Citations

Background— The 2000 European Society of Cardiology/American College of Cardiology definition for myocardial infarction (MI) combines ischemic symptoms, electrocardiographic changes, and troponin rather than creatine kinase levels. The use of troponins will increase the detection of MI by a magnitude to be quantified, and the clinical acceptance of the new definition is unknown. Method and Results— Subjects presenting to an Olmsted County facility with a troponin T value ≥0.03 ng/mL between November 2002 and March 2005 were prospectively classified through the use of standardized MI criteria, relying on cardiac pain, Minnesota coding of the ECG, and troponin, creatine kinase, and its MB fraction measured simultaneously. Through the use of dynamic changes in troponin, 538 MIs were identified versus 327 with creatine kinase and 427 with only the MB fraction of creatine kinase. This represents a 74% (95% confidence interval [CI], 69% to 79%) increase above the number of MIs identified with creatine kinase and a 41% (95% CI, 37% to 46%) increase above the number identified with criteria including only its MB fraction. When relying on single values of troponin, increases in the number of MIs were always large but varied widely according to the threshold used for troponin. Cases meeting only troponin-based criteria were less likely to have electrocardiographic ST-segment elevation and had better survival than those identified with previous criteria. Clinician diagnoses mentioned MI in 42% (95% CI, 34% to 49%) of cases meeting only troponin-based criteria versus 74% (95% CI, 69% to 78%) for MIs meeting the previous criteria ( P <0.001). Conclusions— The prospective application of the new criteria in the community results in a large increase in the number of MIs and a change in case mix. The clinical acceptance of the new criteria is incomplete, and studies that rely exclusively on dismissal diagnoses to assess MI rates may underestimate the burden of disease as presently defined.

Objective— We assessed the clinical significance of intima (IT), media (MT), and intima–media (IMT) thickness of the common carotid artery using B-mode ultrasonographic image processing. Methods and Results— One hundred seventy consecutive patients underwent common carotid artery scanning using high-resolution ultrasonography. A total of 150 patients could be analyzed off-line using ultrasonographic image processing, devised for individual measurement of IT, MT, and IMT. By univariate analysis, IT (range, 0.27 to 0.41 mm) was associated with age, whereas MT (range, 0.27 to 0.74 mm) and IMT (range, 0.49 to 1.12 mm) were associated with age, fibrinogen, and creatinine. Among atherosclerosis risk factors, hypertension was associated with thickness of all 3 layers, whereas smoking was associated with IT only. By multivariate analysis, IT was associated with age, hypertension, and smoking, whereas MT and IMT were associated with age, hypertension, and blood urea nitrogen level. Conclusions— Carotid IT is associated with smoking, whereas age and hypertension are associated with thickness of all 3 arterial layers. Our results suggest a differential response of the vasculature to systemic risk factors.

Objective— We evaluated the role of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), an inflammatory biomarker, in defining risk after myocardial infarction (MI). Methods and Results— Olmsted County, Minn, residents who experienced an MI meeting standardized criteria between 2003 and 2005 (n=271) were prospectively identified and followed. Lp-PLA 2 levels were measured at baseline and evaluated along with traditional risk indicators. Lp-PLA 2 was modestly associated with total and low-density lipoprotein cholesterol, smoking, and age (inversely) but not with MI characteristics or severity, comorbidities, C-reactive protein, or the time from symptom onset to blood sampling. During the first year of follow-up, 42 deaths occurred. The survival estimates (95% confidence intervals [CI]) at 1 year were 92% (86% to 98%), 85% (78% to 93%), and 74% (65% to 84%) in the lowest, middle, and upper Lp-PLA 2 tertiles, respectively ( P =0.007). After adjustment for age and sex, the hazard ratios for death in the middle and upper Lp-PLA 2 tertiles were 2.20 (95% CI: 0.88 to 5.54) and 4.93 (95% CI: 2.10 to 11.60), compared with the lowest tertile, respectively ( P trend <0.001). Further adjustment for other risk indicators resulted in even stronger associations. Lp-PLA 2 also contributed to risk discrimination as indicated by the increases in the area under the receiver operating characteristic curves obtained in each of the models examined (all P ≤0.05). Conclusions— Among community subjects presenting with MI, increased Lp-PLA 2 levels measured early after MI are strongly and independently associated with mortality and provide incremental value in risk discrimination over traditional predictors.

The National Center for Biomedical Ontology is a consortium that comprises leading informaticians, biologists, clinicians, and ontologists, funded by the National Institutes of Health (NIH) Roadmap, to develop innovative technology and methods that allow scientists to record, manage, and disseminate biomedical information and knowledge in machine-processable form. The goals of the Center are (1) to help unify the divergent and isolated efforts in ontology development by promoting high quality open-source, standards-based tools to create, manage, and use ontologies, (2) to create new software tools so that scientists can use ontologies to annotate and analyze biomedical data, (3) to provide a national resource for the ongoing evaluation, integration, and evolution of biomedical ontologies and associated tools and theories in the context of driving biomedical projects (DBPs), and (4) to disseminate the tools and resources of the Center and to identify, evaluate, and communicate best practices of ontology development to the biomedical community. Through the research activities within the Center, collaborations with the DBPs, and interactions with the biomedical community, our goal is to help scientists to work more effectively in the e-science paradigm, enhancing experiment design, experiment execution, data analysis, information synthesis, hypothesis generation and testing, and understand human disease. This paper is part of the special issue of OMICS on data standards.

The mechanism(s) involved in regulation of store operated calcium entry in Darier's disease (DD) is not known. We investigated the distribution and function of transient receptor potential canonical (TRPC) in epidermal skin cells. DD patients demonstrated up-regulation of TRPC1, but not TRPC3, in the squamous layers. Ca2+influx was significantly higher in keratinocytes obtained from DD patients and showed enhanced proliferation compared with normal keratinocytes. Similar up-regulation of TRPC1 was also detected in epidermal layers of SERCA2+/−mice. HaCaT cells expressed TRPC1 in the plasma membrane. Expression of sarco(endo)plasmic reticulum Ca2+ATPase (SERCA)2 small interfering RNA (siRNA) in HaCaT cells increased TRPC1 levels and thapsigargin-stimulated Ca2+influx, which was blocked by store-operated calcium entry inhibitors. Thapsigargin-stimulated intracellular Ca2+release was decreased in DD cells. DD keratinocytes exhibited increased cell survival upon thapsigargin treatment. Alternatively, overexpression of TRPC1 or SERCA2-siRNA in HaCaT cells demonstrated resistance to thapsigargin-induced apoptosis. These effects were dependent on external Ca2+and activation of nuclear factor-κB. Isotretinoin reduced Ca2+entry in HaCaT cells and decreased survival of HaCaT and DD keratinocytes. These findings put forward a novel consequence of compromised SERCA2 function in DD wherein up-regulation of TRPC1 augments cell proliferation and restrict apoptosis. We suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to abnormal keratosis in DD.