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Abstract
Objective To explore the association between serum retinoic acid (RA) level in patients with acute ischemic stroke (AIS) and mortality risk in the 6 months after admission.
Methods From January 2015 through December 2016, patients admitted to 3 stroke centers in China for first-ever AIS were screened. The primary endpoint was all-cause mortality or cardiovascular disease (CVD) mortality in the 6 months after admission. The significance of serum RA level, NIH Stroke Scale score, and established risk factors in predicting mortality were determined. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in statistical analysis.
Results Of the 1,530 patients enrolled, 325 died within 6 months of admission, with an all-cause mortality of 21.2% and CVD-related mortality of 13.1%. In multivariable analysis, RA levels were expressed as quartiles with the clinical variables. The results of the second to fourth quartiles (Q2–Q4) were compared with the first quartile (Q1); RA levels showed prognostic significance, with decreased all-cause and CVD mortality of 55% and 63%, respectively. After RA was added to the existing risk factors, all-cause mortality could be better reclassified, in association with only the NRI statistic (p = 0.005); CVD mortality could be better reclassified with significance, in association with both the IDI and NRI statistics (p < 0.01).
Conclusions Low circulating levels of RA were associated with increased risk of all-cause and CVD mortality in a cohort of patients with first-incidence AIS, indicating that RA level could be a predictor independent of established conventional risk factors.
Glossary
- 9cRA=
- 9-cis-retinoic acid;
- AIS=
- acute ischemic stroke;
- AUC=
- area under the curve;
- BMI=
- body mass index;
- CI=
- confidence interval;
- CV=
- coefficient of variation;
- CVD=
- cardiovascular disease;
- FBG=
- fasting blood glucose;
- HCY=
- homocysteine;
- HDL=
- high-density lipoprotein;
- HOMA-IR=
- homeostasis model assessment of insulin resistance;
- HR=
- hazard ratio;
- Hs-CRP=
- high-sensitivity C-reactive protein;
- IDI=
- integrated discrimination improvement;
- IL-6=
- interleukin-6;
- IQR=
- interquartile range;
- LDL=
- low-density lipoprotein;
- mRS=
- modified Rankin Scale;
- NIHSS=
- NIH Stroke Scale;
- NRI=
- net reclassification improvement;
- OR=
- odds ratio;
- RA=
- retinoic acid;
- RAR=
- retinoic acid receptor;
- ROC=
- receiver operating characteristic;
- SVZ=
- subventricular zone;
- TC=
- total cholesterol;
- TG=
- triglyceride
Footnotes
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.
↵* These authors contributed equally to this work as co–first authors.
↵‡ These authors contributed equally to this work as co–last authors.
- Received May 25, 2018.
- Accepted in final form December 7, 2018.
- © 2019 American Academy of Neurology
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