Exploring the Link Between C-Reactive Protein Change and Stroke Risk: Insights From a Prospective Cohort Study and
Yitong Ling1, Shiqi Yuan2, Hongtao Cheng3,4
1Department of Neurology Jinan University First Affiliated Hospital Guangzhou Guangdong China.
Insights
Changes in C-reactive protein (CRP) levels are linked to increased stroke risk. Elevated or persistently high CRP levels significantly raise the risk of any stroke, ischemic stroke, and hemorrhagic stroke.
Area of Science:
- Biomedical research
- Cardiovascular epidemiology
- Inflammation markers
Background:
- Limited prior research exists on C-reactive protein (CRP) changes predicting stroke risk.
- This study addresses the gap by examining the association between CRP level fluctuations and stroke incidence.
Purpose of the Study:
- To investigate the relationship between changes in CRP levels and the risk of overall stroke and its specific subtypes.
- To explore the genetic underpinnings of the CRP-stroke association.
Main Methods:
- Utilized UK Biobank data from 14,754 participants with a median follow-up of 10.4 years.
- Employed Cox proportional hazards regression for association analysis.
- Conducted genetic analyses including genetic correlation, GWAS, and polygenic risk scores.
Main Results:
- Elevated CRP percentage change correlated with higher risks of any stroke (HR 1.44) and ischemic stroke (HR 1.65).
- Participants with newly elevated or persistently high CRP levels showed increased risks for any stroke and ischemic stroke.
- Persistently high CRP levels were associated with a heightened risk of hemorrhagic stroke (HR 1.91).
- Significant genetic correlation (r_g=0.257) and 5 shared genomic regions were identified between CRP and stroke.
- High stroke polygenic risk scores combined with elevated or high CRP levels indicated the highest stroke risk.
Conclusions:
- Both any stroke and ischemic stroke are associated with elevated and persistently high C-reactive protein levels.
- Persistently high CRP levels are specifically linked to an increased risk of hemorrhagic stroke.
Background:
Previous research on how changes in CRP (C-reactive protein) levels predict stroke risk is limited. This study aimed to examine the association between CRP change and the risk of stroke and its subtypes.
Methods And Results:
Based on the UK Biobank data, we investigated the association between CRP change and the risk of stroke and its subtypes with Cox proportional hazards regression analysis. We further performed genetic analyses including genetic correlation, pairwise genome-wide association study, and polygenic risk score. Our study involved 14 754 participants with a median follow-up time of 10.4 years. After categorizing participants by CRP percentage change and making adjustments for potential confounders, it was observed that those with an elevated percentage of CRP change had a higher risk of any stroke (hazard ratio [HR], 1.44 [95% CI, 1.12-1.85]) and ischemic stroke (HR, 1.65 [95% CI, 1.24-2.18]). After categorization by CRP change types and adjustment for confounders, the group that became high level had a higher any-stroke risk (HR, 1.45 [95% CI, 1.04-2.02]), with the group that remained at a high level facing the greatest risk (HR, 1.74 [95% CI, 1.30-2.33]). Similar trends were observed for ischemic stroke. The group that remained at a high level also had a heightened hemorrhagic stroke risk (HR, 1.91 [95% CI, 1.07-3.44]). Genetic analysis showed a significant genetic correlation between CRP and stroke (rg, 0.257; rg_P=2.39E-07). Pairwise genome-wide association study analysis identified 5 shared genomic regions between CRP and stroke. Polygenic risk score analysis showed that participants with high stroke polygenic risk score and elevated or remaining high CRP levels have the highest risk of stroke.
Conclusions:
Both any stroke and ischemic stroke are related to elevated and remaining high CRP levels, while hemorrhagic stroke is only related to remaining high CRP levels.
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