EndoNAFLD: Relationship Between Fatty Liver Disease and Cardiovascular Diseases

NCT06392828 | Completed

• 1 other identifier: PI-058
• Study Type: observational
• Target: 63
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Non-Alcoholic Fatty Liver Disease; Cardiovascular Diseases

Keywords

endothelial damage; microbiota; liver disease; fatty liver disease; NAFLD; MAFLD; cardiovascular disease

Outcome Measures

Primary Outcomes (3)

• Endothelial damage

  Measure of plasma concentration of Von Willebrand Factor in UI/dL

  5 years

• Endothelial damage

  Measure of plasma concentration of Factor VIII in UI/mL

  5 years

• Endothelial damage

  Measure of plasma concentration of Tissue Factor in ng/mL

  5 years

Secondary Outcomes (8)

• Endothelial dysfunction

  5 years

• Inflammatory status

  5 years

• Ketogenic metabolism

  5 years

• Genomic profile

  5 years

• MicroRNA profile

  5 years

Study Arms (4)

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.

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.

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).

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).

Eligibility Criteria

• Age: 50 Years - 69 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients attending internal medicine services from the collaborating hospitals will be invited to participate. Physicians responsible for their usual care will check inclusion/exclusion criteria before inviting them to participate. All participants are community-dwelling adults from Community of Madrid, Spain.

You may qualify if:

• Men and women
• years old
• With CVD stratification according to ESC 2011 guidelines.
• With data to calculate NAFLD scores.

You may not qualify if:

• 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.

Sponsors & Collaborators

• IMDEA Food: lead
• Sociedad Española de Arteriosclerosis: collaborator
• Hospital HM Montepríncipe: collaborator
• Hospital Central de la Defensa Gómez Ulla: collaborator
• Hospital Universitario 12 de Octubre: collaborator
• Clinica Universidad de Navarra, Universidad de Navarra: collaborator

Study Sites (4)

Clínica Universidad de Navarra

Madrid, Madrid, 28027, Spain

Location

Hospital 12 de Octubre

Madrid, Madrid, 28041, Spain

Location

Hospital Central de la Defensa Gomez Ulla

Madrid, Madrid, 28047, Spain

Location

Hospital HM Montepríncipe

Madrid, Madrid, 28660, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, serum, PBMCs, urine, feces

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Cardiovascular Diseases; Liver Diseases

Condition Hierarchy (Ancestors)

Fatty Liver; Digestive System Diseases

Study Officials

• Lidia Daimiel Ruiz, PhD

  Fundación IMDEA Alimentación

  PRINCIPAL INVESTIGATOR

• Diego Martínez Urbistondo, PhD

  Clínica Universidad de Navarra

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 30, 2024
• Study Start: April 15, 2024
• Primary Completion: February 19, 2026
• Study Completion: February 19, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)