The Effects of Fetuin-A Levels on Aortic Stenosis

  • Abstract
  • FullTEXT
  • Additional info
  • Attachments
  • Related items
  • Video

Aim: We aimed to investigate the relation between fetuin-A and calcific aortic stenosis in non diabetic patients whose renal function were normal. Material and Method: 26 patients followed for aortic stenosis by our cardiology clinic for outpatients and 25 voluntary healthy subjects were included in the study. The fetuin–A levels were measured from the venous blood samples of the study population. All patients underwent transthorasic echocardiography, the aortic valvular area and left ventricular parameters of the patients were measured. Results: The average age of the patients in degenerative aortic stenosis group was significantly higher than the control group. The parameters related to aortic valve were naturally higher in patients with dejenerative aortic valve. There was no significant difference between two groups about fetuin-A levels. Further more there was no significant relation between fetuin-a levels and aortic stenosis severity. Discussion: In conclusion fetuin-A is a multifunctional glycoprotein that plays important role in systemic calcification inhibition and valvular calcification. Finally aortic stenosis is an active process and larger studies that investigate the relation between fetuin-a and the progression and prognosis of aortic stenosis are needed.


The most frequent reason of aortic stenosis in adults is degenerative aortic stenosis due to aging [1]. Degenerative aortic stenosis is seen frequently through elderly patients, it can occur with exertional dyspnea, angina, syncope, heart failure and sudden cardiac death and if not treated it decreases the life quality of the patients [2]. The prevalence of aortic stenosis increases with age, clinically significant aortic stenosis occurs in 2% among people over 65 years old and 5.5% over the age 85 [3-5], whereas aortosclerosis occurring due to aortic calcification and stiffness can be seen in 50% of people between the age 75-80 and %75 over the age 85 [6]. Serum fetuin-A is a negative acute phase reactant glycoprotein that is synthesized in hepatocytes, it is an indicator of acute inflammation [7,8]. Besides it is an important systemic calcification inhibitor. Serum fetuin-A forms colloid formations with calcium phosphate remains and helps it to resolve [9].

In this study we investigated the relation between aortic stenosis and serum fetuin-A in patients with calcific aortic stenosis whose renal functions were normal and had no diabetes.

Material and Method

Our study population was composed of totally 51 people whose approvals determined by the ethic committee were taken. The patient group contained 26 patients who had been followed by our cardiology clinic for outpatients with the diagnosis of aortic stenosis (13 women, 13 men; mean age 67,2 ± 5,4) and the control group contained 25 voluntary healhty people (17 women, 8 men; mean age 60,5 ± 6,8). The exclusion criteria for aortic stenosis were as follows: age under 18 or over 80, malignancy, hipercalsemia, diabetes mellitus and renal failure. The systolic and diastolic blood pressures of the patients were measured. Then the venous blood samples were gained fort the following laboratory measurements after a night of fasting; complet blood counting, glucose, urea, creatinine, potasium, calcium, phosphorus, liver function test, total chlosterol, HDL-C, LDL-C and triglycerids. Fetuin-A analyses were made using enzyme-linked immunosorbent assay (Biovendor Laboratory Medicine İns). The GFR of all patients were estimated by using modification diet of renal disease (MDRD) formula.

Echocardiographic Evaluation: All patients underwent transthorasic echocardiographic evaluation in lateral decubitus position by GE-Vingmed Vivid 3 system (GE-Vingmed Ultrasound AS, Horten, Norway) using multiHz probe transducer. The measurements were made according to American Heart Association criteria [10]. Left ventricular ejection fraction (LVEF), Left ventricular end diastolic diameter (LVEDD), Left ventricular end systolic diameter (LVESD), interventricular septum thickness (IVSD) ve posterior wall thickness (PWD) were measured. Transaortic gradient was estimated with Bernoulli formula (4v2). Furthermore the area of aortic valve was estimated using continuity equation. Valve area > 1.5cm2 was defined as mild aortic stenosis, valve area between 1-1.5cm2 was defined as moderate aortic stenosis and valve area < 1cm2 was defined as severe aortic stenosis. Devereux Formula was used to estimate left ventricular mass (gram) [11]. Left ventricular mass index (LVMI) was estimated by dividing left ventricular mass to body surface area.

Left ventricular mass (g) = 0,8 x 1,04 x [ (LVEDD + IVSD + PWT)3 – LVEDD3] + 0,6

Statistical Analyses

Statistical analyses were made using SPSS 13.00 package programme. All data were defined as mean ± standart deviation. Shapiro- Wilk test was used to investigate whether the data shows normal distribution or not. T-test was used to compare normally distributed data, Mann – Whitney U test was used to compare data not normally distributed and Kruskal Wallis test was used to compare three or more groups. The relations between variables were investigated with Pearson and Spearman correlation coefficients. p values <0.05 were accepted as statistically significant.


The demographic characteristics of groups involved are shown in table 1. Gender, hypertension, obesity, smoking, diabetes mellitus, presence of coronary artery disease, medications and blood analyses were similar in both groups. The average age in degenerative aortic stenosis group was higher and this difference was statistically significant (p<0,001). On the other hand total cholesterol levels in this group were significantly lower (p=0.004). The parameters associated to aortic valve were naturally higher in patients with degenerative valves. But there was no difference between the two groups about fetuinin-A levels.

Moreover serum fetuin-A levels did not differ significantly according to aortic stenosis severity (Table 2).

Further more there was no significant relation between fetuin-A both aortic valve stenosis and left ventricular mass index. (Table 3).


Serum fetuin-A is the most important systemic calcification inhibitor. It does not effect the bone mineralization while preventing ectopic calcification [12]. It can be thought to be a multifunctional protein. In this study we investigated the relation between calcific aortic stenosis which is an active process and serum fetuin-A which is the most important systemic calcification inhibitor showing multifunctional properties. Furthermore we investigated the relation between fetuin-A and the severity of aortic stenosis differently from other studies.

Wang et al showed that fetuin-A levels were significantly low in patients with valvular calcification, atherosclerosis, inflammation and malnutrition in their study on patients undergoing periton dialysis [13]. In another study it was showed that low fetuin-A levels were associated to cardiovascular death and all cause mortality on patients undergoing dialysis [14]. In our study we excluded the patients with renal failure to eliminate the effects of renal failure on fetuin-A levels.

Ix et al [15] found negative correlation between mitral annular calcification and fetuin-A on patients with coronary artery disease who have mitral annular calcification and aortic stenosis but no serious renal disease. Also a negative correlation was detected between serum fetuin-A levels and aortic stenosis in non diabetic patients. However, in diabetic patients no such significant correlation was established. In our study to avoid the influence of diabetes mellitus, diabetic patients were excluded.

In another study on patients with renal failure but no need for dialysis, the relation between fetuin-A and progression of aortic calcification was investigated and the calcium scores of patients with low fetuin-A levels were found to be higher [16]. Kaden et al. investigated systemic and local fetuin-A levels in patients with severe aortic stenosis. They found that serum fetuin-A levels were low in patients with severe aortic stenosis [17].

In our study there was no relation between fetuin-A levels and calcific aortic stenosis. Further more there was no relation between fetuin-A and aortic stenosis severity. The control group was younger than the patient group. This was possibly caused by small number of patients meeting the inclusion criteria and the small number of patients who do not have additional valvular diseases simultaneously. The total cholesterol levels were found to be higher in control group. The patients with aortic stenosis are followed more frequently and they are given medical treatment if needed. Thus, this causes the lower levels of total cholesterol in patient group. The left ventricular mass was found higher in patient group due to the compensatory mechanisms of the left ventricle.

In conclusion fetuin-A is a multifunctional glycoprotein that plays important role in systemic calcification inhibition, acute inflammation, insulin resistance, metabolic syndrome, vascular and valvular calcification. Because it is influenced by multiple independent factors, the patient groups should be determined carefully. Finally aortic stenosis is an active process and larger studies that investigate the relation between fetuin-A and the progression and prognosis of aortic stenosis are needed.

Competing interests

The authors declare that they have no competing interests.


1. Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation 2005;111(7):920-5.

2. Supino PG, Borer JS, Preibisz J, Bornstein A. The epidemiology of valvular heart disease: a growing public health problem. Heart Fail Clin 2006;2(4):379-93.

3. Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Bärwolf C, Levang OW et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J 2003;24(13):1231-43.

4. Rajamannan NM. Calcific aortic stenosis: medical and surgical management in the elderly. Curr Treat Options Cardiovasc Med 2005;7(6):437-42.

5. Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol 1997;29(3):630-4.

6. Lindroos M, Kupari M, Heikkilä J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol 1993;21(5):1220-5.

7. Denecke B, Gräber S, Schäfer C, Heiss A, Wöltje M, Jahnen-Dechent W. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem J 2003;376(Pt 1):135-45.

8. Kalabay L, Cseh K, Jakab L, Pozsonyi T, Jakab L, Benedek S et al. Diagnostic value of the determination of serum alpha2-HS-glycoprotein. Orv Hetil 1992;133(25):1559-60.

9. Heiss A, DuChesne A, Denecke B, Grötzinger J, Yamamoto K, Renné T et al. Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem 2003;278(15):13333-41.

10. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2(5):358-67.

11. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57(6):450-8.

12. Mathews ST, Singh GP, Ranalletta M, Cintron VJ, Qiang X, Goustin AS et al. Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes 2002;51(8):2450-8.

13. Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P et al. Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 2005;20(8):1676-85.

14. Hermans MM, Brandenburg V, Ketteler M, Kooman JP, van der Sande FM, Boeschoten EW et al. Netherlands cooperative study on the adequacy of Dialysis (NECOSAD). Association of serum fetuin-A levels with mortality in dialysis patients. Kidney Int 2007;72(2):202-7.

15. Ix JH, Chertow GM, Shlipak MG, Brandenburg VM, Ketteler M, Whooley MA. Association of fetuin-A with mitral annular calcification and aortic stenosis among persons with coronary heart disease: data from the Heart and Soul Study. Circulation 2007;115(19):2533-9.

16. Koos R, Brandenburg V, Mahnken AH, Mühlenbruch G, Stanzel S, Günther RW et al. Association of fetuin-A levels with the progression of aortic valve calcification in non-dialyzed patients. Eur Heart J 2009;30(16):2054-61.

17. Kaden JJ, Reinöhl JO, Blesch B, Brueckmann M, Haghi D, Borggrefe M et al. Systemic and local levels of fetuin-A in calcific aortic valve stenosis. Int J Mol Med 2007;20(2):193-7.

Additional Info

  • Recieved: 08.10.2014
  • Accepted: 25.11.2014
  • Published Online: 25.11.2014
  • Printed: 01.07.2016
  • DOI: 10.4328/JCAM.2906
  • Author: Ahmet Tutuncu, Taner Kustarci, Can Ozbek, Ali Aydinlar, Dilek Yesilbursa
  • Identifier: J Clin Anal Med. 2016;7(4):445-448
  • Index Page: 445-448
  • How to Cite: Ahmet Tutuncu, Taner Kustarci, Can Ozbek, Ali Aydinlar, Dilek Yesilbursa. The Effects of Fetuin-A Levels on Aortic Stenosis. J Clin Anal Med. 2016;7(4):445-448
  • Running Title: Fetuin-A and aortic stenosis
Download attachments:

Last Issued ACAM

Covers ACAM

Article & Author Search ACAM

Please publish modules in offcanvas position.