Association of aortic stiffness with biomarkers of myocardial wall stress after myocardial infarction
Introduction
Chronic maladaptive transformation processes of the left ventricular (LV) myocardium are associated with a significantly worse prognosis after acute ST-segment elevation myocardial infarction (STEMI) [1], [2], [3]. Early detection and prognostication of LV-remodelling is, therefore, not only an important diagnostic, but also a therapeutic target.
B-type natriuretic peptide (BNP) levels obtained at admission for STEMI have been shown to predict short and long-term ventricular function [4], [5]. Increased wall stress is known to be both a major force driving LV remodelling [1], [2], and a cause of BNP release [6]. Recent studies suggest that BNP is a short-term prognostic marker after STEMI [7] and indicates remodelling before chamber dilation actually occurs [8], [9].
Adrenomedullin (ADM) is a natriuretic and diuretic peptide found in the adrenal medulla and the heart [9]. Plasma levels are increased in hypertension, renal failure and heart failure, where it is correlated to LV ejection fraction (LV-EF) and LV end-diastolic pressure [10], [11]. Its prognostic value after STEMI has been described to be superior to that of BNP [12].
A-type natriuretic peptide (ANP) is synthesized and secreted from atrial and ventricular myocardium and is correlated to atrial pressure. Several measures of ANP activity have a prognostic value after acute myocardial infarction [13].
Current guidelines from the European Society of Cardiology consider the use of carotid–femoral pulse wave velocity (PWV) as the gold-standard for measurement of arterial stiffness [14]. In healthy volunteers, it averages between 4 and 8 m/s and depends on age [15], [16], training status [17], site of the measurement [18] as well as subject's condition [14].
The relation of aortic PWV with BNP has been described in patients with significant coronary artery disease [19]. Moreover, the influence of aortic vascular elasticity on left atrial size in hypertensive patients has been reported [20]. PWV was linked to LV-geometry and -function (LV-EF, E/A) in patients with kidney disease [21] and non-ischemic cardiomyopathy [22]. Cross-sectional data from Hirsch et al. strongly suggest an impact of aortic stiffness on LV-size after myocardial infarction in older patients [23]. This might be not only of diagnostic, but also of special therapeutic interest as PWV has previously been investigated as a therapeutic target [24], [25].
We hypothesised that aortic stiffness might increase ventricular afterload, and therefore wall stress, in patients after STEMI beyond established markers. Therefore, in the present study, we prospectively investigated the relationship of increased aortic stiffness biomarkers of myocardial wall stress 4 months after STEMI.
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Study population
Inclusion criteria for screening were the diagnosis of a STEMI according to the redefined ESC/ACC committee criteria [26] as first cardiac event and successful reperfusion by primary percutaneous coronary intervention and stent implantation (p-PCI). Exclusion criteria were renal dysfunction with a GFR < 30 ml/min/m2, claustrophobia, Killip class > 2, contraindications for CMR, participation in another study and inability to return for 4-month follow-up.
52 patients were initially included in the
Baseline patient characteristics and CMR
The baseline characteristics are summarised in Table 1. Patients were scanned with CMR within a median of 2.5 days (IQR: 1.4–3.9) after the index event. At admission 9 (19%) patients were on beta-blocker, 7 (15%) on angiotensin-converting-enzyme inhibitor and 6 (13%) on angiotensin-receptor antagonist therapy. Patients were stratified in patients below (n = 27) and above (n = 21) the median aortic PWV of 7.00 m/s.
Patients with an aortic PWV above median were older (64.3 ± 9.6 yrs vs. 49.7 ± 8.9 yrs, p <
Discussion
The main finding of this study is that baseline aortic stiffness in patients with first STEMI is associated with biomarker levels of myocardial wall stress measured four months after the index event. These findings indicate an impact of aortic stiffness on left ventricular wall stress and subsequent remodelling after STEMI. We raised the question as to how aortic stiffness might influence myocardial wall stress after STEMI. Cardiovascular risk factors, extensive coronary artery disease and
Conclusion
We have shown for the first time that, beside infarct size, aortic stiffness is a determinant of biomarkers of myocardial wall stress 4 months after first STEMI. Multivariate analysis confirms that this association is independent of age, renal function and ejection fraction. Arterial stiffness is easy to measure non-invasively and has prognostic relevance as a therapeutic target [24]. As this study generates the hypothesis of a role for aortic stiffness in chronic LV-remodelling, these findings
Acknowledgements
This study was supported by a grant from the “Österreichische Kardiologische Gesellschaft” to Gert Klug and Bernhard Metzler and also supported by the intramural funding programme of the Medical University Innsbruck for young scientists MUI-START, Project 2013042016 and the “Hans und Blanca Moser Stiftung” to Gert Klug.
The authors of this manuscript certify that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
Abbreviations
- ACC
- American College of Cardiology
- BL
- baseline
- BMI
- body mass index
- LGE-CMR
- late contrast-enhanced cardiovascular magnetic resonance
- CO
- cardiac output
- CRPmax
- maximum C-reactive-protein
- cTnT
- cardiac Troponin T
- ED
- end-diastole
- EDVI
- end-diastolic volume index
- ESC
- European Society of Cardiology
- ESVI
- end-systolic volume index
- LVEF
- left ventricular ejection fraction
- MMI
- myocardial mass index
- MR-proADM
- mid-region pro-adrenomedullin
- MR-proANP
- MR-pro-A-type natriuretic peptide
- NT-proBNP
- N-terminal pro-B-type natriuretic peptide
- p-PCI
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