Epidemiological Left Ventricular Outcome Research in Europe.

Heart failure affects 15 million Europeans.  EPLORE documented the longitudinal changes in diastolic left ventricular function over 5-year time span in a randomly selected cohort representative for the Flemish population.  We showed that subclinical (asymptomatic) diastolic left ventricular dysfunction affects 25% of the population and is a predictor of cardiac and cardiovascular complications.  We implemented novel and completely non-invasive methods to describe coupling of the left ventricle with the large arteries, in which the heart ejects the blood.  A major achievement of EPLORE was the discovery and validation of urinary biomarkers,  which predict deterioration of the performance of the heart, decline in renal function and the incidence of cardiovascular and cardiac complications.  These urinary biomarkers consist of small molecules (so-called peptides derived from protein) that also shed light on the pathophysiology of heart failure and chronic kidney disease.   We also identified in blood circulating biomarkers associated with cardiomyocyte micro-injury and with calcification of the conduit arteries.  Other metabolic biomarkers in the blood were consistently associated with the function of the heart.  They mainly reflected how the heart uses glucose as opposed to fatty acids as source of energy, and additionally included essential amino-acids with a branched structure that humans need to take up with food and act a metabolic signal throughout the whole body.  The cardiorenal syndrome refers to the observation that decline in cardiac and renal function often go hand in hand.  Along these lines, we found evidence that both the heart and the kidney need a protein (matrix Gla protein) protecting against calcification, calcium deposition in tissues and that helps maintaining the integrity of the microcirculation, i.e., the smallest vessels in the human body that transport oxygen and nutrients to all organs.  Matrix Gla protein needs vitamin K for becoming active.