# Toward practical screening of mortality risk: Insights from interpretable machine learning in NHANES

**Authors:** Yi-Ting Lin, Lian-Yu Lin, Kai-Jen Chuang

PMC · DOI: 10.1016/j.ijcrp.2026.200595 · International Journal of Cardiology. Cardiovascular Risk and Prevention · 2026-02-12

## TL;DR

This study identifies five key factors for predicting mortality risk using interpretable machine learning on a large health dataset.

## Contribution

The study introduces a practical, interpretable model for mortality risk screening using biomarkers and lifestyle factors.

## Key findings

- Age, troponin T, and NT-proBNP were consistently influential predictors of mortality.
- A five-variable model achieved good discrimination (AUC = 0.841) for mortality risk.
- Elevated troponin T and NT-proBNP levels were associated with significantly poorer survival outcomes.

## Abstract

Efficient community-based screening for individuals at high risk of mortality is a major public health challenge. While many predictors have been proposed, there is limited consensus on which factors are both robust and practical for population screening. This study applied interpretable machine learning to identify efficient predictors of all-cause and cardiovascular mortality in a nationally representative cohort.

We analyzed 9957 adults aged ≥40 years from NHANES 1999–2004 with linked mortality follow-up. A total of 134 demographic, lifestyle, and biomarker variables were evaluated across multiple algorithms. Model interpretability was assessed with Shapley Additive Explanations (SHAP), and the prognostic implications of leading predictors were examined with Kaplan–Meier analyses.

Over 5 years, 1293 participants (13.0%) died. Across analytic approaches, age, troponin T (TNT), and N-terminal pro-B type natriuretic peptide (NT-proBNP) consistently emerged as the most influential predictors. Survival analyses demonstrated significantly poorer outcomes among individuals with elevated TNT and NT-proBNP. A parsimonious five-variable model (age, TNT, NT-proBNP, physical activity, gender) retained good discrimination (AUC = 0.841) and calibration.

A parsimonious set of five predictors—age, gender, physical activity, TNT, and NT-proBNP—enabled efficient mortality risk stratification in NHANES, supporting their potential role in practical community screening.

## Linked entities

- **Proteins:** TNNT3 (troponin T3, fast skeletal type)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 280829], TNNT1 (troponin T1, slow skeletal type) [NCBI Gene 7138] {aka ANM, NEM5, STNT, TNT, TNTS}, CRP (C-reactive protein) [NCBI Gene 527553], CST3 (cystatin C) [NCBI Gene 281102], ITIH2 (inter-alpha-trypsin inhibitor heavy chain 2) [NCBI Gene 3698] {aka H2P, ITI-HC2, SHAP}, SHBG (sex hormone binding globulin) [NCBI Gene 404182], B2M (beta-2-microglobulin) [NCBI Gene 280729], LOC783680 (beta-2-microglobulin) [NCBI Gene 783680], NPPB (natriuretic peptide B) [NCBI Gene 4879] {aka BNP, Iso-ANP}
- **Diseases:** infections (MESH:D007239), -cardiovascular death (MESH:D002318), myocardial infarction (MESH:D009203), causes of death (MESH:D003643), hypertension (MESH:D006973), cardiac injury (MESH:D006331), heart failure (MESH:D006333), type 2 diabetes (MESH:D003924), diabetes (MESH:D003920), hyperlipidemia (MESH:D006949), stroke (MESH:D020521), myocardial injury (MESH:D009202)
- **Chemicals:** mercury (MESH:D008628), androstenedione glucuronide (-), thyroxine (MESH:D013974), heavy metals (MESH:D019216), folate (MESH:D005492), glucose (MESH:D005947), cotinine (MESH:D003367), cadmium (MESH:D002104), lead (MESH:D007854), vitamin B12 (MESH:D014805), lipid (MESH:D008055), estradiol (MESH:D004958), oxygen (MESH:D010100), testosterone (MESH:D013739)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12969032/full.md

## References

19 references — full list in the complete paper: https://tomesphere.com/paper/PMC12969032/full.md

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Source: https://tomesphere.com/paper/PMC12969032