ACHAIKI IATRIKI | 2020; 39(3): 163–166
Research Article
Stavros Mantzoukis1, Nikolaos Tsigaridas1, Elisavet Kokkolou2, Marina Gerasimou3
1Department of Cardiology, General Hospital of Ioannina “G. Hatzikosta”, Ioannina, Greece
2Department of Nephrology, General Hospital of Ioannina “G. Hatzikosta”, Ioannina, Greece
3Department of Microbiology, General Hospital of Ioannina “G. Hatzikosta”, Ioannina, Greece
Received: 11 May 2020; Accepted: 1 July 2020
Corresponding author: Marina Gerasimou, MD, MSc Department of Microbiology, General Hospital of Ioannina “G. Hatzikosta”, 1 Makrigianni Str, Ioannina 45500, Greece, Tel.: +2651366434, E-mail: marinagerasimou@gmail.com
Key words: Mitral annular calcification, hemodialysis, chronic kidney disease
Abstract
Background: Mitral annular calcification (MAC) is a chronic, degenerative condition more frequently encountered in haemodialysis patients. The aim of the current study was to determine the incidence of MAC in patients with chronic end-stage renal disease undergoing hemodialysis and to detect any correlations with demographic factors, comorbidities and characteristics of the dialysis process.
Methods: We estimated the prevalence and severity of MAC (through echocardiography) in dialysis patients referred to the Hemodialysis Unit of the General Hospital of Ioannina and evaluated its association with laboratory parameters and time since dialysis initiation (TSDI). The mean values of six-monthly measurements of serum calcium, phosphorus and calcium-phosphorus product levels were recorded and used for statistical analysis. TSDI and history of diabetes, hypertension and dyslipidemia were documented. All data were analyzed with the Stata software.
Results: Mitral annular calcification was observed in 26 patients (56.5%) and in terms of severity, most of them had mild calcification. No statistically significant correlation was observed between the severity of calcification of mitral annulus and calcium, phosphate levels and their product. However, a statistically significant correlation was observed between TSDI and the degree of mitral annulus calcification (p<0.01).
Conclusion: The severity of calcification was significantly related to TSDI. More research is needed on the reasons for this correlation. Possibly the accumulated action of cardiovascular risk factors and hemodynamic effects of the dialysis process are related to the observed changes in the mitral annulus. The effect of the electrolyte composition of dialysis solutions should also be investigated.
Introduction
Mitral annular calcification (MAC) is a chronic degeneration of the fibrous skeleton of the mitral valve. It is often an accidental finding during an echocardiographic examination [1]. Its incidence ranges between 8-15% and is higher in people with multiple cardiovascular risk factors as well as in people with chronic kidney disease. Its pathophysiology is not fully understood. Advanced age, atherosclerosis and its risk factors, female sex as well as disorders of calcium and phosphorus metabolism appear to be involved in its pathophysiology [1]. These electrolyte disturbances are often seen in chronic kidney disease and therefore, mitral annular calcification is more common in patients with chronic end-stage renal disease undergoing dialysis [2-4]. The purpose of this study was to estimate the incidence of MAC in patients with chronic end-stage renal disease undergoing hemodialysis and detect any correlations with demographic factors, comorbidities and characteristics of the dialysis process.
Materials and methods
All patients attending a chronic dialysis program at the Hemodialysis Unit of the General Hospital of Ioannina were eligible to enter the study. For all participants, age, body mass index, history of hypertension, diabetes mellitus and dyslipidemia were recorded, as well as a set of laboratory parameters based on the laboratory values of the last six months. Specifically, the average value of calcium and phosphorus in the last six months was recorded, as well as the average value of the calcium – phosphorus product in the last six months. Time since dialysis initiation (TSDI) was also recorded. Finally, all patients underwent echocardiography and the presence and severity of mitral annular calcification were assessed. Philips EPIQ 7 ECHO machine ECHO images were reviewed by two experienced and certificated in TTE by the European Association of Cardiovascular Imaging (EACVI) cardiologists. More specifically, from a parasternal short axis view at the level of the mitral annulus (PSAX-MV), the degree of mitral annular calcification was assessed as follows: Grade I (mild) – focal noncontiguous calcification limited to <180° total annular circumference with no extra-annular calcification. Grade II (moderate) – dense continuous calcification limited to <270° total annular circumference. Posterior and/or anterior leaflet calcification may be present. Grade III (severe) – dense continuous calcification extending past the commissures into anterior annulus or complete circumferential MAC (≥270° calcification arc). Posterior and/or anterior leaflet calcification may be present. Papillary muscle or ventricular myocardial calcification may be present [1,5]. No other echocardiographic parameters were recorded. There were no exclusion criteria. Patients with calcific aortic stenosis were also enrolled in the study. There was no patient with irradiation history. Written informed consent was obtained from each patient included in the study and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. Statistical analysis was performed using the Stata software both for the use of descriptive statistics and for regression analysis.
Results
In total, the characteristics of 48 patients of the Hemodialysis Unit of the General Hospital of Ioannina G. Hatzikosta were recorded. However, echocardiographic study and determination of the severity of MAC was only performed in 46 patients because the other 2 patients had poor acoustic window and were excluded from the study. The mean age of participants was 71.3 years and 69.57% of the patients were men (36 patients). The average duration of inclusion in a dialysis program was 26.76 months. In terms of comorbidities, diabetes was present in 33.84% of patients (16 patients), hypertension in 65.22% (30 patients) and dyslipidemia in 32.61% (15 patients) as demonstrated in Table 1. The average value of calcium, phosphorus and their product during the study semester was 8.97, 5.1 and 46.96, respectively. Mitral annular calcification was observed in 26 patients (56.5%) and most of them had mild calcification as indicated in Table 2. No statistically significant correlation was observed between the severity of calcification of mitral annulus and calcium and phosphate levels and their product. However, a statistically significant correlation was observed between time since dialysis initiation and the degree of MAC (p<0.01).
Discussion
Mitral annular calcification is associated with the presence of cardiovascular risk factors and an increased risk of cardiovascular disease and death of cardiovascular etiology [1,6-9]. However, chronic kidney disease itself is associated with high cardiovascular risk [10]. This study did not study the association between mitral annular calcification and cardiovascular mortality because this would require much more time (months or years) in order to reliably record morbidity and mortality, which exceeds the time period of our study. However, patients with end-stage renal disease should be considered high cardiovascular risk patients and measures should be taken to aggressively regulate cardiovascular risk factors in order to reduce the incidence of cardiovascular events in these patients.
In patients with chronic end-stage renal disease, there are studies showing association between calcium – phosphorus product and MAC [11,12]. However, no such correlation was observed in the present study. Severe MAC is known to be associated with several conduction disturbances or arrhythmias. In the population of our study, atrial fibrillation was observed only in 5 patients from whom 3 have MAC (2 mild and one severe). This number was too small to detect any correlations.
In addition, the coexistence of mitral annular calcification and atherosclerotic events (coronary heart disease, peripheral arterial disease) led to the development of the theory that these two entities share common risk factors and common pathophysiology [1,8,13-15], although, this has not yet been clearly demonstrated. Several studies have shown an association between patients’ age and the presence of mitral annular calcification [16,17], but no similar association was seen in the present study. No association was found with classic cardiovascular risk factors such as high blood pressure, diabetes and dyslipidemia in contrast to previous studies. This could perhaps be attributed to the short average TSDI (26.76 months) as opposed to previous studies which have shown an association with classic risk factors where the observation period was longer [18]. However, the correlation found with TSDI may be related to the cumulative effect of various classic cardiovascular risk factors as the period increases. Similar findings in terms of TSDI have been described in previous studies [12,16,19].
Future studies should examine possible correlations between MAC and mean serum albumin concentration (as malnutrition index), as well as drug treatment (such as calcitriol, calcium-based phosphate binders). These factors may be able to explain the increased incidence of MAC in patients undergoing hemodialysis.
Conclusions
Mitral annular calcification is more common in hemodialysis patients. In fact, it is related to the time from patient’s enrollment to a chronic dialysis program. More research is needed on the reasons for this correlation. Probably, the accumulated action of cardiovascular risk factors and the hemodynamic effects of the dialysis process are related to the observed changes in the mitral annulus. The effect of the electrolyte composition of dialysis solutions on the occurrence and progression of mitral calcification should also be investigated, but in order to draw safe conclusions, future studies should be carried out during a longer time-period. Moreover, given that past studies have correlated MAC with inflammatory activity, correlations between MAC and inflammation indexes such as C- reactive protein should be examined in future studies. In conclusion, patients with chronic end-stage renal disease undergoing dialysis and especially patients with mitral annulus calcification should be treated with aggressive regulation of cardiovascular risk factors in order to improve their overall cardiovascular profile.
Conflict of interest disclosure
None to declare.
Declaration of funding sources
None to declare.
Author contributions
Αll authors had equal contribution regarding: conception and design; analysis and interpretation of the data; drafting of the article; critical revision of the article for important intellectual content and final approval of the article.
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