Pathobiology of Troponin Elevations White, Harvey D., DSc
Journal of the American College of Cardiology,
06/2011, Letnik:
57, Številka:
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.
The primary aim of treating patients with stable angina is to decrease symptoms and improve quality of life. Percutaneous coronary intervention (PCI), a treatment for patients with angina, does not ...reduce the risk of death from any cause, death from cardiac causes, or myocardial infarction.
1
In this issue of the
Journal
, Rajkumar and colleagues
2
report on the results of the ORBITA-2 trial, which is the first double-blind, randomized, placebo-controlled trial to show that PCI is an effective antianginal treatment in patients with stable angina who have objective evidence of ischemia. ORBITA-2 was an elegant and rigorous trial that was designed . . .
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.
Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ dysfunction. We explored the ...associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with chronic CHD.
The derivation cohort consisted of 605 cases with CV death and 2,788 randomly selected non-cases during 3-5 years follow-up included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial between 2008 and 2010. The replication cohort consisted of 245 cases and 1,042 non-cases during 12 years follow-up included in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study between 1997 and 2000. Biomarker levels were measured with conventional immunoassays and/or with the OLINK PEA panels CVD I and Inflammation. Associations with CV death were evaluated by Random Survival Forest (RF) and Cox regression analyses. Both cohorts had the same median age (65 years) and 20% smokers, while there were slight differences in male sex (82% and 76%), hypertension (70% and 78%), and diabetes (39% and 30%) in the respective STABILITY and LURIC cohorts. The analyses identified 18 biomarkers with confirmed independent association with CV death by Boruta analyses and statistical significance (all p < 0.0001) by Cox regression when adjusted for clinical characteristics in both cohorts. Most prognostic information was carried by N-terminal prohormone of brain natriuretic peptide (NTproBNP), hazard ratio (HR for 1 standard deviation SD increase of the log scale of the distribution of the biomarker in the replication cohort) 2.079 (95% confidence interval CI 1.799-2.402), and high-sensitivity troponin T (cTnT-hs) HR 1.715 (95% CI 1.491-1.973). The other proteins with independent associations were growth differentiation factor 15 (GDF-15) HR 1.728 (95% CI 1.527-1.955), transmembrane immunoglobulin and mucin domain protein (TIM-1) HR 1.555 (95% CI 1.362-1.775), renin HR 1.501 (95% CI 1.305-1.727), osteoprotegerin (OPG) HR 1.488 (95% CI 1.297-1.708), soluble suppression of tumorigenesis 2 protein (sST2) HR 1.478 (95% CI 1.307-1.672), cystatin-C (Cys-C) HR 1.370 (95% CI 1.243-1.510), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) HR 1.205 (95% CI 1.131-1.285), carbohydrate antigen 125 (CA-125) HR 1.347 (95% CI 1.226-1.479), brain natriuretic peptide (BNP) HR 1.399 (95% CI 1.255-1.561), interleukin 6 (IL-6) HR 1.478 (95% CI 1.316-1.659), hepatocyte growth factor (HGF) HR 1.259 (95% CI 1.134-1.396), spondin-1 HR 1.295 (95% CI 1.156-1.450), fibroblast growth factor 23 (FGF-23) HR 1.349 (95% CI 1.237-1.472), chitinase-3 like protein 1 (CHI3L1) HR 1.284 (95% CI 1.129-1.461), tumor necrosis factor receptor 1 (TNF-R1) HR 1.486 (95% CI 1.307-1.689), and adrenomedullin (AM) HR 1.750 (95% CI 1.490-2.056). The study is limited by the differences in design, size, and length of follow-up of the 2 studies and the lack of results from coronary angiograms and follow-up of nonfatal events.
Profiles of levels of multiple plasma proteins might be useful for the identification of different pathophysiological pathways associated with an increased risk of CV death in patients with chronic CHD.
ClinicalTrials.gov NCT00799903.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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