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Peer-reviewedCC BYFrontiers in cardiovascular medicine

Baseline SII and SIRI identify immune-inflammatory susceptibility and improve risk stratification of early subclinical cardiac dysfunction during non-steroidal aromatase inhibitor therapy

  • Cenyu Li1
  • Zhengyu Tao1
  • Yihan Wu2
  • Chen Wu1
  • Zi Wang1
  • Xiaoning Wang1
  • Huijuan Dai3
  • Meng Jiang1
  • Jun Pu1
  1. 1Division of Cardiology, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , ,
  2. 2School of Mathematical Sciences, Shanghai Jiao Tong University , ,
  3. 3Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , ,
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Abstract

Background: Non-steroidal aromatase inhibitors (NSAIs) are a cornerstone of adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive (HR+) breast cancer. Given their prolonged use in an aging population with increasing cardiovascular vulnerability, we investigated whether baseline systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) could identify pretreatment immune-inflammatory susceptibility to NSAI-related early subclinical cardiac dysfunction.

Methods: This single-center retrospective cohort study included 269 postmenopausal women with HR + breast cancer who received letrozole or anastrozole between January 2020 and April 2024. The primary endpoint was study-defined composite cardiac dysfunction, defined as either an absolute decline in left ventricular ejection fraction (LVEF) of ≥10 percentage points from baseline or a relative increase in B-type natriuretic peptide (BNP) of ≥40% from baseline together with a follow-up BNP concentration ≥100 pg/mL. Baseline SII and SIRI were calculated from routine blood counts and analyzed as z-standardized natural log-transformed variables. Logistic regression, restricted cubic spline, receiver operating characteristic curve, decision curve, sensitivity, subgroup, and exploratory machine-learning-assisted risk-stratification analyses were performed.

Results: Among 269 patients, 63 (23.4%) met the criteria for study-defined composite cardiac dysfunction. In fully adjusted models, higher z-lnSII and z-lnSIRI were independently associated with the endpoint (SII: OR 2.148, 95% CI 1.540–2.997; SIRI: OR 1.927, 95% CI 1.376–2.697; both P < 0.001). Associations remained significant in medication- and partial available-case oncology-adjusted sensitivity analyses and remained directionally consistent in post hoc sensitivity analyses using progressively higher follow-up BNP thresholds of 125, 150, 200, and 400 pg/mL. In five-fold logistic prediction analyses, the AUC increased from 0.633 for the base model to 0.745 with SII, 0.733 with SIRI, and 0.745 with both markers.

Conclusion: Baseline SII and SIRI were independently associated with study-defined composite cardiac dysfunction during NSAI therapy and provided incremental discrimination beyond conventional clinical variables.

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Cite

BibTeXRIS
BibTeX
@article{li2026baseline,
  title = {{Baseline SII and SIRI identify immune-inflammatory susceptibility and improve risk stratification of early subclinical cardiac dysfunction during non-steroidal aromatase inhibitor therapy}},
  author = {Cenyu Li and Zhengyu Tao and Yihan Wu and Chen Wu and Zi Wang and Xiaoning Wang and Huijuan Dai and Meng Jiang and Jun Pu},
  journal = {Frontiers in cardiovascular medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fcvm.2026.1888328},
  url = {https://europepmc.org/article/PMC/PMC13691644},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Baseline SII and SIRI identify immune-inflammatory susceptibility and improve risk stratification of early subclinical cardiac dysfunction during non-steroidal aromatase inhibitor therapy
AU  - Cenyu Li
AU  - Zhengyu Tao
AU  - Yihan Wu
AU  - Chen Wu
AU  - Zi Wang
AU  - Xiaoning Wang
AU  - Huijuan Dai
AU  - Meng Jiang
AU  - Jun Pu
PY  - 2026
DA  - 2026/10/09
JO  - Frontiers in cardiovascular medicine
DO  - 10.3389/fcvm.2026.1888328
UR  - https://europepmc.org/article/PMC/PMC13691644
AB  - Background: Non-steroidal aromatase inhibitors (NSAIs) are a cornerstone of adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive (HR+) breast cancer. Given their prolonged use in an aging population with increasing cardiovascular vulnerability, we investigated whether baseline systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) could identify pretreatment immune-inflammatory susceptibility to NSAI-related early subclinical cardiac dysfunction.  Methods: This single-center retrospective cohort study included 269 postmenopausal women with HR + breast cancer who received letrozole or anastrozole between January 2020 and April 2024. The primary endpoint was study-defined composite cardiac dysfunction, defined as either an absolute decline in left ventricular ejection fraction (LVEF) of ≥10 percentage points from baseline or a relative increase in B-type natriuretic peptide (BNP) of ≥40% from baseline together with a follow-up BNP concentration ≥100 pg/mL. Baseline SII and SIRI were calculated from routine blood counts and analyzed as z-standardized natural log-transformed variables. Logistic regression, restricted cubic spline, receiver operating characteristic curve, decision curve, sensitivity, subgroup, and exploratory machine-learning-assisted risk-stratification analyses were performed.  Results: Among 269 patients, 63 (23.4%) met the criteria for study-defined composite cardiac dysfunction. In fully adjusted models, higher z-lnSII and z-lnSIRI were independently associated with the endpoint (SII: OR 2.148, 95% CI 1.540–2.997; SIRI: OR 1.927, 95% CI 1.376–2.697; both P < 0.001). Associations remained significant in medication- and partial available-case oncology-adjusted sensitivity analyses and remained directionally consistent in post hoc sensitivity analyses using progressively higher follow-up BNP thresholds of 125, 150, 200, and 400 pg/mL. In five-fold logistic prediction analyses, the AUC increased from 0.633 for the base model to 0.745 with SII, 0.733 with SIRI, and 0.745 with both markers.  Conclusion: Baseline SII and SIRI were independently associated with study-defined composite cardiac dysfunction during NSAI therapy and provided incremental discrimination beyond conventional clinical variables.
SN  - 2297-055X
ER  -