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ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Cardiovascular Endocrinology

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1648083

This article is part of the Research TopicNovel Strategies for the Clinical Management of Cardiovascular-Kidney-Metabolic SyndromeView all 11 articles

Association Between Onset Age and Mortality Gradients in Advanced Cardio-Kidney-Metabolic Syndrome

Provisionally accepted
Jinjin DaiJinjin Dai1,2Chuanchang WuChuanchang Wu1Shihua LiuShihua Liu2Shuohua ChenShuohua Chen3Xiaodan HongXiaodan Hong1Pengyue ZhangPengyue Zhang1Liufu CuiLiufu Cui3Shouling WuShouling Wu3*Zhenhua ZhangZhenhua Zhang1*
  • 1Department of Infectious Diseases, Second Affiliated Hospital of Anhui Medical University, Hefei, China
  • 2Suzhou Hospital of Anhui Medical University, Suzhou, China
  • 3Kailuan General Hospital, Tangshan, China

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Advanced cardiovascular-kidney-metabolic (A-CKM) syndrome portends severe prognosis, but how onset age affects mortality risk remains unquantified. Among 17,283 incident A-CKM cases matched to age-stratified controls, early-onset patients (<45 y) had the highest relative mortality risk (HR=3.35), which was amplified by smoking (HR=5.27) and inflammation (hsCRP≥3 mg/L: HR=10.15); midlife onset (45-54 y) represented the optimal prevention window (NNT=15), yet with extreme female vulnerability (Stage 4 HR=14.25 vs. male HR=2.54); late-adulthood onset (55-64y) incurred peak absolute burden (ΔRate +8.61/1000 PY), while elderly cases (≥65 y) had an attenuated attributable impact despite higher mortality (33.95 vs. 2.48/1000 PY). These findings support an age-stratified management framework: core age-phased priorities (risk containment <45 y, preventive interception 45-54 y, complication management 55-64 y, and renoprotective optimization ≥65 y) augmented by sex-specific refinements-aggressive inflammation control in young men and intensified midlife monitoring for women-resolving the efficiency-burden paradox through calibrated implementation.

Keywords: cardiovascular-kidney-metabolic syndrome1, Onset Age2, Mortality Gradient3, Absolute Risk Burden4, Stratified Prevention5 URL: The Kailuan Study (registration number: ChiCTRTNRC-11, 001, 489)

Received: 16 Jun 2025; Accepted: 18 Aug 2025.

Copyright: © 2025 Dai, Wu, Liu, Chen, Hong, Zhang, Cui, Wu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Shouling Wu, Kailuan General Hospital, Tangshan, China
Zhenhua Zhang, Department of Infectious Diseases, Second Affiliated Hospital of Anhui Medical University, Hefei, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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