Higher Neuropeptide Y Levels After Acute Stroke Predict Worse Outcomes at One Year in Large Chinese Study | Research

The takeaway

In 3,250 acute ischemic stroke patients, higher plasma neuropeptide Y levels were associated with 56% higher odds of death or major disability at 12 months, suggesting NPY as a prognostic biomarker for stroke outcomes.

OR 1.56 for death/disability
Patients in the highest quartile of plasma neuropeptide Y had 56% higher odds of death or major disability at 12 months after acute ischemic stroke

What the researchers found

In 3,250 acute ischemic stroke patients followed for 12 months, 702 (21.6%) experienced major disability or death. Patients in the highest quartile of plasma NPY had significantly worse outcomes:

- Primary composite (death + major disability): OR 1.56 (95% CI: 1.19-2.04) vs lowest quartile

- Per standard deviation increase in log-NPY: OR 1.18 (1.07-1.30) for primary outcome

- Per SD increase for major disability alone: OR 1.28 (1.15-1.42)

Adding NPY to conventional risk factors improved prediction: category-free net reclassification index 8.82% (P=0.040) and integrated discrimination improvement 0.38% (P=0.011).

Why it matters

Stroke is a leading cause of death and disability worldwide, and predicting which patients will have poor outcomes remains challenging. NPY is already known to participate in cardiovascular pathophysiology, and this large study demonstrates its value as a prognostic biomarker specifically in acute stroke. If validated, a simple blood test measuring NPY levels could help clinicians triage acute stroke patients for intensity of care, rehabilitation planning, and clinical trial enrollment.

How the study worked

Prospective cohort study nested within the China Antihypertensive Trial in Acute Ischaemic Stroke. Plasma NPY levels were measured in 3,250 patients (2,066 men, 1,184 women) during the acute phase of ischemic stroke. The primary outcome was a composite of death and major disability (modified Rankin Scale ≥3) at 12 months. Secondary outcomes included major disability alone, death, and cardiovascular events. Multivariable logistic regression with adjustment for conventional risk factors was used. Predictive improvement was assessed using reclassification indices.

What this study cannot tell us

This is an observational study and cannot establish whether elevated NPY is a cause of poor outcomes or simply a marker of more severe stroke/stress response. The cohort is from a single Chinese clinical trial population, which may limit generalizability to other ethnicities. NPY was measured only at the acute phase — serial measurements might provide more prognostic information. The improvement in risk prediction, while statistically significant, was modest (NRI 8.82%, IDI 0.38%). NPY assays are not widely available in clinical laboratories.

How to read the evidence

This is a large, prospective cohort study (n=3,250) with 12-month follow-up and robust multivariable adjustment. The sample size and study design provide strong epidemiological evidence, though it remains observational and cannot establish causation.

When this study was published

Published in 2025, this study provides current evidence supporting NPY as a stroke prognostic biomarker. The large sample size from a well-characterized clinical trial population strengthens its relevance.

The bigger picture

This study positions neuropeptide Y as a clinically useful biomarker in stroke medicine — expanding its role beyond basic neuroscience. NPY's involvement in sympathetic nervous system activation and cardiovascular stress makes it biologically plausible as a stroke prognosticator. The study also contributes to the broader trend of using circulating peptide levels to predict outcomes in acute cardiovascular events, joining natriuretic peptides (heart failure) and troponins (myocardial infarction) as clinically informative peptide biomarkers.

Questions still open

Does elevated NPY directly contribute to worse stroke outcomes through cardiovascular effects, or is it merely a marker of sympathetic activation severity?
Could pharmacologically blocking NPY signaling in the acute phase improve stroke outcomes?
Would serial NPY measurements during stroke recovery provide additional prognostic information beyond the acute-phase level?

Common questions

What is neuropeptide Y and why does it rise after a stroke?

Neuropeptide Y (NPY) is a peptide released by the sympathetic nervous system during stress. After a stroke, the body mounts a stress response that releases NPY into the bloodstream. Higher levels may indicate a more severe stress response, which in turn is associated with worse cardiovascular and neurological outcomes.

Could measuring NPY help predict stroke recovery?

This study suggests yes — patients with higher NPY levels in the acute phase were significantly more likely to die or have severe disability at one year. Adding NPY to standard risk factors improved prediction accuracy by about 9%, which could help doctors identify patients who need the most intensive care and rehabilitation.

Read the original research

Plasma neuropeptide Y levels and adverse clinical outcomes after acute ischaemic stroke.

European journal of neurology, 32(1), e16548

View on PubMed ↗Publisher’s paper ↗

Citation

Dong, Wenjing; Lu, Yaling; Long, Jiayi; Peng, Yanbo; Ju, Zhong; Xu, Tan; Zhang, Yonghong; Zhai, Guojie; Zhong, Chongke. (2025). Plasma neuropeptide Y levels and adverse clinical outcomes after acute ischaemic stroke.. European journal of neurology, 32(1), e16548. https://doi.org/10.1111/ene.16548