Asymmetric dimethylarginine and vascular indices of atherosclerosis in patients after coarctation of aorta repair
Introduction
Regardless of a successful repair of aortic coarctation (CoA), life expectancy remains reduced in post-repair CoA patients [1]. The most common cause of premature death in this group is myocardial infarction, which is a problem even in young subjects [2]. It is well established that 30–50% of CoA repaired patients exhibit arterial hypertension (AH)[3], [4], which leads to widespread atherosclerosis [2], [5], [6], [7]. However, recently published data suggests early functional and structural atherosclerotic changes even in normotensive patients after CoA repair [8], [9], [10], [11]. In the CoA repaired population impaired endothelium-dependent arterial relaxation as well as increased arterial stiffness and thickening of the intima-media complex were found [8], [9], [10], [11]. The reason for the vascular abnormalities are probably the pathological changes in the precoartaction arteries.
Regardless of the fact that atherosclerosis is an inflammatory disease [12], there are limited data on the role of inflammation in the aforementioned atherosclerotic remodeling in patients after CoA. Isolated papers concerning small groups of patients reported higher serum levels of cytokines and adhesion molecules [13]. Taking into account a crucial role of oxidative stress in the induction of inflammation, it seemed interesting to assess the levels of asymmetric dimethylarginine (ADMA; an endogenous competitive inhibitor of NO synthase) and nitric oxide (NO) in relation to standard inflammation markers such as high-sensitivity C-reactive protein (hsCRP) and vascular indexes in CoA-repaired subjects. Although, it is well known that ADMA concentrations are increased and NO bioavailability is decreased in subjects with atherosclerosis [14], we have not found any study concerning assessment of ADMA nor NO in patients after CoA surgical correction. Moreover, ADMA may have a causative role in atherogenesis and constitutes one of the strongest risk predictors of cardiovascular events [15], [16]. Recognition of these processes is of great clinical importance and having knowledge of this topic may improve the prognosis for CoA-repaired patients.
Thus the aim of the presented study was to assess the role of selected biochemical markers of atherosclerosis: ADMA, nitrite/nitrate (NOx) — a stable end product of NO, and hsCRP in the development of early functional and structural atherosclerotic vascular pathology in patients after CoA repair.
Section snippets
Patients and method
Sixty two patients after CoA repair (37 males) aged 19–64 years (mean age: 34.1 ± 1.4 years) who had undergone an operation at the age of 0.5 to 34 years (11.1 ± 1.1 years) were enrolled in the study. All of them were attending our adult congenital heart disease outpatient clinic. Only the normotensive subjects after CoA repair (group CoA-AH(−): n = 33, 17 males, mean age: 33.9 ± 1.6 years) were involved in the analysis. The control group (group C) consisted of 20 healthy individuals (10 males) aged 24–48
Clinical characteristic
Clinical characteristic of the examined groups is presented in Table 1. The group CoA-AH(−) and the group C were compared as to the age, weight, height, serum glucose and lipids’ levels. Mean value of DBP was significantly higher in the CoA-AH(−) group. Mean heart rate (HR) was comparable between the groups.
Serum concentrations of ADMA, NOx, hsCRP
The serum level of ADMA in the CoA-AH(−) group (0.59 ± 0.04) was higher as compared with group C (0.46 ± 0.03 umol/l; p = 0.035) (Fig. 1). No significant differences were found between those groups
Discussion
In the study presented above, we have focused on the problem whether biochemical markers of atherosclerosis may provide any new information for the vascular parameters and the mechanism of vascular abnormalities in patients after CoA repair. In order to distinguish “pure” CoA-related abnormalities from hypertension-induced vascular remodeling we have analyzed the normotensive patients only.
The results indicate the novel aspects of the vascular pathology observed in patients after CoA repair.
Acknowledgement
The authors of this manuscript have certified that they comply with the Principles of the Ethical Publishing in the International Journal of Cardiology [41].
References (41)
- et al.
Arterial hypertension and cardiovascular prognosis after successful repair of aortic coarctation: a clinical model for the study of vascular function
Nutr Metab Cardiovasc Dis
(2005) - et al.
Increased central aortic stiffness and left ventricular mass in normotensive young subjects after successful coarctation repair
Am Heart J
(2008) - et al.
Vascular dysfunction after coarctation repair is related to the age at surgery
Int J Cardiol
(2005) - et al.
Evidence of vascular dysfunction in young patients with successfully repaired coarctation of aorta
Atherosclerosis
(2005) - et al.
Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine
Lancet
(2001) - et al.
International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow mediated vasodilatation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force
J Am Coll Cardiol
(2002) - et al.
Kawano Y Plasma asymmetric dimethylarginine and coronary and peripheral endothelial dysfunction in hypertensive patients
Am J Hypertens
(2004) - et al.
Myocardial ischemia in asymptomatic adults with repaired aortic coarctation
Int J Cardiol
(2009) - et al.
Vascular remodeling after “successful” repair of coarctation: impact of aortic arch geometry
J Am Coll Cardiol
(2007) - et al.
Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds
Food Cosmet Toxicol
(1976)
Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis
Lancet
Operative survival and 40 year follow up surgical repair of aortic coarctation
Br Heart J
McGoon DC. Coarctation of the aorta. Long term follow-up and prediction of outcome after surgical correction
Circulation
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
Surgery for aortic coarctation: a 30 years experience
Eur J Cardiothorac Surg
Long-term follow-up of patients after coarctation of the aorta repair
Am J Cardiol
Survivors of coarctation repair: fixed but not cured
Heart
Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation
Eur Heart J
Aortic elastic properties in patients with repaired coarctation of aorta
Am J Cardiol
Atherosclerosis: an inflammatory disease
N Engl J Med
Cited by (13)
Arterial stiffness and pulsatile hemodynamics in congenital heart disease
2022, Textbook of Arterial Stiffness and Pulsatile Hemodynamics in Health and DiseaseLow plasma renalase concentration in hypertensive patients after surgical repair of coarctation of aorta
2014, Journal of the American Society of HypertensionCitation Excerpt :The cornerstone of coarctation of aorta consists in a systemic vasculopathy, not only related with the narrowing of the aortic isthmus itself but also related with widespread remodeling of arterial vascular bed.3 Large body of evidence suggests that complex cytokine interactions, involving members of transforming growth factor beta (TGF-β) superfamily,4 lead to profibrotic and antiapoptotic propensity inside the arterial wall, which, in turn, results in stiffening of arteries3,5–8 in addition to endothelial5 and baroreceptor dysfunction.9 The effect of long-term renal ischemia in coarctation of aorta on patients' health status after successful repair is poorly recognized.
Aortic stiffness and left ventricular diastolic function in children following early repair of aortic coarctation
2013, American Journal of CardiologyCitation Excerpt :In young patients with repaired CoA, bicuspid aortic valves, or Marfan syndrome, increased aortic stiffness is thought to be due to primarily abnormal aortic wall structure.1,2,21 However, chronic inflammation and endothelial dysfunction appear to play a role as well in patients with repaired CoA.18,22,23 With increased vascular stiffness, the PW velocity is increased and, thus, the reflected wave returns to the heart early (i.e., in late systole).
Asymmetric dimethylarginine: Is it a risk facgtor in the repair of aortic coarctation?
2021, Journal of Cardiac Surgery