These results support the concept that lipid-mediated inflammatory mechanisms may contribute to the SVD of BPs. These findings suggest that modification of atherosclerotic risk factors with the use of behavioural or pharmacological interventions could help to reduce the incidence of SVD.

The localisation of SPARC to mature blood vessels and its predominant expression in AS valves with a lower calcification grade suggest that the spatial and temporal distribution of this matricellular protein is tightly controlled to participate in the neovascularisation of AS valves.

The AFFIRM Study enrolled 4060 predominantly elderly patients with atrial fibrillation to compare ventricular rate control with rhythm control. The patients in the AFFIRM Study were representative of patients at high risk for complications from atrial fibrillation, which indicates that the results of this large clinical trial will be relevant to patient care.

Objective: To test the hypothesis that valve allograft (VA) calcification results from an ossification process in which bone-regulatory proteins are expressed. Methods: 15 VA that were explanted at the time of surgery for dysfunction were studied. VA were analysed and compared with normal aortic valves (n = 20). Results: All the VA (5 aortic, 10 pulmonary) exhibited heavy calcification and important fibrosis. Immunohistochemistry studies showed that the bone-specific transcription factor Cbfa-1 was expressed by stromal cells. Bone alkaline phosphatase was expressed in calcified regions. Immunostaining for a smooth muscle (a-SM) actin was increased in VA compared with normal valves and in 6 of the 15 valves formed cellular clusters close to the calcified nodules. In VA osteopontin and osteonectin were expressed by stromal cells, whereas osteocalcin was closely associated with the calcified regions. Furthermore, analysis of the bone-regulatory proteins that control bone resorption showed that receptor activator of nuclear factor kB ligand (RANKL), receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) were differentially expressed in calcified VA and normal valves. Normal valve leaflets expressed OPG, whereas OPG expression was absent or faint in calcified VA. RANKL and RANK were not detected in normal valves, whereas calcified VA expressed RANKL and RANK. Conclusion: These data suggest that calcification of VA results from an ossification process, which relies on tight control of bone-regulatory protein expression. The expression pattern of the RANKL/RANK/OPG system suggests that it may have a regulatory role not only in osteoclastogenesis but also in the calcification of human VA.T he clinical performance of valve allografts (VA) is good but the longevity of these valve substitutes is impeded by the calcification process, especially in young patients. 2Calcification of VA is associated with structural valve failure that eventually leads to reoperation.2 In the past, heterotopic calcification was considered to be a passive mechanism through which calcium is deposited in degenerative tissues. More than a decade ago the works of Demer's and Giachelli's groups established that calcification of vascular structures was not the result of a mere passive deposition of calcium but was rather related to an active cellular process.3 4 Recently, calcification of valve tissue was also linked to an active transformation of resident interstitial cells to bone-forming cells.5 Calcification of VA has been related to immune mechanisms and inflammation within the grafts. 6Regulation of the ossification process has, however, not been thoroughly described in VA.In bone, ossification is an exquisitely regulated process that is under the control of numerous molecules including phosphatase, growth factors, extracellular matrix proteins and matricellular proteins. Osteoblast differentiation is regulated through the expression of the bone-specific transcription factor Cbfa-1, which also regulates the rate of bone matrix ...

Objectives: Long-term durability of bioprosthetic heart valves (BPs) are limited by structural valve degeneration (SVD) leading to stenosis and/or regurgitation. In this study, we sought to determine the metabolic markers associated with SVD. Methods: In a cohort of 220 patients with an aortic BP (mean follow-up of 2.5 ± 1.2 years), we compared the metabolic and blood lipid profile including the levels of adiponectin and the proportion of small, dense low-density lipoprotein (LDL) particles (%LDL_<255Å) in individuals developing echocardiographic evidence of early BP hemodynamic dysfunction with subjects having no features of BP dysfunction. Results: Patients developing BP dysfunction (n = 69; 31.3%) had a tendency of higher triglyceride levels. Moreover, patients with BP dysfunction had an increased proportion of %LDL_<255Å. In multivariate linear regression analysis, after adjustment for age, gender, BP size and hypertension, the %LDL_<255Å (p = 0.04) was significantly associated with BP dysfunction. In addition, patients with an elevated level of %LDL_<255Å along with a decreased plasma adiponectin level were at a very high risk of developing early BP hemodynamic dysfunction (OR = 2.54, p = 0.04). Conclusion: BP dysfunction is significantly associated with an increased proportion of small, dense LDL.