Growth differentiation factor 15 and arterial remodeling in adult patients after succesful repair of aortic coarctation (RCD code: IV-5.A.1)
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Abstract
Background: Coarctation of aorta (CoAo) is a congenital heart anomaly associated with high cardiovascular morbidity and mortality attributable to vascular remodeling in adult survivors following surgical management of aortic stenosis. This study sought to adjudicate the significance of novel stress-responsive biomarker, growth differentiation factor 15 (GDF-15), as an indicator of vascular remodeling and its correlation with numerous laboratory and vascular parameters in patients after successful CoAo repair.
Methods and results: This research is a case-control study comprising 33 consecutive patients (19 men, 57.58%; mean age 33.9 ±9.3 years; mean age at surgery: 9.1 ±7 years; mean follow-up duration 24.8 ±6.8 years) admitted to outpatient clinic for routine follow-up after repair of CoAo (mainly Dacron patch technique) and matched with 20 healthy controls (10 men, 50%; mean age 34.8 ±9.9 years). Laboratory (GDF-15, high-sensitivity C-reactive protein) and vascular parameters (intima-media thickness, flow- and nitrate-mediated dilation, pulse-wave velocity, central arterial pressure) were assessed. Significant aortic residual gradient was present in 24 (72.7%). The circulating GDF-15 level was lower in CoAo survivors than in control group (539.56 vs. 744.98 pg/ml respectively; p < 0.001). GDF-15 concentration <550 pg/ml successfully differentiated patients after CoA repair (odds ratio [OR] = 9.2; 95%CI: 2.45–34.56, p = 0.0005). There was no difference in GDF-15 level depending on the presence of significant residual gradient (p = 0.19). No significant correlation between GDF-15 and other variables was observed.
Conclusions: Low concentration of GDF-15 is characteristic of asymptomatic patients following CoAo repair, however, its clinical significance and relationship with vascular remodeling substantiates further investigation. JRCD2013; 1 (2): 5–12
Key words: coarctation of aorta, GDF-15, growth differentiation factor 15, vascular remodeling
Keywords
References
Kuehl KS, Loffredo CA, Ferencz C. Failure to diagnose congenital heart disease in infancy. Pediatrics 1999; 103: 743–747.
Varma C, McLaughlin PR, Hermiller JB, et al. Coarctation of the aorta in adult. Problems of diagnosis and management. Chest 2003; 123: 1749–1752.
Zwoliński R, Cygankiewicz I, Ammer A, et al. Late diagnosis of congenital cardiovascular defect. Cardiol J 2012; 19: 201–213.
van der Linde D, Konings EE, Slager MA, et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 2011; 58: 2241–2247.
van der Bom T, Bouma BJ, Meijboom FJ. The prevalence of adult congenital heart disease, results from a systematic review and evidence based calculation. Am Heart J 2012; 164: 568–575.
Victor S. Patch aortoplasty for coarctation of aorta: technical considerations. Ann Thorac Surg 1995; 59: 1276–1278.
Lock JE, Castaneda-Zuniga WR, Bass JL, et al. Balloon dilatation of excised aortic coarctations. Radiology 1982; 143: 689 –91.
Samánek M, Goetzová J, Fiserová J, et al. Differences in muscle blood flow in upper and lower extremities of patients after correction of coarctation of the aorta. Circulation 1976; 54: 377–381.
Brili S, Tousoulis D, Antoniades C, et al. Evidence of vascular dysfunction in young patients with successfully repaired coarctation of aorta. Atherosclerosis 2005; 182: 97–103.
Vogt M, Kühn A, Baumgartner D, et al. Impaired elastic properties of the ascending aorta in newborns before and early after successful coarctation repair: proof of a systemic vascular disease of the prestenotic arteries? Circulation 2005; 111: 3269–3273.
Trojnarska O, Mizia-Stec K, Gabriel M, et al. Parameters of arterial function and structure in adult patients after coarctation repair. Heart Vessels 2011; 26: 414 – 420.
Sehested J, Baandrup U, Mikkelsen E. Different reactivity and structure of the prestenotic and poststenotic aorta in human coarctation. Implications for baroreceptor function. Circulation 1982; 65: 1060–1065.
O’Sullivan JJ, Derrick G, Darnell R. Prevalence of hypertension in children after early repair of coarctation of the aorta: a cohort study using casual and 24 hour blood pressure measurement. Heart 2002; 88: 163–166.
de Divitiis M, Pilla C, Kattenhorn M, et al. Ambulatory blood pressure, left ventricular mass, and conduit artery function late after successful repair of coarctation of the aorta. J Am Coll Cardiol 2003; 41: 2259–2265.
Meyer AA, Joharchi MS, Kundt G, et al. Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation. Eur Heart J 2005; 26: 617–622.
Corno AF, Botta U, Hurni M, et al. Surgery for aortic coarctation: a 30 years experience. Eur J Cardiothorac Surg 2001; 20: 1202–1206.
Cook SC, Ferketich AK, Raman SV. Myocardial ischemia in asymptomatic adults with repaired aortic coarctation. Int J Cardiol 2009; 133: 95–101.
Cohen M, Fuster V, Steele PM, Driscoll D, McGoon DC. Coarctation of the aorta. Long-term follow-up and prediction of outcome after surgical correction. Circulation 1989; 80: 840–845.
Campbell M. Natural history of coarctation of the aorta. Br Heart J 1970; 32: 633–640.
Ou P, Celermajer DS, Jolivet O, et al. Increased central aortic stiffness and left ventricular mass in normotensive young subjects after successful coarctation repair. Am Heart J 2008; 155: 187–193.
Heger M, Willfort A, Neunteufl T, et al. Vascular dysfunction after coarctation repair is related to the age at surgery. Int J Cardiol 2005; 99: 295–299.
Seirafi PA, Warner KG, Geggel RL, et al. Repair of coarctation of the aorta during infancy minimizes the risk of late hypertension. Ann Thorac Surg 1998; 6: 1378 –1382.
de Divitiis M, Pilla C, Kattenhorn M, et al. Vascular dysfunction after repair of coarctation of the aorta: impact of early surgery. Circulation 2001; 104: I165 –170.
Gardiner HM, Celermajer DS, Sorensen KE, et al. Arterial reactivity is significantly impaired in normotensive young adults after successful repair of aortic coarctation in childhood. Circulation 1994; 89: 1745–1750.
Popovic N, Bridenbaugh EA, Neiger JD, et al. Transforming growth factor-beta signaling in hypertensive remodeling of porcine aorta. Am J Physiol Heart Circ Physiol 2009; 297: H2044–2053.
Otsuka G, Agah R, Frutkin AD, et al. Transforming growth factor beta 1 induces neointima formation through plasminogen activator inhibitor-1-dependent pathways. Arterioscler Thromb Vasc Biol 2006; 26: 737–743.
Bootcov MR, Bauskin AR, Valenzuela SM, et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc Natl Acad Sci 1997; 94: 11514–11519.
Heger J, Schiegnitz E, von Waldthausen D, et al. Growth differentiation factor 15 acts anti-apoptotic and pro-hypertrophic in adult cardiomyocytes. J Cell Physiol 2010; 224: 120–126.
Kempf T, von Haehling S, Peter T, et al. Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol 2007; 1054 –1060.
Baessler A, Strack C, Rousseva E, et al. Growth-differentiation factor-15 improves reclassification for the diagnosis of heart failure with normal ejection fraction in morbid obesity. Eur J Heart Fail 2012; 14: 1240–1248.
Khan SQ, Ng K, Dhillon O, et al. Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. Eur Heart J 2009; 30: 1057–1065.
Nickel N, Kempf T, Tapken H, et al. Growth differentiation factor-15 in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2008; 178: 534–541.
Lankeit M, Kempf T, Dellas C, et al. Growth differentiation factor-15 for prognostic assessment of patients with acute pulmonary embolism. Am J Respir Crit Care Med 2008; 177: 1018–1025.
Eggers KM, Kempf T, Allhoff T, et al. Growth-differentiation factor-15 for early risk stratification in patients with acute chest pain. Eur Heart J 2008; 29: 2327–2335.
Foley PW, Stegemann B, Ng K, et al. Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy. Eur Heart J 2009; 30: 2749–2757.
Norozi K, Buchhorn R, Yasin A, et al. Growth differentiation factor 15: an additional diagnostic tool for the risk stratification of developing heart failure in patients with operated congenital heart defects? Am Heart J 2011; 162: 131–135.
Raedle-Hurst TM, Koenigstein K, Gruenhage F, et al. Growth differentiation factor 15–an early marker of abnormal function of the Fontan circuit in patients with univentricular hearts. Am Heart J 2010; 160: 1105–1112.
Vriend JW, Zwinderman AH, de Groot E et al. Predictive value of mild, residual descending aortic narrowing for blood pressure and vascular damage in patients after repair of aortic coarctation. Eur Heart J 2005; 26: 84–90.
O’Rourke M. Mechanical principles in arterial disease. Hypertension 1995; 26: 2–9.
Borow KM, Newburger JW. Noninvasive estimation of central aortic pressure using the oscillometric method for analyzing systemic artery pulsatile blood flow: comparative study of indirect systolic, diastolic, and mean brachial artery pressure with simultaneous direct ascending aortic pressure measurements. Am Heart J 1982; 103: 879–886.
Kempf T, Wollert KC. Growth-differentiation factor-15 in heart failure. Heart Fail Clin 2009; 5: 537–547.
Xu C, Lee S, Singh TM, et al. Molecular mechanisms of aortic wall remodeling in response to hypertension. J Vasc Surg 2001; 33: 570–578.
Hayenga HN, Hu JJ, Meyer CA, et al. Differential progressive remodeling of coronary and cerebral arteries and arterioles in an aortic coarctation model of hypertension. Front Physiol 2012; 3: 420.
Ho JE, Mahajan A, Chen MH, et al. Clinical and genetic correlates of growth differentiation factor 15 in the community. Clin Chem 2012; 58: 1582–1591.
Kempf T, Horn-Wichmann R, Brabant G, et al. Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem 2007; 53: 284–291.
Mizia-Stec K, Trojnarska O, Szczepaniak-Chicheł L, et al. Asymmetric dimethylarginine and vascular indices of atherosclerosis in patients after coarctation of aorta repair. Int J Cardiol 2012; 158: 364–369.
Trojnarska O, Szczepaniak-Chicheł L, Mizia-Stec K, et al. Vascular remodeling in adults after coarctation repair: impact of descending aorta stenosis and age at surgery. Clin Res Cardiol 2011; 100: 447–455.
Forbes TJ, Kim DW, Du W, Turner DR, CCISC Investigators. Comparison of surgical, stent, and balloon angioplasty treatment of native coarctation of the aorta: an observational study by the CCISC (Congenital Cardiovascular
Interventional Study Consortium). J Am Coll Cardiol 2011; 58: 2664–2
DOI: http://dx.doi.org/10.20418%2Fjrcd.vol1no2.77
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