at 90 days. SBP 170, 180, 190, and 200 loads were positively correlated with the amount of both absolute and relative hematoma enlargement at 24 h in our study. This fact, coupled with the absence of correlation of these thresholds with baseline or 24-hour hematoma volumes, supports a causative effect of high SBP on HG. However, the rela-
SBP Thresholds and Outcome in Acute ICH
Eur Neurol 2014;72:203–208 DOI: 10.1159/000362269
205
Downloaded by: University of Tokyo 157.82.153.40 - 5/20/2015 11:56:21 PM
Table 1. Baseline characteristics
Table 2. Systolic blood pressure load values and their relationship with hematoma growth in univariate and multivariate analyses
SBP load, mm Hg
140 150 160 170 180 190 200
All patients (n = 117)
Hematoma growth (n = 106) univariate
87.6 (61–100) 67.3 (28.4–91.9) 46.5 (11.8–80.5) 20 (1.3–59.2) 6.6 (0–33.9) 0 (0–17.1) 0 (0–3.5)
multivariate
HG (n = 36)
No HG (n = 70)
p value
OR (95% CI)
p value
90.6 (38.4–100) 72 (14.3–98.2) 58.2 (7.7–90.5) 35.7 (1.4–80) 20 (1.4–67.6) 9.5 (0–33.3) 0 (0–17.2)
85.7 (67.6–99.1) 64.1 (32–89.3) 38.7 (12.6–73.5) 11.1 (0–43.1) 1.9 (0–17.6) 0 (0–4.9) 0 (0–1.7)
0.900 0.645 0.330 0.027 0.001 0.001 0.105
0.989 (0.963–1.016) 1.004 (0.979–1.030) 1.021 (0.993–1.050) 1.034 (1.001–1.070) 1.052 (1.010–1.097) 1.049 (0.993–1.109) 1.065 (0.978–1.159)
0.428 0.732 0.142 0.048 0.016 0.089 0.148
SBP load values, in %, are presented as median (interquartile interval). Statistically significant predictors are given in italics. SBP = Systolic blood pressure; HG = hematoma growth.
Table 3. Spearman’s correlation coefficients between different systolic blood pressure loads and baseline and 24-hour hematoma vol-
umes, and the amount of absolute and relative hematoma enlargement (n = 106) SBP load, mm Hg
140 150 160 170 180 190 200
Baseline hematoma volume
24-hour hematoma volume
Absolute hematoma enlargement
Relative hematoma enlargement
r
p value
r
p value
r
p value
r
p value
0.067 0.019 0.029 0.073 0.083 0.068 0.006
0.501 0.848 0.773 0.461 0.380 0.494 0.948
0.063 0.028 0.051 0.139 0.147 0.174 0.076
0.524 0.774 0.606 0.159 0.139 0.077 0.444
0.016 0.028 0.083 0.212 0.304 0.329 0.201
0.870 0.776 0.403 0.031 0.002 0.001 0.041
–0.004 0.030 0.086 0.222 0.311 0.365 0.211
0.969 0.762 0.384 0.023 0.001
Eur Neurol 2014;72:203–208 DOI: 10.1159/000362269
Potential Blood Pressure Thresholds and Outcome in Acute Intracerebral Hemorrhage David Rodriguez-Luna a Marian Muchada a Socorro Piñeiro a Alan Flores a Marta Rubiera a Jorge Pagola a Pilar Coscojuela b Pilar Meler a Estela Sanjuan a Sandra Boned-Riera a Daniel A. Cárcamo a Alejandro Tomasello b Jose Alvarez-Sabin a Marc Ribo a Carlos A. Molina a
a Stroke Unit, Department of Neurology and b Department of Neuroradiology, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain
Key Words Intracerebral hemorrhage · Blood pressure · Hematoma growth · Outcome
were independently related to outcomes at 90 days. Conclusion: In patients with acute ICH, SBP lowering to at least less than 160 mm Hg threshold may be needed to minimize the deleterious effect of high SBP on 24-hour outcomes. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0014–3022/14/0724–0203$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
Elevated blood pressure (BP) is common in acute intracerebral hemorrhage (ICH) [1] and has been associated with hematoma growth (HG) [2–4], early neurological deterioration [4], and death or dependency [5]. That is why blood pressure is considered a major target for treatment in the acute period of ICH. Current European Stroke Organisation (ESO) [6] and American Heart Association (AHA) [7] guidelines for BP management in acute ICH have differing views about the optimal systolic BP (SBP) target. While AHA guidelines recommend maintaining SBP to values below 180 mm Hg, ESO guidelines recommend maintaining SBP below 180 or 160 mm Hg, with a target of 160 or 150 mm Hg, respectively, depending on the prior diagnosis of hypertension. However, these recommendations are based priDavid Rodriguez-Luna, MD, PhD Stroke Unit, Department of Neurology Vall d’Hebron University Hospital Ps. Vall d’Hebron, 119, 08035, Barcelona (Spain) E-Mail rodriguezlunad @ yahoo.es
Downloaded by: University of Tokyo 157.82.153.40 - 5/20/2015 11:56:21 PM
Abstract Background: Little is known about the relationships between different systolic blood pressure (SBP) thresholds and their outcomes in acute intracerebral hemorrhage (ICH). We aimed to determine the associations of potential systolic blood pressure (SBP) thresholds with hematoma growth (HG) and clinical outcome in patients with acute ICH. Methods: 117 patients with acute (50% (83.3–53.7%; AUC = 0.722), SBP 170-load >25.4% (83.3–58.3%; AUC = 0.714), and SBP 200-load >1.9% (66.7–73.1%; AUC = 0.693). Finally, 85 (72.6%) patients had poor outcome at 90 days, including the 35 (29.9%) patients who died. In adjusted multivariate analyses, none of the SBP loads were independently associated with poor outcome or 90-day mortality (table 5).
Discussion
olds, ROC curves identified SBP 170-load >18.7%, SBP 180-load >12.3% and SBP 190-load >2.1% as the cut-off points related to HG with the highest sensitivity–specificity (62.9–58%, 57.1–73.6% and 60–68.1%, respectively). The areas under the curve (AUC) were 0.633, 0.684 and 0.678, respectively. While none of the SBP loads were correlated with baseline or 24-hour ICH volumes, higher (170 to 200) but not lower (140 to 160) loads were correlated with the amount of both absolute and relative hematoma enlargement at 24 h (table 3). Furthermore, both SBP 170 and 180 loads were independently related to HG in multivariate analyses after adjusting by age, GCS score, baseline NIHSS score, hemoglobin, aPTT, baseline ICH volume, intraventricular extension, and the CTA spot sign (table 2). At 24 h, 25 (21.4%) patients experienced END, including the 7 (6%) patients who died. Similarly to HG analysis, both SBP 170 and 180 loads were independently related
Some studies have suggested that SBP reduction to lower thresholds than those recommended by guidelines may prevent the risk of HG in acute ICH. While INTERACT revealed a trend toward lower absolute and relative HG lowering SBP below 140 mm Hg as compared with target of 180 mm Hg [8], another study suggested that SBP lowering below 150 mm Hg may prevent the risk of HG [3]. Moreover, other studies have shown that SBP lowering below both 140 mm Hg [8–10] and 150 mm Hg [17] is safe in acute ICH. However, the optimal SBP treatment threshold remains uncertain. The present study expands previous observations on relationship between different potential SBP thresholds and outcome. This study shows that higher SBP 170 and 180 loads are independently related to HG and END. Further, higher SBP 160, 170 and 200 SBP loads were independently related to 24-hour mortality. However, we did not find a significant relationship between none of the SBP thresholds and clinical outcome at 90 days. These findings suggest a greater impact of the deleterious effect of high BP on outcome during the acute phase than at 90 days. SBP 170, 180, 190, and 200 loads were positively correlated with the amount of both absolute and relative hematoma enlargement at 24 h in our study. This fact, coupled with the absence of correlation of these thresholds with baseline or 24-hour hematoma volumes, supports a causative effect of high SBP on HG. However, the rela-
SBP Thresholds and Outcome in Acute ICH
Eur Neurol 2014;72:203–208 DOI: 10.1159/000362269
205
Downloaded by: University of Tokyo 157.82.153.40 - 5/20/2015 11:56:21 PM
Table 1. Baseline characteristics
Table 2. Systolic blood pressure load values and their relationship with hematoma growth in univariate and multivariate analyses
SBP load, mm Hg
140 150 160 170 180 190 200
All patients (n = 117)
Hematoma growth (n = 106) univariate
87.6 (61–100) 67.3 (28.4–91.9) 46.5 (11.8–80.5) 20 (1.3–59.2) 6.6 (0–33.9) 0 (0–17.1) 0 (0–3.5)
multivariate
HG (n = 36)
No HG (n = 70)
p value
OR (95% CI)
p value
90.6 (38.4–100) 72 (14.3–98.2) 58.2 (7.7–90.5) 35.7 (1.4–80) 20 (1.4–67.6) 9.5 (0–33.3) 0 (0–17.2)
85.7 (67.6–99.1) 64.1 (32–89.3) 38.7 (12.6–73.5) 11.1 (0–43.1) 1.9 (0–17.6) 0 (0–4.9) 0 (0–1.7)
0.900 0.645 0.330 0.027 0.001 0.001 0.105
0.989 (0.963–1.016) 1.004 (0.979–1.030) 1.021 (0.993–1.050) 1.034 (1.001–1.070) 1.052 (1.010–1.097) 1.049 (0.993–1.109) 1.065 (0.978–1.159)
0.428 0.732 0.142 0.048 0.016 0.089 0.148
SBP load values, in %, are presented as median (interquartile interval). Statistically significant predictors are given in italics. SBP = Systolic blood pressure; HG = hematoma growth.
Table 3. Spearman’s correlation coefficients between different systolic blood pressure loads and baseline and 24-hour hematoma vol-
umes, and the amount of absolute and relative hematoma enlargement (n = 106) SBP load, mm Hg
140 150 160 170 180 190 200
Baseline hematoma volume
24-hour hematoma volume
Absolute hematoma enlargement
Relative hematoma enlargement
r
p value
r
p value
r
p value
r
p value
0.067 0.019 0.029 0.073 0.083 0.068 0.006
0.501 0.848 0.773 0.461 0.380 0.494 0.948
0.063 0.028 0.051 0.139 0.147 0.174 0.076
0.524 0.774 0.606 0.159 0.139 0.077 0.444
0.016 0.028 0.083 0.212 0.304 0.329 0.201
0.870 0.776 0.403 0.031 0.002 0.001 0.041
–0.004 0.030 0.086 0.222 0.311 0.365 0.211
0.969 0.762 0.384 0.023 0.001
