High-Sensitive Cardiac Troponin for Prediction of Clinical Heart Failure
2017; Lippincott Williams & Wilkins; Volume: 135; Issue: 16 Linguagem: Inglês
10.1161/circulationaha.117.027681
ISSN1524-4539
AutoresMauro Gori, Michele Senni, Marco Metra,
Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoHomeCirculationVol. 135, No. 16High-Sensitive Cardiac Troponin for Prediction of Clinical Heart Failure Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBHigh-Sensitive Cardiac Troponin for Prediction of Clinical Heart FailureAre We Ready for Prime Time? Mauro Gori, MD, Michele Senni, MD and Marco Metra, MD Mauro GoriMauro Gori From Cardiology, Cardiovascular Department, ASST Papa Giovanni XXIII, Bergamo, Italy (M.G., M.S.); and Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Italy (M.M.). , Michele SenniMichele Senni From Cardiology, Cardiovascular Department, ASST Papa Giovanni XXIII, Bergamo, Italy (M.G., M.S.); and Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Italy (M.M.). and Marco MetraMarco Metra From Cardiology, Cardiovascular Department, ASST Papa Giovanni XXIII, Bergamo, Italy (M.G., M.S.); and Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Italy (M.M.). Originally published18 Apr 2017https://doi.org/10.1161/CIRCULATIONAHA.117.027681Circulation. 2017;135:1506–1508Article, see p 1494Heart failure (HF) prevalence continues to rise, and projections show that in the next 2 decades, ≈45% more HF cases will occur, with a mortality rate remaining as high as 50% within 5 years of diagnosis and high healthcare costs. Hence, there is an unmet need to apply successful preventive programs and reduce HF incidence. Also, according to current guidelines, an effective HF preventive program requires adequately targeting the preclinical stages of the disease, including risk factors for HF, such as hypertension, diabetes mellitus, renal dysfunction, coronary artery disease, and abnormalities of cardiac structure/function associated with HF, such as left ventricular (LV) hypertrophy and low LV ejection fraction.1Recently, efforts to better identify subjects at the highest risk were undertaken. Different biomarkers have been studied for this purpose. Although many candidate biomarkers have been described, few have made the difficult translation from initial promise to clinical application.2Among biomarkers, high-sensitivity cardiac troponin (hs-cTn) can detect small amounts of myocyte injury. Using high-sensitivity assays, detectable levels of cardiac troponin have been demonstrated among apparently healthy individuals in the general population, including stage A HF, as well as in asymptomatic individuals with stable cardiovascular disease, stage B HF, with a prevalence of detectable levels, ranging from 60% to 80% in asymptomatic individuals.3,4Hs-cTn elevation may be caused by multiple mechanisms, in addition to myocardial necrosis. These include cardiomyocyte damage from inflammatory cytokines or oxidative stress, apoptosis, increased cell membrane permeability induced by increased stretch or stress with troponin release by injured but still viable cells, fragmentation of altered troponins with release into the circulation of fragments with an affinity for the troponins immunoassays, and production of membranous blebs containing troponins that could release them in the bloodstream.5 Thus, hs-cTn release may not only occur in the setting of myocardial injury related to atherosclerotic coronary heart disease but may be also an expression of other structural phenotypes correlated to HF risk, such as increased LV mass.3Among 4221 participants in the Cardiovascular Health Study, those with the highest troponin T (TnT) concentrations had a 5- and 6-fold increase in the incidence of death and HF, respectively, compared with those with undetectable cTnT levels, and serial measurements further improved risk classification.4 Of note, it has been demonstrated that the predictive characteristics of hs-cTn for HF or major adverse cardiovascular events in the community are superior as compared with other biomarkers, such as galectin-3 and high-sensitivity C-reactive protein.6 Conversely, hs-cTn and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) predictivity seem to be complementary, reflecting different mechanisms of HF, such as myocardial injury as compared with increased wall stress.7Despite this strong evidence and the potential role for hs-cTn in HF management, widespread measurement of this biomarker in preclinical HF is not formally recommended by current guidelines, and no particular treatment is yet indicated for asymptomatic individuals with minimally elevated troponin levels.8 In this context, the study by Seliger et al,9 published in this issue of Circulation, expands the possible clinical application of hs-cTn. In this original study from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective and ethnically diverse general population cohort free from cardiovascular disease at baseline, the authors related baseline hs-cTnT measurements with changes in cardiac magnetic resonance imaging performed at baseline and after 10 years. It is important to note that a significant proportion of subjects screened with cardiac magnetic resonance at follow-up also underwent a late gadolinium enhancement study for the measurement of fibrosis. Minor elevations of hs-cTnT at baseline were associated with the development of fibrosis at late gadolinium enhancement as well as a greater probability of an increase in left ventricular mass. In this study, the pattern of incident late gadolinium enhancement associated with elevated hs-cTn at baseline was not "ischemic," consistent with the hypothesis that troponin release may not be necessarily related to ischemic injury. Furthermore, the authors found strong associations between even minor elevations of hs-cTnT and an increased risk of incident HF, coronary artery disease events, and cardiovascular death, demonstrating for the first time that these associations persist after accounting for cardiac magnetic resonance measurements of left ventricular structure and function.These data add significant knowledge to existing literature regarding hs-cTn, further suggesting a potential use of hs-cTn assays in daily practice. Nonetheless, some aspects in the era of sensitive troponin assays deserve attention. A first issue to consider is how the reference population used to establish normal values is defined. For example, the recommended cutoff for 99th percentile of the hs-cTnT assay is 14 ng/L. This value was derived from a reference normal population that consisted of 616 apparently healthy volunteers with a mean age of 44 years.10 However, in a recent study involving 3 large community-based cohorts and >12 000 participants, it has been reported that the 99th percentile upper reference limit for this assay varied with age, sex, and ethnicity and was notably >14 ng/L in older men.11 Thus, it has been suggested that a precise delineation of the 99th percentile value should consider age and sex.At the same time, the 99th percentile cutoff varies with different troponin assays. Because previous literature has considered different assays and, likely, more will become available soon, it is somewhat difficult to translate into clinical practice the results obtained with a specific high-sensitivity troponin assay with its peculiar cutoff. Universally validated cutoff values seem useful to have standard values applied in clinical practice. However, hs-cTn values seem to have an age- and sex-independent continuous relation with cardiovascular risk so that individual thresholds or categories are difficult to apply in clinical practice. Therefore, we are left to question what the practical implications of the detection of increased hs-cTn levels in subjects free of cardiovascular disease should be.In the aforementioned MESA, 67% of the population had detectable troponin values, and this value was associated with an increased risk of cardiovascular events and adverse structural phenotypes. However, it seems that these risks became significant for hs-cTn values >7 to 8 ng/L (≈17% of the population). In another community setting, including 1510 subjects with diabetes mellitus, 13% had an hs-cTnT value >14 ng/L, and this cutoff provided incremental risk prediction beyond commonly used markers of risk.12 Thus, a consensus statement on which high-sensitivity troponin assay, which threshold, and in which population would be welcome.As pointed out by Seliger et al,9 the novel insights provided by MESA could lead to a more personalized medication targeting preventive therapy years before detection of structural heart disease and development of symptoms by allowing early differentiation of individuals with similar traditional risk factor profiles who are at highest risk for cardiovascular progression and death. Changes in lifestyle, such as smoking cessation or having physical activity, may have an impact on hs-cTn levels and the incidence of cardiovascular events.13,14 The detection of elevated troponin levels could be used to motivate individuals to adhere to diet and exercise recommendations and justify aggressive targeting of blood pressure and cholesterol goals. Finally, these data provide a framework to inform the design of troponin-guided preventive intervention trials in better selected populations.DisclosuresDr Metra has received consulting honoraria from Amgen, Novartis, Servier, and Relypsa.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Circulation is available at http://circ.ahajournals.org.Correspondence to: Marco Metra, MD, Cardiology, University and Civil Hospitals, Piazza spedali Civili 1, Brescia 25123, Italy. E-mail [email protected]References1. 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Bayes-Genis A, Cediel G, Domingo M, Codina P, Santiago E and Lupón J (2022) Biomarkers in Heart Failure with Preserved Ejection Fraction, Cardiac Failure Review, 10.15420/cfr.2021.37, 8 Gori M, Januzzi J, D'Elia E, Lorini F and Senni M (2021) Rationale for and Practical Use of Sacubitril/Valsartan in the Patient's Journey with Heart Failure and Reduced Ejection Fraction, Cardiac Failure Review, 10.15420/cfr.2020.25, 7 April 18, 2017Vol 135, Issue 16 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.117.027681PMID: 28416522 Originally publishedApril 18, 2017 Keywordsheart failurebiomarkersmyocardial massfibrosisEditorialstroponinpreventionPDF download Advertisement
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