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Serum dickkopf-3 is associated with death and vascular events after ischemic stroke: an observational study from
Zhengbao Zhu1,2, Daoxia Guo1, Chongke Zhong1
1Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province, 215123, China.
Insights
Both low and high serum Dickkopf-3 (Dkk-3) levels are linked to worse outcomes after ischemic stroke. This suggests Dkk-3 may be a key prognostic biomarker for stroke patients.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Neurology
Background:
- Dickkopf-3 (Dkk-3) is recognized for its role in atherosclerosis progression.
- Understanding Dkk-3's impact on ischemic stroke prognosis is crucial for patient outcomes.
Purpose of the Study:
- To investigate the association between serum Dkk-3 levels and the prognosis of ischemic stroke.
- To evaluate Dkk-3 as a potential prognostic biomarker in ischemic stroke patients.
Main Methods:
- Serum Dkk-3 levels were measured in 3,344 patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).
- The primary outcome was a composite of death and vascular events within 3 months post-stroke.
- Multivariable Cox regression and spline analyses were used to assess Dkk-3's prognostic value.
Main Results:
- A U-shaped association was observed between serum Dkk-3 levels and the risk of adverse outcomes (log-rank p = 0.004).
- Both the lowest and highest quintiles of Dkk-3 were associated with significantly increased risks of death and vascular events compared to the median quintile.
- Serum Dkk-3 improved the predictive power of conventional risk factors for primary outcomes (NRI 28.44%, P < 0.001).
Conclusions:
- Both low and high serum Dkk-3 levels are associated with increased risks of death and vascular events within 3 months after ischemic stroke.
- Serum Dkk-3 demonstrates potential as a prognostic biomarker for ischemic stroke.
- Further research is warranted to confirm these findings and establish optimal Dkk-3 levels.
Background:
Dickkopf-3 (Dkk-3) is implicated in the progression of atherosclerosis. This study aimed to investigate the association between serum Dkk-3 and the prognosis of ischemic stroke.
Methods:
We measured serum Dkk-3 levels in 3344 ischemic stroke patients from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was a combination of death and vascular events within 3 months after ischemic stroke.
Results:
During 3 months of follow-up, the cumulative incidence rates of primary outcome among ischemic stroke patients in five quintiles of serum Dkk-3 (from low to high) were 4.49%, 3.74%, 2.54%, 5.23%, and 6.73%, respectively (log-rank p = 0.004). Multivariable Cox proportional hazards regression analyses showed that compared with the third quintile of serum Dkk-3, the adjusted hazard ratios (95% confidence intervals) associated with the first and fifth quintile were 3.49 (1.46-8.34) and 4.23 (1.86-9.64) for primary outcome, 3.47 (1.06-11.36) and 5.30 (1.81-15.51) for death, and 2.66 (1.01-7.01) and 3.35 (1.33-8.40) for vascular events, respectively. Multivariable-adjusted Cox proportional hazards regression model with restricted cubic splines showed a U-shaped association between serum Dkk-3 and the risk of primary outcome (p for nonlinearity = 0.030). Moreover, adding serum Dkk-3 to conventional risk factors could improve the predictive power for primary outcome (net reclassification improvement 28.44%, p < 0.001; integrated discrimination improvement 0.48%, p = 0.001).
Conclusions:
Both low and high serum Dkk-3 levels are associated with increased risks of death and vascular events within 3 months after ischemic stroke, indicating that serum Dkk-3 may have a special effect on the prognosis of ischemic stroke. We also found that serum Dkk-3 might be a prognostic biomarker for ischemic stroke. Further studies are needed to replicate our findings and to determine the optimal levels of serum Dkk-3.
