Overview

CVDs are a major cause of death and disability, and atherosclerosis is the main pathological mechanism. This scientific WP undertakes broad, systematic, in-depth research on new CVD biomarkers based on population studies with a 10-year follow-up. The specific aims are:

• to determine the role of genetic susceptibility, lifestyles and their interactions in atherosclerosis progression, from intermediate (e.g., biochemical, epigenetic, metabolic) biomarkers to subclinical and clinical disease,
• to assess the interaction of different risk factors and biomarkers in CV risk, and
• to improve the predictive capacity of current risk functions. Methods include cross-sectional, case-cohort, cohort study and mend Elian randomization.

Project 1:
Improvement of CVD risk function in primary prevention of CVD. Coordinator: J Marrugat

REGICOR, CDC-Canarias, Talavera and Zaragoza cohorts will be pooled to obtain >25,000 participants. Ten years of follow-up will permit identification of molecular biomarkers of subclinical (carotid intima media thickness) and clinical CVD, of hypertension development in a case-cohort substudy, and the impact of lifestyle (physical exercise, diet and smoking) on the incidence of clinical CVDs and hypertension in the full cohort. The aim is to improve the accuracy and precision of mathematical functions used for 10-year CVD risk prediction in primary prevention.
We will use bioplex x-MAP/MAG to study: 1) inflammatory activity 2) plaque activity; 3) hemodynamic biomarkers (N-terminal pro-brain natriuretic peptide); 4) myocardial necrosis biomarker; 5) coagulation; 6) renal function marker and 7) metabolic biomarkers.

Project 2:
Genetic and environmental determinants of blood pressure. Coordinator: R Elosua

BP is a continuous complex trait determined by interaction of genetic and environmental factors (physical activity, diet, air pollution and cold weather). The aim is to study their role in BP levels and hypertension risk; we will use cross-sectional, cohort and case-cohort designs. Data from the 4 pooled population-based surveys of WP2 project 1 (n >25,000), with prospective follow-up, in which BP and environmental variables were measured with standardized methods, and DNA samples obtained. Our study will prioritize the loci identified in GWAS. Using the mend Elian randomization approach, we will assess the potential modulating role of the interaction between CV risk and protective factors.

Project 3:
Contribution of epigenetic modification to senescence, hypertension and atherosclerosis. Coordinator: G Escolar

Hypertension, diabetes, obesity, and chronic kidney disease are, among other pathologies, bound to atherosclerosis and cardiovascular diseases. These pathologies are complex diseases in which the phenotype arises from a combination of environmental and heritable factors, leading to modifications on the epigenome. The general aim of this project is to assess the effect of proinflammatory and oxidation elements on epigenetic characteristics, such as histones, DNA methylation and other non-codifying elements (microRNA, siRNA).