Extensive Coronary Artery Calcification Research Articles

Repair of a right coronary artery rupture with perforated right ventricle following spontaneous pseudoaneurysm: a case report

BackgroundFollowing the rupture of a coronary artery, a patient’s condition usually deteriorates rapidly due to cardiac tamponade. A pseudoaneurysm due to a coronary artery rupture is rare; however, when a spontaneous coronary artery pseudoaneurysm occurs without tamponade, it creates a fistula in the right ventricle, often requiring surgical repair.Case presentationThis report describes the case of a 68-year-old man who presented with chest discomfort after a 12-day course of antibiotic treatment for bacteremia. Following coronary angiography, echocardiography, and enhanced computed tomography, he was diagnosed with a right coronary artery pseudoaneurysm accompanied with perforation of the right ventricle. Severe adhesions were observed during emergency surgery surrounding the entire heart. The patient presented with risk factors for coronary artery disease, including hypertension and smoking history. His coronary artery was severely calcified due to end-stage renal failure requiring dialysis; thus, a covered stent could not fit inside the arterial lumen. Consequently, coronary artery bypass grafting to the right coronary artery and right ventricle repair were performed. Unfortunately, the patient died postoperatively due to sepsis from intestinal translocation. This rare development was hypothesized to be an incidental result of the combination of severe post-inflammatory adhesions, extensive coronary artery calcification, and rupture of the calcification crevices.ConclusionsIn the case of a severe post-inflammatory response, shock without cardiac tamponade may require further scrutiny by assuming the possibility of inward rupture. For patients in poor condition, two-stage surgical treatment might be considered after stabilization with a covered stent.

CCT‘S CRYSTAL BALL: PREDICTING CARDIOVASCULAR RISK IN AORTIC VALVE STENOSIS PATIENTS UNDERGOING VALVE REPLACEMENT

Abstract Background and Aims Currently, computed tomography cardiac imaging (CTCI) plays a fundamental role in the pre–procedural planning of degenerative–calcific aortic valve stenosis(AS) correction. However, its prognostic role in assessing mortality and major adverse cardiovascular events (MACE) has not been extensively explored. CTCI allows for the evaluation of coronary artery calcification(CAC), mitral annular calcifications (MAC), aortic valve calcifications (CVA), and thoracic aorta calcifications (CAT). The aim of our study was to assess whether the presence and extent of CAC, MAC, CVA, and CAT could influence non–cardiovascular mortality (NCM), cardiovascular mortality (CM), and MACE in patients undergoing valve replacement(VR). Materials and Methods We collected retrospectivelly clinical and instrumental data and reviewed CTCI using a semi–quantitative approach. CACs were classified according to the visual 2022 Coronary Artery Disease–Reporting and Data System. MACs were defined following the Guerrero et al. study, CVAs according to the Win Registry and CATs were assessed in the ascending aorta, aortic arch, and descending aorta according to the Vos classification. Results 244 patients(59% male, mean age 80.1±6.6 years), with 91% undergoing transfemoral VR, were enrolled(2016–2018). CM was significantly higher in patients with hypertension,cerebro/peripheral vascular disease, stage IV–V renal insufficiency and history of atrial fibrillation (p=0.012,p<0.001,p=0.005, p=0.034 and p=0.024, respectively). CM was also more pronounced in patients with STS SCORE≥6.7±5.2 and EuroSCOREII≥ 5.5±5.8(p=0.016 and p=0.037). Extensive CAC(p=0.019), a MAC score>7(p=0.051), moderate and severe AVC (p=0.029 and p=0.053) and TAC>270° in aortic arch(p=0.019) were linked to CM. In multivariate analysis, a high MAC score and the presence of moderate AVC persisted as risk factors for CM. The presence of a MAC score >7(p=0.006) and the extension of descending TAC >1.5 mm (p=0.034) were associated with an increased risk of NCM.The presence of extensive TAC (≥270°) measured in the aortic arch and descending aorta were associated with MACE (p=0.034 and p=0.0504 respectively). Conclusions CTCI emerges as a crucial tool for evaluating prognostic risk in patients undergoing VR for AS. This type of evaluation can assist clinicians in pre–procedural planning and patient management, allowing for better identification of high–risk patients and optimization of therapeutic strategies

Choosing between coronary CT angiography and functional tests in patients with suspected coronary artery disease: mind the (gender) gap

Abstract Introduction There is a need for a simple method to choose between a functional vs. anatomical test as first line approach to patients with suspected coronary artery disease (CAD). While European Guidelines base the decision on pretest probability (PTP) without a clear threshold, American Guidelines rely uniquely on age, with a 65-year-old cut-off for both genders. The aims of this study were: 1) to assess the proportion of patients undergoing coronary CT angiography (CCTA) in whom a functional test could have been more suitable due to extensive coronary artery calcification (CAC) and/or inconclusive CCTA results; 2) compare PTP vs. age to predict the presence of these suboptimal conditions for CCTA. Methods Individuals 40-80 years old were identified in a single center registry of patients with stable chest pain or dyspnea who underwent CCTA. Patients with known CAD, severe valvular disease, or irregular heart rhythms were excluded. PTP of obstructive CAD was calculated using age, sex, and symptom typicality. Patients were considered to have suboptimal conditions for CCTA if extensive CAC was present (defined conservatively as an Agatston score >400) or if one or more segments >2mm were deemed non-evaluable despite CAC score ≤ 400. Results A total of 884 patients (57% women, mean age 62±10 years) were included. Symptoms consisted of chest pain in 705 patients (80%). The median PTP of obstructive CAD was 22% (IQR 14-32). Overall, 162 patients (18%) had suboptimal conditions for CCTA due to CAC score >400 (n=140), or ≥1 non-evaluable segments (n=22). The proportion of patients with suboptimal conditions for CCTA was significantly higher in men than in women (27% vs. 12%, respectively; p<0.001). For both genders, the discriminative power to predict suboptimal CCTA conditions was significantly higher for age than for PTP (c-statistic in men 0.74 vs. 0.64, p<0.001; in women 0.71 vs. 0.62, p=0.012). In every age group, the proportion of patients with suboptimal conditions for CCTA was at least 2 times higher in men than in women, with a 10-15 year gap between genders - Fig. Conclusion Suboptimal conditions for a fully diagnostic CCTA were found in 18% of patients, were more strongly associated with age than with PTP, and were at least 2 times more frequent in men than in women across all age groups. These findings support the use of an age cut-off for anatomical vs. functional testing in men, and the use of CCTA as first line test in most women regardless of age.Proportion of patients suboptimal CCTA

Major Cardiovascular Events after Chemoradiotherapy with or without Durvalumab in Patients with Stage III Non-Small Cell Lung Cancer: Supplementary Analysis

RTOG 0617 showed that cardiac events are relatively common after high-dose thoracic radiotherapy. The aim of this study was to investigate the incidence and risk of major cardiovascular events (MACE) after concurrent chemoradiotherapy (CCRT) with or without durvalumab in patients with stage III non-small cell lung cancer (NSCLC) using the data from a multi-institutional study in Japan. Patients who received CCRT for stage III NSCLC between July 2018 and July 2019 were enrolled in a multi-institutional study in Japan. MACE was defined as follows: symptomatic pericardial effusion, acute coronary syndrome, pericarditis, significant arrhythmia, and heart failure. The cumulative incidence of MACE, accounting for death as a competing risk, was calculated. Pre-existing coronary heart disease (CHD) included coronary artery disease, congestive heart failure, peripheral vascular disease, stroke, and extensive coronary artery calcification. The association between patient/treatment-related factors and MACE was assessed by multivariate analysis. Among 178 patients with a median follow-up period of 42.5 months, 13 patients developed MACEs. The 3-year cumulative incidence of MACE was 6.9% (95% confidence interval [CI], 4.0-11.9%). Univariate analysis showed that female sex and mean heart dose (MHD) were marginally associated (3-year cumulative incidence, male 5.6% vs. female 12.1%; P = 0.12; MHD ≥ 6.3 Gy 4.8% vs. < 6.3 Gy 9.1%; P = 0.13), and pre-existing CHD was significantly associated with an increased risk of MACE (no CHD 4.3% vs. CHD 16.8%; P = 0.026). Consolidation durvalumab was not associated with an increased risk of MACE (no durvalumab 5.2% vs. durvalumab 7.4%; P = 0.89). Multivariate analysis showed that pre-existing CHD was significantly associated with MACE (hazard ratio, 4.22; 95% CI, 1.30-13.7; P = 0.016). The incidence of MACE based on the real-world data in Japan was lower than previously reported. Pre-existing CHD was associated with an increased risk of MACE after CCRT in patients with stage III NSCLC, whereas the administration of consolidation durvalumab was not associated with an increased risk of MACE.

Choosing between coronary CT angiography and functional tests in patients with suspected coronary artery disease - mind the (gender) gap

Abstract Funding Acknowledgements Type of funding sources: None. Introduction There is a need for a simple method to choose between a functional vs. anatomical test as first line approach to patients with suspected coronary artery disease (CAD). While European Guidelines base the decision on pretest probability (PTP) without a clear threshold, American Guidelines rely uniquely on age, with a 65-year-old cut-off for both genders. The aims of this study were: 1) to assess the proportion of patients undergoing coronary CT angiography (CCTA) in whom a functional test could have been more suitable due to extensive coronary artery calcification (CAC) and/or inconclusive CCTA results; 2) compare PTP vs. age to predict the presence of these suboptimal conditions for CCTA. Methods Individuals 40–80 years old were identified in a single center registry of patients with stable chest pain or dyspnea who underwent CCTA. Patients with known CAD, severe valvular disease, or irregular heart rhythms were excluded. PTP of obstructive CAD was calculated using age, sex, and symptom typicality. Patients were considered to have suboptimal conditions for CCTA if extensive CAC was present (defined conservatively as an Agatston score &amp;gt;400) or if one or more segments &amp;gt;2mm were deemed non-evaluable despite CAC score ≤ 400. Results A total of 884 patients (57% women, mean age 62±10 years) were included. Symptoms consisted of chest pain in 705 patients (80%). The median PTP of obstructive CAD was 22% (IQR 14–32). Overall, 162 patients (18%) had suboptimal conditions for CCTA due to CAC score &amp;gt;400 (n=140), or ≥1 non-evaluable segments (n=22). The proportion of patients with suboptimal conditions for CCTA was significantly higher in men than in women (27% vs. 12%, respectively; p&amp;lt;0.001). For both genders, the discriminative power to predict suboptimal CCTA conditions was significantly higher for age than for PTP (c-statistic in men 0.74 vs. 0.64, p&amp;lt;0.001; in women 0.71 vs. 0.62, p = 0.012). In every age group, the proportion of patients with suboptimal conditions for CCTA was at least 2 times higher in men than in women, with a 10–15 year gap between genders - Figure 1. Conclusion Suboptimal conditions for a fully diagnostic CCTA were found in 18% of patients, were more strongly associated with age than with PTP, and were at least 2 times more frequent in men than in women across all age groups. These findings support the use of an age cut-off for anatomical vs. functional testing in men, and the use of CCTA as first line test in most women regardless of age.

Coronary CT and timing of invasive coronary angiography in patients ≥75 years old with non-ST segment elevation acute coronary syndromes

BackgroundThe ability of coronary CT angiography (cCTA) to rule out significant coronary artery disease (CAD) in older patients with non-ST segment elevation acute coronary syndromes (NSTEACS) is unclear since valid...

Distributions and burden of coronary calcium in asymptomatic Saudi patients referred to computed tomography.

BackgroundUnlike Western and Asian populations, the prevalence and severity of coronary artery calcification (CAC) have not been adequately examined in Saudi Arabia and other nearby Arab Gulf countries.ObjectivesTo estimate the age and gender specific percentiles of coronary calcium score (CCS) and to study the severity of CAC in relation to patient risk in a large sample of asymptomatic Saudi patients.MethodsRetrospective cross-sectional study was conducted between July 2007 and December 2017 at a large Cardiac Centre in Riyadh, Saudi Arabia. The target was adult patients without pre-existing CAD referred to (64 multidetector spiral) computed tomography for standard indications.ResultsA total 2863 patients were included in the current analysis. The 90th percentile of CCS was 95.0 in males compared with 53.2 in females and was 823.95 in patients aged ≥ 75 years compared with zero in patients < 40 years. Extensive CAC (CCS > 400) were 3.1% in males compared with 1.6% in females and 14.0% in patients aged ≥ 75 years compared with 0.0% in patients < 40 years. CCS was steadily higher with increasing European systematic coronary risk evaluation; 3.1 ± 22.5 in mild risk, 37.1 ± 201.9 in moderate risk, 116.1 ± 256.1 in high risk, and 131.0 ± 222.0 in very high risk.ConclusionsAs expected, the findings confirm the higher burden of CAC in males, older age, and higher CAD risk. The burden of CAC in current patients is much lower than reported in US and other Western patients. Local cardiologist should consider using local rather than US percentiles of CCS.

Development of the BioHybrid Assay: Combining Primary Human Vascular Smooth Muscle Cells and Blood to Measure Vascular Calcification Propensity.

Background: Vascular calcification is an active process that increases cardiovascular disease (CVD) risk. There is still no consensus on an appropriate biomarker for vascular calcification. We reasoned that the biomarker for vascular calcification is the collection of all blood components that can be sensed and integrated into a calcification response by human vascular smooth muscle cells (hVSMCs). Methods: We developed a new cell-based high-content assay, the BioHybrid assay, to measure in vitro calcification. The BioHybrid assay was compared with the o-Cresolphthalein assay and the T50 assay. Serum and plasma were derived from different cohort studies including chronic kidney disease (CKD) stages III, IV, V and VD (on dialysis), pseudoxanthoma elasticum (PXE) and other cardiovascular diseases including serum from participants with mild and extensive coronary artery calcification (CAC). hVSMCs were exposed to serum and plasma samples, and in vitro calcification was measured using AlexaFluor®-546 tagged fetuin-A as calcification sensor. Results: The BioHybrid assay measured the kinetics of calcification in contrast to the endpoint o-Cresolphthalein assay. The BioHybrid assay was more sensitive to pick up differences in calcification propensity than the T50 assay as determined by measuring control as well as pre- and post-dialysis serum samples of CKD patients. The BioHybrid response increased with CKD severity. Further, the BioHybrid assay discriminated between calcification propensity of individuals with a high CAC index and individuals with a low CAC index. Patients with PXE had an increased calcification response in the BioHybrid assay as compared to both spouse and control plasma samples. Finally, vitamin K1 supplementation showed lower in vitro calcification, reflecting changes in delta Agatston scores. Lower progression within the BioHybrid and on Agatston scores was accompanied by lower dephosphorylated-uncarboxylated matrix Gla protein levels. Conclusion: The BioHybrid assay is a novel approach to determine the vascular calcification propensity of an individual and thus may add to personalised risk assessment for CVD.

Optical coherence tomography versus intravascular ultrasound to evaluate stent implantation in patients with calcific coronary artery disease

AimsStent underexpansion and malapposition are associated with adverse outcomes following percutaneous coronary intervention, but detection and treatment can be challenging in the presence of extensive coronary artery calcification. Frequency domain...

Progression of coronary artery calcification by cardiac computed tomography.

The presence and extent of coronary artery calcification (CAC) is established in primary prevention since the CAC score is the single best predictor of future cardiovascular events. While CAC progresses with increasing age, individual CAC progression can be estimated based on the subject's age, gender, and CAC percentile at first examination. To date, several algorithms and methods for the definition of CAC progression are available in the literature. Increased CAC progression is associated with traditional cardiovascular risk factors including hypertension, diabetes, and smoking status. Also, lipid-lowering therapy may influence the progression of CAC. Epicardial adipose tissue is a further cardiovascular risk marker that may lead to intensified CAC progression if its volume increases. In terms of clinical implications, initial data suggest that extensive CAC progression is linked to worse outcome; however, further studies are needed to establish this relationship and to define appropriate time intervals between repetitive examinations. This review article gives an overview of the existing literature with an emphasis on various definitions of CAC progression, predictors of increased CAC progression, as well as clinical implications.

Low serum testosterone level was associated with extensive coronary artery calcification in elderly male patients with stable coronary artery disease

Coronary artery calcification (CAC) is a pandemic condition in elderly patients with coronary artery disease (CAD) and associated with a worse prognosis. Although available data have shown an association between testosterone levels in men and CAD, the association between testosterone and CAC in elderly male patients with CAD remains unknown. A total of 211 consecutive male patients (age ≥ 65 years) who underwent first multidetector computed tomography and following angiography were enrolled from our institution between March 2009 and September 2014. CAD was angiographically documented as significant stenoses (reduction ≥ 50% of the lumen diameter) on any major coronary vessel. The standard Agatston calcium score was calculated. The relationship of serum testosterone level with the CAC score measured by multidetector computed tomography in elderly male patients with stable CAD was evaluated. For data analyses, the CAC score was divided into four categories: ≤ 10, 11-99, 100-399, and ≥ 400, corresponding to minimal, moderate, increased, and extensive calcification. Patients with higher CAC scores had significantly lower testosterone levels than patients with lower CAC scores (P = 0.048). In logistic regression analysis, testosterone level remained an independent predictor of extensive CAC (odds ratio 0.997, 95% confidence interval 0.994-0.999, P = 0.043). Our findings indicate an inverse association between testosterone level and the susceptibility to extensive CAC in elderly men with stable CAD.

Coronary calcium in patients with and without diabetes: first manifestation of acute or chronic coronary events is characterized by different calcification patterns

BackgroundCoronary artery calcification (CAC) is closely related to coronary atherosclerosis. However, less is known about the clinical significance of extensive CAC (ECAC) in regard to types of first coronary events (acute vs. chronic). Diabetes mellitus (DM) represents a strong risk factor for CAD although its association with CAC is controversial. Aiming to elucidate these controversies we investigated the long-term outcome of coronary artery disease (CAD) in relation to degree of CAC in patients with and without DM from our annual cheek-up outpatient clinic.MethodsCoronary artery computed tomography (CT) was performed in 667 patients who were yearly evaluated during a mean follow-up period of 6.3 ±3.4 year. The following 4 CAC categories were established: calcium absence; total calcium score (TCS): 1–100 AU; TCS: 101–600 AU and ECAC: TCS above 600 AU. Acute event was defined as first acute myocardial infarction (MI) or a new unstable angina. First chronic event was defined as a positive stress test with a consequent elective percutaneous coronary intervention or coronary artery bypass grafting.Results628 subjects (94%) were free from any cardiac events, 39 (6%) experienced first cardiac event: 18 of them suffered acute and 21 chronic events. There were 67 patients with and 600 patients without DM: 78% of patients with DM presented CAC vs. 50% of patients without DM (p < 0.001).The mean TCS was 17 times higher in the chronic than in the acute events group: 914 vs. 55 AU, p < 0.001. In 95% of the patients with chronic events more than one calcified vessel was found, compared to 67% of the patients with acute events and only 30% of those without events (p < 0.001). Incidence of CAD events (all types pooled together) rose consequently from 2% in subjects without CAC to 34% in subjects with ECAC (p < 0.001). However, among the 32 subjects with ECAC, 11 (34%) developed chronic event while none of them had acute event. In contrast, none of subjects with TCS =0 or TCS 1–100 AU presented with chronic events. Subjects with TCS 101–600 AU presented 10 (9%) chronic and 5 (4.5%) acute events (p < 0.001).ConclusionsAsymptomatic subjects with ECAC are not firstly manifested as acute coronary events but presented a high level of chronic CAD-related events during the 6.3 ±3.4 year follow-up. In contrast, first acute CAD-related events occurred mostly in subjects with mild and moderate CAC score.

Accuracy and Predictive Value of Coronary Computed Tomography Angiography for the Detection of Obstructive Coronary Heart Disease in Patients With an Agatston Calcium Score Above 400

We assessed the accuracy of coronary computed tomography angiography (CTA) in patients with an Agatston calcium score (ACS) of greater than 400 by comparing it with invasive coronary angiography (ICA), and we evaluated the predictive value of CTA for obstructive coronary heart disease (CHD) compared with traditional clinical risk assessment. A total of 253 patients who had an ACS of greater than 400 were enrolled in this study. The degree of coronary stenosis was visually and quantitatively estimated by postprocessing imaging using 15-segment coronary models. All patients underwent ICA after a mean (SD) of 34 (24) days, and the degree of coronary stenosis was compared with the results of CTA. Computed tomography angiography accurately diagnosed significant stenosis in 204 (99.0%) of 206 patients and in 649 (83.5%) of 777 segments. When the patients were considered based on their ACS (group A, 400 < ACS ≤ 1000, vs group B, ACS > 1000), group B showed lower specificity (9.1% vs 41.7%) and poorer agreement (k = 0.149 vs 0.495) than for ICA. By segment-based analysis, the agreement between CTA and ICA was good (k = 0.729), and there was no significant difference between groups A (k = 0.728) and B (k = 0.727). Computed tomography angiography was the most powerful predictor (odds ratio = 52.645, P < 0.001), whereas the 10-year CHD risk and pretest probability were not significantly correlated with obstructive CHD. Despite good overall diagnostic accuracy, coronary CTA in this group of patients was limited by low specificity. However, CTA was a better predictor of obstructive CHD compared with clinical predictors, and it avoided unnecessary ICA, even in patients with extensive coronary artery calcification.

Differences in Clinical Profile of Individuals With Severe and Markedly Elevated Coronary Artery Calcification Detected by Electron Beam Computed Tomography

Although several studies have demonstrated the association between coronary artery calcification (CAC) and coronary artery disease events, the underlying mechanism has not been fully elucidated. Furthermore, extensive CAC still remains a poorly understood phenomenon. The objective of this study is to determine the clinical characteristics and differences between 831 asymptomatic individuals with very high CAC scores (CACS ≥ 1000) and 497 asymptomatic individuals with CAC scores of 400 to 999. Individuals with CACS ≥ 1000 were more likely to have hypertension ([HTN]; P = .0004), hypercholesterolemia (P = .0001), diabetes mellitus ([DM] P = .005), and high body mass index ([BMI]; P = .03) compared with individuals with CACS = 400-999. On multivariable analysis, age (P < .0001) and BMI (P = .01) were found to be significant risk factors for the presence of very high CAC. While for males, age (P < .0001), hypercholesterolemia (P = .001), DM (P = .002), and obesity (P = .003) were independent risk factors; in females only HTN (P = .04) was independent risk factor.

Familial Defective Apolipoprotein B-100 and Increased Low-Density Lipoprotein Cholesterol and Coronary Artery Calcification in the Old Order Amish

Elevated low-density lipoprotein cholesterol (LDL-C) levels are a major cardiovascular disease risk factor. Genetic factors are an important determinant of LDL-C levels. To identify single nucleotide polymorphisms associated with LDL-C and subclinical coronary atherosclerosis, we performed a genome-wide association study of LDL-C in 841 asymptomatic Amish individuals aged 20 to 80 years, with replication in a second sample of 663 Amish individuals. We also performed scanning for coronary artery calcification (CAC) in 1018 of these individuals. From the initial genome-wide association study, a cluster of single nucleotide polymorphisms in the region of the apolipoprotein B-100 gene (APOB) was strongly associated with LDL-C levels (P < 10(-68)). Additional genotyping revealed the presence of R3500Q, the mutation responsible for familial defective apolipoprotein B-100, which was also strongly associated with LDL-C in the replication sample (P < 10(-36)). The R3500Q carrier frequency, previously reported to be 0.1% to 0.4% in white European individuals, was 12% in the combined sample of 1504 Amish participants, consistent with a founder effect. The mutation was also strongly associated with CAC in both samples (P < 10(-6) in both) and accounted for 26% and 7% of the variation in LDL-C levels and CAC, respectively. Compared with noncarriers, R3500Q carriers on average had LDL-C levels 58 mg/dL higher, a 4.41-fold higher odds (95% confidence interval, 2.69-7.21) of having detectable CAC, and a 9.28-fold higher odds (2.93-29.35) of having extensive CAC (CAC score ≥400). The R3500Q mutation in APOB is a major determinant of LDL-C levels and CAC in the Amish.

Study design and subject baseline characteristics in the ADVANCE Study: effects of cinacalcet on vascular calcification in haemodialysis patients

The ADVANCE (A Randomized Study to Evaluate the Effects of Cinacalcet plus Low-Dose Vitamin D on Vascular Calcification in Subjects with Chronic Kidney Disease Receiving Haemodialysis) Study objective is to assess the effect of cinacalcet plus low-dose active vitamin D versus flexible dosing of active vitamin D on progression of coronary artery calcification (CAC) in haemodialysis patients. We report the ADVANCE Study design and baseline subject characteristics. ADVANCE is a multinational, multicentre, randomized, open-label study. Adult haemodialysis patients with moderate to severe secondary hyperparathyroidism (intact parathyroid hormone [iPTH] >300 pg/mL or bio-intact PTH >160 pg/mL) and baseline CAC score >or=30 were stratified by CAC score (>or=30-399, >or=400-999, >or=1000) and randomized in a 1:1 ratio to cinacalcet (30-180 mg/day) plus low-dose active vitamin D (cinacalcet group) or flexible dosing of active vitamin D alone (control). The study had three phases: screening, 20-week dose titration and 32-week follow-up. CAC scores obtained by cardiac computed tomography were determined at screening and weeks 28 and 52. The primary end point was percentage change in CAC score from baseline to Week 52. Subjects (n = 360) were randomized to cinacalcet or control. Mean age was 61.5 years, 43% were women, and median dialysis vintage was 36.7 months (range, 2.7-351.5 months). The baseline geometric mean CAC score by the Agatston method was 548.7 (95% confidence interval, 480.5-626.6). Baseline CAC score was independently associated with age, sex, dialysis vintage, diabetes and iPTH. Subjects also had extensive aortic and valvular calcification at baseline. Subjects enrolled in ADVANCE have extensive CAC at baseline. The ADVANCE Study should help determine whether cinacalcet attenuates progression of vascular calcification.

Review: Vascular calcification in chronic kidney disease: the tip of the chalk-berg

The most common cause of death in dialysis patients is cardiovascular disease. As yet, no convincing evidence of useful therapeutic interventions exists. This huge increase in cardiovascular mortality may be due in part to the presence of excess vascular calcification, particularly in the form of extensive coronary artery calcification, which can be observed even in very young dialysis patients. The reasons for this very widespread problem are in fact complicated and numerous, with an interaction between patient characteristics, external changes, such as mineral and bone metabolism parameters, and other less well characterised influences. The use of sevelamer rather than significant doses of calcium as the primary oral phosphate binder seems to be associated with a reduction in the development and progression of vascular calcification, at least in some studies. Br J Diabetes Vasc Dis, 2008; 8: 264—269

Oxidative stress, advanced glycation end product, and coronary artery calcification in hemodialysis patients

Coronary artery calcification is an index of the severity of atherosclerotic vascular disease, and may predict future adverse cardiovascular events in uremic patients undergoing hemodialysis (HD). HD patients are exposed to oxidative stress, and show high plasma levels of advanced glycation end products (AGEs). The association between oxidative stress, AGEs, established cardiovascular risk factors, and coronary artery calcification score (CACS) was studied in 225 HD patients (123 male, 102 female patients). CACS was measured by using multi-detector row computed tomography. Age, systolic blood pressure, calcium, calcium x phosphate, malondialdehyde, lipid peroxides, and pentosidine were significantly and positively correlated with CACS. Duration on HD tended to be positively correlated with CACS. From the independent variables included in the forward stepwise multiple linear regression analysis, only age, systolic blood pressure, lipid peroxides, calcium, and pentosidine were independently associated with CACS. The odds ratios for past history of coronary artery disease and the presence of diabetes mellitus for high CACS (> or =100) were 6.25 (95% confidence interval; 1.83-21.4) and 2.03 (95% confidence interval; 1.02-4.05), respectively. The plasma pentosidine was significantly and positively correlated with indoxyl sulfate. In conclusion, in addition to such traditional cardiovascular risk factors as past history, diabetes mellitus, aging, systolic blood pressure and calcium overload, oxidative stress (lipid peroxides), and AGE (pentosidine) are associated with extensive coronary artery calcification in HD patients. Lipid peroxidation and glycoxidation may be involved in the pathogenesis of coronary artery calcification.

Vascular calcification: A stiff challenge for the nephrologist: Does preventing bone disease cause arterial disease

There has been an explosion of interest in vascular calcification in the last 5 years. Four key "germinal" findings have fallen onto very fertile soil. First, on the background of an increasing cardiovascular disease burden it has been found that at least cross-sectionally, and in a limited fashion prospectively, achieved dialysis plasma phosphate levels are linked to all-cause and cardiovascular mortality. Second, there are increasing reports of calcific uremic arteriolopathy in Australia and the United States. Third, we know know that the mechanical properties of the carotid artery, and the aorta, have a profound influence on survival for dialysis patients. Vascular calcification itself (as assessed by x-ray films and ultrasound) has been linked to aortic stiffness. Fourth, increasing numbers of studies are showing extremely extensive coronary artery calcification (CAC) in dialysis patients, even at a young age. From these apparently unlinked observations the following assertion has been posited-that in the widespread (over) use of calcium-containing oral phosphate binders (OPB) to prevent uremic osteodystrophy in our dialysis population we have unwittingly accelerated widespread uremic vasculopathy and thereby contributed to premature cardiovascular mortality. It is the purpose of this article to discuss vascular calcification (and particularly CAC) in dialysis patients as we understand it today. We will review the published series, with special reference to the Sevelamer Treat to Goal trial and also discuss the new Kidney Disease Outcome Quality Initiative (K-DOQI) guidelines on the use of phosphate binders in chronic kidney disease.

Clinical significance of coronary calcification.

Coronary artery calcification (CAC) was assessed by cinefluoroscopy and its extent was scored (CAC score) in 2,163 consecutive patients undergoing coronary angiography, based on the angiographic and clinical data, the patients were categorized into 8 types of coronary artery disease (CAD). The CAC score was lowest in angiographically normal subjects (0.12+/-0.60) and highest in patients with silent myocardial ischemia (14.31+/-8.61). Risk factors for CAC were advanced age, male sex (at age <80 years), hypertension, diabetes mellitus, and a high grade of organic coronary stenosis. The CAC score in patients with acute coronary syndrome (unstable angina+acute myocardial infarction; 5.48+/-7.42) was significantly lower than that in those with chronic CAD (silent ischemia+stable angina; 9.72+/-8.73; p<0.0001), but was still higher than that in normal subjects or those with vasospastic angina (0.92+/-2.88; p<0.0001). The results indicate that CAC is a manifestation of coronary atherosclerosis and its appearance depends on the pathological type of ischemic heart disease. Fixed stenosis with a slow and chronic process tends to be associated with CAC. The clinical implication of extensive CAC in acute coronary syndrome compared with normal subjects should be further investigated.