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Objective <p>Despite the rigorous application of guideline-directed medical therapy (GDMT) for secondary prevention, the residual risk of recurrent ischemic stroke (IS) remains substantial. This study aimed to evaluate the independent prognostic value of two novel composite biomarkers—the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio (MHR) and the Neutrophil Percentage-to-Albumin Ratio (NPAR), and to determine whether integrating these biomarkers into a standard clinical risk model provides incremental predictive value over the Essen Stroke Risk Score (ESRS).</p> Methods <p>We conducted a retrospective cohort study of 907 patients with acute ischemic stroke admitted to Shanxi Bethune Hospital between January 2021 and December 2023. Patients were stratified into recurrence (<i>n</i> = 168) and non-recurrence (<i>n</i> = 739) groups based on follow-up (median 24.44 months; IQR: 20.57–31.29). We constructed hierarchical multivariable Cox proportional hazards models: Model A (clinical risk factors + discharge medications), Model B (Model A + MHR), and Model C (Model A + MHR + NPAR). The Essen Stroke Risk Score (ESRS) was calculated as a comparative baseline. Prognostic performance was assessed using Harrell’s C-index, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). Time-dependent ROC analysis was utilized to assess the stability of the model’s predictive performance at 12 months, 24 months, and the end of follow-up. Multicollinearity was assessed using Variance Inflation Factors (VIF).</p> Results <p>The cumulative incidence of recurrence was 18.52%. In the fully adjusted Model C, both elevated MHR (HR = 1.43; 95% CI 1.22–1.67; <i>P</i> &lt; 0.001) and NPAR (HR = 4.21; 95% CI 2.87–6.17; <i>P</i> &lt; 0.001) were robust independent predictors of recurrence. Restricted cubic spline analysis revealed a J-shaped non-linear association for MHR (threshold &gt; 0.628). The standard ESRS showed modest predictive ability (C-index = 0.608). In contrast, integrating MHR and NPAR into the clinical model significantly enhanced discrimination, raising the C-index from 0.801 (Model A) to 0.848 (Model C; <i>P</i> &lt; 0.001). The combined model demonstrated substantial improvement in risk stratification (NRI = 0.547, <i>P</i> &lt; 0.001; IDI = 0.088, <i>P</i> &lt; 0.001) with low multicollinearity (VIF &lt; 5 for all covariates). Time-dependent ROC analysis confirmed stable predictive accuracy with AUCs of 0.880 at 12 months and 0.883 at 24 months.</p> Conclusions <p>MHR and NPAR are robust, independent predictors of ischemic stroke recurrence that capture non-redundant biological risks not accounted for by the Essen Stroke Risk Score. Their integration into standard clinical models significantly improves prognostic accuracy, offering a readily accessible tool to identify high-risk patients who may benefit from intensified secondary prevention targeting residual inflammation.</p>

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Residual inflammatory risk in ischemic stroke: incremental prognostic value of MHR and NPAR beyond the Essen stroke risk score

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月21日

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  • Zizhao Yang,
  • Pengyan Qiao,
  • Meiqi Zhang,
  • Yue Liang,
  • Liangyuan Zhao,
  • Pingzhi Wang

摘要

Objective

Despite the rigorous application of guideline-directed medical therapy (GDMT) for secondary prevention, the residual risk of recurrent ischemic stroke (IS) remains substantial. This study aimed to evaluate the independent prognostic value of two novel composite biomarkers—the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio (MHR) and the Neutrophil Percentage-to-Albumin Ratio (NPAR), and to determine whether integrating these biomarkers into a standard clinical risk model provides incremental predictive value over the Essen Stroke Risk Score (ESRS).

Methods

We conducted a retrospective cohort study of 907 patients with acute ischemic stroke admitted to Shanxi Bethune Hospital between January 2021 and December 2023. Patients were stratified into recurrence (n = 168) and non-recurrence (n = 739) groups based on follow-up (median 24.44 months; IQR: 20.57–31.29). We constructed hierarchical multivariable Cox proportional hazards models: Model A (clinical risk factors + discharge medications), Model B (Model A + MHR), and Model C (Model A + MHR + NPAR). The Essen Stroke Risk Score (ESRS) was calculated as a comparative baseline. Prognostic performance was assessed using Harrell’s C-index, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). Time-dependent ROC analysis was utilized to assess the stability of the model’s predictive performance at 12 months, 24 months, and the end of follow-up. Multicollinearity was assessed using Variance Inflation Factors (VIF).

Results

The cumulative incidence of recurrence was 18.52%. In the fully adjusted Model C, both elevated MHR (HR = 1.43; 95% CI 1.22–1.67; P < 0.001) and NPAR (HR = 4.21; 95% CI 2.87–6.17; P < 0.001) were robust independent predictors of recurrence. Restricted cubic spline analysis revealed a J-shaped non-linear association for MHR (threshold > 0.628). The standard ESRS showed modest predictive ability (C-index = 0.608). In contrast, integrating MHR and NPAR into the clinical model significantly enhanced discrimination, raising the C-index from 0.801 (Model A) to 0.848 (Model C; P < 0.001). The combined model demonstrated substantial improvement in risk stratification (NRI = 0.547, P < 0.001; IDI = 0.088, P < 0.001) with low multicollinearity (VIF < 5 for all covariates). Time-dependent ROC analysis confirmed stable predictive accuracy with AUCs of 0.880 at 12 months and 0.883 at 24 months.

Conclusions

MHR and NPAR are robust, independent predictors of ischemic stroke recurrence that capture non-redundant biological risks not accounted for by the Essen Stroke Risk Score. Their integration into standard clinical models significantly improves prognostic accuracy, offering a readily accessible tool to identify high-risk patients who may benefit from intensified secondary prevention targeting residual inflammation.