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Published on: February 22, 2020
Association between high-sensitivity C-reactive protein, functional disability, and stroke recurrence in patients
Hong-Qiu Gu1, Kai-Xuan Yang1, Jin-Xi Lin2
1China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; National Center for Healthcare Quality Management in Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Insights
High-sensitivity C-reactive protein (hsCRP) is linked to stroke recurrence and disability. Stroke recurrence mediates less than 20% of this association, suggesting anti-inflammatory therapies are crucial for improving outcomes.
Area of Science:
- Neurology
- Cardiology
- Inflammation Research
Background:
- High-sensitivity C-reactive protein (hsCRP) is a biomarker for post-stroke inflammation.
- hsCRP directly increases infarct size and functional disability.
- hsCRP indirectly increases stroke recurrence risk by promoting atherosclerosis.
Purpose of the Study:
- To quantify the extent to which stroke recurrence mediates the relationship between hsCRP and functional disability.
- To investigate the causal chain involving hsCRP, stroke recurrence, and functional outcomes in acute ischemic stroke patients.
Main Methods:
- Analysis of 7603 patients with acute ischemic stroke from the Third China National Stroke Registry.
- Assessment of hsCRP levels, stroke recurrence, and functional disability (modified Rankin Scale ≥ 2) at 90 days.
- Mediation analysis using a counterfactual framework to examine the role of stroke recurrence.
Main Results:
- Elevated hsCRP levels were associated with increased risks of both stroke recurrence and functional disability.
- Stroke recurrence explained 16.52% of the association between hsCRP and functional disability at 90 days.
- Only 16.0% of functionally disabled patients experienced stroke recurrence before disability onset.
Conclusions:
- Stroke recurrence mediates less than 20% of the hsCRP-functional disability link in acute ischemic stroke.
- Novel anti-inflammatory therapies, alongside secondary prevention, are important for improving functional outcomes.
- Targeting inflammation directly may be key to mitigating long-term disability post-stroke.
Background:
Post-stroke inflammation biomarker high-sensitivity C-reactive protein (hsCRP) increases cerebral infarct size and results in functional disability directly, it also contributes to the formation and maturation of atherosclerotic plaques, which increase the risk of stroke recurrence and results in functional disability indirectly. However, no study has quantified how much functional disability was mediated by stroke recurrence.
Methods:
Patients with acute ischaemic stroke within 7 days and admitted to 169 hospitals in the Third China National Stroke Registry were analyzed. Blood samples were collected within 24 h of admission. Stroke recurrence and functional disability (defined as a modified Rankin scale score ≥ 2) were assessed via face-to-face interviews at three months. Mediation analysis under the counterfactual framework was performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between hsCRP and functional outcome. Sensitivity analyses were performed across different subgroups and on different scales of hsCRP measurement.
Findings:
Of the 7603 analyzed patients (mean [SD] age, 62.3 [11.3] years; 2392 [31.5%] women), the median (interquartile range [IQR]) of NIHSS score was 3.0 (1.0-6.0). The median (IQR) level of hsCRP was 1.73 (0.81-4.38) mg/L. A total of 496 (6.5%) cases of stroke recurrence and 1884 (24.8%) cases of functional disability were observed at the 90-day follow-up. Each SD increase in the concentration of hsCRP was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.11; 95% CI, 1.04-1.18) and disability (aOR, 1.14; 95% CI, 1.08-1.20) within 90 days. Of 1884 functionally disabled patients, only 16.0 % (n = 302) of patients experienced stroke recurrence before functional disability. Stroke recurrence during follow-up explained 16.52% (95% CI, 5.79%-27.25%) of the relationship between hsCRP and functional disability. Sensitivity analyses in different subgroups and on different scales of hsCRP measurement showed comparable results.
Interpretation:
Stroke recurrence mediates less than 20% of the association between hsCRP and functional disability at 90 days among patients with acute ischaemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes.
Funding:
Beijing Natural Science Foundation, the National Key R&D Program of China, the National Natural Science Foundation of China, and the Beijing Municipal Science & Technology Commission.
