European Journal of Cardiovascular Medicine

Acute ischemic stroke (AIS) is a medical emergency where blood flow to a part of the brain is interrupted or reduced, leading to brain cell damage. It accounts for approximately 87% of all strokes. [1] Understanding the condition involves recognizing its causes, symptoms, diagnostic methods, and treatment strategies. [2]

Formation of a blood clot in one of the brain’s arteries, usually due to atherosclerosis (buildup of fatty deposits). A blood clot or other debris forms away from the brain (often in the heart) and travels through the bloodstream to lodge in a brain artery. [3]

Symptoms of AIS can develop suddenly and may include: Sudden numbness or weakness in the face, arm, or leg, particularly on one side of the body. Confusion, trouble speaking, or difficulty understanding speech. Sudden trouble seeing in one or both eyes. [4] Sudden trouble walking, dizziness, loss of balance, or lack of coordination. Severe headache with no known cause. [5]

The correlation between serum cortisol levels and the severity of acute ischemic stroke has been the subject of various studies, and the relationship is of significant interest in both clinical and research contexts. [6] Cortisol is a hormone released by the adrenal glands in response to stress, and it plays a role in the body’s stress response system. Acute ischemic stroke, being a severe and sudden event, can trigger a significant stress response, leading to elevated cortisol levels. [7]

The severity of an ischemic stroke can be assessed using scales like the National Institutes of Health Stroke Scale (NIHSS). Higher cortisol levels have been associated with greater stroke severity in some studies, suggesting that elevated cortisol might correlate with poorer outcomes. [8]

Cortisol has anti-inflammatory effects, which might influence stroke outcomes. Inflammation and neurovascular injury are key components of stroke pathophysiology. Elevated cortisol could potentially be a marker of more severe inflammatory responses or greater injury. [9] Some research indicates that higher serum cortisol levels at the time of stroke may be associated with poorer functional outcomes and greater disability. However, this relationship can be influenced by various factors, including the timing of cortisol measurement and individual patient differences. [10]

The timing of cortisol measurement can be crucial. Cortisol levels can fluctuate throughout the day, and acute stress responses may cause temporary spikes in cortisol. Measurements taken immediately after the stroke may differ from those taken at later stages. [11] The correlation between cortisol levels and stroke severity can vary among studies. Some studies find a strong correlation, while others do not find significant associations. This variability might be due to differences in study design, patient populations, or methods of cortisol measurement.

This prospective observational study was conducted on 60 patients with acute ischemic stroke. Patients suffered from ischemic stroke for the first time, and were hospitalized within first 12 hours of onset of symptoms. Diagnosis of ischemic stroke was based on CT-scan and MRI (DWI, T1, and T2) findings. A cardiologist visited all patients and the patients under went transthoracic echocardiography and ECG monitoring for 24 hours.

In the case of clinical suspicion, trans-esophageal echo was done and cardioembolic stroke were excluded. Lacunar infarctions are also excluded. The patients with any underlying diseases other than diabetes and hypertension were excluded from the study. We excluded patients with other causes of activation of hypothalamo-pituitary-adrenal axis (e.g., those with surgical procedures with in the last 3 weeks or nosocomial infections), intracranial hemorrhage, malignancy, febrile disorders, acute orchronic inflammatory disease at study enrollment. Patients receiving immune suppressive agents, all types of steroids, and psychotropic drugs were also excluded. Also, patients with any laboratory abnormalities such as elevated ESR or low glucose level were excluded from our study.

In this study, those patients undergoing drug therapy or having systolic blood pressure higher than 140 or diastolic higher than 90 mm/Hg were considered as having hypertension. Patients were also treated diabetic who were under drug therapy or had fasting blood glucose greater than 126 mg/mL or random blood sugar over 200mg/dL with the symptoms of diabetes.

Serum cortisol level was measured at 8 AM on the day after admission by radio immune assay method. Serum cortisol level higher than 25µg/dL was considered abnormal [12]. For every patient, a questionnaire containing demographic information and NIHSS, (which is a criterion with maximum score of 44 for evaluation of clinical condition of patients with stroke) on admission was provided and patients were divided into two groups on the basis of normal and abnormal cortisol levels. Then they were followed for three months and at the end of the third month, they were evaluated in terms of mortality and its relation to cortisol serum levels.

Scandinavian Stroke Scale (SSS) was monitored in all patients from admission. SSS was performed every 2 hours in the first 24 hours, every 4 hours in the next 48 hours and then daily up to day 7.

At follow-up of 3 months SSS, blood pressure and pulse rate were assessed. Cerebral infarction or intracerebral haemorrhage was diagnosed on the basis of clinical findings and CT-scan in all patients. Atrial fibrillation was diagnosed by 12-lead ECG on admission or by continuous ECG-monitors. CT scan of each patient was performed and follow-up CT-scan at 7-8 days.

Statistically Analysis

Power of study was 80% and P≤0.05 was considered statistically significant. Demographic information and other findings were analyzed using descriptive statistics, t-test, chi-square test and logistic regression

A total of 60 patients were included for final analysis

Table 1: Patients characteristics

As described in the table 1, mean age was observed in the current series was 74.14 ± 14.60 years. There were 32 (53.3%) male and 28 (46.7%) female. SSS was observed to be 34 (21-47) on admission. History of hypertension, History of stroke, Diabetes mellitus and Atrial fibrillation was observed in 35 (58.3%), 10 (16.7%), 22 (36.7%) and 9 (15%) respectively.

Table 2: Patient Indicators

The cortisol level was 639 nmol/L on average.

Table 3: CT Brain in Patients

Acute ischemic stroke affected 48 out of the 90 patients, while the acute hemorrhagic stroke affected 12.

Table 4: Scandinavian Stroke Scale

The cortisol mean values for the infarct and haemorrhage were 665 and 7.99, respectively; the standard deviations were 16.7 and 7.99, with a P value of 0.067. Therefore, it was discovered using an unpaired t-test that there is no significant link between blood cortisol levels and infarction or haemorrhage.

Table 5: Levels of Correlation with Serum Cortisol

The SSS and serum cortisol correlation coefficient was -0.990, showing a significant link. High serum cortisol levels were associated with lower SSS scores, and the p-value was < 0.001, indicating statistical significance

S-cortisol was also related to body temperature and blood glucose, two basic paraclinical measures that have been related to stroke severity in previous studies. [13] The relation of s-cortisol to body temperature evolved over time, so that lower body temperature in the first hours was related to high s-cortisol and that higher body temperature later was related to high s-cortisol. This finding is in accordance with earlier reports that mean body temperature from day 2 to day 6 after hospitalisation positively correlated to urinary cortisol excretion and that low body temperature on admission early after stroke onset was associated with severe stroke. [14] We also demonstrated a consistent relation to pulse rate present 4 h after admission, which seems not to have been described earlier. This observation is consistent with the general effects of cortisol. [15] S-cortisol was related to insular involvement in the way that higher values were found in patients with insular involvement and the highest values in patients with right insular involvement.

In this study, insular involvement in less severe stroke was associated with a more substantial cortisol response; however, in multivariate analysis, only stroke severity relat- ed to the occurrence of insular damage. We found a weak relation between the inflammatory response and s-cortisol. One study based on 12 patients with stroke [16] reported a correlation to TNF-a and IL-6 and another study, [17] which was based on 70 patients, reported a relation between white blood cell count and s-cortisol. A possible explanation of this discrepancy may be that our samples were collected earlier after stroke onset in comparison to the other two studies, and we may therefore have missed a later evolving relation.

In univariate analysis, a relation was found to neurological deterioration. After multivariate analysis, it was, how- ever, apparent that this relation was only a reflection of the relation to stroke severity, corroborating earlier findings that neurological deterioration is related to severe stroke. [18]

The relations of the stress response in acute stroke to blood glucose and outcome are consistent with earlier reports. [19] Our patient cohort, however, was larger and the investigations were performed sooner after stroke onset than in other studies, [20] except in two smaller studies [21] in which early recruitment was also achieved. In our study, body temperature, early infarction signs, and other paraclinical parameters were included in the analysis and offered a more detailed picture of the relations.

The stress response reflects the extent of injury, as it reflects initial stroke severity as well as infarction volume and early mortality. We have earlier reported that blood glucose increases during the first 12 h after stroke onset. [22] Since blood glucose is related to s-cortisol, and s-cortisol has the ability to increase blood glucose, we assume that the increasing blood glucose is likely to be caused by the stress response. We also assume that it is cortisol that affects the pulse rate, as the possibility is biologically well docu- mented. This relation was not apparent in the very first hours, and it seems likely that the psychological stress of admission, perhaps especially in minor stroke, may severely confound the initial readings. S-cortisol appears to be independently related to death within the first week of stroke onset in this stroke population where the cause of death was the stroke-induced brain injury. This could be biologically plausible as it has been suggested that gluco- corticoids potentiate ischaemic injury to neurons. [23] 

serum cortisol levels at the time of admission correlates with,

1. Clinical severity which is assessed by National Institute of Health Stroke Scale and
2. Poor prognosis and functional outcome after 15 days which is assessed by Modified Rankin Scale.
3. In summary, while there is evidence suggesting a correlation between elevated serum cortisol levels and increased severity of acute ischemic stroke, the relationship is complex and influenced by various factors. Further research is needed to better understand this correlation and its potential implications for prognosis and treatment strategies.

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