610866 research-article2015

ACC0010.1177/2048872615610866European Heart Journal: Acute Cardiovascular CareFeistritzer et al.

EUROPEAN SOCIETY OF CARDIOLOGY ®

Original scientific paper

N-terminal pro-B-type natriuretic peptide is associated with aortic stiffness in patients presenting with acute myocardial infarction

European Heart Journal: Acute Cardiovascular Care 2016, Vol. 5(8) 560­–567 © The European Society of Cardiology 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2048872615610866 acc.sagepub.com

Hans-Josef Feistritzer1, Sebastian J Reinstadler1, Gert Klug1, Christian Kremser2, Andrea Rederlechner1, Johannes Mair1, Silvana Müller1, Wolfgang-Michael Franz1 and Bernhard Metzler1

Abstract Background: Aortic stiffness is associated with increased left ventricular (LV) afterload, a process which is accompanied by a release of natriuretic peptides. Aortic pulse wave velocity (PWV) has been demonstrated to be the functional surrogate of aortic stiffness. We sought to investigate the impact of aortic PWV on N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in patients with acute myocardial infarction (AMI). Methods: This prospective observational study included 86 consecutive patients undergoing percutaneous coronary intervention for AMI. Aortic PWV was determined 47 h (interquartile range (IQR) 27–64 h) after AMI using an established oscillometric device. NT-proBNP values were measured using a commercially available immunoassay. Results: The mean age of the study cohort was 60±11 years; 19% were female. Median aortic PWV was 7.8 m/s (IQR 6.8–9.4 m/s). Patients with a PWV above the median showed significantly higher NT-proBNP peak concentrations (median=1330 ng/l, IQR: 729–3180 ng/l vs median=498 ng/l, IQR: 124–1575 ng/l, p=0.001). Aortic PWV (beta=0.373, p=0.014) was independently associated with NT-proBNP peak concentrations even after correction for LV function, cardiac troponin T levels, heart rate, blood pressure, body mass index and the primary prevention European Society of Cardiology (ESC) SCORE (model: R=0.542, p=0.014). Conclusion: In patients with AMI, aortic PWV is independently associated with NT-proBNP concentrations. This finding suggests an impact of aortic PWV on myocardial wall stress after AMI. Keywords Aortic stiffness, pulse wave velocity, natriuretic peptides, acute myocardial infarction Date received: 30 April 2015; accepted: 20 September 2015

Introduction N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured in the acute and chronic phase after acute myocardial infarction (AMI) predicts the occurrence of left ventricular (LV) dysfunction, heart failure and death.1–4 Enhanced myocardial wall stress is the most important trigger of NT-proBNP release.5 Consequently, high NT-proBNP concentrations indicate cardiac pressure overload. High aortic stiffness is a major determinant of LV afterload due to early pulse wave reflection and intensified

1University

Clinic of Internal Medicine III, Medical University of Innsbruck, Austria 2Department of Radiology, Medical University of Innsbruck, Austria Corresponding author: Bernhard Metzler, University Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. Email: [email protected]

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Feistritzer et al. augmentation of aortic and LV systolic pressure.6 Estimation of aortic pulse wave velocity (PWV) is the gold standard technique to assess aortic stiffness.7,8 The Mobil-O-Graph device (IEM, Stolberg, Germany) allows for a non-invasive, fast and accurate determination of aortic PWV by transformation of brachial pressure wave curves.9–11 It has also been validated against intra-aortic catheter measurements, the invasive reference technique for the assessment of aortic PWV.12 An association between aortic PWV and NT-proBNP has been described in the general population13 as well as in patients with hypertension14 and coronary artery disease.15 In patients with ST-segment elevation myocardial infarction (STEMI), aortic PWV has been linked to NT-proBNP concentrations four months after the acute event.16,17 However, these studies used cardiac magnetic resonance (CMR) imaging to assess aortic PWV. However, CMR is expensive and is not a widely available technique, and application is restricted to clinically stable patients.18 Therefore, in the present study we sought to prospectively investigate the association between oscillometrically derived aortic PWV and NT-proBNP concentrations in consecutive AMI patients.

Methods Study population Eighty-six consecutive patients presenting with AMI at the coronary care unit of University Hospital of Innsbruck were enrolled in this prospective, observational study. Patients were included if they had: (a) ischaemic symptoms for more than 20 min; (b) a rise and/or fall of cardiac troponin T (cTnT) with at least one value above the 99th percentile upper reference limit; and (c) successful reperfusion of the culprit vessel by percutaneous coronary intervention (PCI), either using an immediate, early or delayed (>14 h) invasive strategy.19,20 The decision for an immediate or early invasive strategy was based on risk assessment of patients, according to current European Society of Cardiology (ESC) guidelines.20,21 To assess the presence or absence of significant ST-segment elevation, the initial electrocardiogram was analysed by a trained physician.19,22 Exclusion criteria were age less than 18 years, presence of cardiogenic shock, and participation in another study. The present study was performed in conformity with the ethical guidelines of the 1975 Declaration of Helsinki. Written informed consent was obtained from all patients before inclusion in the study. The study was approved by the ethics committee of the Medical University of Innsbruck.

Patient characterization Data on patient characteristics, medical history and current medication were prospectively taken during hospitalisation using a standardised questionnaire. Furthermore, all patients

underwent physical examination. We applied the primary prevention ESC SCORE low-risk chart to quantify individual risk profiles with regard to gender, smoking habits, age, blood pressure and total cholesterol.23 Patients were scored into those having one-, two- or three-vessel disease with regard to the presence of significant stenosis (>70%). All infarcts caused by occlusion of the left anterior descending artery were considered as anterior infarcts. For the assessment of LV ejection fraction, transthoracic echocardiography was performed in all patients during index hospitalisation, as described in detail previously.24,25 LV diastolic function was measured using the LV E/A ratio as recommended by imaging guidelines.26

Aortic pulse wave velocity We used a commercially available brachial, oscillometric ambulatory blood pressure monitor (Mobil-O-Graph, IEM, Stolberg, Germany) for blood pressure and PWV assessment.10 All measurements were performed with patients in the supine position. An appropriately sized common blood pressure cuff was centred to the left upper arm. Blood pressure and PWV assessments were repeated every 12 min for one hour. For statistical analysis, the mean value of all five measurements was used. In our cohort, the mean individual range between these five measurements was 0.5 m/s, which corresponds to 6% of median PWV. Aortic PWV was derived from brachial pulse waves, as described in detail previously.10 Briefly, assessing aortic PWV is based on an algorithm, integrating aortic characteristic impedance and pulse wave separation analysis into a mathematical model.9

Biochemical markers Heparinised plasma samples were analysed immediately at the central laboratory of University Hospital of Innsbruck by personnel blinded to study data. NT-proBNP concentrations were measured using a commercially available proBNP II immunoassay using monoclonal antibodies (Roche Diagnostics, Vienna, Austria).17 This assay provides an analytical limit of detection of 5 ng/l. The limit of quantification is 50 ng/l. The intra-assay coefficients of variation (CVs) are 1.9% at a concentration of 64 ng/l and 1.2% at a concentration of 2105 ng/l. The inter-assay CVs are 3.1% at 46 ng/l and 2.7% at 2170 ng/l according to manufacturer´s declaration. All cTnT concentrations were measured using a fifthgeneration high-sensitivity assay (Roche Diagnostics, Mannheim, Germany).27,28 NT-proBNP was measured on admission and subsequently once daily from day 1 to day 4 after infarction or discharge. The level of cTnT was determined three times during the first 24 h after admission and then daily until day 4 or discharge.

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Statistical analysis We used SPSS Statistics 22.0.0 (IBM, Armonk, New York, USA) for statistical analysis. To test for normal distribution (ND), the Shapiro-Wilk test was used. All variables except PWV, heart rate, the ESC SCORE, body mass index, the LV E/A ratio as well as peak cTnT and NT-proBNP concentrations were found to be in a ND. They were log-transformed for multiple linear regression analysis. Results for continuous variables are all expressed as mean±standard deviation if ND or as median with interquartile range (IQR) if not. Categorical data are expressed as numbers and corresponding percentages. To test for correlations of continuous variables, Pearson’s test (if ND) or Spearman’s rank correlation coefficients (if not ND) were calculated. Student´s t-test (if ND) or Mann-Whitney U test (if not ND) were used to assess differences in continuous variables between groups. Differences in categorical variables were assessed by χ2-test or Fisher´s exact test. To test for predictors of NT-proBNP concentrations, a multiple linear regression analysis was performed. Variables, which differed significantly between patients with NT-proBNP concentrations above and below the median value (Table 1), were included in the multivariate analysis (except of age, as part of the ESC SCORE). Two-tailed p values