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).
