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Aminoterminal propeptide of type III procollagen (PIIINP) is associated with ascending aortic aneurysm growth rate
Letters to the Editor
379
Aminoterminal propeptide of type III procollagen (PIIINP) is associated with ascending aortic aneurysm growth rate Olivier Ormezzano a,⁎, Jean-Philippe Baguet a, Frédéric Thony b, Dominique Blin c, Olivier Chavanon c, Bertrand Toussaint d, Candice Trocmé d, Gérald Vanzetto a, Patrice Faure d a
Clinic of Cardiology, UJF, University Hospital of Grenoble, France Clinic of Radiology, UJF, University Hospital of Grenoble, France c Clinic of Cardiovascular Surgery, UJF, University Hospital of Grenoble, France d Department of Biochemistry, Toxicology and Pharmacoloy, UJF, University Hospital of Grenoble, France b
a r t i c l e
i n f o
Article history: Received 2 February 2010 Accepted 14 February 2010 Available online 12 March 2010 Keywords: Thoracic aortic aneurysm Procollagen Aneurysm growth rate
To the Editor Anatomopathological analysis of thoracic aortic aneurysms (TAA) suggests that extracellular matrix metabolism (ECMM) may play a dominant role in the formation and progression of this condition. Aminoterminal propeptide of type III procollagen (PIIINP) is a marker of ECMM activity and its plasma levels have been linked to abdominal aortic aneurysm (AAA) growth rate [1,2]. To our knowledge, PIIINP and its relationship with TAA growth has never previously been studied. We studied 30 consecutive patients in whom an asymptomatic ascending TAA not yet at a surgical stage had been discovered by chance during a cardiovascular or radiological assessment, as part of a single-centre, pilot, prospective study approved by the Grenoble Ethics Committee. Any patients having presented a medical or surgical event within three months prior to inclusion, suffering from a chronic inflammatory disease or presenting the clinical characteristics of Marfan's syndrome were excluded. After obtaining the patient's written consent, a sample of venous blood was taken. PIIINP was measured using a radio immunoassay method (IDS kit). The patients were then followed up in the usual way, by annual angio-CT scan or angio-MRI. The indication for surgery was discussed once the asymptomatic TAA approached a size of 50 mm in the ascending aorta or 65 mm in the descending aorta, or if it was accompanied by an increase in size from one consultation to the next [3]. The context (hypertension, personal and family history, etc.) was also taken into consideration, on a case-by-case basis. The growth rate of the aneurysm was calculated by the ratio for the variation in maximum thoracic aorta diameter over the time interval separating the inclusion examination and the most recent examination performed during the follow-up period (expressed in mm/year). The
Abbreviations: AAA, abdominal aortic aneurysm; ACE, angiotensin converting enzyme; BMI, body mass index; ECMM, extracellular matrix metabolism; PIIINP, aminoterminal propeptide of type III procollagen; TAA, thoracic aortic aneurysm ⁎ Corresponding author. Service de Cardiologie, CHU Michallon, BP 217, 38043 Grenoble Cedex 09, France. Tel.: +33 4 76 76 54 40; fax: +33 4 76 76 55 59. E-mail address: [email protected] (O. Ormezzano).
patients were then divided into two groups: Group 1=patients with a stable TAA or with a slow growth rate (≤2 mm/year) (n=23) and Group 2=patients with a fast-growing TAA (N2 mm/year) (n=7). The data are presented as means ± SD or frequencies. A Mann– Whitney U test was used to compare variables. To determine the independent factors, the logistic regression model was used, including PIIINP, older age, male gender and the initial diameter of the TAA. The mean age of the patients was 65.8 ± 10.8 years. 90% (27/30) were men and the mean body mass index (BMI) was 27.2 ± 4.9 kg/m2. The other characteristics were as follows: serum creatinine= 95 ± 26 μmol/l, total cholesterol = 4.93 ± 1.03 mmol/l, hsCRP = 3.4 ± 4.2 mg/l, PIIINP = 3.66 ± 1.13 μg/l, mean blood pressure = 145 ± 18/87 ± 14 mm Hg. 14% of the patients were current smokers, 43% former smokers and 43% had never smoked, 7.1% were diabetics, 16.7% had obstructive sleep apnoea requiring CPAP management and 77% had hypertension. On assessment, 87% of patients had already taken vasoactive medications (50% beta-blockers, 68% ACE inhibitors or ARBs, 7% calcium-channel blockers). At inclusion, the mean value for maximum aneurysm diameter was 44.6 ± 3.4 mm. Seven patients (23%) presented aneurysm growth of greater than 2 mm/year (3.2 ± 0.8 mm/year, Group 1). The mean follow-up period was 1.6 ± 0.8 years. A univariate analysis showed that the initial size of the AAT is only correlated with patient height (r = 0.377, p = 0.04). The patients presenting a significant increase in maximum aneurysm size have a significantly higher PIIINP level than those demonstrating no or limited growth in maximum aneurysm diameter (4.51 ± 1.09 vs 3.38 ± 0.96 μg/l respectively, p = 0.02) (Fig. 1). There is no difference between the two groups for the other clinical or laboratory parameters measured including the matrix metalloproteinase type 1, known to degrade type III collagen (data not shown). Following multivariate analysis using the logistic regression model incorporating age, gender and initial TAA size, the PIIINP level remains significantly higher in Group 1 (p = 0.03). Circulating PIIINP levels have been found to be higher in patients with AAA than in controls, but recent studies conducted in large patient populations have not found any link between circulating PIIINP levels and the existence of an AAA [4]. However, PIIINP is the only marker to have been linked with an increase in AAA size in two different cohorts [1,2]. Satta et al. [1] demonstrated a link between PIIINP variations, an increase in AAA size and the risk of aneurysm rupture in 139 patients followed up for 24 months. Lindholt et al. [2] found that the PIIINP level was independently correlated with annual AAA growth rate in 99 patients followed up for an average of 2.5 years. To our knowledge, no published study exists to date analysing the relationship between PIIINP and TAA growth rate. Type III collagen is one of the essential fibrillar elements ensuring the mechanical resistance of the aorta wall and limiting its expansion. It has been suggested that this type III collagen may provide the aortic tissue with tensile strength. An increase in aortic aneurysm size is accompanied by increased collagenolytic activity, a degradation in type III collagen and an increase in PIIINP levels [5]. This may explain
380
Letters to the Editor
The main limitation of our study is the fact that the follow-up period is too short to be able to make any link between PIIINP levels and clinical events. Our results suggest that it may in the future be possible to monitor TAAs by means of PIIINP levels. However, only a large-scale prospective study could confirm this possibility. This work was conducted with the support of the French Ministry of Research as part of the Hospital Clinical Research Project. The authors would like to thank Jean-Louis Quesada (CIC 03 INSERM — Grenoble University Hospital, France) for his expert statistical assistance and are indebted to Hélène Pierre, clinical research nurse, for her excellent technical assistance. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [6]. References
Fig. 1. Aminoterminal propeptide of type III procollagen (PIIINP) levels and ascending aortic aneurysm growth rate. Box plot comparing PIIINP levels between patients with a stable TAA or a slow growth rate (b 2 mm/year) (Group 1, n = 23) and those with a fastgrowing TAA (N 2 mm/year) (Group 2, n = 7). The horizontal lines inside the boxes indicate the means and the bottom and top of the boxes represent the 25th and 75th percentiles, respectively.
[1] Satta J, Haukipuro K, Kairaluoma MI, Juvonen T. Aminoterminal propeptide of type III procollagen in the follow-up of patients with abdominal aortic aneurysms. J Vasc Surg 1997;25:909–15. [2] Lindholt JS, Heickendorff L, Vammen S, Fasting H, Henneberg EW. Five-year results of elastin and collagen markers as predictive tools in the management of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2001;21:235–40. [3] Elefteriades JA. Natural history of thoracic aortic aneurysms: indications for surgery, and surgical versus nonsurgical risks. Ann Thorac Surg 2002;74:S1877–80. [4] Golledge J, Tsao PS, Dalman RL, Norman PE. Circulating markers of abdominal aortic aneurysm presence and progression. Circulation 2008;118:2382–92. [5] Bode MK, Soini Y, Melkko J, et al. Increased amount of type III pN-collagen in human abdominal aortic aneurysms. Evidence for impaired type III collagen fibrillogenesis. J Vasc Surg 2000;32:1201–7. [6] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
why the PIIINP level is increased in the group of patients presenting TAA growth in our study. Our results are therefore consistent with studies carried out in patients with an AAA.
0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.02.051
Free breathing cardiac real-time cine MR without ECG triggering Meinrad Beer a,⁎, Heimo Stamm a, Wolfram Machann b, Andreas Weng a, Jan P. Goltz b, Frank Breunig b, Frank Weidemann b, Dietbert Hahn a, Herbert Köstler a a b
Institut für Röntgendiagnostik, Universität Würzburg, Oberdürrbacherstr. 6, D-97080 Würzburg, Germany Medizinische Klinik I und Poliklinik, Universität Würzburg, Oberdürrbacherstr. 6, D-97080 Würzburg, Germany
a r t i c l e
i n f o
Article history: Received 2 February 2010 Accepted 14 February 2010 Available online 11 March 2010 Keywords: Magnetic resonance imaging Cine Parallel imaging Real time imaging Left ventricular function
⁎ Corresponding author. Tel.: +49 931 201 1; fax: +49 931 201 34857. E-mail address: [email protected] (M. Beer).
Cardiac MRI has become an accurate and highly reproducible method for evaluating LV volumes, global function and mass [1]. However, the applied standard cine MRI sequences require patient compliance (repeated breath-holds) and a robust ECG-registration (trigger). Normally, a cine analysis of the left ventricle (LV) is based on 10–12 consecutive breath-holds with duration of up to 15 min [1]. This may be too long in every-day clinical routine especially for severely ill patients. A solution provides here the multislice technique, which allows the acquisition of several or even all necessary slices in one breath-hold [2]. But even here patients have to hold their breath for 10 to 20 s. Free-breathing imaging might overcome this remaining restriction. However, the so far presented techniques use ECG triggering and acquire one complete heart beat per slice [3–5]. In the present study, we wanted to go even further and implemented a real-time (RT) free-breathing sequence without ECG triggering. The accuracy and reliability of RT imaging (temporal resolution 49 ms) was compared to standard ECG triggered breath-hold cine imaging. The study was approved by the local ethics committee and written informed consent was obtained from all subjects. 9 healthy volunteers (5
379
Aminoterminal propeptide of type III procollagen (PIIINP) is associated with ascending aortic aneurysm growth rate Olivier Ormezzano a,⁎, Jean-Philippe Baguet a, Frédéric Thony b, Dominique Blin c, Olivier Chavanon c, Bertrand Toussaint d, Candice Trocmé d, Gérald Vanzetto a, Patrice Faure d a
Clinic of Cardiology, UJF, University Hospital of Grenoble, France Clinic of Radiology, UJF, University Hospital of Grenoble, France c Clinic of Cardiovascular Surgery, UJF, University Hospital of Grenoble, France d Department of Biochemistry, Toxicology and Pharmacoloy, UJF, University Hospital of Grenoble, France b
a r t i c l e
i n f o
Article history: Received 2 February 2010 Accepted 14 February 2010 Available online 12 March 2010 Keywords: Thoracic aortic aneurysm Procollagen Aneurysm growth rate
To the Editor Anatomopathological analysis of thoracic aortic aneurysms (TAA) suggests that extracellular matrix metabolism (ECMM) may play a dominant role in the formation and progression of this condition. Aminoterminal propeptide of type III procollagen (PIIINP) is a marker of ECMM activity and its plasma levels have been linked to abdominal aortic aneurysm (AAA) growth rate [1,2]. To our knowledge, PIIINP and its relationship with TAA growth has never previously been studied. We studied 30 consecutive patients in whom an asymptomatic ascending TAA not yet at a surgical stage had been discovered by chance during a cardiovascular or radiological assessment, as part of a single-centre, pilot, prospective study approved by the Grenoble Ethics Committee. Any patients having presented a medical or surgical event within three months prior to inclusion, suffering from a chronic inflammatory disease or presenting the clinical characteristics of Marfan's syndrome were excluded. After obtaining the patient's written consent, a sample of venous blood was taken. PIIINP was measured using a radio immunoassay method (IDS kit). The patients were then followed up in the usual way, by annual angio-CT scan or angio-MRI. The indication for surgery was discussed once the asymptomatic TAA approached a size of 50 mm in the ascending aorta or 65 mm in the descending aorta, or if it was accompanied by an increase in size from one consultation to the next [3]. The context (hypertension, personal and family history, etc.) was also taken into consideration, on a case-by-case basis. The growth rate of the aneurysm was calculated by the ratio for the variation in maximum thoracic aorta diameter over the time interval separating the inclusion examination and the most recent examination performed during the follow-up period (expressed in mm/year). The
Abbreviations: AAA, abdominal aortic aneurysm; ACE, angiotensin converting enzyme; BMI, body mass index; ECMM, extracellular matrix metabolism; PIIINP, aminoterminal propeptide of type III procollagen; TAA, thoracic aortic aneurysm ⁎ Corresponding author. Service de Cardiologie, CHU Michallon, BP 217, 38043 Grenoble Cedex 09, France. Tel.: +33 4 76 76 54 40; fax: +33 4 76 76 55 59. E-mail address: [email protected] (O. Ormezzano).
patients were then divided into two groups: Group 1=patients with a stable TAA or with a slow growth rate (≤2 mm/year) (n=23) and Group 2=patients with a fast-growing TAA (N2 mm/year) (n=7). The data are presented as means ± SD or frequencies. A Mann– Whitney U test was used to compare variables. To determine the independent factors, the logistic regression model was used, including PIIINP, older age, male gender and the initial diameter of the TAA. The mean age of the patients was 65.8 ± 10.8 years. 90% (27/30) were men and the mean body mass index (BMI) was 27.2 ± 4.9 kg/m2. The other characteristics were as follows: serum creatinine= 95 ± 26 μmol/l, total cholesterol = 4.93 ± 1.03 mmol/l, hsCRP = 3.4 ± 4.2 mg/l, PIIINP = 3.66 ± 1.13 μg/l, mean blood pressure = 145 ± 18/87 ± 14 mm Hg. 14% of the patients were current smokers, 43% former smokers and 43% had never smoked, 7.1% were diabetics, 16.7% had obstructive sleep apnoea requiring CPAP management and 77% had hypertension. On assessment, 87% of patients had already taken vasoactive medications (50% beta-blockers, 68% ACE inhibitors or ARBs, 7% calcium-channel blockers). At inclusion, the mean value for maximum aneurysm diameter was 44.6 ± 3.4 mm. Seven patients (23%) presented aneurysm growth of greater than 2 mm/year (3.2 ± 0.8 mm/year, Group 1). The mean follow-up period was 1.6 ± 0.8 years. A univariate analysis showed that the initial size of the AAT is only correlated with patient height (r = 0.377, p = 0.04). The patients presenting a significant increase in maximum aneurysm size have a significantly higher PIIINP level than those demonstrating no or limited growth in maximum aneurysm diameter (4.51 ± 1.09 vs 3.38 ± 0.96 μg/l respectively, p = 0.02) (Fig. 1). There is no difference between the two groups for the other clinical or laboratory parameters measured including the matrix metalloproteinase type 1, known to degrade type III collagen (data not shown). Following multivariate analysis using the logistic regression model incorporating age, gender and initial TAA size, the PIIINP level remains significantly higher in Group 1 (p = 0.03). Circulating PIIINP levels have been found to be higher in patients with AAA than in controls, but recent studies conducted in large patient populations have not found any link between circulating PIIINP levels and the existence of an AAA [4]. However, PIIINP is the only marker to have been linked with an increase in AAA size in two different cohorts [1,2]. Satta et al. [1] demonstrated a link between PIIINP variations, an increase in AAA size and the risk of aneurysm rupture in 139 patients followed up for 24 months. Lindholt et al. [2] found that the PIIINP level was independently correlated with annual AAA growth rate in 99 patients followed up for an average of 2.5 years. To our knowledge, no published study exists to date analysing the relationship between PIIINP and TAA growth rate. Type III collagen is one of the essential fibrillar elements ensuring the mechanical resistance of the aorta wall and limiting its expansion. It has been suggested that this type III collagen may provide the aortic tissue with tensile strength. An increase in aortic aneurysm size is accompanied by increased collagenolytic activity, a degradation in type III collagen and an increase in PIIINP levels [5]. This may explain
380
Letters to the Editor
The main limitation of our study is the fact that the follow-up period is too short to be able to make any link between PIIINP levels and clinical events. Our results suggest that it may in the future be possible to monitor TAAs by means of PIIINP levels. However, only a large-scale prospective study could confirm this possibility. This work was conducted with the support of the French Ministry of Research as part of the Hospital Clinical Research Project. The authors would like to thank Jean-Louis Quesada (CIC 03 INSERM — Grenoble University Hospital, France) for his expert statistical assistance and are indebted to Hélène Pierre, clinical research nurse, for her excellent technical assistance. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [6]. References
Fig. 1. Aminoterminal propeptide of type III procollagen (PIIINP) levels and ascending aortic aneurysm growth rate. Box plot comparing PIIINP levels between patients with a stable TAA or a slow growth rate (b 2 mm/year) (Group 1, n = 23) and those with a fastgrowing TAA (N 2 mm/year) (Group 2, n = 7). The horizontal lines inside the boxes indicate the means and the bottom and top of the boxes represent the 25th and 75th percentiles, respectively.
[1] Satta J, Haukipuro K, Kairaluoma MI, Juvonen T. Aminoterminal propeptide of type III procollagen in the follow-up of patients with abdominal aortic aneurysms. J Vasc Surg 1997;25:909–15. [2] Lindholt JS, Heickendorff L, Vammen S, Fasting H, Henneberg EW. Five-year results of elastin and collagen markers as predictive tools in the management of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2001;21:235–40. [3] Elefteriades JA. Natural history of thoracic aortic aneurysms: indications for surgery, and surgical versus nonsurgical risks. Ann Thorac Surg 2002;74:S1877–80. [4] Golledge J, Tsao PS, Dalman RL, Norman PE. Circulating markers of abdominal aortic aneurysm presence and progression. Circulation 2008;118:2382–92. [5] Bode MK, Soini Y, Melkko J, et al. Increased amount of type III pN-collagen in human abdominal aortic aneurysms. Evidence for impaired type III collagen fibrillogenesis. J Vasc Surg 2000;32:1201–7. [6] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
why the PIIINP level is increased in the group of patients presenting TAA growth in our study. Our results are therefore consistent with studies carried out in patients with an AAA.
0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.02.051
Free breathing cardiac real-time cine MR without ECG triggering Meinrad Beer a,⁎, Heimo Stamm a, Wolfram Machann b, Andreas Weng a, Jan P. Goltz b, Frank Breunig b, Frank Weidemann b, Dietbert Hahn a, Herbert Köstler a a b
Institut für Röntgendiagnostik, Universität Würzburg, Oberdürrbacherstr. 6, D-97080 Würzburg, Germany Medizinische Klinik I und Poliklinik, Universität Würzburg, Oberdürrbacherstr. 6, D-97080 Würzburg, Germany
a r t i c l e
i n f o
Article history: Received 2 February 2010 Accepted 14 February 2010 Available online 11 March 2010 Keywords: Magnetic resonance imaging Cine Parallel imaging Real time imaging Left ventricular function
⁎ Corresponding author. Tel.: +49 931 201 1; fax: +49 931 201 34857. E-mail address: [email protected] (M. Beer).
Cardiac MRI has become an accurate and highly reproducible method for evaluating LV volumes, global function and mass [1]. However, the applied standard cine MRI sequences require patient compliance (repeated breath-holds) and a robust ECG-registration (trigger). Normally, a cine analysis of the left ventricle (LV) is based on 10–12 consecutive breath-holds with duration of up to 15 min [1]. This may be too long in every-day clinical routine especially for severely ill patients. A solution provides here the multislice technique, which allows the acquisition of several or even all necessary slices in one breath-hold [2]. But even here patients have to hold their breath for 10 to 20 s. Free-breathing imaging might overcome this remaining restriction. However, the so far presented techniques use ECG triggering and acquire one complete heart beat per slice [3–5]. In the present study, we wanted to go even further and implemented a real-time (RT) free-breathing sequence without ECG triggering. The accuracy and reliability of RT imaging (temporal resolution 49 ms) was compared to standard ECG triggered breath-hold cine imaging. The study was approved by the local ethics committee and written informed consent was obtained from all subjects. 9 healthy volunteers (5