【高血压精品英文课件】diapositiva 1

InGenious HyperCare Integrating genomics, clinical research and care in hypertension Genetic, genomics and proteomics of transition from hypertension to heart failure Excellence in phenotyping. Circulating markers of LV growth and dysfunction,JRP B3,PATHWAYS TO HEART FAILURE IN ARTERIAL HYPERTENSION,Stage A HF Stage B HF Stage C HF,The three major causes of heart failure are hypertensive heart disease (HHD), ischemic heart disease associated with prior myocardial infarction(s), and idiopathic dilated cardiomyopathy. Because the prevalence of hypertension is increasing globally, heart failure secondary to HHD will soon become the most common cause of heart failure. (Berk BC et al, J Clin Invest 2007;117:568-575),CLINICAL AND EPIDEMIOLOGICAL RELEVANCE OF HYPERTENSIVE HEART DISEASE,HHD was one of the 15 leading causes of death and burden of disease in 2002. HHD is projected to move up two places (from position 13th to position 11th) in the ranking for 2030 (Mathers CD 3:2011-2030),There is an important need for physicians to detect HHD, understand its mechanisms, and assess adequately treatment options available In this conceptual framework the development of biomarkers for HHD can be of great interest,DEFINITION AND CRITERIA TO BE ACCOMPLISHED BY A BIOMARKER,A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathologic processes, or pharmacological responses to a therapeutic intervention,(NIH, Biomarkers Definiton Working Group, 2001),A biomarker must accomplish several criteria related to its technical measurement in blood . Feasible measurement . Highly sensitive and specific . Able to be reproduced and standardized . With low inherent error in the measurement related to its bio-physiological sense . Changes in its blood level must parallel changes in its tissue expression and must be associated with the assessed process related to its clinical validity . Changes in its blood level must reflect changes in patients clinical status . Changes in its blood level must reflect changes in patients prognosis,STEPS IN THE PROCESS OF DEVELOPMENT OF BIOMARKERS FOR HYPERTENSIVE HEART DISEASE,NATURAL HISTORY OF HYPERTENSIVE HEART DISEASE,(Dez J et al, Nat Clin Pract Cardiovasc Med 2005;2:209-216),MULTIFACETED METHODOLOGICAL APPROACH TO IDENTIFY AND EVALUATE BIOMARKERS OF HHD,Hypertensive patients without LVH with LVH LV dysfunction with LVH and heart failure without ischemic heart disease hypertrophic cardiomyopathy aortic stenosis studied before and after TX,CARDIOTROPHIN-1 SYNTHESIS AND SIGNALING IN THE HEART,(Yamauchi-Takihara K et al, Int J Exp Pathol 2000;81:1-16; Heinrich PC et al, Biochem J 2003;374(pt 1):1-20),CARDIOTROPHIN-1 AS A BIOMARKER OF CARDIOMYOCYTE GROWT?,High BP LVH dysfunction Heart failure,(Lpez B et al, J Hypertens 2005;23:625-632; Gonzlez A et al, J Hypertens 2005;23:2297-2304; Gonzlez A et al, J Hypertens 2007, in press),FIBRILLAR COLLAGEN TYPE I METABOLISM IN THE HEART,(Adapted from Lpez B et al. J Hypertens 2005:23:1445-1451),C-TERMINAL PROPEPTIDE OF PROCOLLAGEN TYPE I AS A BIOMARKER OF COLLAGEN MATRIX INCREASE?,(Querejeta R et al, Circulation 2000;101:1729-1735 - Querejeta R et al, Circulation 2004;110:1263-1268 - Lpez B et al, JACC 2006;48:89-96),High BP LVH dysfunction Heart failure,ANNEXIN A5 SYNTHESIS AND SECRETION IN THE HEART,(Camors E et al, Cardiovasc Res 2005;65:793-802),ANNEXIN A5 AS A BIOMARKER OF CARDIOMYOCYTE APOPTOSIS?,(Ravassa S et al, Eur Heart J, submitted),High BP LVH dysfunction Heart failure,FIBRILLAR COLLAGEN TYPE I METABOLISM IN THE HEART,(Adapted from Lpez B et al. J Hypertens 2005:23:1445-1451),THE MATRIX METALLOPROTEINASE 1 AND TISSUE INHIBITOR OF MMP-1 RATIO AS A BIOMARKER OF COLLAGEN MATRIX DISRUPTION?,(Querejeta R et al, Circulation 2004; 110:1263-1268 - Lpez B et al, J Am Coll Cardiol 2006;48:89-96),High BP LVH dysfunction Heart failure,CIRCULATING BIOMARKERS IN THE DIAGNOSTIC ASSESSMENT OF HHD,High BP LVH dysfunction Heart failure,CIRCULATING BIOMARKERS IN THE THERAPEUTIC EVALUATION OF HHD,(Lpez B et al, Circulation 2001;104:286-91; Lpez B et al, J Am Coll Cardiol 2004;43:20-28-35; Gonzlez A et al, J Hypertens 2005;23:2297-304),High BP LVH dysfunction Heart failure,THE INGENIOUS HYPERCARE NETWORK Opportunity for validation of current biomarkers,Biomarkers of cardiomyocyte changes IL-6, IGF-1, LIF, oncostatin M, neuregulin FAS, FAS-l, TNF, CFLAR Calsequestrin, osteoprotegerin CD36 Biomarkers of collagen matrix changes Osteopontin, thrombospondin, TGF-RIII , CTGF Relaxin MMP-2, MMP-9, TIMP-4, MTCBP-1 Biomarkers of general mediators changes IL-1, MCP-1 MPO, SOD, nitrotyrosin, 8-OH-2deoxyguanosine,THE INGENIOUS HYPERCARE NETWORK Opportunity for exploration of new candidate biomarkers,The Zeptosens proteomic platform incorporates a chip-based technology to perform high throughput multiplexed analysis of hundreds of biological samples on a single experiment.,The Triturus EIA Analyzer is an open and automated ELISA immunoassay analyzer which performs a variety of different tests on a series of samples and process several batches simultaneously,THE INGENIOUS HYPERCARE NETWORK Opportunity for incorporation of high performance methodologies for biomarkers determination,(Kietselaer BL et al, J Nucl Med 2007;48:562-567),Dual-isotope imaging using 201Tl for LV contour detection and, sim