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Background <p>Elevated skin autofluorescence (SAF), a marker of advanced glycation end-products (AGEs), predicts cardiovascular outcomes. However, the predictive value of SAF across diabetes mellitus (DM), chronic kidney disease (CKD), and atherosclerotic cardiovascular disease (ASCVD) remains incompletely compared. This meta-analysis aimed to clarify SAF’s prognostic strength across these populations, highlighting potential mechanisms and therapeutic implications.</p> Methods <p>We performed a systematic search of PubMed, Embase, and Cochrane databases through March 2025, identifying prospective observational studies evaluating associations between SAF and cardiovascular outcomes. Primary endpoints included all-cause mortality, cardiovascular death, cardiovascular disease (CVD), and stroke. Subgroup analyses compared SAF’s predictive value in patients stratified by ESRD status (ESRD vs. non-ESRD), dialysis modality (hemodialysis [HD] vs. peritoneal dialysis [PD]), and diabetes type (type 1 vs. type 2 DM).</p> Results <p>Twenty-four studies involving 12,361 participants were included. Elevated SAF significantly predicted increased risks of all-cause mortality (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.37–1.85, I<sup>2</sup> = 65.4%), cardiovascular death (HR 1.42; 95% CI 1.07–1.88, I<sup>2</sup> = 43.9%), CVD events (HR 1.64; 95% CI 1.34–2.03, I<sup>2</sup> = 78.5%), and stroke (HR 2.33; 95% CI 1.49–3.32, I<sup>2</sup> = 0.0%). Subgroup analyses demonstrated a significantly stronger association between elevated SAF and CVD events in ESRD patients compared to non-ESRD patients (HR 3.51 vs. 1.56; <i>P</i> for interaction = 0.001). Although not statistically significant, PD patients tended to show a stronger SAF-CVD association than HD patients.</p> Conclusions <p>Elevated SAF predicts increased cardiovascular risk, with notably stronger associations in chronic kidney disease and end-stage renal disease. These findings support the biological relevance of systemic AGE accumulation. However, further prospective validation and decision-analytic studies are required to assess SAF’s incremental predictive value beyond established scores and determine its clinical utility for risk stratification.</p>

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Differential impact of advanced glycation end-products on cardiovascular risk across patient populations measured by skin autofluorescence: a meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月26日

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  • Allen Cheng-Wei Li,
  • Shu-Wei Huang,
  • Jui-Ting Chang,
  • Donna Shu-Han Lin

摘要

Background

Elevated skin autofluorescence (SAF), a marker of advanced glycation end-products (AGEs), predicts cardiovascular outcomes. However, the predictive value of SAF across diabetes mellitus (DM), chronic kidney disease (CKD), and atherosclerotic cardiovascular disease (ASCVD) remains incompletely compared. This meta-analysis aimed to clarify SAF’s prognostic strength across these populations, highlighting potential mechanisms and therapeutic implications.

Methods

We performed a systematic search of PubMed, Embase, and Cochrane databases through March 2025, identifying prospective observational studies evaluating associations between SAF and cardiovascular outcomes. Primary endpoints included all-cause mortality, cardiovascular death, cardiovascular disease (CVD), and stroke. Subgroup analyses compared SAF’s predictive value in patients stratified by ESRD status (ESRD vs. non-ESRD), dialysis modality (hemodialysis [HD] vs. peritoneal dialysis [PD]), and diabetes type (type 1 vs. type 2 DM).

Results

Twenty-four studies involving 12,361 participants were included. Elevated SAF significantly predicted increased risks of all-cause mortality (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.37–1.85, I2 = 65.4%), cardiovascular death (HR 1.42; 95% CI 1.07–1.88, I2 = 43.9%), CVD events (HR 1.64; 95% CI 1.34–2.03, I2 = 78.5%), and stroke (HR 2.33; 95% CI 1.49–3.32, I2 = 0.0%). Subgroup analyses demonstrated a significantly stronger association between elevated SAF and CVD events in ESRD patients compared to non-ESRD patients (HR 3.51 vs. 1.56; P for interaction = 0.001). Although not statistically significant, PD patients tended to show a stronger SAF-CVD association than HD patients.

Conclusions

Elevated SAF predicts increased cardiovascular risk, with notably stronger associations in chronic kidney disease and end-stage renal disease. These findings support the biological relevance of systemic AGE accumulation. However, further prospective validation and decision-analytic studies are required to assess SAF’s incremental predictive value beyond established scores and determine its clinical utility for risk stratification.