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Abstract
Objective To study the prognostic significance of multiple novel biomarkers in combination after ischemic stroke.
Methods We derived data from the China Antihypertensive Trial in Acute Ischemic Stroke, and 12 informative biomarkers were measured. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after ischemic stroke, and secondary outcomes included major disability, death, and vascular events.
Results In 3,405 participants, 866 participants (25.4%) experienced major disability or died within 3 months. In multivariable analyses, elevated high-sensitive C-reactive protein, complement C3, matrix metalloproteinase-9, hepatocyte growth factor, and antiphosphatidylserine antibodies were individually associated with the primary outcome. Participants with a larger number of elevated biomarkers had increased risk of all study outcomes. The adjusted odds ratios (95% confidence intervals) of participants with 5 elevated biomarkers were 3.88 (2.05–7.36) for the primary outcome, 2.81 (1.49–5.33) for major disability, 5.67 (1.09–29.52) for death, and 4.00 (1.22–13.14) for vascular events, compared to those with no elevated biomarkers. Simultaneously adding these 5 biomarkers to the basic model with traditional risk factors led to substantial reclassification for the combined outcome (net reclassification improvement 28.5%, p < 0.001; integrated discrimination improvement 2.2%, p < 0.001) and vascular events (net reclassification improvement 37.0%, p = 0.001; integrated discrimination improvement 0.8%, p = 0.001).
Conclusion We observed a clear gradient relationship between the numbers of elevated novel biomarkers and risk of major disability, mortality, and vascular events. Incorporation of a combination of multiple biomarkers observed substantially improved the risk stratification for adverse outcomes in ischemic stroke patients.
Glossary
- aCL=
- anticardiolipin antibodies;
- aPS=
- antiphosphatidylserine antibodies;
- BP=
- blood pressure;
- CATIS=
- China Antihypertensive Trial in Acute Ischemic Stroke;
- CI=
- confidence interval;
- eGFR=
- estimated glomerular filtration rate;
- HGF=
- hepatocyte growth factor;
- hsCRP=
- high-sensitive C-reactive protein;
- IDI=
- integrated discrimination improvement;
- IgG=
- immunoglobulin G;
- IL-6=
- interleukin-6;
- Lp-PLA2=
- lipoprotein-associated phospholipase A2;
- MMP-9=
- matrix metalloproteinase-9;
- mRS=
- modified Rankin Scale;
- NIHSS=
- NIH Stroke Scale;
- NRI=
- net reclassification improvement;
- NT-proBNP=
- N-terminal pro-brain natriuretic peptide;
- OR=
- odds ratio;
- RF=
- rheumatoid factor
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial page 157
- Received April 30, 2018.
- Accepted in final form September 12, 2018.
- © 2018 American Academy of Neurology
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