Pathobiology of Troponin Elevations White, Harvey D., DSc
Journal of the American College of Cardiology,
06/2011, Volume:
57, Issue:
24
Journal Article
A number of nonischemic conditions including myocarditis, pulmonary embolism, acute and chronic heart failure, and sepsis may be associated with elevated troponin levels (1,2), although they may ...include supply-demand imbalance and thus at least some element of ischemia. ...there remains the possibility that 60 min of pacing produced myocyte necrosis of a small number of cells without lactate production as measured in this study. ...the conclusion that ischemia alone caused the increase in hs-cTnT levels is not fully substantiated by the study findings.\n Thus, proteolysis to create small fragments could allow these to pass through a cellular membrane with normal membrane integrity.
Summary Modern management of acute myocardial infarction is built on a clinical evidence base drawn from many studies undertaken over the past three decades. The evolution in clinical practice has ...substantially reduced mortality and morbidity associated with the condition. Key to this success is the effective integration of antithrombotic therapy combined with timely reperfusion, either primary percutaneous coronary intervention or fibrinolysis for ST-elevation myocardial infarction, and invasive investigation and revascularisation for non-ST-elevation myocardial infarction, underpinned by risk stratification and optimised systems of care. After the development of troponin assays for the detection of myonecrosis, the universal definition and classification of myocardial infarction now indicates the underlying pathophysiology. Additionally, an increasing appreciation of the importance of adverse events, such as bleeding, has emerged. Remaining challenges include the effective translation of this evidence to all patients with myocardial infarction, especially to those not well represented in clinical trials who remain at increased risk of adverse events, such as elderly patients and those with renal failure. On a global level, the epidemic of diabetes and obesity in the developed world and the transition from infectious diseases to cardiovascular disease in the developing world will place an increasing demand on health-care infrastructures required to deliver time-dependent and resource-intensive care. This Seminar discusses the underlying pathophysiology, evolving perspectives on diagnosis, risk stratification, and the invasive and pharmacological management of myocardial infarction.
Atrial fibrillation (AF) is associated with an increased risk of stroke, which is currently estimated by clinical characteristics. The cardiac biomarkers N-terminal fragment B-type natriuretic ...peptide (NT-proBNP) and cardiac troponin high-sensitivity (cTn-hs) are independently associated with risk of stroke in AF. Our objective was to develop and validate a new biomarker-based risk score to improve prognostication of stroke in patients with AF.
A new risk score was developed and internally validated in 14 701 patients with AF and biomarkers levels determined at baseline, median follow-up of 1.9 years. Biomarkers and clinical variables significantly contributing to predicting stroke or systemic embolism were assessed by Cox-regression and each variable obtained a weight proportional to the model coefficients. External validation was performed in 1400 patients with AF, median follow-up of 3.4 years. The most important predictors were prior stroke/transient ischaemic attack, NT-proBNP, cTn-hs, and age, which were included in the ABC (Age, Biomarkers, Clinical history) stroke risk score. The ABC-stroke score was well calibrated and yielded higher c-indices than the widely used CHA2DS2-VASc score in both the derivation cohort (0.68 vs. 0.62, P < 0.001) and the external validation cohort (0.66 vs. 0.58, P < 0.001). Moreover, the ABC-stroke score consistently provided higher c-indices in several important subgroups.
A novel biomarker-based risk score for predicting stroke in AF was successfully developed and internally validated in a large cohort of patients with AF and further externally validated in an independent AF cohort. The ABC-stroke score performed better than the presently used clinically based risk score and may provide improved decision support in AF.
NCT00412984, NCT00799903.
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