Prevalence-prognosis effect dissociation of metabolic traits in peripheral artery disease: protocol for a population-based cohort study

This preregistration outlines the full pre-specified statistical‑analysis plan for a secondary observational cohort analysis using publicly available NHANES 1999-2004 data linked to National Death Index (NDI) mortality follow‑up through 31 December 2019. At the time of preregistration, data extraction and statistical modelling had not been completed; no effect estimates, confidence intervals, or P values had been generated. The core hypothesis addresses the prevalence‑prognosis effect‑dissociation phenomenon: whether metabolic markers associated with prevalent peripheral artery disease (PAD) differ from those predictive of long‑term mortality among patients with established PAD. This document archives pre‑specified hypotheses, inclusion and exclusion criteria, variable definitions, complex‑survey weighting procedures, missing‑data handling strategies, statistical models, FDR‑based multiplicity correction rules, boundaries between exploratory and primary analyses, mediation‑analysis specifications, and all planned sensitivity analyses. Primary multiplicity correction applies to six hypothesis tests for three core metabolic traits (BMI, HbA1c, TyG) against prevalent PAD and all‑cause mortality. This preregistration corresponds to a Study Protocol manuscript submitted to JMIR Research Protocols (currently under review). A separate, pre‑specified cross‑sectional NHANES analysis without mortality endpoints will be reported in future manuscripts to mitigate risks of duplicate publication. Authors: Shenji Li, Hongrong Zhang, Qianyu Xie, Honglan Li, Wei Xiang, Xianjie Cheng, Wei Wei, Hongsheng Lin, Shunchi Xu Affiliations: Shenji Li, Hongrong Zhang, Qianyu Xie, Honglan Li, Wei Xiang, Wei Wei, Hongsheng Lin, Shunchi Xu: Department of Interventional Vascular Surgery, The Fourth Hospital of Changsha (Changsha Hospital of Integrated Chinese and Western Medicine), Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan, China Xianjie Cheng: Department of Interventional Vascular Surgery, Changsha County People’s Hospital (Xingsha Campus of Hunan Provincial People’s Hospital), Changsha, Hunan, China Corresponding author and study guarantor: Shunchi Xu (Department Chair, Department of Interventional Vascular Surgery, The Fourth Hospital of Changsha), Email: x.sc001@163.com An earlier OSF registration for this research programme (https://osf.io/qgfub; registered 23 September 2026) recorded an initial version of the analysis plan. The final plan archived on this page was fixed on 29 September 2026, before any data extraction or statistical modelling and before any effect estimates, confidence intervals or P values had been generated. Between the two versions, the primary multiplicity family was narrowed from ten tests to six (BMI, HbA1c and TyG, each assessed against prevalent PAD and all-cause mortality), with fasting triglycerides, HDL cholesterol and the cardiovascular endpoint reclassified as exploratory, and multiple imputation was increased from five to twenty datasets. The earlier registration is retained unchanged for transparency.