Objectives The aims of this study were to assess the prognostic value of cardiac troponin I levels, measured with a new high-sensitivity assay, in low-risk patients with stable coronary artery ...disease (CAD) and to contrast its determinants and prognostic merit with that of high-sensitivity cardiac troponin T (hs-TnT). Background New, highly sensitive cardiac troponin assays permit evaluation of the association between troponin levels and outcomes in patients with stable CAD. Methods High-sensitivity cardiac troponin I (hs-TnI) levels at baseline were assessed in 3,623 patients with stable CAD and preserved systolic function enrolled in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy) trial. Results In total, 98.5% of patients had hs-TnI concentrations higher than the detection level (1.2 pg/ml). hs-TnI correlated moderately with hs-TnT (r = 0.44) and N-terminal pro–B-type natriuretic peptide (r = 0.39) but only weakly with age (r = 0.17) and estimated glomerular filtration rate (r = −0.11). During a median follow-up period of 5.2 years, 203 patients died of cardiovascular causes or were hospitalized for heart failure, and 209 patients had nonfatal myocardial infarctions. In analyses adjusting for conventional risk markers, N-terminal pro–B-type natriuretic peptide, and hs-TnT, hs-TnI levels in the fourth compared with the 3 lower quartiles were associated with the incidence of cardiovascular death or heart failure (hazard ratio: 1.88; 95% confidence interval: 1.33 to 2.66; p < 0.001). There was a significant, albeit weaker association with nonfatal myocardial infarction (hazard ratio: 1.44; 95% confidence interval: 1.03 to 2.01; p = 0.031). In the same models, hs-TnT concentrations were associated with the incidence of cardiovascular death or heart failure but not of myocardial infarction. Conclusions In patients with stable CAD, hs-TnI concentrations are associated with cardiovascular risk independently of conventional risk markers and hs-TnT. (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy PEACE; NCT00000558 )
Objectives The goal of this study was to determine if biomarkers of subclinical myocardial injury and hemodynamic stress identify asymptomatic individuals with left ventricular hypertrophy (LVH) at ...higher risk for heart failure (HF) and death. Background The interaction between LVH, low but detectable cardiac troponin T (cTnT), and elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) on cardiovascular (CV) outcomes in the general population is unknown. Methods Participants in the Dallas Heart Study without clinical HF, LV dysfunction, or chronic kidney disease underwent measurement of LV mass by magnetic resonance imaging (MRI), cTnT by highly sensitive assay, and NT-proBNP analysis (n = 2,413). Subjects were stratified according to LVH and by detectable cTnT (≥3 pg/ml) and increased NT-proBNP (>75th age- and sex-specific percentile) levels. For each analysis, participants were categorized into groups based on the presence (+) or absence (–) of LVH and biomarker levels above (+) or below (–) the predefined threshold. Results Nine percent of participants were LVH+, 25% cTnT+, and 24% NT-proBNP+. Those LVH+ and cTnT+ and/or NT-proBNP+ (n = 144) were older and more likely to be male, with a greater risk factor burden and more severe LVH compared with those who were LVH+ biomarker– (p < 0.01 for each). The cumulative incidence of HF or CV death over 8 years among LVH+ cTnT+ was 21% versus 1% (LVH– cTnT–), 4% (LVH– cTnT+), and 6% (LVH+ cTnT–) (p < 0.0001). The interactions between LVH and cTnT (pinteraction = 0.0005) and LVH and NT-proBNP (pinteraction = 0.014) were highly significant. Individuals who were LVH+ and either cTnT+ or NT-proBNP+ remained at >4-fold higher risk for HF or CV death after multivariable adjustment for CV risk factors, renal function, and LV mass compared with those who were LVH– biomarker–. Conclusions Minimal elevations in biomarkers of subclinical cardiac injury and hemodynamic stress modify the association of LVH with adverse outcomes, identifying a malignant subphenotype of LVH with high risk for progression to HF and CV death.
Objectives This study sought to test 2 hypotheses: 1) fibroblast growth factor (FGF)-23 identifies patients with stable ischemic heart disease (SIHD) at high risk of cardiovascular events independent ...of clinical factors, renal function, and established cardiovascular biomarkers; and 2) FGF-23 identifies patients who derive greater clinical benefit from angiotensin-converting enzyme inhibitor therapy. Background FGF-23 is an endocrine regulator of mineral metabolism and markedly elevated levels are associated with cardiovascular events in patients with chronic kidney disease. Data in patients with SIHD are more sparse. Methods FGF-23 levels were measured in 3,627 patients with SIHD randomly assigned to trandolapril or placebo within the PEACE (Prevention of Events With Angiotensin-Converting Enzyme) trial and followed up for a median of 5.1 years. Results After adjustment for clinical risk predictors, left ventricular ejection fraction, markers of renal function, and established cardiovascular biomarkers, FGF-23 concentration was independently associated with an increased risk of cardiovascular death or heart failure among patients allocated to placebo (quartile 4 hazard ratio: 1.73; 95% confidence interval, 1.09 to 2.74; p = 0.02) and significantly improved metrics of discrimination. Furthermore, among patients in the top quartile of FGF-23 levels, trandolapril significantly reduced cardiovascular death or incident heart failure (hazard ratio: 0.45; 95% confidence interval: 0.28 to 0.72), whereas there was no clinical benefit in the remaining patients (hazard ratio: 1.07; 95% confidence interval: 0.75 to 1.52; p interaction = 0.0039). This interaction was independent of and additive to stratification based on renal function. Conclusions Elevated levels of FGF-23 are associated with cardiovascular death and incident heart failure in patients with SIHD and identify patients who derive significant clinical benefit from angiotensin-converting enzyme inhibitor therapy regardless of renal function. (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy PEACE: NCT00000558 )
Circulating Osteoprotegerin Levels and Long-Term Prognosis in Patients With Acute Coronary Syndromes Torbjørn Omland, Thor Ueland, Anna M. Jansson, Anita Persson, Thomas Karlsson, Camilla Smith, ...Johan Herlitz, Pål Aukrust, Marianne Hartford, Kenneth Caidahl To assess the association between osteoprotegerin (OPG) levels on admission and long-term prognosis in patients with acute coronary syndromes (ACS), serum samples for OPG analysis were obtained within 24 h of admission in 897 patients with ACS and related to the incidence of death, heart failure hospitalizations, myocardial infarction, and stroke. The baseline OPG concentration was strongly associated with increased long-term mortality, heart failure hospitalizations, and recurrent myocardial infarction, but not stroke. After adjustment for conventional risk markers, including troponin I, C-reactive protein, B-type natriuretic peptide, and ejection fraction, the association remained significant for mortality and heart failure hospitalizations.
Abstract Background Secretoneurin (SN) levels are increased in patients with heart failure (HF), but whether SN provides prognostic information and influences cardiomyocyte function is unknown. ...Objectives This study sought to evaluate the merit of SN as a cardiovascular biomarker and assess effects of SN on cardiomyocyte Ca2+ handling. Methods We assessed the association between circulating SN levels and mortality in 2 patient cohorts and the functional properties of SN in experimental models. Results In 143 patients hospitalized for acute HF, SN levels were closely associated with mortality (n = 66) during follow-up (median 776 days; hazard ratio ln SN: 4.63; 95% confidence interval: 1.93 to 11.11; p = 0.001 in multivariate analysis). SN reclassified patients to their correct risk strata on top of other predictors of mortality. In 155 patients with ventricular arrhythmia–induced cardiac arrest, SN levels were also associated with short-term mortality (n = 51; hazard ratio ln SN: 3.33; 95% confidence interval: 1.83 to 6.05; p < 0.001 in multivariate analysis). Perfusing hearts with SN yielded markedly increased myocardial levels and SN internalized into cardiomyocytes by endocytosis. Intracellularly, SN reduced Ca2+ /calmodulin (CaM)-dependent protein kinase II δ (CaMKIIδ) activity via direct SN-CaM and SN-CaMKII binding and attenuated CaMKIIδ-dependent phosphorylation of the ryanodine receptor. SN also reduced sarcoplasmic reticulum Ca2+ leak, augmented sarcoplasmic reticulum Ca2+ content, increased the magnitude and kinetics of cardiomyocyte Ca2+ transients and contractions, and attenuated Ca2+ sparks and waves in HF cardiomyocytes. Conclusions SN provided incremental prognostic information to established risk indices in acute HF and ventricular arrhythmia–induced cardiac arrest.
Gender is an important determinant of cardiovascular risk, and men generally develop cardiovascular disease earlier than women. Increased levels of high-sensitivity cardiac troponin I (hs-TnI) have ...been shown to be predictive of cardiovascular death, with stronger effects in women. However, it remains unclear whether the stronger association between hs-TnI and cardiovascular death in women is based on the ability of hs-TnI to predict myocardial infarction (MI) or heart failure (HF). Accordingly, we aimed to assess the influence of gender on the association between levels of hs-TnI and incident MI and HF. hs-TnI was measured in 5,060 women and 4,054 men participating in the prospective observational Nord-Trøndelag Health Study using the Architect STAT High-Sensitive Troponin assay. All subjects were free from known coronary heart disease at baseline. After a median follow-up of 5,105 and 6,169 days, 292 MIs and 209 admissions for HF were registered, respectively. In our total cohort, hs-TnI was associated with the incidence of both end points, with adjusted hazard ratio per 1 SD in log hs-TnI 1.19 (95% CI 1.02 to 1.39) for MI and 1.58 (1.38 to 1.82) for HF. The corresponding values for women and men were 1.35 (1.02 to 1.78) versus 1.13 (0.93 to 1.38) for MI and 1.55 (1.26 to 1.91) versus 1.61 (1.36 to 1.90) for HF. The C-index for hs-TnI was stronger for women than men for MI (p <0.001), and no such difference was observed for HF (p = 0.06). In conclusion, in the general population, the association between hs-TnI concentrations and MI is stronger in women than in men. For HF, the impact of gender on the prognostic value of hs-TnI is less pronounced. Increased levels of troponin I in women may thus reflect an adverse phenotype more prone to the development of cardiovascular disease.
The new high-sensitivity cardiac troponin T (hs-cTnT) assay seems to provide important prognostic information in patients with stable cardiovascular disease. To understand the merit of hs-cTnT more ...closely in stable cardiovascular disease, we performed extensive echocardiographic characterization of 57 patients with aortic stenosis and myocardial hypertrophy and related hs-cTnT levels to prognosis and echocardiographic indexes of myocardial structure and function. The hs-cTnT levels were above the assay's detection limit in all patients, correlated with echocardiographic indexes of structure and function, most notably with left ventricular mass, and demonstrated prognostic utility of similar strength as N-terminal pro–B-type natriuretic peptide. In conclusion, these findings indicate that hs-cTnT may provide prognostic information in patients with aortic stenosis, and that left ventricular mass is an important determinant of TnT levels in stable patients as measured by the new highly sensitive assay.
Background Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. Stress imposed on the myocardium by repeated severe hypoxemia and/or BP surges during sleep may result in ...subclinical myocardial injury. A high-sensitivity cardiac troponin T (hs-cTnT) assay has been developed. We hypothesized that the severity of OSA, as assessed by the apnea-hypopnea index (AHI), is associated with circulating levels of hs-cTnT in the general population. Methods Five hundred five subjects drawn from the general population (age range, 30–65 years; 45% women) underwent in-hospital polysomnography and had morning blood samples drawn. Oversampling of subjects at high risk of OSA was performed. Results Overall, hs-cTnT was detectable (≥ 3 ng/L) in 216 subjects (42.8%). After categorizing subjects according to AHI cutoffs that correspond to no, mild to moderate, and severe OSA, the proportion of subjects with detectable hs-cTnT levels increased with increasing severity of OSA ( P for trend < .001). Multivariate logistic regression with detectable hs-cTnT as the dependent variable was used to further assess the association between OSA and troponin T. After adjustment for significant univariate predictors of detectable hs-cTnT, the association between AHI and hs-cTnT was no longer statistically significant. Conclusions The prevalence of detectable hs-cTnT increases in proportion to OSA severity, but this association is likely to be caused by a clustering of cardiovascular risk factors among subjects with OSA.
Cardiac Troponins Omland, Torbjørn, MD, PhD, MPH
Journal of the American College of Cardiology,
02/2014, Letnik:
63, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Equally important, prognostic assessment may be used to identify low-risk patients who may safely be treated conservatively, thus avoiding unnecessary invasive investigations and therapeutic ...procedures. ...recently, measurement of cardiac troponin levels has been almost exclusively performed to diagnose acute ischemic injury in patients with suspected acute myocardial infarction (MI). ...retrospective data from the PEACE study failed to show any interaction between cardiac troponin T levels at baseline and the benefit of the angiotensin-converting enzyme inhibitor trandolapril in low-risk patients with stable CAD (4). ...despite the important finding of the LIPID study that serial troponin measurement can refine risk stratification in stable CAD, the clinical benefit of the theoretically beautiful strategy of using cardiac troponins as a management criterion in this patient group remains unproven.
Background Circulating levels of osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, is predictive of death and hospitalization for heart failure after acute coronary ...syndrome. The association between OPG and outcome in patients with chronic heart failure (CHF) is unknown. Methods Plasma OPG levels at baseline were assessed in 1,229 patients with CHF recruited from 51 clinical centers and included in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Heart Failure (GISSI-HF) trial. Patients were randomized to n-3 polyunsaturated fatty acids (1 g/d) or rosuvastatin (10 mg/d) versus placebo. Osteoprotegerin was analyzed by enzyme-linked immunosorbent assay. The association between OPG and outcome was assessed by Cox proportional hazards regression models. Results During a median follow-up time of 3.9 years, 332 patients died; and 791 patients died or were hospitalized because of cardiovascular causes. By univariate analysis, baseline OPG levels were strongly associated with the incidence of death (hazard ratio {HR} 95% CI 1.53 1.40-1.67 per 1-SD increase in log OPG). After adjustment for conventional risk markers, OPG remained a significant predictor of death (HR 95% CI 1.20 1.06-1.35, P < .001). Similar findings were observed for the composite end point (HR 95% CI 1.34 1.07-1.69, P = .012). Conclusion In patients with CHF, OPG is associated with the incidence of death independently of conventional cardiovascular risk factors.
PDF
