Clinical Document Architecture, Release One (CDA R1), became an American National Standards Institute (ANSI)-approved HL7 Standard in November 2000, representing the first specification derived from the Health Level 7 (HL7) Reference Information Model (RIM). CDA, Release Two (CDA R2), became an ANSI-approved HL7 Standard in May 2005 and is the subject of this article, where the focus is primarily on how the standard has evolved since CDA R1, particularly in the area of semantic representation of clinical events. CDA is a document markup standard that specifies the structure and semantics of a clinical document (such as a discharge summary or progress note) for the purpose of exchange. A CDA document is a defined and complete information object that can include text, images, sounds, and other multimedia content. It can be transferred within a message and can exist independently, outside the transferring message. CDA documents are encoded in Extensible Markup Language (XML), and they derive their machine processable meaning from the RIM, coupled with terminology. The CDA R2 model is richly expressive, enabling the formal representation of clinical statements (such as observations, medication administrations, and adverse events) such that they can be interpreted and acted upon by a computer. On the other hand, CDA R2 offers a low bar for adoption, providing a mechanism for simply wrapping a non-XML document with the CDA header or for creating a document with a structured header and sections containing only narrative content. The intent is to facilitate widespread adoption, while providing a mechanism for incremental semantic interoperability.

Abstract-Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years ). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; Pϭ1.032 ⅐ 10 Ϫ14). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16 -3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus. (Hypertension. 2012;59:248-255.) • Online Data Supplement Key Words: genetic epidemiology Ⅲ risk factors Ⅲ genetics association studies Ⅲ NO Ⅲ essential hypertension E ssential hypertension (EH) is a clinical condition affecting a large proportion (25% to 30%) of the adult population and is a major risk factor for cardiovascular and renal diseases. 1,2 It is a complex trait influenced by multiple susceptibility genes, environmental, and lifestyle factors and their interactions. 3 In the last years, huge efforts have been performed in recruiting and genotyping tens of thousands of individuals and meta-analyzing dozens of cross-sectional, population-based studies. In spite of this, the research on the genetics of EH has been frustrated by the small predictive value of the discovered genetic variants and by the fact that these variants explain a small proportion of the phenotypic variation. 4 -13 EH is a late-onset disease and, therefore, the small discovered effect sizes could in part be because of the effect of misclassification, sample selection bias, and inappropriate phenotyping of cases and controls. 9,14,15 The selection of cases and controls may have important effects on the results, because misclassification bias can lead to loss of power. For common traits, such as EH, this bias can be remedied by defining more stringent selection criteria, by recruiting hypernormal controls and adopting a more stringent case definition. 14,15 The HYPERGENES Project pursued a 2-stage study to investigate novel genetic determinants of EH. Cases and controls were recruited from extensively characterized cohorts over many years in different European regions using standardized clinical ascertainment. Particular care was devoted to c...