Systemic and local levels of fetuin-A in calcific aortic valve stenosis.

Calcific aortic valve stenosis, the most frequent heart valve disorder in developed countries, is an actively regulated process with similarities to bone formation. Fetuin-A has recently been identified as a potent circulating inhibitor of calcification. While several studies involving patients with end-stage renal disease have shown an association between low serum fetuin-A and cardiovascular calcification, nothing is known about fetuin-A serum levels in non-renal patients with calcific aortic valve stenosis. Furthermore, while fetuin-A has been localized in calcified areas of atherosclerotic arteries, data about fetuin-A deposition in stenotic aortic valves are unavailable at present. Serum fetuin-A levels were determined in patients with (n=31) and without (n=28) calcified aortic valve stenosis by ELISA. Creatinine and CRP levels were determined and glomerular filtration rate (GFR) was calculated by the MDRD formula. Immunohistochemistry for fetuin-A was performed on human calcified stenotic (n=14) and control (n=8) aortic valves using a monoclonal antibody. Serum fetuin-A levels were lower in patients with calcific aortic stenosis as compared to the control group (1.41+/-0.33 versus 1.57+/-0,27 mg/dl; p=0.046). This difference was particularly evident in individuals with a normal GFR >or=60 ml/min (1.36+/-0.24 versus 1.63+/-0.27 mg/dl; p=0.007). Furthermore, specific staining of fetuin-A was found in stenotic valves but not in healthy control valves. The data suggest a role of fetuin-A in the pathogenesis calcific aortic valve stenosis independently of the renal function and support the concept that mechanisms of calcium homeostasis are involved in the development of calcific aortic stenosis.

Lower serum calcium levels are associated with greater calcium hydroxyapatite deposition in native aortic valves of male patients with severe calcific aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship between serum calcium levels and the degree of calcification found in stenotic aortic valves. METHODS: Using atomic absorption spectroscopy, the hydroxyapatite content of 228 excised human stenotic aortic valves was determined and expressed as a percentage of valve mass. Left heart catheterization preceded valve replacement. In addition, serum levels of calcium and creatinine were determined before native calcific aortic valve excision. RESULTS: Valves from male patients contained more hydroxyapatite than those of female patients (26 +/- 9 versus 22 +/- 9 mass%; p < 0.001). Patients presenting with lower serum calcium levels showed a slight trend towards higher levels of valve calcification (r = -0.15, p = 0.026), but this association appeared only within the subgroup of male patients. Male patients with lowest serum calcium levels displayed greatest valvular hydroxyapatite deposition (1st calcium tertiary: 29.5 +/- 8.9 mass% versus 2nd calcium tertiary 26.4 +/- 7.8 mass% versus 3rd calcium tertiary 21.4 +/- 8.9 mass%; n = 122; p = 0.001; r = -0.25; p = 0.006). This association was even more distinct in male patients with normal serum creatinine levels. Furthermore, serum calcium was inversely and significantly associated with serum C-reactive protein in male patients (r = - 0.34; p < 0.001). CONCLUSION: Serum calcium levels appear to be inversely related to valve calcification in patients with severe calcific aortic stenosis (AS). This finding indicates the importance of systemic calcium metabolism in calcific AS, independent of manifest disorders of calcium metabolism or renal function. Interestingly, this association was evident only in male patients, suggesting a gender-dependent pathogenesis.

Prevalence of atherosclerosis of the coronary and extracranial cerebral arteries in patients undergoing aortic valve replacement for calcified stenosis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate the coexistence of various atherosclerotic changes in patients with non-rheumatic calcific aortic valve stenosis (AS), since calcific AS shares various clinical risk factors with atherosclerosis. METHODS: In 282 consecutive patients with severe calcific stenosis of a tricuspid aortic valve scheduled for aortic valve replacement, the prevalence of atherosclerotic changes of the coronary and extracranial cerebral arteries were assessed using coronary angiography and Doppler sonography, respectively. RESULTS: The severities of coronary and extracranial cerebral artery atherosclerosis were significantly associated (p = 0.005). The prevalence and severity of both coronary and extracranial cerebral artery atherosclerosis were age-dependent. Coronary or extracranial cerebral artery stenosis was present in 59% and 16% of patients, respectively, while 91% of the study population and all patients aged > 80 years showed atherosclerosis of the coronary and/or extracranial cerebral arteries. CONCLUSION: The data obtained indicated a very high prevalence of atherosclerotic changes in patients with calcific AS, suggesting pathogenetic similarities of both disorders. Routine screening of the extracranial cerebral arteries is warranted in all patients with calcific AS and scheduled for valve replacement.