Evidence mapPaperPMID 40565076Full record

ReviewInternational journal of molecular sciences2025

Low LDL-Cholesterol and Hemorrhagic Risk: Mechanistic Insights and Clinical Perspectives.

Carmine Siniscalchi, Manuela Basaglia, Tiziana Meschi, Egidio Imbalzano, Francesca Futura Bernardi, Alessandro Perrella, Ugo Trama, Angelica Passannanti, Pierpaolo Di Micco, Concetta Schiano

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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.

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

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
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  10. Article
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

10 authors.

Carmine SiniscalchiInternal Medicine Department, Parma University Hospital, 43120 Parma, Italy.ORCID 0000-0002-0613-1074
Manuela BasagliaInternal Medicine Department, Parma University Hospital, 43120 Parma, Italy.
Tiziana MeschiInternal Medicine Department, Parma University Hospital, 43120 Parma, Italy.
Egidio ImbalzanoDepartment of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy.ORCID 0000-0003-2656-5467
Francesca Futura BernardiCoordination of the Regional Health System, General Directorate for Health Protection, Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy.
Alessandro PerrellaUOC Emerging Infectious Disease and High Contagiousness, AORN Ospedale dei Colli, PO D. Cotugno, 80131 Naples, Italy.
Ugo TramaDirectorate-General for Health Protection, Campania Region, Coordination of the Regional Health System, General Directorate for Health Protection, 80131 Naples, Italy.
Angelica PassannantiUOC Division of Clinical Immunology, Immunohematology, Department of Internal Medicine and Specialistics, University of Campania Luigi Vanvitelli, 80138 Naples, Italy.
Pierpaolo Di MiccoAFO Medicina, PO Santa Maria delle Grazie, Pozzuoli Naples Hospital 2 Nord, 80078 Naples, Italy.ORCID 0000-0002-8484-4598
Concetta SchianoDepartment of Advanced Medical and Surgical Sciences (DAMSS), University of Campania Luigi Vanvitelli, 80138 Naples, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Low-density lipoprotein cholesterol (LDL-C) plays a central role in lipid metabolism and is a well-established therapeutic target for the prevention of atherosclerotic cardiovascular diseases (CVDs). In recent years, increasingly aggressive lipid-lowering strategies have been adopted to achieve ultra-low LDL-C concentrations (<55 mg/dL or even <30 mg/dL) in high-risk patients. While the benefits of LDL-C reduction in lowering the incidence of myocardial infarction and ischemic stroke are well documented, emerging clinical evidence has raised concerns about a potential association between very low LDL-C levels and an increased risk of bleeding, particularly hemorrhagic stroke and gastrointestinal hemorrhage. This review critically examines the molecular mechanisms by which reduced LDL-C levels may influence the hemostatic system and vascular integrity. It explores the complex interplay between cholesterol availability and platelet function, endothelial barrier stability, and coagulation pathways. In addition, we assess experimental and clinical studies supporting this association and discuss how these findings may inform risk stratification and personalized lipid-lowering strategies. A deeper understanding of the biological basis of this paradoxical risk is essential for achieving a safe, balanced, and effective approach to cardiovascular prevention.

Indexed as

Cholesterol, LDLHemorrhageAnimalsAtherosclerosisCardiovascular DiseasesHumansRisk FactorsCholesterol, LDLatherosclerosischolesterolhemostasispersonalized medicinevascular integrity

Identifiers

PMID40565076
PMCPMC12192760

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.