26 research outputs found
On the variance and skewness of the swap rate in a stochastic volatility interest rate model
This paper provides new insight in the distribution of the (forward par) swap rate in a stochastic volatility model for the dynamics of the forward rate curve. First the swap rate dynamics are obtained in a multi-curve environment with deterministic spread. Then, the variance of the swap rate is derived making use of a result on the distribution of random variables generated by extended square-root diffusion processes. Also, the skewness is derived by ItĂŽ calculus. These results give rise to moment-matching swaption price formulas which are expected to permit a fast approximate calibration of the model
Identification of acute myocardial infarction in patients with atrial fibrillation and chest pain with a contemporary sensitive troponin I assay
Bone marrow and plasma FGFâ23 in heart failure patients : novel insights into the heartâbone axis
Aims: Fibroblast growth factor 23 (FGFâ23) is known to be elevated in patients with congestive heart failure (CHF). As FGFâ23 is expressed in the bone but can also be expressed in the myocardium, the origin of serum FGFâ23 in CHF remains unclear. It is also unclear if FGFâ23 expressed in the bone is associated with outcome in CHF. The aim of the present study was to investigate FGFâ23 levels measured in bone marrow plasma (FGFâ23âBM) and in peripheral blood (FGFâ23âP) in CHF patients to gain further insights into the heartâbone axis of FGFâ23 expression. We also investigated possible associations between FGFâ23âBM as well as FGFâ23âP and outcome in CHF patients.
Methods and results: We determined FGFâ23âP and FGFâ23âBM levels in 203 CHF patients (85% male, mean age 61.3 years) with a left ventricular ejection fraction (LVEF) â€45% and compared them with those of 48 healthy controls (48% male, mean age 39.2 years). We investigated the association between FGFâ23âBM and FGFâ23âP with allâcause mortality in CHF patients, 32 events, median followâup 1673 days, interquartile range [923, 1828]. FGFâ23âP (median 60.3 vs. 22.0 RU/mL, P < 0.001) and FGFâ23âBM (median 130.7 vs. 93.1 RU/mL, P < 0.001) levels were higher in CHF patients compared with healthy controls. FGFâ23âBM levels were significantly higher than FGFâ23âP levels in both CHF patients and in healthy controls (P < 0.001). FGFâ23âP and FGFâ23âBM correlated significantly with LVEF (r = â0.37 and r = â0.33, respectively), N terminal pro brain natriuretic peptide levels (r = 0.57 and r = 0.6, respectively), New York Heart Association status (r = 0.28 and r = 0.25, respectively), and estimated glomerular filtration rate (r = â0.43 and r = â0.41, respectively) (P for all <0.001) and were independently associated with allâcause mortality in CHF patients after adjustment for LVEF, estimated glomerular filtration rate, New York Heart Association status, and N terminal pro brain natriuretic peptide, hazard ratio 2.71 [confidence interval: 1.18â6.20], P = 0.018, and hazard ratio 2.80 [confidence interval: 1.19â6.57], P = 0.018, respectively.
Conclusions: In CHF patients, FGFâ23 is elevated in bone marrow plasma and is independently associated with heart failure severity and allâcause mortality. The failing heart seems to interact via FGFâ23 within a heartâbone axis
GDF-15 predicts cardiovascular events in acute chest pain patients
Background Treatment of patients presenting with possible acute myocardial infarction (AMI) is based on timely diagnosis and proper risk stratification aided by biomarkers. We aimed at evaluating the predictive value of GDF-15 in patients presenting with symptoms suggestive of AMI. Methods Consecutive patients presenting with suspected AMI were enrolled in three study centers. Cardiovascular events were assessed during a follow-up period of 6 months with a combined endpoint of death or MI. Results From the 1818 enrolled patients (m/f = 1208/610), 413 (22.7%) had an acute MI and 63 patients reached the combined endpoint. Patients with MI and patients with adverse outcome had higher GDF-15 levels compared with non-MI patients (967.1pg/mL vs. 692.2 pg/L, p<0.001) and with event-free patients (1660 pg/mL vs. 756.6 pg/L, p< 0.001). GDF-15 levels were lower in patients with SYNTAX score <= 22 (797.3 pg/mL vs. 947.2 pg/L, p = 0.036). Increased GDF-15 levels on admission were associated with a hazard ratio of 2.1 for death or MI (95% CI: 1.67-2.65, p< 0.001) in a model adjusted for age and sex and of 1.57 (1.13-2.19, p = 0.008) adjusted for the GRACE score variables. GDF-15 showed a relevant reclassification with regards to the GRACE score with an overall net reclassification index (NRI) of 12.5% and an integrated discrimination improvement (IDI) of 14.56% (p = 0.006). Conclusion GDF-15 is an independent predictor of future cardiovascular events in patients presenting with suspected MI. GDF-15 levels correlate with the severity of CAD and can identify and risk-stratify patients who need coronary revascularization
Bone marrow and plasma FGFâ23 in heart failure patients: novel insights into the heartâbone axis
Aims: Fibroblast growth factor 23 (FGFâ23) is known to be elevated in patients with congestive heart failure (CHF). As FGFâ23 is expressed in the bone but can also be expressed in the myocardium, the origin of serum FGFâ23 in CHF remains unclear. It is also unclear if FGFâ23 expressed in the bone is associated with outcome in CHF. The aim of the present study was to investigate FGFâ23 levels measured in bone marrow plasma (FGFâ23âBM) and in peripheral blood (FGFâ23âP) in CHF patients to gain further insights into the heartâbone axis of FGFâ23 expression. We also investigated possible associations between FGFâ23âBM as well as FGFâ23âP and outcome in CHF patients.
Methods and results: We determined FGFâ23âP and FGFâ23âBM levels in 203 CHF patients (85% male, mean age 61.3 years) with a left ventricular ejection fraction (LVEF) â€45% and compared them with those of 48 healthy controls (48% male, mean age 39.2 years). We investigated the association between FGFâ23âBM and FGFâ23âP with allâcause mortality in CHF patients, 32 events, median followâup 1673 days, interquartile range [923, 1828]. FGFâ23âP (median 60.3 vs. 22.0 RU/mL, P < 0.001) and FGFâ23âBM (median 130.7 vs. 93.1 RU/mL, P < 0.001) levels were higher in CHF patients compared with healthy controls. FGFâ23âBM levels were significantly higher than FGFâ23âP levels in both CHF patients and in healthy controls (P < 0.001). FGFâ23âP and FGFâ23âBM correlated significantly with LVEF (r = â0.37 and r = â0.33, respectively), N terminal pro brain natriuretic peptide levels (r = 0.57 and r = 0.6, respectively), New York Heart Association status (r = 0.28 and r = 0.25, respectively), and estimated glomerular filtration rate (r = â0.43 and r = â0.41, respectively) (P for all <0.001) and were independently associated with allâcause mortality in CHF patients after adjustment for LVEF, estimated glomerular filtration rate, New York Heart Association status, and N terminal pro brain natriuretic peptide, hazard ratio 2.71 [confidence interval: 1.18â6.20], P = 0.018, and hazard ratio 2.80 [confidence interval: 1.19â6.57], P = 0.018, respectively.
Conclusions: In CHF patients, FGFâ23 is elevated in bone marrow plasma and is independently associated with heart failure severity and allâcause mortality. The failing heart seems to interact via FGFâ23 within a heartâbone axis
Troponin I Assay for Identification of a Significant Coronary Stenosis in Patients with Suspected Acute Myocardial Infarction and Wide QRS Complex
Background Common ECG criteria such as ST-segment changes are of limited value in patients with suspected acute myocardial infarction (AMI) and bundle branch block or wide QRS complex. A large proportion of these patients do not suffer from an AMI, whereas those with ST-elevation myocardial infarction (STEMI) equivalent AMI benefit from an aggressive treatment. Aim of the present study was to evaluate the diagnostic information of cardiac troponin I (cTnI) in hemodynamically stable patients with wide QRS complex and suspected AMI. Methods In 417 out of 1818 patients presenting consecutively between 01/2007 and 12/2008 in a prospective multicenter observational study with suspected AMI a prolonged QRS duration was observed. Of these, n = 117 showed significant obstructive coronary artery disease (CAD) used as diagnostic outcome variable. cTnI was determined at admission. Results Patients with significant CAD had higher cTnI levels compared to individuals without (median 250ng/L vs. 11ng/L; p<0.01). To identify patients needing a coronary intervention, cTnI yielded an area under the receiver operator characteristics curve of 0.849. Optimized cut-offs with respect to a sensitivity driven rule-out and specificity driven rule-in strategy were established (40ng/L/96ng/L). Application of the specificity optimized cut-off value led to a positive predictive value of 71% compared to 59% if using the 99th percentile cut-off. The sensitivity optimized cut-off value was associated with a negative predictive value of 93% compared to 89% provided by application of the 99th percentile threshold. Conclusion cTnI determined in hemodynamically stable patients with suspected AMI and wide QRS complex using optimized diagnostic thresholds improves rule-in and rule-out with respect to presence of a significant obstructive CAD
Urinary neutrophil gelatinase-associated lipocalin and cystatin C compared to the estimated glomerular filtration rate to predict risk in patients with suspected acute myocardial infarction
Introduction: Impaired renal function, reflected by estimated glomerular filtration rate (eGFR) or cystatin C, is a strong risk predictor in the presence of acute myocardial infarction (AMI). Urinary neutrophil gelatinase associated lipocalin (uNGAL) is an early marker of acute kidney injury. uNGAL might also be a good predictor of outcome in patients with cardiovascular disease. Aim of the present study was to evaluate the prognostic value of uNGAL compared to eGFR and cystatin C in patients with suspected AMI. Methods: 1818 patients were enrolled with suspected AMI. Follow-up information on the combined endpoint of death or non-fatal myocardial infarction was obtained 6 months after enrolment and was available in 1804 patients. 63 events (3.5%) were registered. Results: While cystatin C and eGFR were strong risk predictors for the primary endpoint even adjusted for several variables, uNGAL was not independently associated with outcome: When applied continuously uNGAL was associated with outcome but did not remain a statistically significant predictor after several adjustments (i.e. eGFR). By adding cystatin C or uNGAL to GRACE risk score variables, only cystatin C could improve the predictive value while uNGAL showed no improvement. Conclusion: We could show that cystatin C is an independent risk predictor in patients with suspected AMI and cystatin C can add improvement to the commonly used GRACE risk score. In contrast uNGAL is not independently associated with outcome and seems not to add further prognostic information to GRACE risk score. (C) 2017 Elsevier B.V. All rights reserved
Estimation of Values below the Limit of Detection of a Contemporary Sensitive Troponin I Assay Improves Diagnosis of Acute Myocardial Infarction
BACKGROUND: The limit of detection (LoD) is the minimal amount of a substance that can be consistently detected. In the diagnosis of acute myocardial infarction (AMI) many patients present with troponin concentrations below the LoD of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored values below the LoD influence the diagnostic performance of these assays compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the impact of a new approach for interpolation of the left-censored data of a cs-cTnI assay in the evaluation of patients with suspected AMI. METHODS: Our posthoc analysis used a real world cohort of 1818 patients with suspected MI. Data on cs-cTnI was available in 1786 patients. As a comparator the hs-cTnI version of the assay was used. To reconstruct quantities below the LoD of the cs-cTnI assay, a gamma regression approach incorporating the GRACE (Global Registry of Acute Coronary Events) score variables was used. RESULTS: Censoring of cs-cTnI data below the LoD yielded weaker diagnostic information [area under the curve (AUC), 0.781; 95% CI, 0.731-0.831] regarding AMI compared to the hs-cTnI assay (AUC, 0.949; CI, 0.936-0.961). Use of our model to estimate cs-cTnI values below the LoD showed an AUC improvement to 0.921 (CI, 0.902-0.940). The cs-cTnI LoD concentration had a negative predictive value (NPV) of 0.950. An estimated concentration that was to be undercut by 25% of patients presenting with suspected AMI was associated with an improvement of the NPV to 0.979. CONCLUSIONS: Estimation of values below the LoD of a cs-cTnI assay with this new approach improves the diagnostic performance in evaluation of patients with suspected AMI. (C) 2015 American Association for Clinical Chemistr
INTRA-INDIVIDUAL CHANGES IN HIGH-SENSITIVE TROPONIN I AND T LEVELS IMPROVE DIAGNOSTIC PERFORMANCE FOR ACUTE MYOCARDIAL INFARCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Improved risk stratification in prevention by use of a panel of selected circulating microRNAs
Risk stratification is crucial in prevention. Circulating microRNAs have been proposed as biomarkers in cardiovascular disease. Here a miR panel consisting of miRs related to different cardiovascular pathophysiologies, was evaluated to predict outcome in the context of prevention. MiR-34a, miR-223, miR-378, miR-499 and miR-133 were determined from peripheral blood by qPCR and combined to a risk panel. As derivation cohort, 178 individuals of the DETECT study, and as validation cohort, 129 individuals of the SHIP study were used in a case-control approach. Overall mortality and cardiovascular events were outcome measures. The Framingham Risk Score(FRS) and the SCORE system were applied as risk classification systems. The identified miR panel was significantly associated with mortality given by a hazard ratio(HR) of 3.0 (95% (CI): 1.09-8.43; p = 0.034) and of 2.9 (95% CI: 1.32-6.33; p = 0.008) after adjusting for the FRS in the derivation cohort. In a validation cohort the miR-panel had a HR of 1.31 (95% CI: 1.03-1.66; p = 0.03) and of 1.29 (95% CI: 1.02-1.64; p = 0.03) in a FRS/SCORE adjusted-model. A FRS/SCORE risk model was significantly improved to predict mortality by the miR panel with continuous net reclassification index of 0.42/0.49 (p = 0.014/0.005). The present miR panel of 5 circulating miRs is able to improve risk stratification in prevention with respect to mortality beyond the FRS or SCORE