Current Hypertension Reports (2021) 23:3

https://doi.org/10.1007/s11906-020-01120-7

GUIDELINES / CLINICAL TRIALS/META-ANALYSIS (WJ KOSTIS, SECTION EDITOR)

Blood Pressure Management in Acute Ischemic Stroke

Dariusz Gąsecki 1 & Mariusz Kwarciany 1 & Kamil Kowalczyk 1 & Krzysztof Narkiewicz 2 & Bartosz Karaszewski 1

# The Author(s) 2020

Abstract
Purpose of Review Abrupt blood pressure (BP) rise is the most common clinical symptom of acute ischemic stroke (AIS).
However, BP alterations during AIS reflect many diverse mechanisms, both stroke-related and nonspecific epiphenomena, which
change over time and across patients. While extremes of BP as well as high BP variability have been related with worse outcomes
in observational studies, optimal BP management after AIS remains challenging.
Recent Findings This review discusses the complexity of the factors linking BP changes to the clinical outcomes of patients with
AIS, depending on the treatment strategy and local vessel status and, in particular, the degree of reperfusion achieved. The
evidence for possible additional clinical markers, including the presence of arterial hypertension, and comorbid organ dysfunc-
tion in individuals with AIS, as informative and helpful factors in therapeutic decision-making concerning BP will be reviewed,
as well as recent data on neurovascular monitoring targeting person-specific local cerebral perfusion and metabolic demand,
instead of the global traditional parameters (BP among others) alone.
Summary The individualization of BP management protocols based on a complex evaluation of the homeostatic response to
focal cerebral ischemia, including but not limited to BP changes, may be a valuable novel goal proposed in AIS, but further trials
are warranted.

Keywords Blood pressure . Hypertension . Acute ischemic stroke . Management

Introduction within minutes. The tissue surrounding the core is severely

hypoperfused and functionally impaired but still viable. This
Stroke is globally a leading cause of mortality and long-term zone, called the penumbra, is at high risk of infarction. It
disability in adults. Even though the prevalence and death rate permits cell survival for a certain period of time; however, it
due to stroke have decreased over the last years, the overall is extremely vulnerable to CBF fluctuations, which depend on
burden remains high, and the absolute number of people af- both local and global factors, such as cerebral vasoreactivity
fected continues to increase [1, 2]. Acute ischemic stroke or collaterals and systemic components, especially blood pres-
(AIS) accounts for approximately 70–85% of all strokes sure (BP). Therefore, the salvation of the ischemic penumbra
worldwide. is the holy grail of vascular neurology. There are two funda-
AIS is caused by a critical reduction in blood flow to the mental factors which allow this aim: (i) early recanalization
brain. Cerebral blood flow (CBF) is almost totally arrested in and reperfusion and (ii) the maintenance of CBF before reper-
the core region of the insult, which leads to neuronal death fusion occurs.
Strategies aiming at fast reperfusion, including intrave-
nous thrombolysis (IVT) and mechanical thrombectomy
This article is part of the Topical Collection on Guidelines / Clinical
Trials/Meta-Analysis (MT) within 4.5 and 6 h (in selected patients, up to 24),
respectively, from the stroke onset, remain the most effec-
* Dariusz Gąsecki tive therapeutic methods in standard care. However, the
[email protected] proper management of multiple clinical problems other
than—or secondary to—arterial occlusion is also signifi-
1
Department of Adult Neurology, Medical University of Gdańsk, ul, cantly associated with the final outcome. In this regard,
Dębinki 7, 80-952 Gdańsk, Poland hemodynamics plays a special role.
2
Department of Hypertension and Diabetology, Medical University of BP is one of the most important modifiers of vascular func-
Gdańsk, ul, Dębinki 7, 80-952 Gdańsk, Poland tion and organ perfusion, and its abnormalities are related to
 3 Page 2 of 11 Curr Hypertens Rep (2021) 23:3

vascular dysfunction, with cerebral circulation appearing as thresholds for defining HT dichotomously as a risk factor for
one of the most susceptible to BP dysregulations. stroke should be reconsidered.
Ischemic stroke is a consequence of a variety of patholog- Although sustained hypertension clearly increases the inci-
ical conditions, resulting from either systemic cardiovascular dence of stroke, also a transient and repetitive rise in BP,
(CV) diseases or primary cerebrovascular diseases, which, in referred to as BP variability (BPV), both short-term (day-
the great majority, may be considered as hypertensive or hy- night) and long-term (seasonal or visit-to-visit) BPV are relat-
pertension related. Therefore, a large proportion of AIS is a ed to an increased risk of stroke [6]. Moreover, an abnormal
consequence of chronic hypertension (HT). BP circadian course, characterized by an insufficient nocturnal
On the other hand, acute BP elevation is one of the most systolic BP (SBP) decrease (i.e., < 10%) compared to daily
common phenomena observed in the first hours and days after values, was proven to be associated with an increased risk of
AIS onset, which potentially strongly influences clinical deci- stroke [7]. Morning surge, characterized by an extreme SBP
sions and modifies the risk of acute complications. rise during the wake-up time, appears to be of particular rele-
There is a growing body of evidence that BP may be an vance and represents subpopulations at an elevated risk of
important factor related to stroke outcome; however, the avail- ischemic stroke and other stroke subtypes [8••].
able evidence shows conflicting results. Indeed, BP elevation Racial disparities in the burden of hypertension-related dis-
after stroke, being a common aspect of many processes, is eases may account for stroke incidence. African Americans as
rather descriptive, if not an epiphenomenon of a plethora of well as sub-Saharan Africans are known to have a higher
influencing factors, and further data is needed to predict stroke prevalence of HT, nocturnal HT, and a non-dipping BP profile
outcome. which starts earlier than in white people [9, 10]. They also
We believe that the associations of BP in the acute phase of have higher cardiovascular risk than white people, including
stroke with its clinical course should be analyzed as part of a ischemic stroke, which is largely driven by nocturnal BP [11].
long-standing process, which might begin even many years A steeper association of BP with stroke among Asians than
before the event, rather than as an acute phenomenon occur- among European populations was also observed [12]. A sim-
ring only in the first days after the disease onset. It seems to us ilar pattern was reported in Latin American countries, with the
that a paradigm shift in the management of BP in AIS is mean patient age at stroke onset being approximately 10 years
needed: from simplistic, based just on sole BP values, to more younger than in high-income countries (e.g., North America)
complex, including the identification and management of [13].
compensatory mechanisms, modified by chronic diseases, es- Based on the aforementioned, it is highly probable that an
pecially HT and, what is even more relevant, adjusted to local excess risk of stroke, partially beyond pure office BP values,
hemodynamic and metabolic demands in the ischemic area. may exist in the majority of ethnic groups worldwide.
The aim of this review is to discuss recent changes in the field
of the influence of BP and its management in AIS and to
present the perspectives of a complex approach to this impor-
tant aspect of AIS care. Blood Pressure in Acute Stroke

In the acute phase of AIS, increased BP (often reflecting a

Pre-stroke Blood Pressure transient reaction thus called acute hypertensive response,
AHR) is observed in approximately 75% of patients [14].
Pre-stroke HT is reported in 30–80% of AIS patients and, AHR is usually at its highest within the first hours after stroke
according to the INTERSTROKE study, accounts for approx- onset, then gradually declines [15], and usually settles within
imately 32 to 45% of the population-attributable risk of AIS. the first 7–10 days after stroke onset [16, 17].
Moreover, hypertension has been shown to be the main con- Interestingly, in some patients (particularly younger ones),
tributor to stroke mortality [3]. The prevalence of HT is the the absolute values of increased BP remain within “normoten-
highest among patients with large artery and small vessel pa- sive” limits. The mechanisms of this clinical setting are not
thologies and less common in patients with cardioembolic clear and probably very heterogenous.
stroke [4]. It is noteworthy that the frequency of hypertension AHR is a phenomenon caused by a myriad of factors [18].
increases with age, regardless of the stroke subtype [4]. On one hand, it might be related to preexisting conditions,
It is clear that the incidence and mortality in AIS are asso- including inadequately treated or undiagnosed hypertension
ciated with BP ≥ 140/90 mmHg (hypertension), but the risk [19–22] or diabetes mellitus [23]. On the other hand, it may
also increases when BP exceeds values as low as 115/ be linked to stroke-related factors such as damage to the brain
75 mmHg, especially when such values occurred early in life regions involved in autonomic regulation [24] or secondary
(higher BP load). Indeed, even prehypertension infers a great- sympathetic adrenomedullary pathway activation due to the
er risk of stroke than optimal BP levels [5]. Thus, the stroke itself [25–28].
Curr Hypertens Rep (2021) 23:3 Page 3 of 11 3

Frequently, it is associated with AIS consequences, e.g., BP patterns may also influence outcomes even in patients
urine retention, infection, cerebral edema, headache [29, 30], with poor collaterals. Lower BP fluctuations after reperfusion
or stress related to hospitalization [21, 31]. were shown to be associated with better long-term outcomes
Early recanalization can be achieved in up to 30% of pa- in patients undergoing MT.
tients treated with IVT alone [32], and the rate may increase to
even 80–90% [33, 34] in patients treated with MT. But even in
a best-case scenario, only up to 50% of patients who receive
this treatment may achieve functional independence, partially Blood Pressure Management
due to the fact that the core of the insult is already too large at
the time of reperfusion [35]. Recently, however, it has been Pre-hospital Phase
postulated that tissue outcome following AIS is associated
with multiple factors and mechanisms, other than those direct- The proper management in the pre-hospital phase is de-
ly related to local hypoperfusion, the potential outcome-based cisive in the treatment of ischemic stroke. As recanaliza-
significance of which is illustrated by a recently described tion and reperfusion are crucial factors influencing long-
reverse mismatch phenomenon [36–38]. term functional outcome [55], shortening of the onset-to-
This partially depends on individual factors such as vascular recanalization time should be the main aim of pre-
compliance or collaterals [39]. The latter are crucial in main- hospital treatment. However, since recanalization may
taining CBF in the penumbra, distally from the occluded artery not result in a clinical improvement in up to half of
[40]. Collaterals are associated with lower infarct volume patients [35], one should not neglect other potentially
growth and thus with better functional outcome [41]. As it modifiable conditions, such as blood oxygenation, glu-
has been recently shown in patients undergoing endovascular cose level, body temperature, and BP. According to the
treatment, the odds for a good clinical outcome were threefold current American Heart Association (AHA) guidelines
higher in patients with good collaterals than in patients with [56••] and European Stroke Organization (ESO)
absent collaterals [42]. However, collateral blood flow not only Consensus Statements and Recommendations [57], both
depends on individual anatomy but also on adaptive features published in 2018, BP should not be lowered in the pre-
like cerebral autoregulation (CA). Studies indicate that dynamic hospital phase. This has been confirmed by recently pub-
CA may be damaged by AIS, irrespective of the stroke subtype, lished results of the RIGHT-2 trial [58••], which showed
for up to 96 h, and remain abnormal for at least 1–2 weeks after that in patients with a presumed stroke and elevated BP,
the stroke [43]. Previous studies on static CA showed that it pre-hospital antihypertensive treatment with transdermal
may remain preserved in AIS [44]. In the case of dysregulated glyceryl trinitrate (GTN) does not improve functional
CA, CBF within the penumbra depends on systemic BP [45]. outcome. However, this study, together with previous
Within recent years, the relationship between blood pressure smaller trials [59], showed that ambulance-based studies
and collateral blood flow has been investigated. It is postulated are feasible and needed. A new study assessing transder-
that BP may influence collateral blood flow in AIS. mal GTN in the hyperacute phase of ischemic stroke is
On the other hand, BP values in the acute phase of stroke currently ongoing [60].
may reflect the individual efficacy of local (collaterals) and
systemic (volemia, cardiac output, vascular reaction) compen-
satory mechanisms. Intrahospital Phase
Sufficient collateral blood flow results in slower [46] and
smaller ischemic lesion growth [47]. Both the AHA and ESO guidelines indicate that in pa-
The majority of studies indicate that higher acute phase BP tients who are not qualified for either IVT or MT, BP
is associated with better collaterals in ischemic stroke patients s ho u l d n ot b e l o w e r ed , u nl es s i t e xc e ed s 2 2 0/
[48–52]. There is, however, some evidence from a few studies 120 mmHg. It is, however, highlighted that patients with
showing that lower BP may favor better pial collateral recruit- AIS, presenting symptoms of other severe, acute comor-
ment [53]. bidities (e.g., acute coronary event, acute heart failure,
The majority of studies indicate that higher BP may be an aortic dissection, or preeclampsia/eclampsia), may require
important factor improving cerebral blood flow in the penum- an emergency BP reduction. It is underlined that a BP
bra, however, under one major condition—reperfusion. A reduction should be careful and individualized since an
study by Hong et al. suggests that higher BP may result in a exaggerated drop in BP can result in complications, such
smaller infarct volume but only in patients with major reper- as stroke progression or acute kidney injury [56••, 57].
fusion. In the case of reperfusion failure, sustained high BP According to the AHA, a reasonable goal is a 15% re-
may result in increased infarct growth and an unfavorable duction in the initial BP [56••]. To date, no BP reduction
outcome [54••]. strategy has been shown to be superior.
 3 Page 4 of 11 Curr Hypertens Rep (2021) 23:3

Specific Treatment increased baseline thrombus burden or impaired endogenous

fibrinolysis [69•].
Intravenous Thrombolysis
Mechanical Thrombectomy
According to the current AHA and ESO guidelines, patients
who are eligible for treatment with intravenous thrombolysis Since 2015, mechanical thrombectomy has been a standard of
(IVT) should have their BP carefully lowered so that their treatment for ischemic stroke patients with anterior circulation
SBP is < 185 mmHg and their diastolic BP (DBP) is < large artery occlusions. In patients undergoing MT, and who
110 mmHg before IVT is initiated and < 180/105 mmHg dur- have not received IVT, both the AHA and ESO recommend
ing the first 24 h after the treatment [56••, 57]. These thresh- maintaining BP at ≤ 185/110 mmHg before the procedure, as
olds are extrapolated from thrombolysis trials in myocardial it was in 5 of 6 RCTs that demonstrated clinical benefits from
infarction as well as from the National Institute of Neurologic MT with stent retrievers up to 6 h from stroke onset
Disorders (NINDS) t-PA Trial [61]. (REVASCAT [70], SWIFT PRIME [71], EXTEND-IA [72],
However, BP levels higher than those recommended are THRACE [73], and MR CLEAN [74]) [56••, 57]. It is sug-
observed in up to 50% of patients who are eligible for IVT gested to maintain BP at ≤ 180/105 mmHg during, and for the
[62]. 14 h after, the procedure, regardless of whether or not the
It has been retrospectively shown that higher BP signifi- recanalization has been achieved [56••, 57]. These guidelines,
cantly increased the risk of hemorrhagic transformation [61, however, are not based on strong, scientifically proven data.
63]. The risk increased linearly, being four times higher in There are, however, several new studies which have addressed
patients with SBP > 170 mmHg compared to those at 141– the problem of BP treatment on functional outcome in patients
150 mmHg [64]. undergoing MT. It has been shown that either pre-, intra-, and
Moreover, it also increased in patients with higher BP var- postprocedural low and high BP and BP fluctuations may
iability [64–66]. This is in line with a finding that a cumulative negatively influence outcome in this group.
decline in SBP > 50 mmHg or an acute drop of > 30 mmHg The post hoc analysis of MR CLEAN demonstrated a U-
was associated with a decreased likelihood of a favorable out- shaped relationship between baseline SBP and poor functional
come. It is noteworthy that an acute drop in SBP, DBP, or outcome. The most favorable BP was 120 mmHg, and a 21%
MBP > 60 mmHg was associated with an increased risk of increase in the relative risk of hemorrhage for every 10 mmHg
death [67]. above this value was shown [75].
The exact BP at which the risk of hemorrhage after intra- This is in line with an analysis of baseline BPs from over
venous thrombolysis increases is rather individual and proba- 1300 patients enrolled in the Endovascular Treatment in
bly depends on BP per se but also on other acute and chronic Ischemic Stroke registry. In this group, there was a higher risk
factors [68••]. of mortality of 3.78 and 1.81 times for SBP < 110 mmHg and
Recently, ENCHANTED, a randomized control trial > 180 mmHg, respectively, compared with SBP 150–
(RCT) conducted in patients treated with IVT, showed a 160 mmHg as a reference [76–78].
reduced risk of hemorrhagic transformation in patients Intraprocedural BP is another important hemodynamic fac-
treated intensively (target systolic blood pressure at 130– tor influencing outcome in patients undergoing MT. In a large
140 mmHg) when compared to patients treated according study, patients with a favorable outcome presented moderately
to the guidelines over the first 72 h after stroke onset. elevated SBP (average maximal SBP 164 mmHg) compared
This, however, did not translate into an improved clinical with those with an unfavorable outcome (average maximal
outcome [68••]. SBP 181 mmHg) [79]. On the other hand, intraprocedural
In a recent meta-analysis, Malhotra et al. evaluated the hypotension is a strong predictor of poor outcome. In a study
impact of pre- and postthrombolysis BP values on clinical by Lowhagen Henden et al., a mean BP (MBP) fall of > 40%
outcome in over 56,000 AIS patients. In this group, a higher from the baseline was an independent predictor of an unfavor-
pre- and posttreatment SBP was associated with a higher risk able neurological outcome, in addition to well-established risk
of symptomatic intracerebral hemorrhage (sICH). factors such as a high baseline NIH Stroke Scale (NIHSS) or a
Moreover, elevated pre- and postinfusion BP was associat- lack of successful recanalization [80]. The results have been
ed with worse long-term functional outcome, even after ad- confirmed by more recent studies [81, 82].
justment for potential confounders [69•]. One of the most important factors influencing blood pres-
Another interesting finding of Malhotra’s meta-analysis is sure levels during the MT procedure is anesthesia. In recent
that higher mean pre-treatment SBP levels were recorded in years, conscious sedation (CS) has been preferred over gener-
AIS patients with proximal intracranial occlusion who did not al anesthesia (GA) as it was shown to be related with better
achieve tissue plasminogen activator-induced recanalization. functional outcome and decreased mortality [83]. This was
This suggests that elevated SBP might be a surrogate of mainly related to the effect GA may have on hemodynamics.
Curr Hypertens Rep (2021) 23:3 Page 5 of 11 3

Among MR CLEAN patients, the use of GA was associated aortic dissection, and blood loss, including retroperitoneal
with larger drops in MBP and longer episodes of hypotension hemorrhage and peri-procedural hemorrhage during MT. A
[84]. However, CS also carries a risk of hypotension. In a significant BP drop may occur during the induction phase of
study by Wahlin et al., among patients treated with MT under GA during MT, since a drop in BP is a side effect of most
CS, an MBP drop of ≥ 10% was associated with the highest anesthetic medications [96]. However, not only GA but also
risk of poor outcome. MBP < 85 mmHg before reperfusion, CS causes a decline in BP [97, 98] (see above).
and every 10 mmHg a drop in mean arterial pressure to below According to the latest AHA/ASA recommendations, hy-
100 mmHg were also associated with a worse prognosis [85]. potension and hypovolemia should be corrected to maintain a
Recent data from prospective trials can contribute to a systemic perfusion level necessary to support organ function
change in everyday practice. The GOLIATH, SIESTA, and [56••]. It is not indicated whether colloids or crystalloids
AnSTROKE studies showed no differences in the clinical should be used. The authors, however, do not indicate the
effect, regardless of the type of anesthesia. Although GA BP level below which the treatment should be initiated, how
was associated with more frequent drops in MBP > 20% from long it should be maintained, and which BP level should be a
the baseline compared to CS, there was no significant differ- treatment goal.
ence in large falls in MBP (either defined as a decline of > One should, however, remember that excessive fluid ther-
40% or MBP < 70 mmHg) between GA and CS [86•, 87•, 88]. apy may exacerbate chronic diseases like anemia and eventu-
These results are important evidence that CS and GA can be ally result in ischemic lesion growth [99].
equivalent methods of anesthesia in patients undergoing me- Recently, Bang et al. published the results of a randomized
chanical thrombectomy. study, evaluating the impact of phenylephrine-induced hyper-
BP treatment in the post MT period is another important tension on short- and long-term outcome in patients with non-
issue. Recanalization is achieved in up to 70–80% of patients cardioembolic stroke, causing a major neurologic deficit
[33, 34], which in a large portion of patients leads to a spon- (baseline NIHSS score 4–18 points), who were ineligible for
taneous reduction of BP. In those in which BP remains ele- recanalization therapy (IVT or MT) or who experienced a
vated, it increases the risk of hemorrhagic transformation and progression of the stroke. Patients with SBP > 170 mmHg
therefore poor functional outcome. In a study by Goyal et al., were excluded from the study. Induced hypertension was as-
patients with intensively (< 140/90 mmHg) and moderately sociated with early neurologic improvement and functional
(< 160/90 mmHg) lowered BP levels experienced lower mor- independence at 90 days, without severe complications
tality rates when compared to patients with permissive BP [100••]. This is the first randomized trial in this field, which
levels (< 220/120 mmHg or < 180/110 mmHg if IVT was may contribute to a change in future guidelines.
administered) [78]. This is in line with the finding that higher
peak values of SBP in the first 24 h after MT are associated
with worse functional outcomes at 90 days and greater sever- BP Management in Acute Ischemic Stroke
ity of hemorrhagic complications within 48 h after MT [89]. Patients With and Without Hypertension
The studies in the field of BP management during MT have
been summarized in a recent systematic review by Maier et al. In contrast to BP values, it is speculated that the history of
The results indicate particularly that BP drops during the pro- hypertension may serve as a reliable predictor of stroke out-
cedure may be associated with poor functional outcome come. The presence of hypertension and related end organ
[90••]. The data show that in the studies where the BP level damage should be accounted for in the individual overall car-
was strictly maintained between 120 (140) and 180 mmHg, diovascular risk, in general, as important determinants of both
there was no association between the BP level and the out- vascular and overall health.
come [91, 92]. Indeed, AIS patients with premorbid HT have an increased
risk of cerebral hypoperfusion or edema with a decline or rise
in BP, respectively. Moreover, patients with AIS and
Low Blood Pressure in AIS premorbid HT have a better prognosis at higher admission
BP values compared with those with preexisting normotonia
Low BP levels are detected in about 5–10% of patients with [101].
ischemic stroke, and this was shown to be related with poor Recent data have also suggested that the results of BP re-
functional outcome [93, 94]. Of note, the etiology of AIS ductions in AIS should be adjusted for premorbid
presenting low BP might be unrelated to occlusive vessel dis- hypertension.
ease, but this is beyond the scope of the article. In a Chinese trial, CATIS (China Antihypertensive Trial in
Low BP may be triggered by conditions other than neuro- Acute Ischemic Stroke), conducted among 4071 patients with
logical ones, such as hypovolemia [95], myocardial infarction, non-thrombolyzed ischemic stroke within 48 h of onset and
heart failure [94], takotsubo syndrome, cardiac arrhythmia, elevated systolic blood pressure, it was found that early
 3 Page 6 of 11 Curr Hypertens Rep (2021) 23:3

antihypertensive treatment was not associated with a com- return of reflected pressure waves to the heart, excessive aug-
bined primary outcome, defined as death or significant dis- mentation of central BP, and the transmission of flow pulsa-
ability (modified Rankin Scale score ≥ 3 > 2 points), at day 14 tions to the periphery) has emerged as one of the earliest
or hospital discharge, among patients with or without hyper- manifestations of vascular disease [106].
tension. However, a history of premorbid hypertension ap- Arterial stiffness is a potent risk factor for cardiovascular
peared to be discriminative regarding secondary stroke pre- complications, including stroke, in the same way as hyperten-
vention. In patients with pre-stroke hypertension, early anti- sion, and irrespective of BP levels.
hypertensive treatment was associated with a lower rate of 3- We and other authors showed that higher PWV is associ-
month recurrent strokes. Conversely, non-hypertensive pa- ated with a worse early and late clinical outcome after ische-
tients treated with antihypertensives in the initial stages of mic stroke [107–112]. Increased PWV was also found to be
AIS tended to have more recurrent strokes (p = 0.06) associated with a higher risk of vascular death [113].
[102••]. Of note, the results of the CATIS trial should be Furthermore, our team demonstrated that acute hypertensive
interpreted with caution, because they may not be valid for response, the most typical hemodynamic consequence of AIS,
other populations than the Chinese, where the prevalence of is independently associated with increased aortic stiffness
hypertension is high, and stroke is more common than coro- [114].
nary heart disease, especially in rural areas [103]. Another of our studies revealed that preserved left ventric-
Hypertension may also modify the clinical outcome in pa- ular ejection fraction and aortic compliance are associated,
tients undergoing a specific treatment of AIS. Available evi- independently of each other, with better neurologic outcome
dence shows that arterial hypertension is related to poor func- 10 days after ischemic stroke onset; the worst outcome was
tional outcome after intravenous thrombolysis [104]. observed in patients with both stiff aorta and low ejection
However, in a recently published multicentre study of ische- fraction [112].
mic stroke in patients eligible for intravenous thrombolysis The central augmentation index (cAIx) is a marker indirect-
(ENCHANTED study), hypertension favored neither ly associated with arterial stiffness and dependent on other
guideline-recommended blood pressure lowering nor inten- cardiovascular factors, such as heart rate, systolic ejection pe-
sive blood pressure lowering [68••]. Importantly, this trial ex- riod, and peripheral vasoconstriction. Central pressure is the
cluded patients with SBP > 185 mmHg. main drive for target organs, and therefore it seems to be a
In a recent meta-analysis on the effects of hypertension in more reliable haemodynamic parameter than peripheral BP,
patients undergoing mechanical thrombectomy (MT), it was both in physiology and pathology.
shown that the presence of hypertension was associated with a Studies on the association between cAIx and outcome after
lower rate of 90-day independence, regardless of the stroke ischemic stroke are conflicting, as are studies on the relation-
severity. However, this relationship was observed in ship between central pressure parameters and cardiovascular
Europeans, but not in Asian and American populations. events. Recently, we showed that a rise in the augmentation
Furthermore, hypertensive patients had also a higher rate of index between days 1 and 6 after stroke onset is associated
mortality after 3 months. Interestingly, there were no associa- with a better both early and late functional status [115]. The
tions between hypertension status and symptomatic intracere- significance of central BP parameters may also be of great
bral hemorrhage in patients with acute ischemic stroke treated interest and still may not be fully understood, requiring further
with MT [105]. research.
In summary, HT is not only one of the most important risk Of note, BP, as one of the key components of the complex
factors of ischemic stroke but also it may have an influence on hemodynamic response during ischemic stroke, is varied and
functional outcome. However, whether it is necessary to have inter-personally individualized according to acute and chronic
different BP management strategies for patients with acute mechanisms attempting to counteract the blood compromise
ischemic stroke with or without a history of hypertension be- in the ischemic brain area. Therefore, the individualization of
fore stroke onset is unclear. management protocols, depending on a more complex evalu-
ation of cerebral and global circulation, may be important in
the future.
Future Perspectives
Neuromonitoring: Dynamic and Personalized
Other Hemodynamic Parameters in Ischemic Stroke Hemodynamic Control

Extensive research demonstrates that arterial stiffening (re- Recently, local and global intracranial parameters, including
duced compliance and distensibility of arterial walls due to abnormal patterns of cerebral blood flow in cerebral large
their structural and functional alterations, with a resultant rise arteries or increased intracranial pressure, as assessed with
in pulse wave velocity (PWV), along with the premature transcranial Doppler (TCD), have been found to be predictive
Curr Hypertens Rep (2021) 23:3 Page 7 of 11 3

of tissue recovery and functional outcome after ischemic 24 h [121]. A novel study found that multimodal brain
stroke [116]. In a small Chinese RCT study, adequate TCD- imaging performed in acute stroke may accurately predict
guided BP control improved the prognosis of patients with reduced left ventricle ejection fraction (LVEF). The arte-
AIS in the anterior circulation who underwent MT. For those rial input function width on perfusion computed tomog-
who presented ultrasonographic signs of blood flow deceler- raphy has been shown to correlate with LVEF in AIS
ation or features of intracranial hypertension, BP manipulation and to identify patients with a reduced LVEF and in-
under the guidance of TCD monitoring appeared to reduce creased risk of worse clinical outcome 3 months after
early neurological deterioration and improved the final func- the event [122].
tional outcome. Furthermore, obstructive sleep apnea (OSA), a disorder
Similarly, dynamic instead of fixed BP thresholds have characterized by recurrent episodes of upper respiratory
been postulated as a guide for individualizing hemodynamic tract obstruction during sleep, accompanied by intermittent
management in AIS. In a small observational study from the hypoxia, is very common in AIS patients, with a preva-
USA, Petersen et al. proposed a novel approach to define the lence of 61.9%. Of importance, patients with AIS and
limits of autoregulation (LA) using near-infrared spectroscopy OSA have been shown to demonstrate a higher SBP after
(NIRS). Continuous non-invasive NIRS neuromonitoring in an ictus, as well as a higher rate of cardiac alterations,
response to changes in mean arterial pressure was found to including an increased left ventricular wall thickness and
identify and track the patient-specific BP range at which auto- left atrial diameter [123]. Both OSA and cardiac damage
regulation was optimally functioning in individual patients play a crucial role in AIS.
after large-vessel ischemic stroke [117]. Thus, metabolic and hemodynamic optimization, both at
Data suggests that LA values are not stable but change over the local and global level, may need to be considered as a
time and vary among individuals with AIS. Exceeding these potent neuroprotective strategy, though RCTs are needed to
individual and flexible thresholds of autoregulation was asso- determine the optimal hemodynamic approach.
ciated with worse functional outcome compared to the BP
range within LA. An increased risk of sICH and neurological
worsening was associated with elevated BP relative to each Conclusions
patient’s personalized upper LA, rather than the absolute in-
creased BP alone [118]. AIS is a major medical emergency with heterogenous patho-
This novel approach to define personalized, physiology across patients and over time. Elevated BP is the
autoregulation-based BP thresholds in acute ischemic stroke most common clinical symptom recorded at stroke presenta-
may present a better treatment strategy as compared with tra- tion; however, low BP may also occur, yet much less
ditional BP management, which aims to maintain BP below frequently.
the fixed thresholds, but therapies based on patients’ The physiological basis for the abrupt changes in BP short-
autoregulatory statuses need further research in randomized ly after focal cerebral ischemia remains poorly understood.
trials. Such changes represent many mechanisms, both nonspecific
and stroke related, that resolve within hours and days in the
Complex Cardiopulmonary Monitoring: Confounders vast majority of subjects, but it remains debatable as to wheth-
Influencing Bp and Outcome er they are of therapeutic relevance.
Recent data show the importance not only of pre-
Finally, traditional monitoring parameters (heart rate, BP, ox- recanalization but also intra- and postprocedural BP and its
ygen saturation) are secondary to many compensatory mech- variability.
anisms, depending on the patient and stroke baseline However, measures other than BP, including stroke and
characteristics. patient characteristics, may need to be considered in the early
Approximately 25% of AIS are of cardiac origin evaluation of the prognosis and treatment of altered BP in
[119]. Cardiac dysfunction can worsen the pre-stroke ce- AIS.
rebral damage. An adequate cardiac output (CO) corre- Individual parameters of cerebral circulation, such as
sponds to adequate oxygen delivery. Recently, CO has autoregulation-derived, personalized BP range, as well
been shown to be better associated with cerebral perfu- as the broader aspects of hemodynamic homeostasis
sion than blood pressure in ischemic stroke and with (cardiac output, pulse wave velocity) have also been
stroke outcome [120]. Indeed, cardiovascular complica- postulated as more robust and reliable predictors of
tions, including acute on-chronic coronary syndrome, ar- functional outcome in patients with AIS than BP alone.
rhythmias, autonomic dysfunction, and takotsubo syn- Advanced cerebral and systemic hemodynamic monitor-
drome, with or without subsequent heart failure, are ob- ing might be valuable goals in order to optimize the
served in the majority of AIS patients within the first penumbral perfusion in AIS.
 3 Page 8 of 11 Curr Hypertens Rep (2021) 23:3

Compliance with Ethical Standards middle-income versus high-income countries. Hypertension.

2016;68:1328–37.
11. Lackland DT, Roccella EJ, Deutsch AF, Fornage M, George MG,
Conflict of Interest The authors declare no conflicts of interest relevant
Howard G, et al. Factors influencing the decline in stroke mortal-
to this manuscript.
ity. A statement from the American Heart Association/American
Stroke Association. Stroke. 2014;45(1):315–53.
Human and Animal Rights and Informed Consent This article does not 12. Perkovic V, Huxley R, Wu Y, Prabhakaran D, Macmahon S. The
contain any studies with human or animal subjects performed by any of burden of blood pressure-related disease. A neglected priority for
the authors. global health. Hypertension. 2007;50:991–7.
13. Saposnik G, Hachinski V. The pathway towards an effective re-
Open Access This article is licensed under a Creative Commons duction of stroke burden worldwide: teamwork. Lancet Neurol.
Attribution 4.0 International License, which permits use, sharing, adap- 2019;18:622–3.
tation, distribution and reproduction in any medium or format, as long as 14. Qureshi AI, Ezzeddine MA, Nasar A, Suri MFK, Kirmani JF,
you give appropriate credit to the original author(s) and the source, pro- Hussein HM, et al. Prevalence of elevated blood pressure in 563,
vide a link to the Creative Commons licence, and indicate if changes were 704 adult patients with stroke presenting to the ED in the United
made. The images or other third party material in this article are included States. Am J Emerg Med. 2007 Jan;25(1):32–8.
in the article's Creative Commons licence, unless indicated otherwise in a 15. Broderick J, Brott T, Barsan W, Haley EC, Levy D, Marler J, et al.
credit line to the material. If material is not included in the article's Blood pressure during the first minutes of focal cerebral ischemia.
Creative Commons licence and your intended use is not permitted by Ann Emerg Med. 1993;22(9):1438–43.
statutory regulation or exceeds the permitted use, you will need to obtain
16. Wallace J, Levy L. Blood pressure after stroke. JAMA.
permission directly from the copyright holder. To view a copy of this
1981;246(19):2177–80.
licence, visit http://creativecommons.org/licenses/by/4.0/.
17. Britton M, Carlsson A, de Faire U. Blood pressure course in pa-
tients with acute stroke and matched controls. Stroke. 1986;17(5):
861–4.
18. Karaszewski B, Kwarciany M, Gąsecki D. Reply to: “Arterial
stiffness, central blood pressures, wave reflections, and acute hy-
References pertensive response in stroke.” Atherosclerosis. 2016;252:197–
198.
19. Fischer U, Cooney MT, Bull LM, Silver LE, Chalmers J,
Papers of particular interest, published recently, have been Anderson CS, et al. Acute post-stroke blood pressure relative to
highlighted as: premorbid levels in intracerebral haemorrhage versus major isch-
aemic stroke: a population-based study. Lancet Neurol.
• Of importance 2014;13(4):374–84.
•• Of major importance 20. Jørgensen HS, Nakayama H, Christensen HR, Raaschou HO,
Kampmann JP, Olsen TS. Blood pressure in acute stroke. The
1. Bill F, Foundation MG. Global, regional, and national burden of Copenhagen Stroke Study Cerebrovasc Dis. 2002;13:204–9.
stroke, 1990–2016: a systematic analysis for the Global Burden of 21. Toyoda K, Okada Y, Fujimoto S, Hagiwara N, Nakachi K,
Disease Study 2016. Lancet Neurol. 2016;18:439–58. Kitazono T, et al. Blood pressure changes during the initial week
2. Feigin VL, Norrving B, Mensah GA. Global burden of stroke. after different subtypes of ischemic stroke. Stroke. 2006;37(10):
Circ Res. 2017;120:439–48. 2637–9.
3. Pistoia F, Sacco S, Degan D, Tiseo C, Ornello R, Carolei A. 22. Semplicini A, et al. Hypertension in acute ischemic stroke. Arch
Hypertension and stroke: epidemiological aspects and clinical Intern Med. 2003;163:211–6.
evaluation. High Blood Press Cardiovasc Prev. 2016;23(1):9–18. 23. Toyoda K, Okada Y, Jinnouchi J, Gotoh S, Yokoyama Y,
4. Hauer AJ, Ruigrok YM, Algra A, Dijk EJ Van, Koudstaal PJ, Fujimoto S, et al. High blood pressure in acute ischemic.
Cerebrovasc Dis. 2006;22:355–61.
Luijckx G, et al. Age-specific vascular risk factor profiles accord-
ing to stroke. J Am Heart Assoc. 2017;6(e005090) 24. Qureshi AI. Acute hypertensive response in patients with stroke
pathophysiology and management. Circulation. 2008;118(2):
5. Egan BM, Stevens-Fabry S. Prehypertension—prevalence, health
176–87.
risks, and management strategies. Nat Rev Cardiol. 2015;12:289–
25. Olsson T, Marklund N, Gustafson Y, Nasman B. Abnormalities at
300.
different levels of the hypothalamic-pituitary-adrenocortical axis
6. Rothwell PM, Howard SC, Dolan E, O’Brien E, Dobson JE, early after stroke. Stroke. 1992;23:1573–6.
Dahlöf B, et al. Prognostic significance of visit-to-visit variability, 26. Myers MG, W NJ, Hachinski VC, J SM Plasma norepinephrine in
maximum systolic blood pressure, and episodic hypertension. stroke Stroke 1981;12(2):200–204.
Lancet. 2010;375(9718):895–905. 27. Fiehler J, Cognard C, Gallitelli M, Jansen O, Kobayashi A, Mattle
7. O’Brien E, Sheridan J, O’Malley K. Dippers and non-dippers. HP, et al. European recommendations on organisation of interven-
Lancet. 1988;332(8607):397. tional care in acute stroke (EROICAS). Eur Stroke J. 2016;1(3):
8.•• Kario K. Perfect 24-hr blood pressure control: up-to-date 2020. 155–70.
Curr Hypertens Rev. 2020;16:2–10. This article highlights the 28. Jansen PAF, Thien T, Gribnau FWJ, Schulte BPM, Willemsen JJ,
importance of best possible 24-hour blood pressure control Lamers KJB, et al. Blood pressure and both venous and urinary
and the need for individualized HT management. catecholamines after cerebral infarction. Clin Neurol Neurosurg.
9. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, 1988;90(1):41–5.
Cushman M, et al. Heart disease and stroke statistics-2015 update: 29. Chamorro Á, Amaro S, Vargas M, Obach V, Cervera Á, Gómez-
a report from the American Heart Association. Circulation. 2015. Choco M, et al. Catecholamines, infection, and death in acute
e29–322. ischemic stroke. J Neurol Sci. 2007;252:29–35.
10. Countries MVH, Owolabi M, Olowoyo P, Miranda JJ, Akinyemi 30. Olsen TS, Larsen B, Herning M, Skriver E, Lassen N. Original
R, Feng W, et al. Gaps in hypertension guidelines in low- and contributions blood flow and vascular reactivity in collaterally
Curr Hypertens Rep (2021) 23:3 Page 9 of 11 3

perfused brain tissue evidence of an ischemic penumbra in patients 49. Wufuer A, Xiaoning Z. Blood pressure and collateral circulation
with acute stroke. Stroke. 1983;14(3):332–41. in acute ischemic stroke. Herz. 2019;44:455–9.
31. Carlberg B, Asplund K, Hägg E. Factors influencing admission 50. Rusanen H, Saarinen T, Sillanpää N. The association of blood
blood pressure levels in patients with acute stroke. Stroke. 1991 pressure and collateral circulation in hyperacute ischemic stroke
Apr;22(4):527–30. patients treated with intravenous thrombolysis. Cerebrovasc Dis.
32. Menon BK, Al-Ajlan FS, Najm M, Puig J, Castellanos M, 2015;39:130–7.
Dowlatshahi D, et al. Association of clinical, imaging, and throm- 51. Jiang B, Churilov L, Kanesan L, Dowling R, Mitchell P, Dong Q.
bus characteristics with recanalization of visible intracranial oc- Blood pressure may be associated with arterial collateralization in
clusion in patients with acute ischemic stroke. JAMA. anterior circulation ischemic stroke before acute reperfusion ther-
2018;320(10):1017–1026. apy. J Stroke. 2017;19(2):222–8.
33. Froehler MT. Interhospital transfer before thrombectomy is asso- 52. Raychev R, Liebeskind DS, Yoo AJ, Rasmussen M, Arnaudov D,
ciated with delayed treatment and worse outcome in the STRATIS Brown S, et al. Physiologic predictors of collateral circulation and
registry (systematic evaluation of patients treated with infarct growth during anesthesia – detailed analyses of the
neurothrombectomy devices for acute ischemic stroke). GOLIATH trial. J Cereb Blood Flow Metab. 2020;40(6):1203–12.
Circulation. 2017;136:2311–21. 53. Christoforidis GA, Saadat N, Kontzialis M, Karakasis CJ, Slivka
34. Zaidat OO, Castonguay AC, Nogueira RG, Haussen DC, English AP. Predictors for the extent of pial collateral recruitment in acute
JD, Satti SR, et al. TREVO stent-retriever mechanical ischemic stroke. Neuroradiol J. 2020;33(2):98–104.
thrombectomy for acute ischemic stroke secondary to large vessel 54.•• Hong L, Cheng X, Lin L, Bivard A, Ling Y, Butcher K, et al. The
occlusion registry. J NeuroIntervent Surg. 2018;516–524. blood pressure paradox in acute ischemic stroke. Ann Neurol.
35. Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, 2019;85(3):331–9. This study suggests that higher BP may re-
et al. Intra-arterial prourokinase for acute ischemic stroke. JAMA. sult in a smaller infarct volume in patients with major reper-
1999;282(21):2003–11. fusion. In the case of reperfusion failure, high BP may result in
36. Karaszewski B, Jabłoński B, Żukowicz W. The salvageable brain increased infarct growth and an unfavorable outcome.
in acute ischemic stroke. The concept of a reverse mismatch: a 55. Goyal M, Menon BK, Van Zwam WH, Dippel DWJ, Mitchell PJ,
mini-review. Metab Brain Dis 2020;35:237–240. Demchuk AM, et al. Endovascular thrombectomy after large-
37. Karaszewski B, Thomas RGR, Chappell FM, Armitage PA, vessel ischaemic stroke: a meta-analysis of individual patient data
Carpenter TK, Lymer GKS, et al. Brain choline concentration. from five randomised trials. Lancet. 2016;387:1723–31.
Early quantitative marker of ischemia and infarct expansion? 56.•• Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM,
Neurology. 2010;75:850–6. Bambakidis NC, Becker K, et al. Guidelines for the early man-
38. Karaszewski B, Wardlaw JM, Marshall I, Cvoro V, Wartolowska agement of patients with acute ischemic stroke: 2019 update to
K, Haga K, et al. Early brain temperature elevation and anaerobic the 2018 guidelines for the early management of acute ischemic
metabolism in human acute ischaemic stroke. Brain. 2009;132: stroke. Stroke. 2019;50:e344–418. These are the current rec-
955–64. ommendations for treatment of AIS patients.
39. Baron J. Perfusion thresholds in human cerebral ischemia: histor- 57. Ahmed N, Audebert H, Turc G, Cordonnier C, Christensen H,
ical perspective and therapeutic implications. Cerebrovasc Dis. Sacco S, et al. Consensus statements and recommendations from
2001;11(suppl 1):2–8. the ESO-Karolinska Stroke Update Conference, Stockholm 11–13
40. Brozici M, van der Zwan A, Hillen B. Anatomy and functionality November 2018. Eur Stroke J 2018;4(4):307–317.
of leptomeningeal anastomoses: a review. Stroke. 2003:2750–62. 58.•• Bath PM, Scutt P, Anderson CS, Appleton JP, Berge E, Cala L,
41. Bang OY, Saver JL, Buck BH, Alger JR, Starkman S, Ovbiagele et al. Prehospital transdermal glyceryl trinitrate in patients with
B, et al. Impact of collateral flow on tissue fate in acute ischaemic ultra-acute presumed stroke (RIGHT-2): an ambulance-based,
stroke. J Neurol Neurosurg Psychiatry. 2008;79:625–9. randomised, sham-controlled, blinded, phase 3 trial. Lancet.
42. Berkhemer OA, Jansen IGH, Beumer D, Fransen PSS, Berg LA Van 2019;393:1009–20. This is a randomized controlled trial show-
Den, Yoo AJ, et al. Collateral status on baseline computed tomograph- ing that pre-hospital treatment with transdermal GTN does
ic angiography and intra-arterial treatment effect in patients with prox- not seem to improve functional outcome in patients with pre-
imal anterior circulation stroke. Stroke. 2016;768–776. sumed stroke.
43. Dawson SL, Panerai B, Potter JF. Serial changes in static and 59. Shaw L, Price C, Mclure S, Howel D, Mccoll E, Younger P, et al.
dynamic cerebral autoregulation after acute ischaemic stroke. Paramedic initiated lisinopril for acute stroke treatment (PIL-
Cerebrovasc Dis. 2003;16:69–75. FAST): results from the pilot randomised controlled trial. Emerg
44. Xiong L, Liu X, Shang T, Smielewski P, Donnelly J, Guo Z, et al. Med J. 2014;31:994–9.
Impaired cerebral autoregulation: measurement and application to 60. Van Den Berg SA, Dippel DWJ, Hofmeijer J, Fransen PSS,
stroke. J Neurol Neurosurg Psychiatry. 2017;520–531. Caminada K. Multicentre randomised trial of acute stroke treatment
45. Jordan JD, Powers WJ. Cerebral autoregulation and acute ische- in the ambulance with a nitroglycerin patch (MR ASAP): study pro-
mic stroke. Am J Hypertens. 2012;25(9):946–50. tocol for a randomised controlled trial. Trials. 2019;20(1):383.
46. Arenillas JF, Cortijo E, Garcı P, Levy EI, Jahan R, Liebeskind D, 61. The National Institute of Neurological Disorders and Stroke rt-PA
et al. Relative cerebral blood volume is associated with collateral Stroke Study Group. Tissue plasminogen activator for acute ische-
status and infarct growth in stroke patients in SWIFT PRIME. J mic stroke. N Engl J Med. 1995 Dec 14;333(24):1581–7.
Cereb Blood Flow Metab. 2018;38(10):1839–1847. 62. Vitt JR, Trillanes M, Hemphill JC. Management of blood pressure
47. Puhr-Westerheide D, Tiedt S, Rotkopf LT, Herzberg M, Reidler P, during and after recanalization therapy for acute ischemic stroke.
Fabritius MP, et al. Clinical and imaging parameters associated Front Neurol. 2019;10(138):1–13.
with hyperacute infarction growth in large vessel occlusion stroke. 63. Butcher K, Christensen S, Parsons M, Silva DA De, Ebinger M,
Stroke. 2019;50:2799–804. Levi C, et al. Postthrombolysis blood pressure elevation is associ-
48. Mechtouff L, Bochaton T, Paccalet A, Da Silva CC, Buisson M, ated with hemorrhagic transformation. Stroke. 2009;41:72–77.
Amaz C, et al. Matrix metalloproteinase-9 and monocyte 64. Ahmed N, Wahlgren N, Brainin M, Castillo J, Ford GA, Kaste M,
chemoattractant protein-1 are associated with collateral status in et al. Relationship of blood pressure, antihypertensive therapy, and
acute ischemic stroke with large vessel occlusion. Stroke. outcome in ischemic stroke treated with intravenous thrombolysis:
2020;51:2232–5. retrospective analysis from Safe Implementation of Thrombolysis
 3 Page 10 of 11 Curr Hypertens Rep (2021) 23:3

in Stroke-International Stroke Thrombolysis Register (SITS- outcome in patients undergoing endovascular therapy for acute
ISTR. Stroke. 2009 Jul;40(7):2442–2449. ischemic stroke. Interv Neurol. 2015;4:151–7.
65. Yong M, Kaste M. Association of characteristics of blood pressure 80. Löwhagen Hendén P, Rentzos A, Karlsson J, Rosengren L,
profiles and stroke outcomes in the ECASS-II trial. Stroke. Sundeman H, Reinsfelt B. Hypotension during endovascular
2008;39(2):366–72. treatment of ischemic stroke is a risk factor for poor neurological
66. Stead LG, Gilmore RM, Vedula KC, Weaver AL, Decker outcome. Stroke. 2015;46:2678–80.
WWBRJ. Impact of acute blood pressure variability on ischemic 81. Bennett AE, Wilder MJ, Mcnally JS, Wold JJ, Stoddard GJ,
stroke outcome. Neurology. 2006;66(12):1878–81. Majersik JJ, et al. Increased blood pressure variability after
67. Silver B, Lu M, Morris DC, Mitsias PD, Lewandowski C, Chopp endovascular thrombectomy for acute stroke is associated with
M. Blood pressure declines and less favorable outcomes in the worse clinical outcome. J NeuroIntervent Surg. 2018;10:823–7.
NINDS tPA stroke study. J Neurol Sci. 2008;271:61–7. 82. Maïer B, Turc G, Taylor G, Desilles J, Redjem H, Ciccio G, et al.
68.•• Anderson CS, Huang Y, Lindley RI, Chen X, Arima H, Chen G, Prognostic significance of pulse pressure variability during me-
et al. Intensive blood pressure reduction with intravenous throm- chanical thrombectomy in acute ischemic stroke patients. J Am
bolysis therapy for acute ischaemic stroke (ENCHANTED): an Hear Assoc. 2018;7:1–8.
international, randomised, open-label, blinded-endpoint, phase 3 83. Abou-Chebl A, Zaidat OO, Castonguay AC, Gupta R, Sun CJ,
trial. Lancet. 2019;393:877–88. This randomized controlled tri- Martin CO, et al. North American SOLITAIRE Stent-Retriever
al showed a reduced risk of hemorrhagic transformation in Acute Stroke Registry. Stroke. 2014;45:1396–1401.
patients undergoing IVT treated intensively when compared 84. Treurniet KM, Berkhemer OA, Immink RV, Lingsma HF, Stam
to patients treated according to the guidelines over the first VMCW Der, Hollmann MW, et al. A decrease in blood pressure is
72h after stroke onset. This, however, did not translate into an associated with unfavorable outcome in patients undergoing
improved clinical outcome. thrombectomy under general anesthesia. J NeuroIntervent Surg.
69.• Malhotra K, Ahmed N, Filippatou A, Katsanos AH, Goyal N, 2018;10:107–111.
Alexandrov AW, et al. Association of elevated blood pressure 85. Whalin XMK, Halenda XKM, Haussen XDC, Rebello XLC,
levels with outcomes in acute ischemic stroke patients treated with Frankel XMR, Gershon XRY, et al. Even small decreases in blood
intravenous thrombolysis: a systematic review and meta-analysis. pressure during conscious sedation affect clinical outcome after
2019;21(1):78–90. This review and meta-analysis stroke thrombectomy: an analysis of hemodynamic thresholds.
demonsrated higher risk of sICH and unfavorable outcome Am J Neuroradiol. 2017;38:294–8.
in patients undergoing IVT and higher pre- and post-stroke 86.• Simonsen CZ, Yoo AJ, Sørensen LH, Juul N, Johnsen SP,
SBP. Andersen G, et al. Effect of general anesthesia and conscious
70. Tomasello A, Castaño C, Blasco J, Aja L, Dorado L. sedation during endovascular therapy on infarct growth and clin-
Thrombectomy within 8 hours after symptom onset in ischemic ical outcomes in acute ischemic stroke: a randomized clinical trial.
stroke. N Engl J Med. 2015;372:2296–306. JAMA Neurol. 2018;75(4):470–477. This is a randomized con-
71. Saver JL, Goyal M, Bonafe A, Diener H-C, Levy EI, Pereira VM, trolled trial showing that in patients undergoing
et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA thrombectomy for AIS caused by large vessel occlusions in
alone in stroke. N Engl J Med. 2015;372:2285–95. the anterior circulation, GA did not result in worse tissue or
72. Campbell BCV, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, clinical outcomes compared with CS.
Yassi N, et al. Endovascular therapy for ischemic stroke with 87.• Löwhagen Hendén P, Rentzos A, Karlsson JE, Rosengren L,
perfusion-imaging selection. N Engl J Med. 2015;372:1009–18. Leiram B, Sundeman H, et al. General anesthesia versus con-
73. Bracard S, Ducrocq X, Mas JL, Soudant M, Oppenheim C, scious sedation for endovascular treatment of acute ischemic
Moulin T, et al. Mechanical thrombectomy after intravenous stroke. The AnStroke Trial (Anesthesia During Stroke). Stroke.
alteplase versus alteplase alone after stroke (THRACE): a 2017;48:1601–7. This randomized controlled trial shows no
randomised controlled trial. Lancet Neurol. 2016;15(11):1138– difference between GA and CS in neurological outcome 3
47. months after stroke.
74. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, 88. Schönenberger S, Möhlenbruch M, Pfaff J, Mundiyanapurath S,
Lingsma HF, Yoo AJ, et al. A randomized trial of intraarterial Kieser M, Bendszus M, et al. Sedation vs. Intubation for
treatment for acute ischemic stroke. N Engl J Med. 2015;372: Endovascular Stroke TreAtment (SIESTA) - a randomized
11–20. monocentric trial. Int J Stroke. 2015;10(6):969–78.
75. Mulder MJHL, Ergezen S, Lingsma HF, Berkhemer OA, Fransen 89. Mistry EA, Mistry AM, Nakawah MO, Khattar NK, Fortuny EM,
PSS, Beumer D, et al. Baseline blood pressure effect on the benefit Cruz AS, et al. Systolic blood pressure within 24 hours after
and safety of intra-arterial treatment in MR CLEAN (multicenter thrombectomy for Acute Ischemic Stroke Correlates With
randomized clinical trial of endovascular treatment of acute ische- Outcome. Am Hear Assoc. 2017;6:e006167.
mic stroke in the Netherlands). Stroke. 2017;48(7):1869–76. 90.•• Maïer B, Fahed R, Khoury N. Association of blood pressure dur-
76. Maïer B, Gory B, Taylor G, Labreuche J, Blanc R, Obadia M, ing thrombectomy for acute ischemic stroke with functional out-
et al. Mortality and disability according to baseline blood pressure come. Stroke. 2019;50:2805–12. This current meta-analysis
in acute ischemic stroke patients treated by thrombectomy: a col- highlights that BP drops during MT may be associated with
laborative pooled analysis. J Am Heart Assoc. 2017;6(10). a worse functional outcome. It also suggests that if strict SBP
77. Goyal N, Tsivgoulis G, Iftikhar S, Khorchid Y, Fawad Ishfaq M, targets are achieved, no association between BP and function-
Doss VT, et al. Admission systolic blood pressure and outcomes al outcome is noted.
in large vessel occlusion strokes treated with endovascular treat- 91. Rasmussen M, Espelund US, Juul N, Yoo AJ, Sørensen LH,
ment. J Neurointerv Surg. 2017;9(5):451–4. Sørensen KE, et al. The influence of blood pressure management
78. Goyal N, Tsivgoulis G, Pandhi A, Dillard K, Alsbrook D, Chang on neurological outcome in endovascular therapy for acute isch-
JJ, et al. Blood pressure levels post mechanical thrombectomy and aemic stroke. Br J Anaesth. 2018;120(6):1287–94.
outcomes in non-recanalized large vessel occlusion patients. 92. Schönenberger S, Uhlmann L, Ungerer M, Pfaff J, Nagel S, Klose
Neurology. 2017;89:540–7. C, et al. Association of blood pressure with short- and long-term
79. John S, Hazaa W, Uchino K, Thebo U, Hussain MS, Toth G, et al. functional outcome after stroke thrombectomy. Post hoc analysis
Lower intraprocedural systolic blood pressure predicts good of the SIESTA trial. Stroke. 2018;49:1451–6.
Curr Hypertens Rep (2021) 23:3 Page 11 of 11 3

93. Leonardi-Bee J, Bath PMW, Phillips SJ, Sandercock PAG. Blood outcome after ischemic stroke. Atherosclerosis. 2012;225(2):348–
pressure and clinical outcomes in the international stroke trial. 52.
Stroke. 2002;33(5):1315–20. 109. Ishizuka K, Hoshino T, Shimizu S, Shirai Y, Mizuno S, Toi S,
94. Wohlfahrt P, Krajcoviechova A, Jozifova M, Mayer O, Vanek J, et al. Brachial-ankle pulse wave velocity is associated with 3-
Filipovsky J, et al. Low blood pressure during the acute period of month functional prognosis after ischemic stroke.
ischemic stroke is associated with decreased survival. J Hypertens. Atherosclerosis. 2016;255:1–5.
2015;33:339–45. 110. Lee Y-B, Park J-H, Kim E, Kang C-K, Park H-M. Arterial stiff-
95. Kreimeier U. Pathophysiology of fluid imbalance. Crit Care. ness and functional outcome in acute ischemic stroke. J
2000;4(suppl 2):S3–7. Cerebrovasc Endovasc Neurosurg. 2014;16(1):11.
96. Fandler S, Stefan H, Placido H, Delgado A, Kneihsl M, Hassler E, 111. Matsushima H, Hosomi N, Hara N, Yoshimoto T, Neshige S,
et al. Single mean arterial blood pressure drops during stroke Kono R, et al. Ability of the ankle brachial index and brachial-
thrombectomy under general anaesthesia are associated with poor ankle pulse wave velocity to predict the 3-month outcome in pa-
outcome. J Neurol. 2020;267(5):1331–9. tients with non-cardioembolic stroke. J Atheroscler Thromb.
97. Petersen NH, Ortega-gutierrez S, Wang A, Lopez GV, Strander S, 2017;24(11):1167–73.
Kodali S, et al. Decreases in blood pressure during thrombectomy 112. Rojek A, Gasecki D, Fijalkowski M, Kowalczyk K, Kwarciany
are associated with larger infarct volumes and worse functional M, Wolf J, et al. Left ventricular ejection fraction and aortic stiff-
outcome. Stroke. 2019;50:1797–804. ness are independent predictors of neurological outcome in acute
98. Valent A, Sajadhoussen A, Maier B, Lapergue B, Labeyrie M-A, ischemic stroke. J Hypertens. 2016;34:2441–8.
Reiner P, et al. A 10% blood pressure drop from baseline during
113. Ahn KT, Jeong J, Jin S, Kim M, Oh JK, Seong S, et al. Brachial-
mechanical thrombectomy for stroke is strongly associated with
ankle PWV for predicting clinical outcomes in patients with acute
worse neurological outcomes. J NeuroIntervent Surg. 2020;12:
stroke. Blood Press. 2017;26:204–10.
363–9.
99. Bellwald S, Balasubramaniam R, Nagler M, Burri MS, Fischer 114. Kwarciany M, Gasecki D, Kowalczyk K, Rojek A, Laurent S,
SDA, Hakim A, et al. Association of anemia and hemoglobin Boutouyrie P, et al. Acute hypertensive response in ischemic stroke
decrease during acute stroke treatment with infarct growth and is associated with increased aortic stiffness. Atherosclerosis.
clinical outcome. PLoS One. 2018;13(9):1–13. 2016;251:1–5.
100.•• Bang OY, Chung J-W, Kim S-K, Kim SJ, Lee MJ, Hwang J, et al. 115. Kowalczyk K, Jabłoński B, Kwarciany M, Narkiewicz K, Gąsecki
Therapeutic-induced hypertension in patients with D. Changes of augmentation index early after ischaemic stroke
noncardioembolic acute stroke. Neurology. 2019;93(21):e1955– predict functional outcome. Blood Press. 2020;29:327–335.
63. The study suggests that phenylephrine-induced hyperten- 116. Chen H, Su Y, He Y, Zhang Y, Sun Y, Fan L. Controlling blood
sion may be safe and may result in early- and long-term neu- pressure under transcranial Doppler guidance after endovascular
rologic improvement in patients ineligible for revasculariza- treatment in patients with acute ischemic stroke. Cerebrovasc Dis.
tion therapy and those with progressive stroke. 2020;49:160–9.
101. Okumura K, Ohya Y, Maehara A, Wakugami K, Iseki K, 117. Wang A, Sheth K, Marshall R, Mampre D, Hebert R, Matouk C,
Takishita S. Effects of blood pressure levels on case fatality after et al. Autoregulation-based blood pressure optimization after
acute stroke. J Hypertens. 2005 Jun;23(6):1217–23. large-vessel ischemic stroke using non-invasive near-infrared
102.•• Zhang R, Zhong C, Zhang Y, Xie X, Zhu Z, Wang A, et al. spectroscopy monitoring. Neurology. 2018;90(suppl 15):S21.008.
Immediate antihypertensive treatment for patients with acute is- 118. Petersen NH, Silverman A, Strander SM, Kodali S, Wang A,
chemic stroke with or without history of hypertension: a second- Sansing LH, et al. Fixed compared with autoregulation-oriented
ary analysis of the CATIS randomized clinical trial. JAMA Netw blood pressure thresholds after mechanical thrombectomy for is-
open. 2019;2(7):e198103. Data from a secondary analysis of chemic stroke. Stroke. 2020;51:914–21.
the randomized clinical trial suggesting that early antihyper- 119. Paciaroni M, Agnelli G, Caso V, Venti M, Milia P, Silvestrelli G,
tensive therapy may be associated with a decreased rate of et al. Atrial fibrillation in patients with first-ever stroke: frequency,
recurrent stroke among patients with a history of antithrombotic treatment before the event and effect on clinical
hypertension. outcome. J Thromb Haemost. 2005;3:1218–23.
103. Zhao D, Liu J, Wang M, Zhang X, Zhou M. Epidemiology of 120. Byun JI, Jung KH, Kim YD, Kim JM, Roh JK. Cardiac function
cardiovascular disease in China: current features and implications. and outcome in patients with cardio-embolic stroke. PLoS One.
Nat Rev Cardiol. 2019;16:203–12. 2014;9(4):e95277.
104. Zonneveld TP, Algra A, Dippel DWJ, Kappelle LJ, van 121. Gunnoo T, Hasan N, Khan MS, Slark J, Bentley P, Sharma P.
Oostenbrugge RJ, Roos YBWEM, et al. The ThRombolysis in Quantifying the risk of heart disease following acute ischaemic
UnconTrolled Hypertension (TRUTH) protocol: an observational stroke: a meta-analysis of over 50 000 participants. BMJ Open.
study on treatment strategy of elevated blood pressure in stroke 2016;6(e009535).
patients eligible for IVT. BMC Neurol. 2015;15:1–6. 122. Garcia-Esperon C, Spratt NJ, Gangadharan S, Miteff F, Bivard A,
105. Yuan Z, Chen N, Zhou M, Guo J, Zhang Y, Li Y, et al. Effects of Lillicrap T, et al. Computed tomography perfusion identifies pa-
hypertension in patients receiving mechanical thrombectomy. tients with stroke with impaired cardiac function. Stroke. 2020;51:
Medicine (Baltimore). 2020;99(16):e19803. 498–503.
106. Cavalcante JL, Lima JAC, Redheuil A, Al-Mallah MH. Aortic
123. Mattaliano P, Lombardi C, Sangalli D, Faini A, Corrà B, Adobbati
stiffness: current understanding and future directions. J Am Coll
L, et al. Impact of obstructive sleep apnea on cardiac organ dam-
Cardiol. 2011;57(14):1511–22.
age in patients with acute ischemic stroke. J Hypertens.
107. Gąsecki D, Rojek A, Kwarciany M, Kubach M, Boutouyrie P,
2018;36(6):1351–9.
Nyka W, et al. Aortic stiffness predicts functional outcome in
patients after ischemic stroke. Stroke. 2012;43:543–4.
108. Gasecki D, Rojek A, Kwarciany M, Kowalczyk K, Boutouyrie P, Publisher’s Note Springer Nature remains neutral with regard to jurisdic-
Nyka W, et al. Pulse wave velocity is associated with early clinical tional claims in published maps and institutional affiliations.