Blood pressure in acute ischaemic stroke : blood pressure and stress in the acute phase of stroke and influence of initial blood pressure on stroke-outcome

Background and objectives: Most patients (70-80%) with acute ischaemic or haemorrhagic stroke exhibit a high systemic blood pressure (BP) on admission to hospital even in the absence of a history of hypertension (=50%). In matched-control patients admitted to hospital for other acute diseases the proportion of high BP is only 36%. For most patients this high initial BP falls spontaneously without anti-hypertensive treatments over the next few days. The cause and exact mechanism of high BP during the acute phase of stroke is still unknown and mental stress is often suggested as a main contributing factor. There is conflicting evidence regarding the relationship between high initial BP, lowering of high initial BP and outcome after acute stroke.

The objectives of this thesis were (I) to examine the relationship between nimodipine (a calcium channel blocker) induced reduction of BP and outcome, 01) to evaluate the relationship between high initial BP and outcome, (III) to investigate whether heterogeneity exists between stroke subtypes in the response to BP lowering treatment and (IV) to investigate the relationship between BP and stress as evaluated by salivary cortisol and psychological tests in patients with acute ischaemic stroke.

Subjects & methods: To fulfil objectives I-III, a dataset from a previously performed clinical trial (Intravenous Nimodipine West European Stroke Trial, INWEST) was analysed and to fulfil objective IV, a prospective study was performed. In both studies, patients with a clinical diagnosis of stroke (within 24-hours of symptoms onset) were studied after exclusion of haemorrhage by computer tomography scans. In INWEST, patients were consecutively all ocated to placebo (n=100), 1mg/hour (low-dose) intravenous (i.v.) nimodipine (n=101) or 2mg/hour (high-dose) i.v. nimodipine (n=94) for 5 days followed by oral treatment for 16 days in a double blind manner. Thirty patients were excluded from the analysis (n=8 in placebo, 8 and 14 in low-dose and high-dose group respectively). In the prospective study, 58 patients were recruited. BP and pulse rate was recorded by non-invasive automatic monitoring hourly for 24-hours. Stress was evaluated by testing the level of salivary cortisol (4-samples within 24hours after inclusion) and psychological tests at the time of inclusion.

Results & conclusion: Nimodipine treatment (i.v.) resulted in a statistically significant reduction of systolic BP (SBP) and diastolic BP (DBP) compared to placebo. In the high-dose nimodipine group, DBP reduction during the first 48-hours but not SBP was associated with neurological worsening at 2 1 -days. A DBP reduction of > 20% by high-dose nimodipine was associated with poor outcome of combined death or dependency (Barthel Index<60) and death alone compared to placebo. For DBP reduction of <20% by high-dose nimodipine, and any DBP reduction by low-dose nimodipine the results were not conclusive (paper I).

For all treatment groups combined (n=265) and also for placebo (n=92), patients with high initial BP (>160/90 mm Hg) had a poor functional outcome (combined death or dependency) at 21-days compared to patients with normal initial BP (120-160/60-90 min Hg). Patients with low initial BP (<120/60) also had a poor functional outcome compared to patients with normal initial BP (paper II).

While classifying stroke according to the OCSP (Oxfordshire Community Stroke Project), 106 patients were identified as having Total Anterior Circulation Infarcts (TACI) with hemiparesis, dysphasia and homonymous hemianopia and 62 as non-TACI after exclusion of any of the above symptoms. Nimodipine treatment and BP change had no significant effect on outcome for TACT patients. For non-TACI patients, DBP reduction was associated with poor neurological outcome and high-dose minodipine worsened both neurological and functional outcome (paper III).

A biological marker of stress, salivary cortisol, was positively related to 24-hours SBP and night-time BP, suggesting that stress is a contributing factor for high BP in acute stroke. Psychological stress tests were difficult to perform in acute stroke and those performed did not correlate with BP or cortisol level (paper IV).

List of scientific papers

I. Ahmed N, Nasman P, Wahlgren NG (2000). Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke. 31(6): 1250-5.
https://pubmed.ncbi.nlm.nih.gov/10835440

II. Ahmed N, Wahlgren G (2001). High initial blood pressure after acute stroke is associated with poor functional outcome. J Intern Med. 249(5): 467-73.
https://pubmed.ncbi.nlm.nih.gov/11350571

III. Ahmed N, Wahlgren NG (2003). Effects of blood pressure lowering in the acute phase of total anterior circulation infarcts and other stroke subtypes. Cerebrovasc Dis. 15(4): 235-43.
https://pubmed.ncbi.nlm.nih.gov/12686786

IV. Ahmed N, de la Torre B, Wahlgren NG (2003). The relationship between blood pressure and stress as evaluated by salivary cortisol and psychological tests in patients with acute ischaemic stroke. [Submitted]