Comparison of surgically removed cardiac valves of patients with ESRD with those of the general population.
ABSTRACT Patients with end-stage renal disease (ESRD) have increased vascular and valvular calcification compared with the general population. Recently, 44% of renal transplant recipients were found to have vascular calcification of the medial layer of the inferior epigastric artery that was associated with deposition of bone matrix proteins. Similar findings have been reported for native and bioprosthetic cardiac valves surgically removed from patients without ESRD.
To determine whether valvular calcification in patients with ESRD is similar to that in patients without ESRD, we retrospectively examined surgically excised native cardiac valves of all hemodialysis patients and compared them pathologically with those of matched controls without renal failure. Valves were examined by using routine stains and immunohistochemistry for markers to endothelial cells, macrophages, B and T lymphocytes, alkaline phosphatase, osteopontin, and bone morphogenic protein 4.
Histologically, 7 of 10 valves from patients with ESRD had moderate to severe inflammation compared with 1 of 10 valves from control patients. Patients with ESRD had more endothelial cells/vascularity (P = 0.002) and macrophages (P = 0.069). There was no difference between the 2 groups with respect to B and T lymphocytes, alkaline phosphatase, osteopontin, or bone morphogenic protein 4.
The noncollagenous proteins bone morphogenic protein and osteopontin have been shown in surgically removed cardiac valves of patients with ESRD and the general population. However, valvular calcification in patients with ESRD is associated with enhanced inflammation, consistent with the previously reported greater C-reactive protein levels in this patient population and their increased risk for death.
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ABSTRACT: To identify valvar heart disease in patients with chronic uraemia by conventional and colour coded Doppler echocardiography. Case series of an unselected group of 62 patients with end stage renal failure. Centre for haemodialysis in a referral hospital in Switzerland. 62 patients on chronic haemodialysis. Frequency of structural and functional valve abnormalities and their relation to clinical findings. Structural changes were seen in 40 (64%) of 62 patients after 50 months (range 3-178 months) on haemodialysis. The mitral annulus and aortic cusps were thickened in 25 (40%) and in 34 (55%) patients respectively. Aortic stenosis was present in eight (mean (SD) age 60.5 (8.5) years), with a maximal instantaneous pressure gradient of 41 (14) mm Hg. Aortic regurgitation was seen in eight, mitral regurgitation in seven, and mitral stenosis in three patients. Patients with aortic stenosis had been on haemodialysis for significantly longer than the remaining patients (101 (43) v 46 (43) months, p = 0.01) and had significantly higher concentrations of serum alkaline phosphatase (176 (89) v 117 (47) IU/l, p less than 0.01) and of parathyroid hormone (54 (66) v 19 (29) ng/ml, p less than 0.02). Patients on long-term haemodialysis had an increased frequency of haemodynamically relevant changes in the aortic and mitral valves. The degenerative valve disease may be related in part to the duration of haemodialysis and to alterations in calcium metabolism as indicated by increased plasma concentrations of alkaline phosphatase and parathyroid hormone.Heart 04/1992; 67(3):236-9.
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ABSTRACT: Dystrophic mineralization remains the leading cause of stenotic or regurgitant failure in native human and porcine bioprosthetic heart valves. We hypothesized that cellular expression of noncollagenous matrix proteins (osteopontin, osteocalcin, and osteonectin) that regulate skeletal mineralization may orchestrate valvular calcification. Porcine bioprosthetic heart valves and native human heart valves obtained during replacement surgery were analyzed for cells, matrix proteins that regulate mineralization, and vessels. Cell accumulation and calcification were correlated for both valve types (rho = 0.75, P = 0.01, native; rho = 0.42, P = 0.08, bioprosthetic). Osteopontin expression correlated with cell accumulation (rho = 0.58, P = 0.04) and calcification (rho = 0.52, P = 0.06) for bioprosthetic valves. Osteocalcin expression correlated with calcification (rho = 0.77, P = 0.04) and cell accumulation (rho = 0.69, P = 0.07) in native valves. Comparisons of calcified versus noncalcified native and bioprosthetic valves for averaged total matrix protein mRNA signal score revealed increased noncollagenous proteins mRNA levels in calcified valves (P = 0.07, group I vs. group II; P = 0.02, group III vs. group IV). When stratified according to positive versus negative mRNA signal status, both calcified bioprosthetic valves (P = 0.03) and calcified native valves (P = 0.01) were significantly more positive for noncollagenous proteins mRNA than their noncalcified counterparts. Local cell-associated expression of proteins regulating mineralization suggests a highly coordinated mechanism of bioprosthetic and native valve calcification analogous to physiologic bone mineralization. Modulation of cellular infiltration or cellular expression of matrix proteins that regulate mineralization, may offer an effective therapeutic approach to the prevention of valve failure secondary to calcification.Journal of Clinical Investigation 04/1997; 99(5):996-1009. · 12.81 Impact Factor
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ABSTRACT: Cardiovascular diseases represent the major cause of death in hemodialysis patients. However, little information is available about the repercussion of uremia on cardiac valves. We retrospectively investigated the incidence rate of aortic stenosis (AS), from 1991 to 1996, in 110 hemodialysis patients followed by Doppler-echocardiography. Progressive AS was diagnosed in 16 patients who had a decrease in their indexed aortic valve area from 1.24 +/- 0.09 to 0.66 +/- 0.21 cm2/m2 of BSA in 16.8 +/- 1.9 months. The mean incidence of AS per year was of 3.3%, ranging from 1.5 to 8.0%. Eight patients died in less than 3 years after the diagnosis of AS with a mean survival time of 23.0 +/- 9.5 months. Survival curves using Kaplan-Meier estimates showed a statistically significant decrease in the survival rate of patients with AS compared with patients without valvulopathy (p < 0.001). They were older than patients with normal valve, 68.6 +/- 11.1 versus 56.7 +/- 16.0 years, respectively. Men were 4 times more affected than women and showed a significantly more rapid progression to AS than women. The calcium-phosphorus product was higher in AS patients, 5.43 +/- 0.98 than in patients without AS, 3.95 +/- 0.50 mM. It was mainly due to hyperphosphatemia without hypercalcemia and the hyperphosphatemia was associated with biological signs of hypoparathyroidism or adynamic bone disease in 62% of the cases. Plasma vitamin D3 was also higher in patients with AS, 20.5 +/- 13.5 ng/ml than in those with normal valves, 9.6 +/- 6.3 ng/ml. Logistic regression showed that age, vitamin D3 and hyperphosphatemia correctly predicted 56% of the AS cases. In conclusion, AS is frequent and of poor outcome in hemodialysis patients. Age, relatively high plasma vitamin D3 levels, and hyperphosphatemia, mostly due to hypoparathyroidism, must be considered as risk factors.Néphrologie 01/1999; 20(4):217-25.