Low Circulating Retinoic Acid Levels Linked to Mortality in Acute Ischemic Stroke

Diffusion MRI of the brain, axial section, showing left cerebrovascular ischemia 5 hours after a stroke in a 60 year oldmale patient. The FLAIR (left), diffusion (middle), and app arent diffusion coefficient (ADC; right) sequence images show an ischemic area around the left middle cerebral artery, corresponding to an interruption in blood circulation.
Low circulating serum levels of retinoic acid may be predictive of 6-month all cause and cardiovascular disease mortality risk in patients with acute ischemic stroke.

In patients with first-incidence acute ischemic stroke, low circulating serum levels of retinoic acid (RA), a metabolic product derived from vitamin A, may be predictive of 6-month all-cause mortality and cardiovascular disease (CVD) mortality risk, according to study results published in Neurology.

Patients with acute ischemic stroke who were admitted to 3 different hospitals in China between January 2015 and December 2016 were enrolled in the study (n=1530). Researchers examined all-cause mortality and CVD mortality (ie, death due to coronary heart disease, congestive heart failure, or fatal stroke) at 6 months following hospital admission.

Associations were examined between the primary outcome measure and serum RA level, National Institutes of Health (NIH) Stroke Scale score, and established risk factors predictive of mortality.

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The researchers also evaluated functional outcome at 6 months using the modified Rankin Scale (mRS) for neurologic disability, with an mRS of 0 to 2 and <2 defined as a good functional outcome and a poor outcome, respectively.

During a 6-month follow-up period, a total of 325 patients died, representing all-cause mortality and CVD-related mortality rates of 21.2% (95% CI, 19.2%-23.3%) and 13.1% (95% CI, 11.4%-14.8%), respectively. Patients with higher serum RA levels were younger, had a lower body mass index (BMI), were less likely to present with hypertension, diabetes, or coronary heart disease, and a high NIHSS score, and had a smaller infarct volume.

Serum RA levels were associated with NIHSS score (P <.001), hs CRP (P <.001), age (P <.05), BMI (P <.05), cholesterol (P <.05), and infarct volume (P <.05).

Lower levels of RA were found more often in surviving patients (0.83 [interquartile range (IQR), 0.45-2.85 ng/mL] vs 3.69 [IQR, 0.99-5.23 ng/mL]; Z = 12.527; P <.001). Serum RA level was considered an independent factor for its ability to predict all-cause mortality in this population (adjusted odds ratio [aOR], 0.755; 95% CI, 0.683-0.803; P <.001).

Levels of serum RA were also lower in patients with CVD mortality vs other patients (0.80 [IQR, 0.44-2.61 ng/mL] vs 3.52 [IQR, 0.88-5.16 ng/mL]; Z = 10.986; P <.001). The adjusted analysis revealed RA as as an independent predictor for CVD mortality (aOR, 0.733; 95% CI, 0.669-0.792; P <.001).

Study limitations include the short follow-up period, the lack of data on patient baseline nutritional status, the inclusion of only patients who were admitted to Chinese hospitals, and the measurement of serum RA levels only once at baseline.

The investigators wrote that “for patients with stroke who had a low level of RA, whether supplementing with RA or vitamin A would be beneficial for mortality prevention should be further investigated with long-term controlled clinical trials.”


Tu WJ, Qiu HC, Zhang Y, et al. Lower serum retinoic acid level for prediction of higher risk of mortality in ischemic stroke [published online March 8, 2019]. Neurology. doi:10.1212/WNL.0000000000007261