Lan Lin, Liqing Chen, Kailing Yu, Qianwen Li, Junqian Huang, Ling Li, Yizhen Chen, Xiaoling Ke, Junping Wen, Jianbin You
HOXD9 emerged as a key prognostic candidate and showed incremental prognostic value beyond pathologic stage in the TCGA-LIHC training cohort. However, this stage-adjusted independent association was not reproduced in the LIRI-JP multivariable validation model. HOXD9 should therefore be considered a candidate prognostic marker requiring further validation.
BACKGROUND: Hypothyroidism represents a multisystem endocrine disorder involving cardiovascular, renal, and metabolic alterations beyond thyroid hormone deficiency. However, validated tools for hypertension (HTN) risk stratification specifically designed for patients with hypothyroidism remain lacking. This study aimed to develop and externally validate a hypothyroidism-specific HTN prediction model incorporating routinely available clinical variables.
METHODS: This retrospective multicohort study included patients with hypothyroidism from a hospital-based cohort and an independent external population-based cohort. Eligible participants were identified according to predefined diagnostic criteria, and individuals with missing key clinical variables or incomplete outcome information were excluded. Candidate predictors were selected using regression-based approaches, and a multivariable prediction model was developed in the derivation cohort and subsequently evaluated in internal and external validation cohorts. An interpretable HTN risk profile was developed and evaluated using internal validation, external validation, and subgroup analyses.
RESULTS: Age, serum creatinine (SCr), anion gap (AG), and diabetes mellitus (DM) constituted a clinically interpretable risk profile reflecting vascular aging, renal vulnerability, and metabolic dysregulation. The model demonstrated robust discrimination, good calibration, and favorable clinical utility across training, testing, and external validation cohorts.
CONCLUSIONS: A disease specific HTN risk profile was developed and externally validated in patients with hypothyroidism. This model provides a practical approach for individualized cardiovascular risk stratification and supports the application of precision endocrine medicine.