EndoNAFLD: Relationship Between Fatty Liver Disease and Cardiovascular Diseases

NCT ID: NCT06392828

Last Updated: 2024-05-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

112 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-04-15

Study Completion Date

2025-12-31

Brief Summary

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Management of risk factors is the primary approach to prevent cardiovascular disease (CVD). In this regard the accurate scoring of disease risk is fundamental. Non-alcoholic fatty liver disease (NAFLD) has emerged recently as a potential mediator of CVD onset and progression. The hypothesis is that NAFLD can be a predictive CVD risk factor, independent of other classical and well-known risk factors.

Preliminary epidemiological studies suggested that the fat infiltration in the liver mirrored the cardiometabolic status of the patient. But recent studies postulate that NAFLD could be a potential independent predictor of vascular injury.

The mechanisms that link liver function and endothelial damage include modulation of adipose tissue function, lipid metabolism regulation or glycemic homeostasis, among others. But new mechanisms that could link NAFLD and ECV are emerging. The synthesis of ketone bodies in the liver is closely related to the cardiovascular system function. Ketone bodies can provide up to 50% of energy required by specific tissues. Plasma concentration of β-hydroxybutyrate is a biomarker of NAFLD. Plasma β-hydroxybutyrate and acetoacetate levels are also inversely associated with endothelial injury.

Other biomarkers on endothelial damage like von Willebrand factor, ICAM, VCAM or coagulation factors (Factor VIII) can be used to stratify patients according to the risk of CVD. The improvement in the sensitivity, specificity and accuracy of scores such as FLI, HIS and FIB-4 and non-invasive techniques such as elastography allow the study of the relationship between liver disease and other comorbidities.

The aim is to evaluate the potential of NAFLD to stratify patients according to the risk of CVD and to investigate the molecular mechanisms linking NAFLD and CVD.

Detailed Description

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The hypothesis is that the prevalence of NAFLD and its degree, evaluated with non-invasive techniques and biomarkers is an independent risk factor of cardiovascular disease and can be used in scoring systems to stratify patients according to CVD risk.

The specific objectives are:

O1) To define the association between NAFLD prevalence and degree and endothelial damage.

The investigators will use non-invasive methods to determine the presence and degree of NAFLD (FLI, echography, elastography, FIB-4, NAFLD score and Hepamet) and the investigators will compare plasma concentrations of endothelial damage biomarkers (Von Willebrand Factor, Factor VIII and Tissue Factor) among NAFLD degrees.

O2) To describe the role of hepatic ketogenic metabolism as mediator of endothelial damage.

The investigators will correlate plasma concentrations of β-hydroxybutyrate and keto acetone with plasma concentrations of biomarkers of endothelial damage.

O3) To compare the expression of genes and microRNAs involved in endothelial function and liver metabolism and inflammation biomarkers among groups.

Liver metabolism is strictly regulated through the regulation of the expression of genes encoding metabolic enzymes responsible for the metabolic reactions and transporters of intermediate metabolites. The expression of such genes also depends on epigenetic mechanisms like microRNAs. Thus, the investigators will compare the expression of a selected panel of genes and microRNAs in blood samples of participants according to the clinicopathological group. The investigators will measure circulating microRNAs in plasma and cellular genes and microRNAs in the cellular fraction of the blood samples.

O4) To determine the role of the microbiome as mediator of the link between NAFLD and CVD.

The investigators will collect fecal samples from participants, and the investigators will compare alpha diversity and composition of the gut microbiota of the volunteers of the different clinicopathological groups. The investigators will also carry out comparative metagenomic studies.

Objectives 1 to 4 will be developed through a cross-sectional study in the participants.

O5) To associate NAFLD with the incidence of CVD events or changes in endothelial damage biomarkers.

Recruited participants with or without prevalent CVD will be followed up for 5 years to evaluate if the prevalence of NAFLD is associated with the incidence of CVD major events (cardiovascular mortality, myocardial infarction, stroke or chest angina).

To develop this aim, the investigators will carry out a longitudinal cohort study for 5 years. Participants recruited in any of the 4 clinicopathological groups will be contacted annually for 5 years to collect clinical, lifestyle and anthropometrical data. They will be also submitted to usual care protocols for their pathologies. Clinical records will be checked to assess the incidence of CVD events.

The aim is to recruit 112 participants, men and women, 50-69 years old that will be segregated according to NAFLD and CVD status:

Group 1: no NAFLD, no prevalent CVD. Group 2: NAFLD, no prevalent CVD Group 3: no NAFLD, prevalent CVD Group 4: NAFLD, prevalent CVD No NAFLD is described as Fatty Liver Index (FLI) \<30 or hepatic echography negative for liver steatosis if FLI \>30 or FLI \< 60, con SCORE2 \< 5 %.

NAFLD is described as FLI \> 60 or hepatic echography positive for liver steatosis if FLA\>30 or FLI \< 60, con SCORE2 \> 5 %.

Prevalent CVD is defined according to ESC 2011 guidelines (chest angina, stroke, acute coronary syndrome or acute myocardial infarction).

Conditions

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Non-Alcoholic Fatty Liver Disease Cardiovascular Diseases

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Group 1: no NAFLD, no prevalent CVD.

The aim of this group is to serve as control group. FLI \<30 or hepatic echography negative for liver steatosis if FLI \>30; FLI \< 60, con SCORE2 \< 5 % and no prevalent CVD according to ESC 202122.

No interventions assigned to this group

Group 2: NAFLD, no prevalent CVD

FLI \>60 or hepatic echography positive for liver steatosis if FLI \>30; FLI \< 60, con SCORE2 \> 5 % and no prevalent CVD according to ESC 202122.

No interventions assigned to this group

Group 3: no NAFLD, prevalent CVD

FLI \<30 or hepatic echography negative for liver steatosis if FLI \>30; FLI \< 60, con SCORE2 \< 5 % and prevalent CVD (chest angina, stroke, acute coronary syndrome, accute myocardial infarction).

No interventions assigned to this group

Group 4: NAFLD, prevalent CVD

FLI \>60 or hepatic echography positive for liver steatosis if FLI \>30; FLI \< 60, con SCORE2 \> 5 % and prevalent CVD (chest angina, stroke, acute coronary syndrome, accute myocardial infarction).

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Men and women
* 50-69 years old
* With CVD stratification according to ESC 2011 guidelines.
* With data to calculate NAFLD scores.

Exclusion Criteria

* Type 1 or type 2 diabetes.
* Taking hypoglycemic drugs.
* Familiar hypercholesterolemia according to ESC criteria.
* Congenital defects on lipid metabolism.
* Taking hypolipidemic drugs targeting PCSK9.
* Participating on other clinical trials.
* Chronic renal disease with filtration rate \< 30 ml/min (RCD degree 4 KDIGO).
* Active cancer
* Liver disease no NAFLD.
* Von Willebrand disease or any other genetic condition with an impact on the plasma concentration of this biomarker.
* Systemic autoimmune disease.
* Uncapable of giving informed consent.
* Any other physical or cognitive condition that could affect the participation in the study.
Minimum Eligible Age

50 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sociedad Española de Arteriosclerosis

OTHER

Sponsor Role collaborator

Clinica Universidad de Navarra, Universidad de Navarra

OTHER

Sponsor Role collaborator

Hospital HM Montepríncipe

UNKNOWN

Sponsor Role collaborator

Hospital Central de la Defensa Gómez Ulla

OTHER

Sponsor Role collaborator

Hospital Universitario 12 de Octubre

OTHER

Sponsor Role collaborator

IMDEA Food

OTHER

Sponsor Role lead

Responsible Party

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Lidia Daimiel Ruiz

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lidia Daimiel Ruiz, PhD

Role: PRINCIPAL_INVESTIGATOR

Fundación IMDEA Alimentación

Diego Martínez Urbistondo, PhD

Role: STUDY_CHAIR

Clínica Universidad de Navarra

Locations

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Clínica Universidad de Navarra

Madrid, , Spain

Site Status RECRUITING

Hospital 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Central de la Defensa Gomez Ulla

Madrid, , Spain

Site Status RECRUITING

Hospital HM Montepríncipe

Madrid, , Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Lidia Daimiel Ruiz, PhD

Role: CONTACT

+34917278100 ext. 309

Diego Martínez Urbistondo, PhD

Role: CONTACT

+34644330272

Facility Contacts

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Diego Martínez Urbistondo, PhD

Role: primary

+34644330272

Agustín Blanco, D

Role: primary

+34654572332

María García Blanco, PhD

Role: primary

+34675198225

Rafael Suárez, Phd

Role: primary

+34637449870

Other Identifiers

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PI-058

Identifier Type: -

Identifier Source: org_study_id

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