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PubMed2004

Determinants of coronary artery calcification in diabetics with and without nephropathy.

BACKGROUND: In the general population, including those with diabetes mellitus, coronary artery calcification (CAC) correlates with atherosclerotic plaque burden. On the other hand, accumulating evidence suggests that disordered mineral metabolism significantly contributes to the vascular calcification in individuals with end-stage renal disease (ESRD). METHODS: In order to determine the relative contribution of accelerated atherosclerosis and disordered mineral metabolism to CAC in chronic kidney disease, a pilot study of 90 patients with type 2 diabetes mellitus was done [age, 40-65 years; normoalbuminuria, N= 30; diabetic nephropathy (DN), N= 60]. RESULTS: CAC was more prevalent and severe among individuals with DN compared to diabetic controls (odds ratio for prevalence 8.1, 95% CI 2.3-28.5; median scores, 66 vs. 4, P < 0.001). None of the 4 measures of disordered mineral metabolism evaluated in this study (serum calcium, phosphorus, parathyroid hormone, and 1,25 di-hydroxy vitamin D levels) correlated with the prevalence or severity of CAC, or accounted for the differences seen between DN and diabetic controls. On the other hand, the difference in the severity of hypertension (number of antihypertensive medications) appeared to account for the differences in CAC burden seen between DN and diabetic controls. CONCLUSION: This first such study of nondialyzed individuals with DN suggests that, unlike ESRD patients, the high CAC burden seen at earlier stages of diabetic chronic kidney disease is probably unrelated to disordered mineral metabolism. The relationship between the severity of hypertension and CAC burden provides a probable target for intervention in the predialysis phase of DN.

Adult↗
PubMed2005

Peripheral vascular disease and serum phosphorus in hemodialysis: a nested case-control study.

BACKGROUND: Serum phosphorus (P) and the product of serum calcium x serum P (Ca x P), are frequently elevated in end-stage renal disease patients on maintenance hemodialysis (HD). Elevated P and Ca x P have been associated with vascular calcification in dialysis patients. OBJECTIVE: [corrected] To examine the role of P and Ca x P as risk factors for incident peripheral vascular disease (PVD) in HD patients with pre-existing CVD. METHODS: This nested case-control study is drawn from the 11 incident PVD events reported in the cohort of the Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease (SPACE): a randomized placebo-controlled trial. PVD was defined clinically and confirmed ultrasonographically. Each individual with a PVD event was matched for SPACE treatment group (vitamin E or placebo), age (in 4-year categories) and gender with two individuals who had no CVD end point during the follow-up period. RESULTS: Serum P and Ca x P levels were significantly higher in PVD patients than in controls. In univariate logistic regression analysis, only serum P predicted PVD in this population (OR 2.02, 95% CI 1.07 - 3.81, p = 0.03). In multivariate analysis, adjustment was made for variables dissimilar by PVD status including underlying renal disease, diabetes, smoking, history of angina pectoris, prescription for vitamin D3, erythropoietin, calcium channel blockers and aspirin. In this model, serum P remained the only significant predictor of incident PVD (OR 2.4, 95% CI 1.01 - 5.74, p = 0.04). CONCLUSIONS: Findings of the present study are consistent with a role for serum P and Ca x P in the pathogenesis of PVD in HD patients.

Adult↗
PubMed1998

Calcification of the fetal heart--four case reports and a literature review.

Calcification of the heart and vessels in fetuses is a rare condition. It may be dystrophic or metastatic. An extremely rare form of vascular calcification has been termed 'idiopathic arterial calcification of infancy', which is inherited in an autosomal recessive pattern. We report four cases of myocardial calcifications of different origin diagnosed in utero. The correct diagnosis is very important in regard to genetic counselling.

Adult↗
PubMed2006

Carotid artery plaque thickness is associated with increased serum calcium levels: the Northern Manhattan study.

BACKGROUND: Elevated serum calcium concentrations are associated with vascular calcification and cardiovascular disease. It is unknown whether there is a relationship between high-normal serum calcium levels and sub-clinical vascular effects. We investigated the association between serum calcium and carotid plaque thickness, a powerful early predictor of clinical coronary and cerebrovascular events. METHODS: Epidemiological study of 1194 subjects from the Northern Manhattan Study cohort, a prospective community-based study designed to investigate risk factors for vascular disease in different race-ethnic groups. RESULTS: Subjects with carotid plaque had higher corrected serum calcium levels within the normal range than those without carotid plaque (2.21+/-0.09 mmol/L versus 2.19+/-0.09 mmol/L, p<0.002). The relationship between carotid plaque and serum calcium persisted after adjustment for traditional cardiovascular risk factors. Subjects in the top quintile of maximal carotid plaque thickness (>or=1.7 mm) were more likely to be in the highest quintile of serum calcium level (OR=1.64, 95% CI=1.17-2.29, p<0.004). The interaction of age and corrected serum calcium was the most significant predictor of carotid plaque thickness when traditional vascular risk factors were considered (p<0.001). CONCLUSIONS: Serum calcium levels in a multi-ethnic population of older men and women were positively associated with carotid plaque thickness, a powerful early predictor of clinical coronary and cerebrovascular events.

Black or African American↗
PubMed1996

Are there gender differences regarding coronary artery calcification.

This article reviews the current knowledge about coronary artery calcification in women, concentrating on the pathophysiology of atherosclerotic calcification, the gender and age differences in the detection of calcification by electron beam computed tomography (EBCT), and the clinical significance of detected coronary calcium. The effects of estrogen and vitamin D on vascular calcification are examined with respect to data that point to similarities between the processes of calcification and bone matrix formation. Gender and age differences in EBCT coronary calcium detection, with emphasis on differences and consequences of calcium prevalence, are also examined. Lastly, the diagnostic and prognostic significance of coronary calcification is discussed, noting that it is more significant in symptomatic, older, and high-risk adults than it is in younger individuals of either gender.

Age Factors↗
PubMed2004

Uremia accelerates both atherosclerosis and arterial calcification in apolipoprotein E knockout mice.

Chronic renal failure (CRF) favors the development of atherosclerosis and excessive calcification of atheromatous lesions. CRF was induced in apolipoprotein E knockout (apoE(-/-)) mice to study (1) a possible acceleration of aortic atherosclerosis, (2) the degree and type of vascular calcification, and (3) factors involved in the calcification process. For creating CRF, 8-wk-old apolipoprotein E gene knockout (apoE(-/-)) mice underwent partial kidney ablation. Control animals underwent sham operation. Aortic atherosclerotic plaques and calcification were evaluated using quantitative morphologic image processing. At 6 wk after nephrectomy, CRF mice had significantly higher serum urea, cholesterol, and triglyceride concentrations than non-CRF controls. The serum levels of advanced oxidation protein products were elevated in the uremic group and were correlated with serum urea levels. Atherosclerotic lesions in thoracic aorta were significantly larger in uremic apoE(-/-) mice than in nonuremic controls. The relative proportion of calcified area to total surface area of both atherosclerotic lesions and lesion-free vascular tissue was increased in aortic root of uremic apoE(-/-) mice when compared with controls. The calcium deposits were made of hydroxyapatite and calcite crystals. In addition, plaques from uremic animals showed a significant increase in collagen content, whereas the degree of macrophage infiltration was comparable in both groups. There was no difference in mean arterial BP. These findings demonstrate that CRF aggravates atherosclerosis in apoE(-/-) mice. Moreover, CRF enhances arterial calcification at both atheromatous intimal sites and atheroma-free medial sites. We anticipate that this experimental model will be useful to test treatment strategies aimed at decreasing the accelerated atherosclerosis and arterial calcification in uremia.

Animals↗
PubMed2004

Relationship between immunological rejection and matrix GLA protein in cryopreserved vascular allografts.

INTRODUCTION: Cryopreserved tissue allografts used for cardiovascular diseases become calcified as a late complication after transplantation, probably caused by immunological rejection. Recent attention has been focused on the inhibitory effect of matrix Gla protein (MGP) on ectopic vascular calcification, but the behavior of MGP in cryopreserved allografts is uncertain. In this study we examined the relationship between immunological rejection and MGP in cryopreserved rat aortic grafts after transplantation. METHODS: Cryopreserved rat aortae were isografted or allografted intraperitoneally. Fresh isografts were also tested. The grafts were retrieved 9 days after transplantation and the intragraft MGP mRNA was measured by a real-time quantitative PCR method. The effect of daily administration of FK506 on MGP mRNA levels in cryopreserved isografts and allografts after transplantation was also evaluated. RESULTS: There was no significant difference in intragraft MGP mRNA levels between fresh and cryopreserved isografts 9 days after transplantation. MGP expression levels in cryopreserved allografts were significantly lower as compared to those in cryopreserved isografts (P < .01). Daily administration of FK506 enhanced intragraft MGP mRNA (ninefold) in cryopreserved allografts (P < .01), but not in cryopreserved isografts. CONCLUSIONS: Immunological rejection is likely to inhibit MGP expression in cryopreserved vascular allografts, resulting in late-onset calcification.

Animals↗
PubMed2007

Contribution of VCAF-positive cells to neovascularization and calcification in atherosclerotic plaque development.

Calcification of the vessel wall is a regulated process with many similarities to osteogenesis. Progenitor cells may play a role in this process. Previously, we identified a novel gene, Vascular Calcification Associated Factor (VCAF), which was shown to be important in pericyte osteogenic differentiation. The aim of this study was to determine the localization and expression pattern of VCAF in human cells and tissues. Immunohistochemical analysis of seven atherosclerotic arteries confirmed VCAF protein expression within calcified lesions. In addition, individual VCAF-positive cells were detected within the intima and adventitia in areas where sporadic 3G5-positive pericytes were localized. Furthermore, VCAF-positive cells were identified in newly formed microvessels in association with CD34-positive/CD146-positive/c-kit-positive cells as well as in intact CD31-positive endothelium in internal mammary arteries. Western blot analysis confirmed the presence of VCAF (18 kD) in protein lysates extracted from human smooth muscle cells, endothelial cells, macrophages, and osteoblasts. In fracture callus samples from three patients, VCAF was detected in osteoblasts and microvessels. This study demonstrates the presence of VCAF in neovessels and raises the possibility that VCAF could be a new marker for vascular progenitor cells involved in a number of differentiation pathways. These data may have implications for the prevention or treatment of vascular disease.

Atherosclerosis↗
PubMed2001

Calciphylaxis: a poor prognostic indicator for limb salvage.

INTRODUCTION: Calciphylaxis (calcific uremic arteriolopathy) is a rare complication of end-stage renal disease in patients with secondary hyperparathyroidism. Subcutaneous skin nodules and extensive tissue necrosis with vascular calcification characterize this process. DESIGN AND SETTING: The design of the study included case series and literature review. The study was set in a tertiary care hospital. PATIENTS: Four patients presented over an 8-month period with extensive tissue loss and the subsequent diagnosis of calciphylaxis. Two of these patients were revascularized. One underwent primary amputation, and the final patient died before revascularization. The mortality rate for this group was 75%. All patients had significant vascular complications outside the area of initial presentation. CONCLUSIONS: These individuals represent a subset of patients who may not benefit from revascularization or may require extensive regulation of divalent metabolism before consideration for revascularization.

Aged↗
PubMed2001

Cerebral imaging changes in patients with chronic renal failure treated conservatively or in hemodialysis.

BACKGROUND: Nonuremic patients with apparently normal memory and behavior, studied by means of cerebral computed tomography and found to have cerebral atrophy (CA), evidenced functional intellectual deficits when they underwent psychometric testing. The finding of CA has been repeatedly reported in limited case groups of uremic patients who also demonstrated functional intellectual deficits on the basis of the same tests. This retrospective study considered all diagnostic cerebral computed tomography scans done in our department between 1981 and 1998. Fifty-five uremic patients in conservative treatment (CT) and 111 patients in hemodialysis treatment (HT) were selected on the basis of the following two criteria: primary nephropathy as the cause of uremia and an age < or =55 years to exclude involutive brain changes occurring with age. AIMS: The aims of the study were to determine the percent of uremic patients with CA, the characteristics of their CA (cortical or subcortical), and eventual associated morphological lesions. RESULTS: CA was detected in 50.9% (cortical atrophy in 47.3% and subcortical atrophy in 3.6%) of the uremic patients in CT and in 77.5% of those in HT (cortical atrophy in 65.7% and subcortical atrophy in 7.7%). The average degree of CA was 0.872 in the patients in CT and 1.765 in the patients in HT. Thirty-four of the patients in the CT group and 46 in the HT group were hypertensive: these patients had a more severe degree of CA than the nonhypertensive subjects. In the CT group, the degree of CA in the hypertensive patients was 1.205 versus 0.428 for the nonhypertensive subjects. In the HT group, the degree of CA was 2.087 for the hypertensive patients versus 1.538 for the nonhypertensive patients. Of the overall population, 7.8% had ischemic lesions, 9.6% had endocranial calcifications, and 5.4% evidenced periventricular white matter hyperintensities. CONCLUSIONS: The high percent of CA found in young uremic patients increased in subjects in HT and, even more so in hypertensive patients. Vascular calcifications, focal ischemia and leukoaraiosis, well-known expressions of a chronic state of cerebrovascular insufficiency, were also found in HT patients; hypertension alone is a recognized accelerator of vascular damage. Thus, early and severe atherosclerosis and related hypoperfusion can be considered as the paramount causes of parenchymal cerebral damage in uremia.

Adult↗
PubMed1977

Calcification of the intrarenal branches of the renal arteries.

Mild to extensive calcification of the intrarenal branches of the renal arteries seen in 13 patients over a period of 12 months is described. This type of renal vascular calcification appeared to be associated with generalised atherosclerosis in patients of advancing age. The association of diabetes mellitus and intrarenal arterial calcification could not be supported by the cases presented here.

Age Factors↗
PubMed1992

Multiple metastatic calcifications detected by bone scintigraphy and demonstrated by CT.

Metastatic calcifications according to histopathologic and scintigraphic findings have been well-defined. The authors report a postoperative case of hyperparathyroidism with multiple metastatic calcifications in the lung, kidney, stomach, heart, and vessels that were primarily detected by bone scintigraphy and demonstrated by CT. Tc-99m MDP bone scintigraphy showed a markedly increased accumulation of radioactivity diffusely throughout the lung, left ventricular wall, both kidneys, and the gastric cardia and body. In the lung, plain films showed almost normal lung. CT, however, demonstrated patchy, slightly increased densities in the lung bilaterally. Cardiac CT indicated a considerably increased density of the ventricular myocardium and remarkable calcification in or near the atrioventricular septum or annulus fibrosus. Upper abdominal CT demonstrated increased densities diffusely throughout the gastric mucosa and renal cortex. Only vascular calcifications were depicted by plain films. Using both bone scintigraphy and CT provides accurate information about each lesion and each tissue, allowing precise diagnosis of even a questionable lesion in the early stage of metastatic calcification. Early diagnosis and early therapy offer the best chance for cure or palliative therapy.

Bone and Bones↗
PubMed2004

Osteoprotegerin and bone mineral metabolism in renal failure.

PURPOSE OF REVIEW: This review focuses on the impact of a recent breakthrough in bone cell biology for understanding the pathophysiology of bone/vascular abnormalities associated with uraemia. RECENT FINDINGS: Osteoprotegerin is a humoral osteoclastogenesis/osteoclast activation inhibitory factor, which belongs to the TNF-alpha receptor superfamily. Serum osteoprotegerin levels are elevated along with the deterioration of the glomerular filtration rate. The circulating osteoprotegerin molecules were likely to preserve the activity of osteoclastogenesis inhibition, and the levels in many dialysis patients were high enough to inhibit osteoclastogenesis. The higher serum osteoprotegerin levels were related to the development of vascular calcification. SUMMARY: Osteoprotegerin is a potential uraemic toxin that increases the skeletal resistance to PTH. However, the roles of increased circulating osteoprotegerin on bone and/or vascular abnormalities in uraemia remain to be clarified.

Bone Density↗
PubMed1989

Favorable effects of prostacyclin infusion in a patient given a renal transplant and with severe vascular disease secondary to diabetes--a case report.

Microangiopathy is one of the most frequent diseases in diabetic patients. A diabetic man with a kidney transplant and with severe and progressive vasculopathy with early necrosis of the fingers and toes was submitted to three prostacyclin (PGI2) intravenous infusions (5 ng/kg/min for forty-eight hours) during a period of two months. Three months after the last infusion, radiographs of the hands and feet showed a marked reduction in the extent of the vascular calcifications and healing of the ischemic-necrotic areas. The authors discuss the immediate and later effects of PGI2 infusion in a case of diabetic vascular disease.

Adult↗
PubMed2006

Statins and tissue mineralization: putative involvement of alkaline phosphatase.

Many clinical trials have clearly demonstrated the benefit of statins in the prevention of coronary heart disease. Although other effects have subsequently been described, the so-called pleiotropic effects of statins, there is a tendency to relate all those effects, more or less directly, to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A. Several clinical and laboratory studies show an association between statins and increased bone formation and/or density, but no clear explanation for that statin effect has emerged. We therefore hypothetized that statins may have an effect on alkaline phosphatase activity (ALP), an enzyme with an important role in bone mineralization and that may also contribute to pathological mineralization in other tissues, such as vascular calcification. Our experience with drug effects on ALP lead us to admit the possibility of finding a statin with an ALP increasing effect on bone but not on vascular tissue, or with a more marked effect upon one of the ALP isoforms or isoenzymes. That information would allow the design of clinical trials to confirm the suitability of a specific statin to a specific clinical condition.

Alkaline Phosphatase↗
PubMed2004

Coronary artery calcification measured with electron-beam computerized tomography correlates poorly with coronary artery angiography in dialysis patients.

BACKGROUND: Coronary artery calcification measured by electron-beam computerized tomography (EBCT) correlates with plaque burden and vessel stenosis and is predictive of future cardiac events in the general population. Uremic vascular calcification is common and widespread, tends to be medial as well as intimal, and may not relate solely to atherosclerotic lesions. Despite this difference and in the absence of any direct evidence in uremic patients, it is generally implied that coronary artery calcification equates to occlusive atherosclerosis. METHODS: We set out to compare the predictive value of coronary artery calcification assessed by EBCT with contemporaneous coronary angiography. We studied 18 patients with end-stage renal disease undergoing maintenance dialysis. Seventy-two coronary vessels were analyzed for angiographic evidence of stenotic disease and correlated with individual vessel calcification score. RESULTS: There was no significant correlation between degree of vessel stenosis and calcification score for individual vessels in patients with a positive calcium scan. Specificity was 48% and the positive predictive value was 53%. However, a calcification score <20 strongly correlated with the absence of significant luminal narrowing, and a 0 calcification score had a negative predictive value of 87.5%. CONCLUSION: Coronary artery calcification measured by EBCT is not an accurate marker of the degree of vessel stenosis in coronary artery disease in uremic patients and should not be used as a single screening test for atherosclerotic coronary disease.

Calcinosis↗
PubMedDate not supplied

[Chorea as the presenting form of progressive systemic sclerosis].

We present an exceptional case of a patient with hemichorea of ischemic origin as a form of presentation of progressive systemic sclerosis. The neurologic complications, both central and peripheral, of this condition are considered infrequent and may be due to coexisting or iatrogenic factors, or may be a direct complication of progressive systemic sclerosis. There have been occasional reports of cerebrovascular disease in progressive systemic sclerosis, and this apparent rarity may be related to structural and morphological variations in brain arteries. Recently, there have been reports of primary cerebrovascular changes and vascular calcifications in progressive systemic sclerosis. There are no reported cases associated with movement disorders. The patient is a 66-year-old ex-smoker, and no other vascular risk factors, with chronic Raynaud's phenomenon affecting both hands, and polyarthralgias. Three months previously he began to complain of choreic movements affecting the right-sided limbs without any other neurological manifestations. The abnormal movements responded to haloperidol. There were skin changes suggestive of progressive systemic sclerosis, and capillaroscopy showed abundant avascular zones with dilated capillary loops. Anticentromere antibody titer was elevated to 1/1280. Brain arteriography was normal, and the brain SPECT showed bilateral hypoperfusion bilaterally, predominantly on the left side. Brain MR imaging confirmed an infarct in the left caudate and adjacent internal capsule. The study of this case supports the hypothesis of a direct primary cerebrovascular damage in progressive systemic sclerosis.

Aged↗