When CKM Syndrome Stage Is Not a Severity Scale: Audiometric Hearing Thresholds in Older U.S. Adults
Le, D. M., Tran, S. T., Nguyen, V. C.
epidemiology
Quick verdict
Cross-sectional NHANES study (ages 70-79) finds CKM stage does not track measured hearing; unusually transparent, but sparse stages limit the null's strength.
Summary
This preprint tests whether the 2026 AHA/ACC/ADA/ASN cardiovascular-kidney-metabolic (CKM) syndrome stage, operationalized from ascertainable domains in NHANES 2017–March 2020, tracks objectively measured hearing in U.S. adults aged 70–79. Among 285 participants analyzed with fasting-subsample weights, the five-stage omnibus Wald test was significant (F(4,25)=21.405, p=9.01e-8), but Stage 0 contained a single participant and adjusted PTA4 means were nonmonotonic (9.49, 24.3, 31.0, 29.0, 33.4 dB HL); no Stage 2–4 contrast survived Holm adjustment, and a Stage 2–4-only model showed no heterogeneity (p=0.197), so the hypothesis of progressively poorer hearing with advancing stage was not supported. Of nine continuous CKM-related measures modeled separately, only waist circumference survived nine-test Holm adjustment (1.57 dB HL per 10 cm; 95% CI 0.74–2.39; n=778), remaining stable across top-code exclusion, tympanometric restriction, spline, and leave-one-PSU diagnostics. Stage-by-component interactions were non-estimable across five stages and null after adjustment within Stages 2–4. Strengths include rigorous survey methodology, predefined multiplicity families, and rare candor: the authors disclose a post-outcome staging-algorithm correction, retain Stage 0 non-estimability as a result, and show the five-stage model collapses without one PSU. Key limitations: extreme sparsity at the healthy end, stage indeterminate for 291 of 994 eligible participants (selective ascertainment), cross-sectional design, and an operational exposure missing several guideline phenotypes.
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Assessment at a glance
5
risk flags identified
● high 0
● medium 3
● low 2
5 strengths · 5 weaknesses · 5 author questions
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Key claims under review
- In U.S. adults aged 70–79, bilateral PTA4 does not worsen progressively across operational CKM syndrome stages: Stage 2–4 contrasts were null after Holm adjustment and the Stage 2–4-only model showed no heterogeneity (p=0.197).
- The statistically significant five-stage omnibus test (p=9.01e-8) should not be interpreted as stable stage separation because Stage 0 contained one participant and the model structurally depends on a single PSU.
- Waist circumference was the only one of nine continuous CKM-related measures associated with PTA4 after nine-test Holm correction (1.57 dB HL per 10 cm; 95% CI 0.74–2.39), a small association of uncertain individual-level clinical significance.
- Component–PTA4 slopes do not differ across Stages 2–4 after multiplicity adjustment, and five-stage interaction models were non-estimable due to the Stage 0 singleton.
Strengths
Unusually candid handling of fragile results
The authors decline to interpret their own significant omnibus (F(4,25)=21.405, p=9.01e-8), retain Stage 0 non-estimability as the H3 result rather than collapsing categories, and report that removing the single Stage-0 PSU renders the five-stage model non-estimable (§3.2, §4.1).
Disciplined, family-based multiplicity control
Holm adjustment applied within three predefined families (three Stage 2–4 contrasts; nine H2 component tests; six H3 interaction tests); the omnibus is kept separate from the directional hypothesis and no post-outcome trend test was added (§2.5).
Correct complex-survey practice
Extensive pre-specified robustness program
Transparency about the analytic history
Weaknesses
Structural fragility of the primary design
Severe, plausibly informative selection into the sample
Exposure is an operational proxy, not the guideline construct
Waist association is a small, unisolated signal
Reproducibility gap and cross-sample opacity
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Scope & Claims
This medRxiv preprint (posted 2026-09-17) asks whether the 2026 AHA/ACC/ADA/ASN cardiovascular-kidney-metabolic (CKM) syndrome stage — operationalized from ascertainable domains in NHANES 2017–March 2020 — tracks objective hearing sensitivity (bilateral PTA4 at 0.5/1/2/4 kHz) in U.S. adults aged 70–79. Three preregistered questions structure the paper: H1 (stage differences in PTA4 and the directional worse-hearing-with-higher-stage hypothesis), H2 (nine continuous CKM-related measures versus PTA4), and H3 (whether component–PTA4 slopes vary by stage). The title and Conclusion frame a negative result: CKM stage is not a severity scale for hearing. Claims are modest and, unusually, mostly self-limiting — the authors explicitly decline to interpret their only highly significant statistic.
The remaining sections cover Methodology Assessment, Statistical Evidence, Results & Reproducibility, Limitations & Risks, and Verdict & Recommendations.
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- 5 risk flags with severity, section & reviewer questions
- Methods & statistical evidence assessment
- 5 questions a peer reviewer would ask
- Full six-dimension evaluation report & recommendations
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Frequently asked questions
Does a worse CKM syndrome stage mean worse hearing in older adults?
Not according to this NHANES study of 70–79-year-olds. Adjusted hearing thresholds (bilateral PTA4) did not worsen progressively across CKM stages 0–4; all planned Stage 2–4 comparisons were non-significant after Holm correction, and a Stage 2–4-only model found no overall heterogeneity (p=0.197).
What was the one significant finding in the study?
Greater waist circumference was associated with slightly higher hearing thresholds: bilateral PTA4 rose 1.57 dB HL per 10 cm of waist (95% CI 0.74–2.39; Holm-adjusted p=0.00547, n=778). It was the only one of nine CKM-related measures to survive multiplicity correction, and the authors caution its individual-level clinical relevance is uncertain.
Why was the overall stage test significant if there is no hearing gradient?
The significant omnibus (p=9.01×10⁻⁸) was driven by a single Stage 0 participant whose adjusted mean was 9.49 dB HL versus roughly 24–33 dB HL in other stages. With one person in Stage 0, the model depends on one survey PSU and becomes non-estimable if that PSU is removed, so the authors explicitly decline to interpret it as stage separation.
What data does the study use and can it be reproduced?
It uses public NHANES 2017–March 2020 audiometry and examination data: 994 adults aged 70–79 were age-eligible, and the primary stage analysis included 285 with ascertainable stage, bilateral PTA4, and complete covariates. The analysis was preregistered on OSF and run in R with the survey package; however, the complete analytic code archive was not yet confirmed publicly deposited, so exact reproduction currently requires reimplementing the staging logic.
About this review
This is an AI-generated preliminary review by Evolve.Pub, produced from the openly available text of the paper. It is not peer review and does not represent the authors' views. The canonical record of the paper is at the publisher link above.
- Supplementary Methods S1 (full tri-state gate logic, corrective chronology detail, PREVENT audit) was not included in the extracted text; staging-implementation judgments rely on the main-text summary.
- Figure 1 is available only as its caption; underlying distributions and diagnostic plots could not be inspected.
- This is a non-peer-reviewed medRxiv preprint; all results are author-reported and were not independently verified.
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