Evidence map›Paper›PMID 42518228›Full record

ArticleSleep2026

The Respiration-Limb Coactivation Index (RLCI): A Continuous Signal-Based Biomarker for Stratifying Cardiovascular Disease Risk in a Cross-Sectional Sleep Cohort.

Shenghan Wen, Raffaele Ferri, Qichen Li, Wanlu Deng, M Brandon Westover, Robert J Thomas, Samaneh Nasiri

Abstract read
In one paragraph

Article in Sleep, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Shenghan WenEmory University School of Medicine, Atlanta, GA, United States.ORCID 0009-0004-7296-8122
Raffaele FerriClinical Neurophysiology Research Unit, Department of Neurology and Sleep Research Centre, Oasi Research Institute-IRCCS, Troina, Italy.ORCID 0000-0001-6937-3065
Qichen LiEmory University School of Medicine, Atlanta, GA, United States.
Wanlu DengDepartment of Statistics and Data Science, Tsinghua University, Beijing, China.
M Brandon WestoverStanford University, Palo Alto, CA, United States.
Robert J ThomasHarvard Medical School, Boston, MA, United States.ORCID 0000-0002-5575-3953
Samaneh NasiriEmory University School of Medicine, Atlanta, GA, United States.ORCID 0000-0002-4216-026X

Funding

Late-onset Unexplained Epilepsy as a Risk Factor for DementiaR01NS130119 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Alice D Lam · 2023 to 2026
$8.7M
Data-Driven Sleep Biomarkers of Brain Health, Heart Health, and MortalityR01HL161253 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CLIFFORD, GARI DAVID, MIGNOT, EMMANUEL J · 2022 to 2025
$8.3M
Comparative Safety of Seizure Prophylaxis within the Medicare ProgramR01AG073410 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Lidia Maria Veras Rocha de Moura · 2021 to 2026
$4.1M
Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and InattentionR01AG073598 · NIA · STANFORD UNIVERSITY · PI Miles Berger · 2022 to 2026
$3.8M
Prospective Validation of Neurophysiologic Outcome Prediction in Acute Brain InjuryR01NS126282 · NINDS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Aaron F Struck, Michael Brandon Westover · 2023 to 2026
$2.9M
Comparative Effectiveness of EEG-Guided Anti-Seizure Treatment in Acute Brain InjuryR01NS131347 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Sahar F Zafar · 2024 to 2026
$1.9M
NHLBI NIH HHS R01 HL161253NIA NIH HHS R01 AG073410NIA NIH HHS R01 AG073598NINDS NIH HHS R01 NS126282NINDS NIH HHS R01 NS130119NINDS NIH HHS R01 NS131347
6 · The paper itself

Abstract

STUDY

objectivesConventional respiratory-related limb movement (RRLM) metrics rely on event definitions and overlap rules that miss continuous respiratory-motor coupling intensity. We developed the respiration-limb coactivation index (RLCI), an algorithmic continuous biomarker, and evaluated associations with cardiovascular disease (CVD).

methodsIn Human Sleep Project polysomnography, RLCI was computed in S0001 (N = 20 737) as the interaction between respiratory-flow recovery and phasic leg-EMG envelope. The locked S0001 pipeline, without parameter tuning, was applied to two independent HSP centers (I0004, I0006). Prevalent coronary heart disease (CHD), cerebrovascular disease (CER), and peripheral vascular disease (PVD) associations were assessed by multivariable logistic regression with stage-restricted comparisons against LMI, PLMI, and RRLMI and signal-processing sensitivity analyses.

resultsAfter covariate adjustment, whole-night RRLMI was not significant for CHD or CER, whereas RLCI metrics, especially in N1 and first-half sleep, remained associated with CER and PVD. RLC N1 showed the strongest CER association (per-1-SD OR 1.11, 95% CI 1.06-1.15), and RLC FirstHalf was associated with PVD (OR 1.07, 95% CI 1.03-1.11). Stage-restricted RRLMI_N1 was significant for all four outcomes, supporting stage-matched benchmarking. Mutual adjustment suggested complementary RLCI information for CER and PVD, while conventional N1 respiratory-related movements better captured CHD. Findings were stable in sensitivity analyses and external validation.

conclusionsRLCI associations with CER and PVD suggest respiratory-linked motor coactivation captures autonomic surges distinct from cumulative hypoxia or sleep fragmentation and may complement AHI-based cardiovascular risk stratification.

Indexed as

BiomarkerCardiovascular DiseaseRespiratory-Related Leg Movements (RRLM)Sleep Apnea

Identifiers

PMID42518228
PMCPMC13682168

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.