Evidence map›Paper›PMID 41299502›Full record

Observational studyCardiovascular diabetology2025

Neutrophil cathepsin G and risk of cardiovascular events in patients with diabetes mellitus.

Francesco Baratta, Simona Bartimoccia, Daniele Pastori, Nicholas Cocomello, Vittoria Cammisotto, Valentina Castellani, Cristina Nocella, Maurizio Forte, Vittorio Picchio, Roberto Carnevale and 3 more

2 registry-linked trialsAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01882114 unknown statusnot on this map

Study of Atherosclerotic Risk Factors and Oxidative Stress in Atrial Fibrillation. Relation to Cardiovascular Events

TypeobservationalSponsorUniversity of Roma La SapienzaRan2007 to 2020Enrolled3,000ConditionsAtrial Fibrillation, Metabolic Syndrome, Oxidative Stress, Atherosclerosis
NCT04036357 recruitingnot on this map

Progression of LIver Damage and Cardiometabolic Disorders in Non-alcoholic Fatty Liver dIsease: an Observational Cohort STUDY. The Plinio Study

TypeobservationalSponsorUniversity of Roma La SapienzaRan2011 to 2036Enrolled2,000ConditionsNAFLD, Liver Fibroses, Cardiovascular Diseases, Cardiovascular Risk Factor
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
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

13 authors.

Francesco Baratta *Geriatric Unit, Department of Internal Medicine and Medical Specialties, AOU Policlinico Umberto I, Rome, Italy. francesco.baratta@uniroma1.it.
Simona Bartimoccia *Department of Medical and Cardiovascular Sciences, University of Rome "Sapienza", Rome, Italy.
Daniele PastoriDepartment of Medical and Cardiovascular Sciences, University of Rome "Sapienza", Rome, Italy.
Nicholas CocomelloDepartment of Anatomical Sciences, Histological, Legal Medical and Locomotor, Sapienza University of Rome, Rome, Italy.
Vittoria CammisottoDepartment of Medical and Cardiovascular Sciences, University of Rome "Sapienza", Rome, Italy.
Valentina CastellaniDepartment of Translational and Precision Medicine, "Sapienza", University of Rome, Rome, Italy.
Cristina NocellaDepartment of Medical and Cardiovascular Sciences, University of Rome "Sapienza", Rome, Italy.
Maurizio ForteIRCCS Neuromed, Pozzilli, IS, Italy.
Vittorio PicchioDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
Roberto CarnevaleDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
Giovambattista DesideriDepartment of Medical and Cardiovascular Sciences, University of Rome "Sapienza", Rome, Italy.
Pasquale PignatelliDepartment of Medical and Cardiovascular Sciences, University of Rome "Sapienza", Rome, Italy.
Francesco VioliDepartment of Medical and Cardiovascular Sciences, University of Rome "Sapienza", Rome, Italy. francesco.violi@uniroma1.it.

Funding

European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS; PNRR-MAD-2022-12376779; CUP: F23C220010900006
6 · The paper itself

Abstract

backgroundType 2 diabetes mellitus (T2DM) is a major risk factor for atherosclerosis and cardiovascular events (CVEs), partly due to increased platelet activation and inflammation. Neutrophil-derived cathepsin G (CatG), a prothrombotic protease, may play a role in this process by promoting platelet aggregation. However, its association with CVEs in T2DM has not been previously explored. This study aimed to evaluate whether circulating CatG levels independently predict CVEs in patients with T2DM.

methodsWe included 485 T2DM patients from two prospective cohorts (PLINIO and ATHERO-AF studies). The primary outcome was a composite of cardiovascular death, non-fatal coronary and cerebrovascular events, and peripheral artery events. Cardiovascular death, all-cause death, non-fatal coronary and cerebrovascular events were tested as secondary outcomes. Multivariate Cox-regression was used to assess associations between the top (V) CatG quintile and outcomes. A subgroup analysis was conducted in 312 patients with available neutrophil count data and after a propensity score matching, to test the correlation between CatG and plasma soluble P-selectin (sP-selectin), an in vivo marker of platelet activation.

resultsDuring the follow-up yielding for 2,437.6 person-years, 86 CVEs occurred. Patients developing CVEs had higher CatG (2.9 [1.9-4.4] ng/mL vs. 2.1 [1.6-2.6] ng/mL; p < 0.001) compared to CVEs-free patients. The CVEs incidence rate in patients in the V CatG quintile was 10.4% per year (V quintile versus each other quintile: p < 0.001). V CatG quintile associated with increased CVEs (adjusted Hazard Ratio (aHR) 6.081 [95% confidence interval (CI) 3.887-9.514], p < 0.001) and its component incidence, including cardiovascular mortality or non-fatal coronary events or all-cause mortality. The association between higher CatG levels and CVEs remained significant after adjustment for neutrophil count (aHR 4.051 [95% CI 2.098-7.820], p < 0.001). Neutrophil count was also independently associated with CVEs (aHR 1.177 [95% CI 1.009-1.372], p = 0.038). Finally, in the propensity score matching analysis CatG independently correlated with sP-selectin (Beta: 0.443; p < 0.001).

conclusionsCirculating CatG is an independent predictor of cardiovascular events in T2DM, suggesting a novel biomarker linking inflammation to athero-thrombosis. PRE-REGISTERED CLINICAL TRIAL NUMBER: NCT01882114, NCT04036357.

Indexed as

Cardiovascular DiseasesCathepsin GDiabetes Mellitus, Type 2NeutrophilsAgedBiomarkersFemaleHeart Disease Risk FactorsHumansMaleMiddle AgedPrognosisProspective StudiesP-SelectinRisk AssessmentRisk FactorsBiomarkersCathepsin GCTSG protein, humanP-SelectinSELP protein, humanCardiovascular diseaseCathepsin GDiabetesNeutrophils

Identifiers

PMID41299502
PMCPMC12659094

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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.