Correlation between plasma osteopontin levels and aortic valve calcification: Potential insights into the pathogenesis of aortic valve calcification and stenosis

Objective

The inflammatory process of aortic stenosis involves the differentiation of aortic valve myofibroblasts into osteoblasts. Osteopontin, a proinflammatory glycoprotein, both stimulates differentiation of myofibroblasts and regulates the deposition of calcium by osteoblasts. Osteopontin levels are increased in patients with such conditions as end-stage renal disease, ectopic calcification, and autoimmune disease. We hypothesized that increased plasma osteopontin levels might be associated with the presence of aortic valve calcification and stenosis.

Methods

Venous blood from volunteers older than 65 years undergoing routine echocardiographic analysis or aortic valve surgery for aortic stenosis was collected. Plasma osteopontin levels were measured by means of enzyme-linked immunosorbent assay. The presence of aortic stenosis was defined as an aortic valve area of less than 2.0 cm². Aortic valve calcification was assessed by using a validated echocardiographic grading system (1, none; 2, mild; 3, moderate; 4, severe). Comparisons were performed with nonpaired t tests.

Results

Aortic stenosis was present in 23 patients (mean age, 78 years) and was absent in 7 patients (mean age, 72 years). Aortic valve calcification scores were 3.5 ± 0.6 and 1.3 ± 0.5 in patients with and without aortic stenosis, respectively (P < .001). Patients with no or mild aortic valve calcification had lower osteopontin levels compared with patients with moderate or severe aortic valve calcification (406.1 ± 165.8 vs 629.5 ± 227.5 ng/mL, P = .01). Similarly, patients with aortic stenosis had higher osteopontin levels compared with patients without aortic stenosis (652.2 ± 218.7 vs 379.7 ± 159.9 ng/mL, P < .01).

Conclusion

Increased levels of plasma osteopontin are associated with the presence of aortic valve calcification and stenosis. These findings suggest that osteopontin might play a functional role in the pathogenesis of calcific aortic stenosis.