ABSTRACT
Data suggest a link of aortic stenosis (AS) with calcium and bone metabolism. To further investigate this, the following parameters were analyzed in 38 patients with severe AS and in 38 age- and gender-matched controls, without obstructive coronary artery disease and with preserved renal function: calcium, phosphate, 1,25(OH(2))-vitamin D(3), intact parathyroid hormone (iPTH), and osteoprotegerin. Patients with AS had significantly higher serum levels of calcium (2.63 +/- 0.28 vs 2.48 +/- 0.23 mmol/L, p <0.01) and phosphate (1.56 +/- 0.33 vs 1.38 +/- 0.26 mmol/L, p <0.01) and increased calcium-phosphorus products (4.16 +/- 1.13 vs 3.44 +/- 0.89 mmol/L(2), p = 0.003). Notably, the iPTH concentration in the AS group was lower, and significantly more patients in the AS group had levels less than the study median of 60 ng/L. Osteoprotegerin was elevated in patients with AS, confirming reports in other populations (9.94 +/- 5.96 vs 6.73 +/- 4.28 pmol/L, p = 0.009). The relations of several parameters to iPTH were also altered (AS vs controls): calcium and iPTH, 0.071 +/- 0.034 versus 0.046 +/- 0.023, p <0.0001; phosphate and iPTH, 0.042 +/- 0.020 versus 0.025 +/- 0.013, p <0.0001; vitamin D and iPTH, 0.99 +/- 0.61 versus 0.63 +/- 0.46, p = 0.006; and osteoprotegerin and iPTH, 0.24 +/- 0.15 versus 0.12 +/- 0.09, p <0.0001. In conclusion, these data support a hypothesis connecting (severe) AS to altered calcium and bone homeostasis.
Subject(s)
Aortic Valve Stenosis/blood , Calcium/blood , Kidney Function Tests , Aged , Aortic Valve Stenosis/physiopathology , Cholecalciferol/blood , Creatinine/blood , Female , Humans , Male , Osteoprotegerin/blood , Parathyroid Hormone/blood , Phosphates/bloodABSTRACT
BACKGROUND AND AIM OF THE STUDY: Calcific aortic stenosis (AS) is the most frequently acquired valvular disease of the elderly in the Western world. A genetic background for AS has been proposed. The deposition of calcium hydroxyapatite is the key problem of valve calcification; vitamin D and parathyroid hormone are major factors in calcium homeostasis. The vitamin D receptor (VDR) gene and parathyroid hormone (PTH) gene variants were selected as candidate genes. METHODS: A total of 538 patients with severe calcific AS (identified echocardiographically) were characterized by left heart catheterization. A group of 536 patients in whom heart disease had been excluded by left heart catheterization served as a control population. The cardiovascular risk profile was assessed, and three gene variants were analyzed, namely VDR rs1544410, VDR rs1073810, and PTH rs6254. RESULTS: Patients with AS were found to have a higher prevalence of the PTH AA genotype (108 +/- 20.1% versus 71 +/- 13.2%; p = 0.007), while the VDR gene revealed a marginal, but statistically non-significant, association. The age and risk profile was similar in both groups. CONCLUSION: To date, the association of the PTH gene variant has been the only positive association studied in patients with AS in a large population. Hence, the polymorphism is within an intron; the molecular mechanisms of altered gene expression should undergo further investigation.