An observational study in Non-Alcoholic Fatty Liver Disease and Cardiovascular Diseases, sponsored by IMDEA Food. Completed at 4 sites in Spain. Open to participants aged 50 Years to 69 Years. Per ClinicalTrials.gov, last updated 2026-03-25.
Sponsored by IMDEA Food · Observational
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.
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).
1,617 studies on the registry are indexed under Non-alcoholic Fatty Liver Disease; 324 are open to participants now.
This study's enrollment of 63 is below the median of 153 across 390 observational studies indexed under Non-alcoholic Fatty Liver Disease.
Browse Non-alcoholic Fatty Liver Disease studies →IMDEA Food is the lead sponsor of 17 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Inclusion Criteria:
Exclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
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).
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).
Endothelial damage
Measure of plasma concentration of Von Willebrand Factor in UI/dL
Time frame: 5 years
Endothelial damage
Measure of plasma concentration of Factor VIII in UI/mL
Time frame: 5 years
Endothelial damage
Measure of plasma concentration of Tissue Factor in ng/mL
Time frame: 5 years
Endothelial dysfunction
Measure of plasma concentration of ICAM and VCAM measured, both, in ng/mL
Time frame: 5 years
Inflammatory status
Measure of plasma concentration of TNF-alpha, IL-1B and IL-6, measured in ng/mL
Time frame: 5 years
Ketogenic metabolism
Measure of blood levels of beta-hydroxybutyrate
Time frame: 5 years
Genomic profile
Measure of the relative expression, through Real-Time qPCR, of a panel of selected genes.
Time frame: 5 years
MicroRNA profile
Measure of the relative expression, through Real-Time qPCR, of a panel of selected microRNAs.
Time frame: 5 years
Microbiota diversity
Measure of alpha diversity and gut microbial composition through 16S sequencing of fecal samples.
Time frame: 5 years
Microbiota functionality
Metagenomic analysis of microbiota genes by sequencing
Time frame: 5 years
Cardiovascular disease incidence
Registration of major cardiovascular events (cardiovascular mortality, chest angina, accute myocardial infarction and stroke)
Time frame: 5 years
Plan to share: No — IPD will no be available for other researchers. Study database can be accessible totally or partially upon request to study coordinator.
No publications or documents are linked to this record.
Ran from Apr 2024 to primary completion in Feb 2026, 22 months.
Of 159 non-industry observational studies under Non-alcoholic Fatty Liver Disease, half reached primary completion within 55 months of starting (the median), counting those still running; a quarter within 29 and three quarters within 125. This study's 22 months is below that.
Counting every sponsor, half of 170 studies reached it within 49 months; a quarter within 25 and three quarters within 124.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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