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1.  Quantification of Lower Leg Arterial Calcifications by High-Resolution Peripheral Quantitative Computed Tomography 
Bone  2013;58:42-47.
Vascular calcifications and bone health seem to be etiologically linked via common risk factors such as aging and subclinical chronic inflammation. Epidemiologic studies have shown significant associations between low bone mineral density (BMD), fragility fractures and calcifications of the coronary arteries and the abdominal aorta. In the last decade, high-resolution peripheral quantitative computed tomography (HR-pQCT) has emerged as in-vivo research tool for the assessment of peripheral bone geometry, density, and microarchitecture. Although vascular calcifications are frequently observed as incidental findings in HR-pQCT scans, they have not yet been incorporated into quantitative HR-pQCT analyses. We developed a semi-automated algorithm to quantify lower leg arterial calcifications (LLAC), captured by HR-pQCT. The objective of our study was to determine validity and reliability of the LLAC measure.
HR-pQCT scans were downscaled to a voxel size of 250 µm. After subtraction of bone volumes from the scans, LLAC were detected and contoured by a semi-automated, dual-threshold seed-point segmentation. LLAC mass (in mg hydroxyapatite; HA) was calculated as the product of voxel-based calcification volume (mm3) and mean calcification density (mgHA/cm3)/1000. To determine validity, we compared LLAC to coronary artery calcifications (CAC), as quantified by multi-detector computed tomography (MDCT) and Agatston scoring in forty-six patients on chronic hemodialysis. Moreover, we investigated associations of LLAC with age, time on dialysis, type-2 diabetes mellitus, history of stroke, and myocardial infarction. In a second step, we determined intra- and inter-reader reliability of the LLAC measure.
In the validity study, LLAC were present (>0 mgHA) in 76% of patients, 78% of patients had CAC (>0 mgHA). Median LLAC was 6.65 (0.08 – 24.40) mgHA and median CAC as expressed by Agatston score was 266.3 (15.88 – 1877.28). We found a significant positive correlation between LLAC and CAC (rho=0.6; p<0.01). Dialysis patients with type-2 diabetes mellitus (DM; 35%) and history of stroke (13%) had higher median LLAC than patients without those conditions (DM 20.0 fold greater, p=0.006; Stroke 5.1 fold greater, p=0.047;). LLAC was positively correlated with time on dialysis (rho=0.337, p=0.029), there was a trend towards a positive association of LLAC and age (rho=0.289, p=0.053). The reliability study yielded excellent intra- and inter-reader agreement of the LLAC measure (intra-reader ICC=0.999, 95% CI=0.998–1.000; inter-reader ICC=0.998, 95% CI=0.994–0.999).
Our study indicates that the LLAC measure has good validity and excellent reliability. The use of HR-pQCT for the simultaneous evaluation of arterial calcifications, peripheral bone geometry, bone density, and bone microarchitecture should facilitate future research on osteo-vascular interactions and potential associations with cardiovascular events.
doi:10.1016/j.bone.2013.08.006
PMCID: PMC4042679  PMID: 23954758
HR-pQCT; Lower Leg Arterial Calcifications; Quantification; Agatston-Score
2.  Risk factors of one year increment of coronary calcifications and survival in hemodialysis patients 
BMC Nephrology  2010;11:10.
Background
Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality. Several studies have been published with similar results. Most of them were mainly cross-sectional and some of the prospective protocols were aimed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium, phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents. The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival.
Methods
81 patients on hemodialysis were studied, with a wide age range and HD vintage. Several classic parameters and some less classic risk factors were studied like fetuin-A, CRP, 25-OHD and leptin. Calcifications, as Agatston scores, were evaluated with Multislice CT basally and after 12-18 months.
Results
Coronary artery calcifications were observed in 71 of 81 patients. Non parametric correlations between Agatston scores and Age, HD Age, PTH and CRP were significant. Delta increments of Agatston scores correlated also with serum calcium, CaxP, Fetuin-A, triglycerides and serum albumin. Logistic regression analysis showed Age, PTH and serum calcium as important predictors of Delta Agatston scores. LN transformation of the not normally distributed variables restricted the significant correlations to Age, BMI and CRP. Considering the Delta Agatston scores as dependent, significant predictors were Age, PTH and HDL. A strong association was found between basal calcification scores and Delta increment at one year. By logistic analysis, the one year increments in Agatston scores were found to be predictors of mortality. Diabetic and hypertensive patients have significantly higher Delta scores.
Conclusions
Progression of calcification is of common occurrence, with special regard to elevated basal scores, and is predictive of survival. Higher predictive value of survival is linked to the one year increment of calcification scores. Some classic and non classic risk factors play an important role in progression. Some of them could be controlled with appropriate management with possible improvement of mortality.
doi:10.1186/1471-2369-11-10
PMCID: PMC2903573  PMID: 20565936
3.  Regression of vascular calcification following an acute episode of calciphylaxis: a case report 
Introduction
In clinical situations, vascular calcification tends to progress and is difficult to completely arrest or reverse. Calciphylaxis, a severe complication of end-stage renal disease, is a specific form of vascular calcification. Control studies have provided evidence that monotherapy with sodium thiosulfate or cinacalcet delays the progression of vascular calcification. Successful treatment of calciphylaxis with sodium thiosulfate or cinacalcet has also been reported. We report a case demonstrating the regression of vascular calcification following an acute episode of necrotic skin lesions suspected to be calciphylaxis. During the successful multimodal treatment, sodium thiosulfate and cinacalcet were sequentially administered in addition to surgical debridement and percutaneous transluminal angioplasty.
Case presentation
We describe the case of a 71-year-old Asian woman on hemodialysis who presented with suspected calciphylaxis lesions in her lower left leg. Plain radiographs revealed diffuse calcified vessel changes in her lower extremities. During the initial wound treatment with a course of intravenous sodium thiosulfate, our patient’s predialysis serum levels of total calcium markedly increased, yielding no calciphylaxis improvement. The necrotic wounds began healing only after surgical debridement. A percutaneous transluminal angioplasty was performed to dilate a 70% stenosis in her left posterior tibial artery. Our patient was then treated with cinacalcet, resulting in improved control of her calcium, phosphate and parathyroid hormone serum levels. The lesions completely healed after six months of multimodal treatment. Repeated plain radiographs in the following two years revealed gradual vascular calcification regression in her lower extremities.
Conclusion
In addition to the favorable outcome of our patient’s wounds, radiology was used to document the regression of calcification in the large and small arteries of her lower limbs. However, it is difficult to determine the precise mechanism of the multimodal treatment that caused the vascular calcification regression and wound healing. The clinical course suggested that the surgical treatment and percutaneous transluminal angioplasty substantially contributed to healing her wounds. Cinacalcet and sodium thiosulfate may have played distinct roles in the regression of her vascular calcification. A well-controlled study or large case series are required to assess the additive effects of these agents when treating vascular calcification.
doi:10.1186/1752-1947-8-52
PMCID: PMC3930056  PMID: 24524553
Calciphylaxis; Cinacalcet; Sodium thiosulfate; Vascular calcification
4.  Phosphate binders: Sevelamer in the prevention and treatment of hyperphosphataemia in chronic renal failure 
Hippokratia  2011;15(Suppl 1):22-26.
In chronic kidney disease patients, bone and mineral abnormalities have a major impact on morbidity and mortality. Hyperphosphatemia has been associated with increased mortality and with the development of cardiovascular calcification, an independent predictor of mortality. Sevelamer, or more precisely 'sevelamer hydrochloride', is a weakly basic anion-exchange resin in the chloride form that was introduced in 1997 for the treatment of the hyperphosphataemia of patients with end-stage renal failure. Sevelamer sequesters phosphate within the gastrointestinal tract, so prevents its absorption and enhances its faecal excretion. Over the succeeding years, large numbers of patients have been treated with sevelamer, and it has fulfilled expectations in helping to control the hyperphosphataemia of end-stage renal failure. Additionally treatment with sevelamer was accompanied with lower incidence of hypercalcemia, decreased incidence of low PTH levels, a 15-31% decrease of LDL-cholesterol both in dialysis and predialysis patients, decreased C-reactive protein, amelioration of hyperuricemia and low fetuin A, decrease of uremic toxins, suggesting an overall anti-inflammatory effect. In incident dialysis patients, treatment with sevelamer has been associated with better survival, while in prevalent patients a clear benefit could only be demonstrated in older patients and in patients treated for more than 2 years. In dialysis patients, the treatment of hyperphospathemia with calcium based compounds, when compared with sevelamer, is associated with more frequent episodes of hypercalcemia, suppression of intact PTH and with progression of coronary calcifications. In the presence of adynamic bone disease, calcium load has a significantly higher impact on aortic calcifications and stiffening. Sevelamer treatment resulted in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate, but bone formation rate increased and trabecular architecture improved only with sevelamer. In conclusion, the treatment of hyperphosphatemia with sevelamer hydrochloride, a noncalcium and non-metal containing phosphate binder, is associated with a beneficial effect on vascular calcification progression, bone disease and most likely with a survival benefit in some hemodialysis patients populations. Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients. Sevelamer carbonate formulated as a powder for oral suspension presents a novel, patient- friendly alternative to tablet phosphate binders. Safety and efficacy of sevelamer carbonate powder compared with sevelamer hydrochloride tablets in CKD patients are equivalent, with Sevelamer carbonate having fewer side effects from gastrointestinal tract.
PMCID: PMC3139674  PMID: 21897754
sevelamer hydrochloride; sevelamer carbonate; hyperphosphatemia; vascular calcification
5.  Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism 
Background
Secondary hyperparathyroidism (SHPT) is one of the common complications in dialysis patients, and is associated with increased risk of vascular calcification. The effects of cinacalcet hydrochloride treatment on bone and mineral metabolism have been previously reported, but the benefit of cinacalcet on vascular calcification remains uncertain. The aim of this study was to evaluate the impact of cinacalcet on abdominal aortic calcification in dialysis patients.
Subjects and methods
Patients were on maintenance hemodialysis with insufficiently controlled SHPT (intact parathyroid hormone [PTH] >180 pg/mL) by conventional therapies. All subjects were initially administered 25 mg cinacalcet daily, with concomitant use of calcitriol analogs. Abdominal aortic calcification was annually evaluated by calculating aortic calcification area index (ACAI) using multidetector computed tomography (MDCT), from 12 months before to 36 months after the initiation of cinacalcet therapy.
Results
Twenty-three patients were analyzed in this study. The mean age was 59.0±8.7 years, 34.8% were women, and the mean dialysis duration was 163.0±76.0 months. After administration of cinacalcet, serum levels of intact PTH, phosphorus, and calcium significantly decreased, and mean Ca × P values significantly decreased from 67.4±7.9 mg2/dL2 to 52±7.7 mg2/dL2. Although the ACAI value did not decrease during the observation period, the increase in ACAI between 24 months and 36 months after cinacalcet administration was significantly suppressed.
Conclusion
Long-term administration of cinacalcet was associated with reduced progression of abdominal aortic calcification, and achieving appropriate calcium and phosphorus levels may reduce the rates of cardiovascular events and mortality in patients on hemodialysis.
doi:10.2147/IJNRD.S54731
PMCID: PMC3872220  PMID: 24379691
abdominal aortic calcification; cinacalcet hydrochloride; hemodialysis
6.  Progressive coronary calcification despite intensive lipid‐lowering treatment: a randomised controlled trial 
Heart  2006;92(9):1207-1212.
Objectives
To evaluate the effect of intensive lipid‐lowering treatment on coronary artery calcification in a substudy of a trial recruiting patients with calcific aortic stenosis.
Methods
In a double blind randomised controlled trial, 102 patients with calcific aortic stenosis and coronary artery calcification were randomly assigned by the minimisation technique to atorvastatin 80 mg daily or matched placebo. Coronary artery calcification was assessed annually by helical computed tomography.
Results
48 patients were randomly assigned to atorvastatin and 54 to placebo with a median follow up of 24 months (interquartile range 24–30). Baseline characteristics and coronary artery calcium scores were similar in both groups. Atorvastatin reduced serum low density lipoprotein cholesterol (−53%, p < 0.001) and C reactive protein (−49%, p < 0.001) concentrations whereas there was no change with placebo (−7% and 17%, p > 0.95 for both). The rate of change in coronary artery calcification was 26%/year (0.234 (SE 0.037) log arbitrary units (AU)/year; n  =  39) in the atorvastatin group and 18%/year (0.167 (SE 0.034) log AU/year; n  =  49) in the placebo group, with a geometric mean difference of 7%/year (95% confidence interval −3% to 18%, p  =  0.18). Serum low density lipoprotein concentrations were not correlated with the rate of progression of coronary calcification (r  =  0.05, p  =  0.62).
Conclusion
In contrast to previous observational studies, this randomised controlled trial has shown that, despite reducing systemic inflammation and halving serum low density lipoprotein cholesterol concentrations, statin treatment does not have a major effect on the rate of progression of coronary artery calcification.
doi:10.1136/hrt.2005.080929
PMCID: PMC1861190  PMID: 16449511
7.  Vascular calcification in chronic kidney disease: Pathogenesis and clinical implication 
World Journal of Nephrology  2012;1(2):43-53.
Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Vascular calcification (VC) is one of the independent risk factors associated with cardiovascular disease and cardiovascular mortality in both the general population and CKD patients. Earlier evidence revealed substantially higher prevalence of VC in young adults on chronic hemodialysis compared to the general population in the same age range, indicating the influence of CKD-related risk factors on the development of VC. Pathogenesis of VC involves an active, highly organized cellular transformation of vascular smooth muscle cells to bone forming cells evidenced by the presence of bone matrix proteins in the calcified arterial wall. VC occurs in both the intima and the media of arterial wall with medial calcification being more prevalent in CKD. In addition to traditional cardiovascular risks, risk factors specific to CKD such as phosphate retention, excess of calcium, history of dialysis, active vitamin D therapy in high doses and deficiency of calcification inhibitors play important roles in promoting the development of VC. Non-contrast multi-slice computed tomography has often been used to detect coronary artery calcification. Simple plain radiographs of the lateral lumbar spine and pelvis can also detect VC in the abdominal aorta and femoral and iliac arteries. Currently, there is no specific therapy to reverse VC. Reduction of calcium load, lowering phosphate retention using non-calcium containing phosphate binders, and moderate doses of active vitamin D may attenuate progression. Parenteral sodium thiosulfate has also been shown to delay VC progression.
doi:10.5527/wjn.v1.i2.43
PMCID: PMC3782198  PMID: 24175241
Coronary calcification; Cardiovascular; Vascular smooth muscle cells; Osteoblast; Bone; Phosphate; Vitamin D
8.  Vascular calcifications, vertebral fractures and mortality in haemodialysis patients 
Background. Vascular calcifications and the bone fractures caused by abnormal bone fragility, also called osteoporotic fractures, are frequent complications associated with chronic kidney diseases (CKD). The aim of this study was to investigate the association between vascular calcifications, osteoporotic bone fractures and survival in haemodialysis (HD) patients.
Methods. A total of 193 HD patients were followed up to 2 years. Vascular calcifications and osteoporotic vertebral fractures (quoted just as vertebral fractures in the text) were assessed by thoracic, lumbar spine, pelvic and hand X-rays and graded according to their severity. Clinical, biochemical and therapeutic data gathered during the total time spent on HD were collected.
Results. The prevalence of aortic calcifications was higher in HD patients than in a random-based general population (79% versus 37.5%, P < 0.001). Total time on any renal replacement therapy (RRT) and diabetes were positively associated with a higher prevalence of vascular calcifications. In addition to these factors, time on HD was also positively associated with the severity of vascular calcifications, and higher haemoglobin levels were associated with a lower prevalence of severe vascular calcifications in large and medium calibre arteries. The prevalence of vertebral fractures in HD patients was similar to that of the general population (26.5% versus 24.1%). Age and time on HD showed a positive and statistically significant association with the prevalence of vertebral fractures. Vascular calcifications in the medium calibre arteries were associated with a higher rate of prevalent vertebral fractures. In women, severe vascular calcifications and vertebral fractures were positively associated with mortality [RR = 3.2 (1.0–10.0) and RR = 4.8 (1.7–13.4), respectively].
Conclusions. Positive associations between vascular calcifications, vertebral fractures and mortality have been found in patients on HD.
doi:10.1093/ndt/gfn466
PMCID: PMC2639312  PMID: 18725376
haemodialysis; mortality; osteoporotic fractures; vascular calcifications; vertebral fractures
9.  Progression of coronary calcification in healthy postmenopausal women 
Background
Coronary artery calcium score incrementally improves coronary risk prediction beyond that provided by conventional risk factors. Limited information is available regarding rates of progression of coronary calcification in women, particularly those with baseline scores above zero. Further, determinants of progression of coronary artery calcification in women are not well understood. This study prospectively evaluated rates and determinants of progression of coronary artery calcium score in a group of healthy postmenopausal women.
Methods
We determined coronary calcium score by computed tomography and recorded demographic, lifestyle and health characteristics of 914 postmenopausal women, a subset of those enrolled in the Women's Health Initiative Observational Study. The 305 women with calcium score ≥10 Agatston units at baseline were invited for repeat scan. This analysis includes the 94 women who underwent second scans.
Results
Mean age of study participants was 65 ± 9 years (mean ± SD), body mass index was 26.1 ± 6.1 kg/m2, and baseline calcium score was 162 ± 220 Agatston units. Mean interval between scans was 3.3 ± 0.7 years. A wide range of changes in coronary calcium score was observed, from -53 to +452 Agatston units/year. Women with lower scores at baseline had smaller annual increases in absolute calcium score. Coronary calcium scores increased 11, 31 and 79 Agatston units/year among women with baseline calcium score in the lowest, middle and highest tertiles. In multivariate analysis, age was not an independent predictor of absolute change in coronary calcium score. Hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use at baseline was a negative predictor (p = 0.015), whereas baseline calcium score was a strong, positive predictor (p < 0.0001) of progression of coronary calcification.
Conclusion
Among postmenopausal women with coronary calcium score ≥ 10 Agatston units, rates of change of coronary calcium score varied widely. In multivariate analysis, statin use was a negative independent determinant, whereas baseline calcium score was a strong positive predictor of annual change in coronary calcium score.
doi:10.1186/1471-2261-4-21
PMCID: PMC535923  PMID: 15574196
10.  FGF-23 associated with the progression of coronary artery calcification in hemodialysis patients 
BMC Nephrology  2013;14:241.
Background
Disordered mineral metabolism is implicated in the pathogenesis of vascular calcification in hemodialysis (HD) patients. Fibroblast growth factor 23 (FGF-23) is the main regulator of phosphate metabolism. In this prospective study, we aimed to investigate the association of serum FGF-23 with progression of coronary artery calcification in HD patients.
Methods
Seventy-four HD patients (36 male/38 female, mean age: 52 ± 14 years) were included. Serum FGF-23 levels were measured by ELISA. Coronary artery calcification score (CACS) was measured twice with one year interval. Patients were grouped as progressive (PG) (36 patients-48%) and non-progressive (NPG).
Results
Age, serum phosphorus, baseline and first year CACS were found to be significantly higher in the PG compared to NPG group. Serum FGF-23 levels were significantly higher in PG [155 (80–468) vs 147 (82–234), p = 0.04]. Patients were divided into two groups according to baseline CACS (low group, CACS ≤ 30; high group, CACS > 30). Serum FGF-23 levels were significantly correlated with the progression of CACS (ΔCACS) in the low baseline CACS group (r = 0.51, p = 0.006), but this association was not found in high baseline CACS group (r = 0.11, p = 0.44). In logistic regression analysis for predicting the PG patients; serum FGF-23, phosphorus levels and baseline CACS were retained as significant factors in the model.
Conclusions
Serum FGF-23 was found to be related to progression of CACS independent of serum phosphorus levels. FGF-23 may play a major role in the progression of vascular calcification especially at the early stages of calcification process in HD patients.
doi:10.1186/1471-2369-14-241
PMCID: PMC3830511  PMID: 24180481
Fibroblast growth factor-23; Coronary artery calcification; Vascular calcification; Hemodialysis
11.  Lowering vascular calcification burden in chronic kidney disease: Is it possible? 
World Journal of Nephrology  2013;2(3):49-55.
High prevalence of atherosclerosis and arterial calcification in chronic kidney disease is far beyond the explanation by common cardiovascular risk factors such as aging diabetes, hypertension and dyslipidemia. The magnitude of coronary artery calcification is independently and inversely associated with renal function. In addition to cardiovascular risk factors, other chronic kidney disease-related risks such as phosphate retention, excess of calcium and prolonged dialysis vintage also contribute to the development of vascular calcification. Strategies to lower vascular calcification burden in chronic kidney disease population should include minimizing chronic kidney disease and atherosclerotic risk factors. Current therapies available are non-calcium containing phosphate binders, low dose active vitamin D and calcimimetic agent. The role of bisphosphonates in vascular calcification in chronic kidney disease population remains unclear. Preliminary data on sodium thiosulfate are promising, however, larger studies on efficacy and patient outcomes are necessary. Several large randomized controlled trials have confirmed the lack of benefit of statin in attenuating the progression of vascular calcification.
doi:10.5527/wjn.v2.i3.49
PMCID: PMC3832912  PMID: 24255887
Coronary calcification; Coronary artery calcification; Renal failure; Phosphate; Vitamin D
12.  Cardiovascular risk markers associated with arterial calcification in patients with chronic kidney disease Stages 3 and 4 
Clinical Kidney Journal  2014;7(2):167-173.
Background
The contribution of pro-inflammatory markers to cardiovascular (CV) risk and vascular calcification in chronic kidney disease (CKD) remains largely to be elucidated. We investigated the association between plasma levels of several biomarkers and calcification volume in three different vascular beds in CKD Stages 3 and 4 patients.
Methods
This is a cross-sectional, exploratory study in patients with an estimated glomerular filtration rate (eGFR) ≥20 and ≤45 mL/min/1.73 m2 and serum phosphorus ≥3.5 and <6.0 mg/dL enrolled in a previously published randomized, double blind, placebo-controlled single-centre trial. Ethylenediaminetetraacetic acid (EDTA) plasma samples were collected at baseline before patients received study medication and analysed for the presence of a number of biomarkers. Coronary artery calcium (CAC), thoracic aortic calcification (TAC) and abdominal aortic calcification (AAC) volumes were measured using standard electron-beam computed tomography protocols. Associations were adjusted for age, sex, smoking, body mass index, diabetes mellitus status, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure and eGFR.
Results
Associations with CAC were found for β2-microglobulin (B2M), fibroblast growth factor 23 (FGF23), interleukin-8 (IL-8) and IL-18. AAC was associated with: B2M, FGF23 and IL-2 receptor alpha (IL-2 RA). TAC was associated with: B2M, FGF23, IL-2 RA, IL-18 and tumour necrosis factor receptor type I. For most of the analysed biomarkers, there were non-significant trends of associations with calcification.
Conclusions
This exploratory study found that elevated plasma levels of several inflammatory biomarkers are significantly associated with arterial calcification in CKD Stages 3 and 4 patients. A greater understanding of inflammation and calcification in CKD patients may help the development of CV risk-assessment algorithms for better management of these patients.
doi:10.1093/ckj/sfu017
PMCID: PMC3968563  PMID: 24683472
arterial calcification; biomarkers; cardiovascular risk; chronic kidney disease; inflammation
13.  Phosphorus Is Associated with Coronary Artery Disease in Patients with Preserved Renal Function 
PLoS ONE  2012;7(5):e36883.
High serum phosphorus levels have been associated with mortality and cardiovascular events in patients with chronic kidney disease and in the general population. In addition, high phosphorus levels have been shown to induce vascular calcification and endothelial dysfunction in vitro. The aim of this study was to evaluate the relation of phosphorus and coronary calcification and atherosclerosis in the setting of normal renal function. This was a cross-sectional study involving 290 patients with suspected coronary artery disease and undergoing elective coronary angiography, with a creatinine clearance >60 ml/min/1.73 m2. Coronary artery obstruction was assessed by the Friesinger score and coronary artery calcification by multislice computed tomography. Serum phosphorus was higher in patients with an Agatston score >10 than in those with an Agatston score ≤10 (3.63±0.55 versus 3.49±0.52 mg/dl; p = 0.02). In the patients with Friesinger scores >4, serum phosphorus was higher (3.6±0.5 versus 3.5±0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23 was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum phosphate was associated with a 7.4% higher odds of having a Friesinger score >4 (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01). Fibroblast growth factor 23 was a negative predictor of Friesinger score (p = 0.002). In conclusion, phosphorus is positively associated with coronary artery calcification and obstruction in patients with suspected coronary artery disease and preserved renal function.
doi:10.1371/journal.pone.0036883
PMCID: PMC3349637  PMID: 22590632
14.  Malnutrition, a new inducer for arterial calcification in hemodialysis patients? 
Background
Arterial calcification is a significant cardiovascular risk factor in hemodialysis patients. A series of factors are involved in the process of arterial calcification; however, the relationship between malnutrition and arterial calcification is still unclear.
Methods
68 hemodialysis patients were enrolled in this study. Nutrition status was evaluated using modified quantitative subjective global assessment (MQSGA). Related serum biochemical parameters were measured. And the radial artery samples were collected during the arteriovenous fistula surgeries. Hematoxylin/eosin stain was used to observe the arterial structures while Alizarin red stain to observe calcified depositions and classify calcified degree. The expressions of bone morphogenetic protein 2 (BMP2) and matrix Gla protein (MGP) were detected by immunohistochemistry and western blot methods.
Results
66.18% hemodialysis patients were malnutrition. In hemodialysis patients, the calcified depositions were mainly located in the medial layer of the radial arteries and the expressions of BMP2 and MGP were both increased in the calcified areas. The levels of serum albumin were negatively associated with calcification score and the expressions of BMP2 and MGP. While MQSGA score, serum phosphorus and calcium × phosphorus product showed positive relationships with calcification score and the expressions of BMP2 and MGP.
Conclusions
Malnutrition is prevalent in hemodialysis patients and is associated with arterial calcification and the expressions of BMP2 and MGP in calcified radial arteries. Malnutrition may be a new inducer candidate for arterial calcification in hemodialysis patients.
doi:10.1186/1479-5876-11-66
PMCID: PMC3608064  PMID: 23506394
Arterial calcification; Hemodialysis; Malnutrition; Bone morphogenetic protein 2; Matrix Gla protein
15.  Biomarkers Associated with Vascular and Valvular Calcification in Chronic Hemodialysis Patients 
Disease markers  2013;34(4):229-235.
Background: Cardiovascular calcification, including arterial intimal and medial calcification (AIC and AMC) and valvular calcification (VC) are important predictors of outcome in chronic dialysis patients. We aimed to compare their prevalence and analyze respective risk factors in hemodialysis (HD) patients.
Methods: A total of 81 HD patients were enrolled. Vascular calcification was assessed by plain film radiography of the pelvis and VC was diagnosed by echocardiography. Demographic data was reviewed and serum levels of calcification-relevant biomarkers were determined. Patients with and without calcification were then compared.
Results: The prevalence study indicated that 36 patients had AIC (44.4%), 17 had AMC (21%) and 60 (74.1%) had VC. Patients with vascular calcification were older, and had a higher prevalence of diabetes. Their IL-6, osteoprotegerin, and uric acid levels were higher. Serum fetuin-A was lower in patients with VC. Logistic regression analysis revealed age, uric acid and diabetes to be independently associated with AIC; uric acid, diabetes and osteoprotegerin with AMC. Fetuin-A was the sole associate of VC.
Conclusions: It is concluded that the prevalence of cardiovascular calcification in chronic HD patients was high with cardiac valve involvement more frequent. Factors associated with different type of calcification were not identical. Changes in biomarkers may represent clinical clues for assessment of cardiovascular calcification in HD patients.
doi:10.3233/DMA-130965
PMCID: PMC3810241  PMID: 23396289
Vascular calcification; valvular calcification; hemodialysis; biomarker
16.  Vitamin K-Antagonists Accelerate Atherosclerotic Calcification and Induce a Vulnerable Plaque Phenotype 
PLoS ONE  2012;7(8):e43229.
Background
Vitamin K-antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE−/− model of atherosclerosis.
Methodology/Principal Findings
A total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE−/− mice (10 weeks) received a Western type diet (WTD) for 12 weeks, after which mice were fed a WTD supplemented with vitamin K1 (VK1, 1.5 mg/g) or vitamin K1 and warfarin (VK1&W; 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden.
Conclusions/Significance
VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE−/− mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle.
doi:10.1371/journal.pone.0043229
PMCID: PMC3430691  PMID: 22952653
17.  Multidetector Computed Tomography for Coronary Artery Disease Screening in Asymptomatic Populations 
Executive Summary
Objective
This evidence-based health technology assessment systematically reviewed the published literature on multidetector computed tomography (MDCT) angiography (with contrast) as a diagnostic tool for coronary artery disease (CAD), and applied the results of the assessment to health care practices in Ontario.
Clinical Need
Coronary artery disease is the leading cause of death in the western world. Occlusion of coronary arteries reduces coronary blood flow and oxygen delivery to the myocardium (heart muscle). The rupture of an unstable atherosclerotic plaque may result in myocardial infarction. If left untreated, CAD can result in heart failure and, subsequently, death. According to the Heart and Stroke Foundation of Canada, 54% of all cardiovascular deaths are due to CAD. Patient characteristics (e.g., age, sex, and genetics), underlying clinical conditions that predispose to cardiac conditions (e.g., diabetes, hypertension, and elevated cholesterol), lifestyle characteristics, (e.g., obesity, smoking, and physical inactivity), and, more recently, determinants of health (e.g., socioeconomic status) may predict the risk of getting CAD.
In 2004/2005, The Ontario government funded approximately 15,400 percutaneous (through the skin) coronary interventions and 7,840 coronary bypass procedures for the treatment of CAD. These numbers are expected to reach 22,355 for percutaneous coronary interventions and 12,323 for coronary bypass procedures in 2006/2007. It was noted that more than one-half of all first coronary events occur in people without symptoms of CAD. In Ontario in 2000/2001, $457.9 million (Cdn) was spent on invasive ($237.4 million) and noninvasive ($220.5 million) cardiac services. The use of noninvasive cardiac tests, in particular, is rising rapidly.
The Technology
Computed tomography (CT) is a medical imaging method employing tomography where digital geometry processing is used to generate a 3-dimensional image of the internals of an object from a large series of 2-dimensional X-ray images taken around a single axis of rotation. Multidetector computed tomography is performed for noninvasive imaging of the coronary arteries. Computer software quantifies the amount of calcium within the coronary arteries and calculates a coronary artery calcium score.
Compared with conventional CT scanning, MDCT can provide smaller pieces of information and cover a larger area faster. Advanced MDCT technology (that is, 8-, 16-, 32-, and 64-slice systems) can produce more images in less time. For general CT scanning, this faster capability can reduce the length of time people are required to be still during the procedure and thereby reduce potential movement artifact. However, the additional clinical utility of images obtained from faster scanners compared with the images obtained from conventional CT scanners for current CT indications (i.e., nonmoving body parts) is unknown.
Review Strategy
The Medical Advisory Secretariat completed a computer-aided search limited to English-language studies in humans from 1998 to 2007 in multiple medical literature databases, including MEDLINE, EMBASE, The Cochrane Library, and INAHTA/CRD. Case reports, letters, editorials, nonsystematic reviews, and comments were excluded. Additional studies that met the inclusion and exclusion criteria were obtained from reference lists of included studies. Inclusion and exclusion criteria were applied to the results according to the criteria listed below.
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of the body of evidence (defined as 1 or more studies) supporting the research questions explored in this systematic review.
Summary of Findings and Conclusions
Screening the asymptomatic population for CAD using MDCT does not meet World Health Organization criteria for screening; hence, it is not justifiable. Coronary artery calcification measured by MDCT is a good predictor of future cardiovascular events. However, MDCT exhibits only moderately high sensitivity and specificity for detection of CAD in an asymptomatic population. If population-based screening were implemented, a high rate of false positives would result in increased downstream costs and interventions. Additionally, some cases of CAD would be missed, as they may not be developed, or not yet have progressed to detectable levels. There is no evidence for the impact of screening on patient management. Cardiovascular risk factors are positively associated with the presence of coronary artery calcification and cardiovascular events; however, risk factor stratification to identify high-risk asymptomatic individuals is unclear given the current evidence-base.
Safety of MDCT screening is also an issue because of the introduction of increased radiation doses for the initial screening scan and possible follow-up interventions.
No large randomized controlled trials of MDCT screening have been published, which indicates an important area of future research.
Lastly, the policy implications for MDCT screening for CAD in the asymptomatic population are significant. There is no evidence on the long-term implications of screening, and the potential impact on the resources of the health care system is considerable.
PMCID: PMC3377586  PMID: 23074503
18.  Associations of fetuin-A and osteoprotegerin with arterial stiffness and early atherosclerosis in chronic hemodialysis patients 
BMC Nephrology  2013;14:122.
Background
Cardiovascular morbidity and mortality remains excessive in patients with chronic kidney disease. The association of vascular changes with regulators of extraosseous calcification in this patient population is still under investigation. The aim of the present study was to investigate the associations of the calcification inhibitor fetuin-A, and the anti-osteoclastic factor osteoprotegerin (OPG) with vascular pathology in chronic hemodialysis patients.
Methods
In this cross-sectional study including 81 stable chronic hemodialysis patients, we measured carotid-to-femoral pulse wave velocity (cfPWV) with applanation tonometry, reflecting arterial stiffness, and common carotid intima-media thickness (ccIMT), a surrogate of early atherosclerosis, as well as serum levels of fetuin-A and OPG. Co-morbidities, traditional cardiovascular risk factors, inflammatory markers and mineral-bone disease serology parameters were also recorded.
Results
cfPWV correlated inversely with fetuin-A (r=−0.355, p=0.001) and positively with OPG (r=0.584, p<0.001). In multilinear regression analysis including age, gender, diabetes, cardiovascular disease, hypertension, pulse pressure, LDL, logCRP, both fetuin-A and OPG were independently associated with cfPWV (p=0.024 and p=0.041 respectively). ccIMT was negatively associated with fetuin-A (r=−0.312, p=0.005) and positively with OPG (r=0.521, p<0.0001); however these associations lost statistical significance after adjustment for age.
Conclusion
In chronic hemodialysis patients both fetuin-A and OPG levels are independently associated with arterial stiffness but not with early atherosclerotic vascular changes.
doi:10.1186/1471-2369-14-122
PMCID: PMC3700830  PMID: 23758931
Intima-media thickness; Fetuin-A; Hemodialysis; Osteoprotegerin; Pulse wave velocity
19.  Predictive value of coronary calcifications for future cardiac events in asymptomatic patients with diabetes mellitus: A prospective study in 716 patients over 8 years 
Background
To establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus.
Methods
We included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2 ± 15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1 ± 1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined.
Results
During the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475 ± 208) was significantly higher compared to those without cardiac events (236 ± 199, p < 0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p < 0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p < 0.01.
Conclusion
By determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.
doi:10.1186/1471-2261-8-27
PMCID: PMC2569906  PMID: 18847481
20.  Fetuin-A, inflammation, and coronary artery calcification in hemodialysis patients 
Indian Journal of Nephrology  2011;21(2):90-94.
Hemodialysis patients have extremely increased cardiovascular mortality. Vascular calcification, inflammation, and low serum fetuin-A levels are implicated for increased mortality. In this study, relationship between coronary artery calcification, inflammation, and serum fetuin-A levels were investigated. Seventy-eight hemodialysis patients (38 male, 40 female, mean age: 52±14.5 years) were included. All patients were on dialysis for more than 6 months. Coronary artery calcium scores (CACS) are determined by electron-beam computed tomography. Serum CRP, IL-1β, IL-6, TNF-α, and serum fetuin-A levels were measured. Mean CACS value was 488.5±94.5. Serum fetuin-A levels were negatively correlated with CACS (r:–0.30, P=0.009). Patients are divided into two groups according to total CACS value; group 1 (CACS<10), group 2 (CACS≥10). There was a statistically significance difference in fetuin-A levels between CACS group 1 and group 2 (P=0.001). In this study, serum fetuin-A levels were associated with total CACS. This Fetuin-A may play a role in increased mortality in this group of patients via facilitating CAC.
doi:10.4103/0971-4065.82128
PMCID: PMC3132345  PMID: 21769170
Fetuin-A; hemodialysis; inflammation; vascular calcification
21.  Effect of Heart Rate and Coronary Calcification on the Diagnostic Accuracy of the Dual-Source CT Coronary Angiography in Patients with Suspected Coronary Artery Disease 
Korean Journal of Radiology  2009;10(4):347-354.
Objective
To evaluate the diagnostic accuracy of a dual-source computed tomography (DSCT) coronary angiography, with a particular focus on the effect of heart rate and calcifications.
Materials and Methods
One hundred and nine patients with suspected coronary disease were divided into 2 groups according to a mean heart rate (< 70 bpm and ≥ 70 bpm) and into 3 groups according to the mean Agatston calcium scores (≤ 100, 101-400, and > 400). Next, the effect of heart rate and calcification on the accuracy of coronary artery stenosis detection was analyzed by using an invasive coronary angiography as a reference standard. Coronary segments of less than 1.5 mm in diameter in an American Heart Association (AHA) 15-segment model were independently assessed.
Results
The mean heart rate during the scan was 71.8 bpm, whereas the mean Agatston score was 226.5. Of the 1,588 segments examined, 1,533 (97%) were assessable. A total of 17 patients had calcium scores above 400 Agatston U, whereas 50 had heart rates ≥ 70 bpm. Overall the sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) for significant stenoses were: 95%, 91%, 65%, and 99% (by segment), respectively and 97%, 90%, 81%, and 91% (by artery), respectively (n = 475). Heart rate showed no significant impact on lesion detection; however, vessel calcification did show a significant impact on accuracy of assessment for coronary segments. The specificity, PPV and accuracy were 96%, 80%, and 96% (by segment), respectively for an Agatston score less than 100% and 99%, 96% and 98% (by artery). For an Agatston score of greater to or equal to 400 the specificity, PPV and accuracy were reduced to 79%, 55%, and 83% (by segment), respectively and to 79%, 69%, and 85% (by artery), respectively.
Conclusion
The DSCT provides a high rate of accuracy for the detection of significant coronary artery disease, even in patients with high heart rates and evidence of coronary calcification. However, patients with severe coronary calcification (> 400 U) remain a challenge to diagnose.
doi:10.3348/kjr.2009.10.4.347
PMCID: PMC2702043  PMID: 19568462
Dual-source computed tomography; Coronary artery disease; Coronary angiography
22.  Expression of osteopontin in calcified coronary atherosclerotic plaques. 
Journal of Korean Medical Science  2000;15(5):485-493.
Advanced atherosclerosis is often associated with dystrophic calcification and remodeling of extracellular matrix of vascular wall. Recently many studies have documented a general relationship between calcification and severity of coronary disease, and discussed the feasibility of electron beam computed tomography for detecting and quantifying the coronary artery calcification in the patients. The present study investigated the expression and the localization of osteopontin, one of noncollagenous bone matrix protein, within the calcified coronary arteries. Autopsy-derived coronary artery specimens were scanned and reconstructed to visualize the pattern of coronary calcification using a novel microscopic computed tomography technique. The localization of the osteopontin were evaluated by immunohistochemial stain with LF7. The present study showed that the pattern of coronary calcification is variable and the expression of osteopontin is localized mainly to calcified lesion. The smooth muscle cells in addition to macrophage expressed osteopontin protein in human coronary atherosclerotic plaques. Soluble osteopontin released near to the sites of vascular calcification may represent an adaptive mechanism aimed at regulating the process of vascular calcification.
PMCID: PMC3054686  PMID: 11068982
23.  Recent progress in the treatment of vascular calcification 
Kidney international  2010;78(12):1232-1239.
Vascular calcification is common in patients with advanced chronic kidney disease and is associated with poorer outcomes. Although the pathophysiology is not completely understood, it is clear that it is a multifactorial process involving altered mineral metabolism, as well as changes in systemic and local factors that can promote or inhibit vascular calcification, and all of these are potential therapeutic targets. Current therapy is closely linked to strategies for preventing disordered bone and mineral metabolism in advanced kidney disease and involves lowering the circulating levels of both phosphate and calcium. The efficacy of compounds that specifically target calcification, such as bisphosphonates and thiosulfate, has been shown in animals but only in small numbers of humans, and safety remains an issue. Additional therapies, such as pyrophosphate, vitamin K, and lowering of pH, are supported by animal studies, but are yet to be investigated clinically. As the mineral composition of vascular calcifications is the same as in bone, potential effects on bone must be addressed with any therapy for vascular calcification.
doi:10.1038/ki.2010.334
PMCID: PMC3184001  PMID: 20861819
bone; chronic kidney disease; vascular calcification; vascular disease
24.  Multi-Detector Computed Tomography Angiography for Coronary Artery Disease 
Executive Summary
Purpose
Computed tomography (CT) scanning continues to be an important modality for the diagnosis of injury and disease, most notably for indications of the head and abdomen. (1) According to a recent report published by the Canadian Institutes of Health Information, (1) there were about 10.3 scanners per million people in Canada as of January 2004. Ontario had the fewest number of CT scanners per million compared to the other provinces (8 CT scanners per million). The wait time for CT in Ontario of 5 weeks approaches the Canadian median of 6 weeks.
This health technology and policy appraisal systematically reviews the published literature on multidetector CT (MDCT) angiography as a diagnostic tool for the newest indication for CT, coronary artery disease (CAD), and will apply the results of the review to current health care practices in Ontario. This review does not evaluate MDCT to detect coronary calcification without contrast medium for CAD screening purposes.
The Technology
Compared with conventional CT scanning, MDCT can provide smaller pieces of information and can cover a larger area faster. (2) Advancing MDCT technology (8, 16, 32, 64 slice systems) is capable of producing more images in less time. For general CT scanning, this faster capability can reduce the time that patients must stay still during the procedure, thereby reducing potential movement artefact. However, the additional clinical utility of images obtained from faster scanners compared to the images obtained from conventional CT scanners for current CT indications (i.e., non-moving body parts) is not known.
There are suggestions that the new fast scanners can reduce wait times for general CT. MDCT angiography that utilizes a contrast medium, has been proposed as a minimally invasive replacement to coronary angiography to detect coronary artery disease. MDCT may take between 15 to 45 minutes; coronary angiography may take up to 1 hour.
Although 16-slice and 32-slice CT scanners have been available for a few years, 64-slice CT scanners were released only at the end of 2004.
Review Strategy
There are many proven, evidence-based indications for conventional CT. It is not clear how MDCT will add to the clinical utility and management of patients for established CT indications. Therefore, because cardiac imaging, specifically MDCT angiography, is a new indication for CT, this literature review focused on the safety, effectiveness, and cost-effectiveness of MDCT angiography compared with coronary angiography in the diagnosis and management of people with CAD.
This review asked the following questions:
Is the most recent MDCT angiography effective in the imaging of the coronary arteries compared with conventional angiography to correctly diagnose of significant (> 50% lumen reduction) CAD?
What is the utility of MDCT angiography in the management and treatment of patients with CAD?
How does MDCT angiography in the management and treatment of patients with CAD affect longterm outcomes?
The published literature from January 2003 to January 31, 2005 was searched for articles that focused on the detection of coronary artery disease using 16-slice CT or faster, compared with coronary angiography. The search yielded 138 articles; however, 125 were excluded because they did not meet the inclusion criteria (comparison with coronary angiography, diagnostic accuracy measures calculated, and a sample size of 20 or more). As screening for CAD is not advised, studies that utilized MDCT for this purpose or studies that utilized MDCT without contrast media were also excluded. Overall, 13 studies were included in this review.
Summary of Findings
The published literature focused on 16-slice CT angiography for the detection of CAD. Two abstracts that were presented at the 2005 European Congress of Radiology meeting in Vienna compared 64-slice CT angiography with coronary angiography.
The 13 studies focussing on 16-slice CT angiography were stratified into 2 groups: Group 1 included 9 studies that focused on the detection of CAD in symptomatic patients, and Group 2 included 4 studies that examined the use of 16-slice CT angiography to detect disease progression after cardiac interventions. The 2 abstracts on 64-slice CT angiography were presented separately, but were not critically appraised due to the lack of information provided in the abstracts.
16-Slice Computed Tomography Angiography
The STARD initiative to evaluate the reporting quality of studies that focus on diagnostic tests was used. Overall the studies were relatively small (fewer than 100 people), and only about one-half recruited consecutive patients. Most studies reported inclusion criteria, but 5 did not report exclusion criteria. In these 5, the patients were highly selected; therefore, how representative they are of the general population of people with suspicion if CAD or those with disease progression after cardiac intervention is questionable. In most studies, patients were either already taking, or were given, β-blockers to reduce their heart rates to improve image quality sufficiently. Only 6 of the 13 studies reported interobserver reliability quantitatively. The studies typically assessed the quality of the images obtained from 16-slice CT angiography, excluded those of poor quality, and compared the rest with the gold standard, coronary angiography. This practice necessarily inflated the diagnostic accuracy measures. Only 3 studies reported confidence intervals around their measures.
Evaluation of the studies in Group 1 reported variable sensitivity, from just over 60% to 96%, but a more stable specificity, at more than 95%. The false positive rate ranged from 5% to 8%, but the false negative rate was at best under 10% and at worst about 30%. This means that up to one-third of patients who have disease may be missed. These patients may therefore progress to a more severe level of disease and require more invasive procedures. The calculated positive and negative likelihood ratios across the studies suggested that 16-slice CT angiography may be useful to detect disease, but it is not useful to rule out disease. The prevalence of disease, measured by conventional coronoary angiography, was from 50% to 80% across the studies in this review. Overall, 16-slice CT angiography may be useful, but there is no conclusive evidence to suggest that it is equivalent to or better than coronary angiography to detect CAD in symptomatic patients.
In the 4 studies in Group 2, sensitivity and specificity were both reported at more than 95% (except for 1 that reported sensitivity of about 80%). The positive and negative likelihood ratios suggested that the test might be useful to detect disease progression in patients who had cardiac interventions. However, 2 of the 4 studies recruited patients who had been asymptomatic since their intervention. As many of the patients studied were not symptomatic, the relevance of performing MDCT angiography in the patient population may be in question.
64-Slice Computed Tomography Angiography
An analysis from the interim results based on 2 abstracts revealed that 64-slice CT angiography was insufficient compared to coronary angiography and may not be better than 16-slice CT angiography to detect CAD.
Conclusions
Cardiac imaging is a relatively new indication for CT. A systematic review of the literature was performed from 2003 to January 2005 to determine the effectiveness of MDCT angiography (16-slice and 64-slice) compared to coronary angiography to detect CAD. At the time of this report, there was no published literature on 64-slice CT for any indications.
Based on this review, the Medical Advisory Secretariat concluded that there is insufficient evidence to suggest that 16-slice or 64-slice CT angiography is equal to or better than coronary angiography to diagnose CAD in people with symptoms or to detect disease progression in patients who had previous cardiac interventions. An analysis of the evidence suggested that in investigating suspicion of CAD, a substantial number of patients would be missed. This means that these people would not be appropriately treated. These patients might progress to more severe disease and possibly more adverse events. Overall, the clinical utility of MDCT in patient management and long-term outcomes is unknown.
Based on the current evidence, it is unlikely that CT angiography will replace coronary angiography completely, but will probably be used adjunctively with other cardiac diagnostic tests until more definitive evidence is published.
If multi-slice CT scanners are used for coronary angiography in Ontario, access to the current compliment of CT scanners will necessarily increase wait times for general CT scanning. It is unlikely that these newer-generation scanners will improve patient throughput, despite the claim that they are faster.
Screening for CAD in asymptomatic patients and who have no history of ischemic heart disease using any modality is not advised, based on the World Health Organization criteria for screening. Therefore, this review did not examine the use of multi-slice CT for this purpose.
PMCID: PMC3382628  PMID: 23074474
25.  Inflammation, Coronary Artery Calcification and Cardiovascular Events in Incident Renal Transplant Recipients 
Atherosclerosis  2010;212(2):589-594.
Objective
Coronary artery calcification (CAC) predicts cardiovascular events in the general population. We conducted a prospective study to determine if inflammatory markers were predictive of CAC and if CAC predicted cardiovascular events and mortality in incident renal transplant recipients.
Methods
A prospective cohort of 112 asymptomatic incident renal transplant recipients who had no prior history of coronary artery revascularization or myocardial infarction had coronary calcifications measured early post-transplant and at least 18 months later by Agatston score and volume method.
Results
The mean CAC score was 367.7 (682.3). Inflammatory markers such as WBC and CRP were predictive of CAC severity. Recipients with cardiovascular events (n=11) or death (n=12) during the follow-up period had higher mean [675.1 (669.3) vs. 296.8(669.0), p=0.02] and median [434.8 vs. 28.9, p=0.01] CAC score compared to those without them. Recipients with CAC score less than 100 had a better cumulative survival rate compared to the recipients with CAC score greater than 100 [95.1 vs. 82.3%, p=0.03]. We found a significant unadjusted and adjusted association between CAC score and cardiovascular events and mortality. A quarter (25.9%) of recipients had CAC progression. Coronary calcification progression also predicted cardiovascular events and mortality after adjustment for diabetes, age, dialysis vintage and presence of CAC at time of transplant.
Conclusion
CAC is prevalent in renal recipients and is predictive of cardiovascular events and mortality. Changes in coronary calcification are common and predict clinical outcomes. Inflammatory markers are predictive of CAC severity at time of transplant, but are not predictive of future cardiovascular event or mortality.
doi:10.1016/j.atherosclerosis.2010.05.016
PMCID: PMC2953547  PMID: 20934074
coronary calcification; EBCT; renal transplant; inflammation; C-reactive protein

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