Serum phosphorus concentration and its association with the degree and pattern of intracranial arterial calcification.

BACKGROUND AND AIM: The aim of this study was to determine whether the serum phosphorus concentrations (SPC) are associated with the degree and pattern of intracranial arterial calcification (IAC) in patients with normal renal function or mild-moderate renal impairment. METHODS AND RESULTS: A total of 513 patients were enrolled in this study. The degree of IAC measured by IAC scores was evaluated on non-contrast head computed tomography (CT) images and IAC was classified as intimal or medial calcification. Study participants were classified according to IAC degrees (mild, moderate and severe) and patterns (intimal and medial calcification). A multivariate regression model was used to assess the independent relationship of SPC with IAC scores and patterns. Of 513 study participants (mean [SD] age, 68.3 [10.3] years; 246 females [48%]), the mean SPC was 1.07 ± 0.17 mmol/L and IAC scores was 4.0 (3.0-5.0). Multivariate analysis showed that higher serum phosphorus was a significant risk factor for moderate/severe IAC in both patients with eGFR ≥60 ml/min/1.73 m2 (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.01-1.59; P < 0.05) and eGFR <60 ml/min/1.73 m2 (OR, 1.92; 95% CI, 1.04-3.57; P < 0.05), when those with mild IAC were considered as the reference group. However, higher SPC was associated with an increased odds of medial calcification only in patients with eGFR <60 ml/min/1.73 m2 (OR, 1.67; 95% CI, 1.08 to 2.61). CONCLUSIONS: High levels of serum phosphorus were positively correlated with the degree of IAC, and this significant effect on medial IAC was only present in patients with impaired renal function (eGFR <60 ml/min/1.73 m2).

Use of Tourniquet During Knee Arthroplasty in Patients With Radiographic Arterial Calcifications.

BACKGROUND: Use of tourniquet during total knee arthroplasty (TKA) in patients with radiographic arterial calcifications is controversial. Intimal arterial calcifications are feared to be associated with ischemic complications such as delayed wound healing and arterial thrombosis, whereas medial calcifications stiffen the arterial wall, possibly leading to tourniquet failure and increased blood loss. METHODS: We conducted a prospective cohort study to determine the incidence of tourniquet failure (inflated up to 300 mm Hg), blood transfusions, wound healing, and ischemic complications in thighs with and without arterial calcifications on preoperative radiographs, in 2548 consecutive primary TKAs conducted in our unit over a 5-year period. Eighty-six thighs showed vascular calcifications: 58 medial and 28 intimal. RESULTS: Thighs with vascular calcifications had higher risk of tourniquet failure as compared to those without calcifications (P < .001), but with no significant increase in incidence of blood transfusions. All cases of tourniquet failure in the calcification group occurred in thighs with medial calcifications, whereas all cases of tourniquet failure in the control group occurred in obese patients. There was no difference in wound healing and ischemic complications in limbs with and without arterial calcifications. CONCLUSION: The presence of arterial calcifications on preoperative radiographs increases the risk of tourniquet failure at 300 mm Hg in patients undergoing TKA, with no significant increase in rate of blood transfusions, wound healing or ischemic complications.

The relationship between bone health and type of intracranial internal carotid calcifications in patients with ischemic stroke.

INTRODUCTION: Vascular calcifications, primarily in the aorta and its proximal branches, are commonly observed among subjects with impaired bone health. In this study, we sought to determine if a comparable association holds true for the calcifications in the intracranial internal carotid arteries (IICA), in general and also for particular calcification patterns. METHODS: A consecutive series of ischemic stroke patients were prospectively enrolled into the study, where computed tomography angiography source images were used to determine the presence and type of IICA calcifications, and dual-energy X-ray absorptiometry was used to determine the bone mineral density in the left femoral neck region. IICA calcifications were categorized as none, intimal, medial, and mixed types based on previously validated classification schemes. Their relationships with femoral bone T-scores were evaluated by bivariate and multivariate analyses. RESULTS: Femoral neck T-score was highest among patients without any vascular calcifications (n=65), when compared to the bone density measures among patients with any type of calcification (n=185) (p<0.001). After adjustment for age, gender, vascular risk factors, and serum biomarkers related to bone health, the T-score remained significantly associated only with the pattern of intimal calcification [OR 0.63 (0.42 - 0.95), p=0.028]. CONCLUSIONS: Our findings suggest that the intracranial vasculature, in particular the internal carotid arteries, is not immune to the interplay between suboptimal bone health and vascular calcifications. This association was most robust for an intimal type of IICA calcification pattern, while no such relationship could be demonstrated for other types of vascular calcifications.

The pathophysiology and management of vascular calcification in chronic kidney disease patients.

INTRODUCTION: Vascular calcification (VC) which is the pathological mineral deposition in the vascular system, predominantly at the intimal and medial layer of the vessel wall, is an important comorbidity in patients with chronic kidney disease (CKD) leading to significant morbidity and mortality while necessitating appropriate treatment. Our review aims to provide an in-depth analysis of the current understanding of VC. AREAS COVERED: In this review, we first discuss the pathophysiology of VC in CKD patients, then we explain the methods to predict and assess VC. Afterwards, we provide the currently available as well as the potential therapeutic approaches of VC. We finally discuss our understanding regarding the current situation surrounding VC in our expert opinion section. EXPERT OPINION: Predicting, assessing and treating VC is crucial and the future advances in the field of research surrounding VC will potentially occur in one or more of these three areas of clinical management. There is a current lack of evidence and consensus regarding specific therapeutic options for alleviating VC and this situation may not necessitate VC to be determined, detected, and documented before the available options are implemented. Regardless, the prediction and assessment of VC is still important and requires further improvement together with the developments in therapeutic alternatives. The future has the potential to bring better research which would guide and improve the management of this patient group. A more specialized approach consisting of targeted therapies and more tailored management plans for patients with CKD and VC is on the horizon.

Lower limb arterial calcification and its clinical relevance with peripheral arterial disease.

Lower limb arterial calcification (LLAC) is associated with an increased risk of mortality and it predicts poor outcomes after endovascular interventions in patients with peripheral artery disease (PAD). Detailed histological analysis of human lower artery specimens pinpointed the presence of LLAC in two distinct layers: the intima and the media. Intimal calcification has been assumed to be an atherosclerotic pathology and it is associated with smoking and obesity. It becomes instrumental in lumen stenosis, thereby playing a crucial role in disease progression. On the contrary, medial calcification is a separate process, systematically regulated and linked with age advancement, diabetes, and chronic kidney disease. It prominently interacts with vasodilation and arterial stiffness. Given that both types of calcifications frequently co-exist in PAD patients, it is vital to understand their respective mechanisms within the context of PAD. Calcification can be easily identifiable entity on imaging scans. Considering the highly improved abilities of novel imaging technologies in differentiating intimal and medial calcification within the lower limb arteries, this review aimed to describe the distinct histological and imaging features of the two types of LLAC. Additionally, it aims to provide in-depth insight into the risk factors, the effects on hemodynamics, and the clinical implications of LLAC, either occurring in the intimal or medial layers.

Mast cells participate in smooth muscle cell reprogramming and atherosclerotic plaque calcification.

BACKGROUND: Calcification, a key feature of advanced human atherosclerosis, is positively associated with vascular disease burden and adverse events. We showed that macrocalcification can be a stabilizing factor for carotid plaque molecular biology, due to inverse association with immune processes. Mast cells (MCs) are important contributors to plaque instability, but their relationship with macrocalcification is unexplored. With a hypothesis that MC activation negatively associates with carotid plaque macrocalcification, we aimed to investigate the link between MCs and carotid plaque vulnerability, and study MC role in plaque calcification via smooth muscle cells (SMCs). METHODS: Pre-operative computed tomography angiographies of patients (n = 40) undergoing surgery for carotid stenosis were used to characterize plaque morphology. Plaque microarrays (n = 40 and n = 126) were used for bioinformatic deconvolution of immune cell populations. Tissue microarrays (n = 103) were used to histologically validate the contribution of activated and resting MCs in plaques. RESULTS: Activated MCs and their typical markers were negatively correlated with macrocalcification. The ratio of activated vs. resting MCs was increased in low-calcified plaques from symptomatic patients. There was no modulating effect of medication on MC ratios. In vitro experiments showed that SMC calcification attenuated MC activation, while both active and resting MCs stimulated SMC calcification and induced dedifferentiation towards a pro-inflammatory-, osteochondrocyte-like phenotype, without modulating their migro-proliferative function. CONCLUSIONS: Integrative analyses from human plaques showed that MC activation is inversely associated with macrocalcification and positively with parameters of plaque vulnerability. Mechanistically, MCs induce SMC osteogenic reprograming, while matrix calcification in turn attenuates MC activation, offering new therapeutic avenues for exploration.

Pathological Analysis of Medial and Intimal Calcification in Lower Extremity Artery Disease: Impact of Hemodialysis.

Background: The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features have not yet been evaluated. Objectives: The aim of the study was: 1) to compare lesion characteristics of lower extremity artery disease in HD vs non-HD patients; and 2) to determine factors associated with severe medial calcification. Methods: Seventy-seven lower limb arteries were assessed from 36 patients (median age 77 years; 23 men; 21 HD and 15 non-HD) who underwent autopsy or lower limb amputation. Arteries were serially cut at 3- to 4-mm intervals creating 2,319 histological sections. Morphometric analysis and calcification measurements were performed using ZEN software. Calcification with a circumferential angle (arc) ≥180° was defined as severe calcification. Multivariable logistic regression was used to identify risk factors for severe medial calcification. Results: The degree of the medial calcification arc was significantly higher in the HD group compared to the non-HD group (P < 0.0001). In the multivariable analysis, HD was associated with severe medial calcification in below-the-knee lesions (OR: 17.1; P = 0.02). The degree of intimal calcification in above-the-knee lesions was also significantly higher in HD patients with a higher prevalence of advanced atherosclerotic plaque (P = 0.02). The prevalence of severe bone formation was more common in the HD patients (P = 0.01). Conclusions: Hemodialysis patients demonstrated a higher degree of medial and intimal calcification compared with non-HD patients. The difference was more prominent in the medial calcification of below-the-knee lesions.

The association of renal impairment with different patterns of intracranial arterial calcification: Intimal and medial calcification.

BACKGROUND AND AIMS: Increasing knowledge about calcification together with improved imaging techniques provided evidence that intracranial arterial calcification (IAC) can be divided into two distinct entities: intimal and medial calcification. The purpose of this study was to investigate the association between kidney function and the two patterns of IAC, which could clarify the underlying mechanisms of intimal or medial calcification and its clinical consequence. METHODS: A total of 516 participants were enrolled in this study. Kidney function was assessed using the estimated glomerular filtration rate (eGFR) based on modified glomerular filtration rate estimating equation. The degree of IAC measured by IAC scores was evaluated on non-contrast head computed tomography (CT) images and IAC was classified as intimal or medial calcification. Associations of kidney function with IAC scores and patterns were assessed sing multivariate logistic regression analysis. RESULTS: In 440 patients (85.27%) with IAC, 189 (42.95%) had predominant intimal calcifications and 251 (57.05%) had predominant medial calcifications. Multivariate analysis revealed that lower eGFR level (eGFR <60 ml/min/1.73 m2) was associated with higher IAC scores (odds ratio [OR] 2.01; 95% confidence interval [CI], 1.50-2.71; p < 0.001). Medial calcification was more frequent in the lower eGFR group (eGFR <60 ml/min/1.73 m2) compared to the other two groups with eGFR 60 to 89 and eGFR >90 ml/min/1.73 m2 (78.72% vs. 53.65%, p < 0.001; 78.72% vs. 47.78%, p < 0.001). In multivariable analysis, impaired kidney function was associated with an increased odds of medial calcification presence in patients with eGFR <60 ml/min/1.73 m2 (OR, 1.47; 95% CI, 1.05 to 2.06). CONCLUSIONS: Our findings demonstrated that impaired renal function was independently associated with a higher degree of calcification in intracranial arteries, especially medial calcification, which reflects a distinction between two types of arterial calcification and raise the possibility for specific prevention of lesion formation.

Arterial calcification and long-term outcome in chronic limb-threatening ischemia patients.

PURPOSE: Within five years after presentation 50-60% of patients with chronic limb-threatening ischemia (CLI) have died or had an amputation. We assessed the predictive value of lower extremity arterial calcification on computed tomography (CT) characteristics on both 7-years amputation-free survival and 10-years all-cause mortality in patients with CLI. METHOD: Included were 89 CLI patients (mean age 73.1 ±â€¯11.6 years) who underwent a CT angiography of the lower extremities. In the femoropopliteal and crural arteries based on a CT score the following calcification characteristics were assessed: severity, annularity, thickness and continuity. The predictive value of different arterial calcification characteristics was analysed by age- and sex-adjusted multivariate Cox regression analysis. RESULTS: Complete annular calcifications were common (femoropopliteal 43.7%, n = 38; crural, 63.2%, n = 55). Mean survival was 278.4 weeks (95% CI 238.77-318.0 weeks). Patients with complete annular calcifications had a higher all-cause 10-year mortality (femoropopliteal unadjusted HR 1.64, p = 0.04 and adjusted for age and sex HR 1.68, p = 0.04; crural unadjusted HR 1.92, p = 0.02, adjusted for age and sex HR 2.29, p = 0.006) than patients with other calcification characteristics. CONCLUSIONS: Annularity of calcification of both femoropopliteal and crural arteries is a predictor for 10-year all-cause survival, its hazard being even higher than the traditional prognostic risk factors for CLI and therefore could be involved in the poor survival of these patients.

Angiopoietin-like 2 has auxo-action in atherosclerosis by promoting atherosclerotic calcification.

OBJECTIVE: To study the effects of angiopoietin-like 2 (Angptl2) on atherosclerotic calcification in aortic artery of ApoE-/- mice. METHODS: Twelve 6-week-old male mice were randomly divided into control group (n=6) and interventional group (n=6), the control group were fed with high fat diet and the interventional group were fed with high fat diet and at the eighth week interventional group mice were infused (intravenously) with purified recombinant Angptl-2 once a week for one month. All mice were sacrificed when the mice were 16 weeks old, blood was collected and plasma triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC) were measured, aortic sections were stained with hematoxylin and eosin (HE) or Von Kossa and were observed under microscope. Calcium content and alkaline phosphatase activity of aorta were measured to measure the degree of vascular calcification. The expressions of Runx2 protein and mRNA levels in aortic sections of mice were detected by immunohistochemistry, Western Blot and qRT-PCR respectively. RESULTS: The plasma TG, TC and LDLC level in interventional group was significantly higher than that in control group and the expression of Runx2 in aortic had the similar results. HE staining demonstrated significant thickening of the intima, with typical atherosclerotic plaque formation in interventional group mice, and Von Kossa staining showed spotty black clumps of aortic calcification under the fibrous cap plaque, while control group had atherosclerotic plaques without significant calcium deposits formation; The quantitative analysis showed that aortic vascular wall calcium and alkaline phosphatase activity were significantly higher in the intervention group than that of the control group (P<0.01). CONCLUSIONS: Angptl-2 could increase ApoE-/- mice plasma lipid level, it also facilitate the expression of Runx2, calcium content and ALP activity in aortic and then accelerate atherosclerotic calcification. Our experiments demonstrated that Angptl2 could accelerate atherosclerotic calcification. It reminded us that by controlling or decreasing the Anglt-2 level in plasma could help inhibit atherosclerotic calcification and then provides a new target to prevent coronary heart disease.