CRP can flag patients at risk for post-stroke delirium

Adding serum C-reactive protein (CRP) assessment to other clinical predictors may help identify patients who will experience delirium after stroke, new research has found.

Analysis of data from over 450 participants in the Polish Prospective Observational Delirium Study (PROPOLIS), who were admitted to hospital for stroke or transient ischemic attack (TIA), showed that those who developed delirium had higher CRP levels than those who did not have delirium — with a median difference between the groups of nearly 9 mg/L.

In addition, a CRP level above 7.09 mg/L was associated with an increased risk of delirium.

The ability to predict who might develop post-stroke delirium was improved when CRP was added to two other clinical models.

“CRP adds predictive information for post-stroke delirium by moderately improving discrimination and reclassification compared to easily assessed clinical predictors,” writes Elzbieta Klimiec-Moskal, Department of Neurology, Jagiellonian University Medical College, Krakow, Poland, and his colleagues.

The results were published online August 23 in Acta Psychiatrica Scandinavica.

Accurate prediction needed

Delirium affects approximately 25% of acute stroke patients and is associated with an increased risk of poor functional outcomes and mortality, the researchers note.

Accurate prediction of delirium is important so that preventive strategies can be implemented, high-risk patients can be closely monitored, and patient selection can be facilitated for future delirium clinical trials, they add.

Investigators point out that current evidence “does not support the use of any delirium biomarker in clinical practice.” However, biomarkers “can potentially aid in the diagnosis, prediction, and monitoring of delirium.”

In particular, inflammatory biomarkers are “of particular interest” because experimental and clinical studies have suggested that systemic inflammation contributes to the pathophysiology of delirium, the researchers note.

Previous findings suggest that CRP can predict delirium after surgery and in critically ill patients. Since serum CRP is often measured in patients who have had a stroke to monitor infectious complications, the goal was to “determine whether adding CRP to a model based on readily available clinical predictors improves the accuracy of prediction of delirium in acute stroke”. the patients.”

The current researchers analyzed data from PROPOLIS, a single-center observational study of adult patients with ischemic stroke, TIA or intracerebral hemorrhage who were admitted to hospital within 48 hours of symptom onset.

The current study included only patients whose CRP was measured at admission within 24 hours of onset of stroke symptoms (n=459; median age, 73 years; 52.7% female) .

Delirium was assessed using the Brief Confusion Assessment Method for verbal patients and the ICU Confusion Assessment Method for non-verbal patients.

The researchers also assessed patients’ neurological deficits at admission using the National Institutes of Health Stroke Scale (NIHSS). The median NIHSS score for study participants was 7.

Pre-stroke dependency was defined as a modified Rankin Scale score of 3 to 5. The Polish version of the Informant’s Questionnaire on Cognitive Decline in Older Adults was used to diagnose pre-stroke cognitive impairment .

Potential biomarker?

Nearly a third of the participants (29.2%) suffered from delirium. Most (46.2%) had mixed delirium, followed by hypoactive delirium (39.2%) and hyperactive delirium (14.2%); 3.7% had no motor subtype.

Results showed that patients who developed delirium had higher CRP levels than those who did not develop delirium (median level, 13.2 vs. 4.4 mg/L; P

The area under the curve (AUC) for serum CRP was 0.72. Investigators compared this with AUCs for age and NIHSS score – which were 0.64 and 0.75 respectively.

The 7.09 mg/L threshold for CRP differentiated patients with from those without delirium, with a sensitivity and specificity of 74% and 62%, respectively. The age threshold (72.5 years) had a sensitivity and specificity of 68% and 54%, while the NIHSS threshold (a score of 7.5) had a sensitivity and specificity of 78% and 65% .

Univariate analysis showed that elevated CRP was associated with an increased risk of delirium, as well as several other predictors (all Ps

Risk factor OR (95% CI)
PCR > 7.09 mg/L 4.59 (2.94 – 7.16)
Age 1.04 (1.03 – 1.06)
Diabetic sugar 2.19 (1.41 – 3.38)
Atrial fibrillation 2.72 (1.73 – 4.26)
Addiction before stroke 5.25 (2.96 – 9.34)
Pre-stroke cognitive decline 3.16 (1.87 – 5.32)
NIHSS score at admission 1.12 (1.09 – 1.16)
hemorrhagic stroke 3.79 (1.92 – 7.48)
OR = odds ratio; CI = confidence interval

When the researchers performed a multivariate analysis adjusting for the aforementioned variables, CRP “remained an independent predictor of delirium” (OR, 2.98; 95% CI, 1.71, 5.19; P

The researchers then added a CRP of more than 7.09 mg/L to the two predictive models that included other risk factors.

Adding it to Model A, which included age and NIHSS score at admission, increased AUC from 0.77 to 0.80 (P = 0.038). Addition to Model B, which included NIHSS score at admission, atrial fibrillation, diabetes mellitus, prestroke dependence, and hemorrhagic stroke, increased AUC from 0.81 to 0.84 (P = 0.016).

“The improvement in discrimination observed in our study after the addition of CRP to the clinical models was moderate,” the researchers write. However, this is consistent with studies “showing that some validated prognostic markers only slightly improve the discriminatory properties of predictive models.”

They note that a limitation of the study was the possibility that some patients already had delirium on admission, as no formal examination assessing the presence of delirium was performed at that time. Additionally, the findings “require confirmation in an independent cohort.”

Despite these limitations, “CRP could be considered as a potential biomarker to stratify the risk of delirium after stroke,” the researchers write.

Common Complications

Commenting for Medscape Medical NewsTerence Quinn, MD, MBChB (hons), Honorary Reader and Consultant Physician, School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Scotland, said the study “is a reminder of how delirium is common complicates acute stroke.”

Predicting who will develop post-stroke delirium is “difficult,” said Quinn, who was not involved in the study. However, predicting those at risk is “important because multicomponent interventions have been shown to be effective in preventing delirium.”

Elevated CRP “may be a marker of infection or other pathology causing a systematic inflammatory response,” he noted.

“Finding an elevated CRP can be a trigger to reevaluate the patient and make sure there are no infections or other issues,” Quinn said.

Acta Psychiatrist Scand. Published online August 23, 2022. Summary

No source of funding for the studies has been listed. Investigators have not reported any relevant financial relationships. Quinn received financing of the Stroke Association and Chief Scientist O ffice Scotland for delirium and stroke research .

Batya Swift Yasgur MA, LSW, is a freelance writer with a consulting firm in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-focused health books, as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped Freedom (the memoirs of two brave Afghan sisters who told him their story).

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