Vascular Calcification

Vascular calcifications constitute an important risk factor for mortality in chronic kidney disease patients. A better knowledge of physiopathologic phenomena responsible for vascular mineralization leads to emerging biological markers of vascular calcifications. In calcified arteries, presence of bone matrix as well as osteoblast cells suggest that vascular calcification is an active and highly regulated process. In uremic environment, vascular smooth muscle cells can transdifferentiate into osteoblast-like cells. The OPG–RANK–RANKL system is clearly of central significance in controlling vascular calcifications as in bone metabolism. Converging results suggest that circulating OPG determination should be a relevant marker of calcifications. Impairment in inhibitory system such as Matrix Gla Protein and fetuin-A promotes bone matrix calcification. Finally, FGF-23, an early and sensitive marker of bone and mineral disorders in chronic kidney disease patients, appears as a promising ...

The consequences of atherosclerosis can be detected by multislice computed tomography (MSCT), invasive coronary angiogram (CAG) and the resultant myocardial ischaemia by myocardial perfusion single photon emission computed tomography (MPS). In this study an attempt is made to compare MSCT with MPS and also to compare the MSCT findings with that of invasive CAG in patients suspected to have coronary artery disease (CAD). A total of 99 patients suspected to have CAD underwent both MSCT and MPS with (99m)Tc sestamibi. The MSCT studies were classified as having no CAD, significant CAD (>50% diameter stenosis), and insignificant CAD (<50% diameter stenosis). Myocardial perfusion single photon emission computed tomography was reported as normal and reversible ischaemia. In a subgroup of 33 patient invasive CAG was done. In 99 patients, 396 coronaries were evaluated with MSCT and MPS. Coronary artery calcium scoring (CACS) in these patient ranged from 0 to 2200. No CAD was noted in 1...

In the present study, we examined the expression of regulators of bone formation and osteoclastogenesis in human atherosclerosis because accumulating evidence suggests that atherosclerotic calcification shares features with bone calcification. The most striking finding of this study was the constitutive immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein in nondiseased aortas and the absence of bone morphogenetic protein (BMP)-2,

Objectives: We aimed to assess arterial stiffness parameters and to investigate the relationship between these parameters and aortic calcification in patients with aortic arch calcification and without symptomatic atherosclerotic disease. Study design: The population of this study consisted of 41 patients with aortic arch calcification verified by chest X-ray (group I, 17 males, mean age 70±5 years) and individuals without aortic arch calcification (group II, 17 males, mean age 68±6 years). Subjects with symptomatic or known vascular disease were excluded from the study. The arterial stiffness parameters of all subjects were measured non-invasively with a SphygmoCor device. Aortic pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx) and heart rate normalized augmentation index (AIx@75) were used as parameters of arterial stiffness. Results: The two groups were compared according to demographic characteristics, medications currently being taken, and levels ...

Vascular calcifications represent a severe complication of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) stage 5. The factors influencing the development of this complication are in close relation with the pathology of chronic dialysis premorbid condition, and with therapy as well. The present article highlights the association between several factors and the development or the aggravation of vascular calcifications in continuous ambulatory peritoneal dialysis (CAPD) patients. The results are not always in accordance with similar literature data, but there is a lack of researches regarding mineral metabolism in peritoneal dialysis patients versus those on chronic hemodialysis.

When fed high fat diets, male LDLR-/- mice develop obesity, hyperlipidemia, hyperglycemia, and arteriosclerotic calcification. An osteogenic Msx-Wnt regulatory program is concomitantly upregulated in the vasculature. To better understand the mechanisms of diabetic arteriosclerosis, we generated SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR-/- mice, assessing the impact of Msx1+Msx2 gene deletion in vascular myofibroblast and smooth muscle cells. Aortic Msx2 and Msx1 were decreased by 95% and 34% in SM22Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR-/- animals, respectively, vs. Msx1(fl/fl);Msx2(fl/fl);LDLR-/- controls. Aortic calcium was reduced by 31% and pulse wave velocity - an index of stiffness - was decreased in SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR-/- mice vs. controls. Fasting blood glucose and lipids did not differ, yet SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR-/- siblings became more obese. Aortic adventitial myofibroblasts from SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR-/- mice exhibited reduced osteog...

This study sought to determine the frequency and impact of coronary calcification among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). Small studies in patients with stable coronary artery disease have suggested a worse prognosis after PCI of calcified compared with noncalcified lesions. Little is known about the impact of coronary calcification on outcomes after PCI for patients presenting with non-ST-segment elevation and ST-segment elevation ACS. Data from 6,855 patients presenting with ACS in whom PCI was performed were pooled from 2 large-scale randomized, controlled trials, ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction). One-year outcomes were analyzed according to the severity of PCI target lesion calcification (none/mild, moderate, or severe) as assessed by an independent angiographic core laborator...

To investigate the association between regular coffee consumption and the prevalence of coronary artery calcium (CAC) in a large sample of young and middle-aged asymptomatic men and women. This cross-sectional study included 25 138 men and women (mean age 41.3 years) without clinically evident cardiovascular disease who underwent a health screening examination that included a validated food frequency questionnaire and a multidetector CT to determine CAC scores. We used robust Tobit regression analyses to estimate the CAC score ratios associated with different levels of coffee consumption compared with no coffee consumption and adjusted for potential confounders. The prevalence of detectable CAC (CAC score >0) was 13.4% (n=3364), including 11.3% prevalence for CAC scores 1-100 (n=2832), and 2.1% prevalence for CAC scores >100 (n=532). The mean ±SD consumption of coffee was 1.8±1.5 cups/day. The multivariate-adjusted CAC score ratios (95% CIs) comparing coffee drinkers of <1,...

Recent advances in our understanding of the excess mortality of chronic kidney disease (CKD) due to cardiovascular complications, obtained through observational studies, demonstrate that vascular calcification and hyperphosphatemia are major cardiovascular risk factors. Mechanistic studies demonstrate that these two risk factors are related and that hyperphosphatemia directly stimulates vascular calcification. The role of hyperphosphatemia in stimulating vascular calcification in CKD is associated with a block to the skeletal reservoir function in phosphate balance due to excess bone resorption. This has led to the realization that renal osteodystrophy is linked to vascular calcification by disordered mineral homeostasis (phosphate) and that a multiorgan system fails in CKD, leading to cardiovascular mortality. In children with renal disease, the multiorgan system fails, just as in adults, but the outcomes have been less well studied, and perceptions of differences from adults are possibly incorrect. Vascular calcification and cardiovascular mortality are less prevalent among pediatric patients, but they are present. However, CKD-induced vascular disease causes stiffness of the arterial tree causing, in turn, systolic hypertension and left ventricular hypertrophy as early manifestations of the same pathology in the adult. Because of the role of the skeleton in these outcomes, renal osteodystrophy has been renamed as the CKD mineral bone disorder (CKD-MBD). This review, which focuses on the pediatric patient population, describes our current state of knowledge with regards to the pathophysiology of the CKD-MBD, including the new discoveries related to early stages of CKD. As a new necessity, cardiovascular function issues are incorporated into the CKD-MBD, and new advances in our knowledge of this critical component of the disorder will lead to improved outcomes in CKD.

In past decades, extraosseous (including cardiovascular) calcification was predominantly regarded as a passive process of limited pathophysiological significance. It was thought that a calcium (Ca) x phosphate (P) product in excess of Ca and P solubility was the key trigger of progressive hydroxyapatite precipitation and deposition in vessels and soft tissues. Recently, however, it became apparent that calcification is a complex and highly regulated process involving inhibitors, inducers, and cell differentiation processes. It further became evident that cardiovascular manifestations of calcification predict patient outcomes in general populations, but in particular, in patients with chronic kidney disease. This review discusses the role of fetuin-A in the regulation of extraosseous and especially cardiovascular calcification processes. Fetuin-A is an inflammation-related Ca-regulatory glycoprotein and the prototype of a systemically acting calcification inhibitor. The emerging role...