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EPidemiological Left ventriclar Outcomes Research in Europe

Final Report Summary - EPLORE (EPidemiological Left ventriclar Outcomes Research in Europe)

EPLORE documented the longitudinal changes in diastolic left ventricular function over time. We proved that sub-clinical (asymptomatic) diastolic left ventricular dysfunction is a predictor of cardiac and cardiovascular complications. We developed new diagnostic thresholds to capture heart size, in particular in obese people. 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 in collaboration with Mosaiques Diagnostic and Therapeutics AG, Hannover, Germany (Professor Harald Mischak), which predict deterioration of the heart function, decline in renal function and the incidence of cardiac and cardiovascular events. 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. One urinary biomarker, named CKD273, which predicts deterioration of renal function at a very early stage received a letter from the American Food and Drug Administration encouraging its further development. We also identified circulating biomarkers associated with cardiomyocyte micro-injury and with calcification of the conduit arteries. Other 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 acid 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 kidney need a 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. This protein needs vitamin K for becoming active. This observation highlights a new avenue to increase health by healthy dietary habits. Vitamin K is abundantly present in leafy vegetables and fermented food, such as cheese. The work on vitamin K was done in collaboration with Research and Development Group VitaK, Maastricht University, The Netherlands (Professor Cees Vermeer). In summary, EPLORE, discovered and validated a range of biomarkers allowing intervention in people at risk of heart failure and chronic kidney disease. The prevalence of diastolic left ventricular dysfunction in European populations is as high as 25%. EPLORE biomarkers inform clinicians about the condition of asymptomatic people at risk of cardiac or renal dysfunction and tell doctors that intervention is needed mainly by the proper management of major risk factors for left ventricular or renal dysfunction, such as hypertension, obesity, and insulin resistance. Diastolic heart failure represents 50% of all heart failure cases with a 5 year death rate of 30% after the first hospital admission. Health care costs for heart failure are currently exceeding those of cancer.