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Background <p>This study aimed to investigate the associations of multiple noninvasive liver fibrosis scores with cardiovascular-kidney-metabolic (CKM) syndrome severity and clinical outcomes.</p> Methods <p>This retrospective cohort study included 8,592 participants from the National Health and Nutrition Examination Survey 2005–2018. Six noninvasive liver fibrosis scores, including LiverRisk, metabolic dysfunction-associated fibrosis 5 (MAF-5), nonalcoholic fatty liver disease fibrosis score (NFS), Fibrosis-4 (FIB-4), steatosis-associated fibrosis estimator (SAFE), and aspartate aminotransferase-to-platelet ratio index (APRI), were evaluated. Logistic regression was used to assess associations with advanced CKM syndrome. Cox proportional hazards models and Fine–Gray competing-risk models were applied to evaluate associations with all-cause mortality and cardiovascular disease (CVD) mortality, respectively. Restricted cubic spline, subgroup, sensitivity, and incremental prediction analyses were also performed.</p> Results <p>The participants had a mean age of 50.82 ± 0.22 years, 51.85% were female, and 12.30% had advanced CKM syndrome. During a median follow-up of 7.42 years, 599 all-cause deaths and 166 CVD deaths occurred. Higher LiverRisk, MAF-5, NFS, FIB-4, and SAFE scores were significantly associated with advanced CKM syndrome, whereas APRI was not. All six fibrosis scores were significantly associated with increased all-cause mortality. For CVD mortality, higher LiverRisk, NFS, FIB-4, and SAFE were significantly associated with increased risk, with corresponding sHRs of 3.84, 3.54, 2.25, and 3.63, respectively (all <i>P</i> &lt; 0.05), whereas MAF-5 and APRI were not significantly associated with CVD mortality. These findings were supported by dose-response analyses and remained materially unchanged in sensitivity analyses.</p> Conclusion <p>Higher LiverRisk, MAF-5, NFS, FIB-4, and SAFE scores were associated with advanced CKM syndrome, whereas all six scores were associated with all-cause mortality. LiverRisk, NFS, FIB-4, and SAFE showed more consistent associations with CVD mortality.</p>

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Association of noninvasive liver fibrosis scores with severity and outcomes among individuals with cardiovascular-kidney-metabolic syndrome: evidence from the NHANES 2005–2018

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Yue Gao,
  • Huiwen Chen,
  • Jiawen Li,
  • Mengli Chen,
  • Haifeng Zhang

摘要

Background

This study aimed to investigate the associations of multiple noninvasive liver fibrosis scores with cardiovascular-kidney-metabolic (CKM) syndrome severity and clinical outcomes.

Methods

This retrospective cohort study included 8,592 participants from the National Health and Nutrition Examination Survey 2005–2018. Six noninvasive liver fibrosis scores, including LiverRisk, metabolic dysfunction-associated fibrosis 5 (MAF-5), nonalcoholic fatty liver disease fibrosis score (NFS), Fibrosis-4 (FIB-4), steatosis-associated fibrosis estimator (SAFE), and aspartate aminotransferase-to-platelet ratio index (APRI), were evaluated. Logistic regression was used to assess associations with advanced CKM syndrome. Cox proportional hazards models and Fine–Gray competing-risk models were applied to evaluate associations with all-cause mortality and cardiovascular disease (CVD) mortality, respectively. Restricted cubic spline, subgroup, sensitivity, and incremental prediction analyses were also performed.

Results

The participants had a mean age of 50.82 ± 0.22 years, 51.85% were female, and 12.30% had advanced CKM syndrome. During a median follow-up of 7.42 years, 599 all-cause deaths and 166 CVD deaths occurred. Higher LiverRisk, MAF-5, NFS, FIB-4, and SAFE scores were significantly associated with advanced CKM syndrome, whereas APRI was not. All six fibrosis scores were significantly associated with increased all-cause mortality. For CVD mortality, higher LiverRisk, NFS, FIB-4, and SAFE were significantly associated with increased risk, with corresponding sHRs of 3.84, 3.54, 2.25, and 3.63, respectively (all P < 0.05), whereas MAF-5 and APRI were not significantly associated with CVD mortality. These findings were supported by dose-response analyses and remained materially unchanged in sensitivity analyses.

Conclusion

Higher LiverRisk, MAF-5, NFS, FIB-4, and SAFE scores were associated with advanced CKM syndrome, whereas all six scores were associated with all-cause mortality. LiverRisk, NFS, FIB-4, and SAFE showed more consistent associations with CVD mortality.