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Extent of arterial calcification by conventional vitamin K antagonist treatment.
Hasific, S, Øvrehus, KA, Gerke, O, Hallas, J, Busk, M, Lambrechtsen, J, Urbonaviciene, G, Sand, NPR, Nielsen, JS, Diederichsen, L, et al
PloS one. 2020;(10):e0241450
Abstract
BACKGROUND AND AIMS Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD). METHODS We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007-2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1-99, 100-399, ≥400) was investigated by ordered logistic regression adjusting for covariates. RESULTS The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009-1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935-1.074). There was no significant interaction between VKA treatment duration and age on CAC category. CONCLUSIONS Adjusted for cardiovascular risk factors, VKA treatment-contrary to NOAC-was associated to higher CAC category.
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Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial.
Achenbach, S, Paul, JF, Laurent, F, Becker, HC, Rengo, M, Caudron, J, Leschka, S, Vignaux, O, Knobloch, G, Benea, G, et al
European radiology. 2017;(2):821-830
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OBJECTIVES To demonstrate non-inferiority of iobitridol 350 for coronary CT angiography (CTA) compared to higher iodine content contrast media regarding rate of patients evaluable for the presence of coronary artery stenoses. METHODS In this multicentre trial, 452 patients were randomized to receive iobitridol 350, iopromide 370 or iomeprol 400 and underwent coronary CTA using CT systems with 64-detector rows or more. Two core lab readers assessed 18 coronary segments per patient regarding image quality (score 0 = non diagnostic to 4 = excellent quality), vascular attenuation, signal and contrast to noise ratio (SNR, CNR). Patients were considered evaluable if no segment had a score of 0. RESULTS Per-patient, the rate of fully evaluable CT scans was 92.1, 95.4 and 94.6 % for iobitridol, iopromide and iomeprol, respectively. Non-inferiority of iobitridol over the best comparator was demonstrated with a 95 % CI of the difference of [-8.8 to 2.1], with a pre-specified non-inferiority margin of -10 %. Although average attenuation increased with higher iodine concentrations, average SNR and CNR did not differ between groups. CONCLUSIONS With current CT technology, iobitridol 350 mg iodine/ml is not inferior to contrast media with higher iodine concentrations in terms of image quality for coronary stenosis assessment. KEY POINTS • Iodine concentration is an important parameter for image quality in coronary CTA. • Contrast enhancement must be balanced against the amount of iodine injected. • Iobitridol 350 is non-inferior compared to CM with higher iodine concentrations. • Higher attenuation with higher iodine concentrations, but no SNR or CNR differences.
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Spotty calcification as a marker of accelerated progression of coronary atherosclerosis: insights from serial intravascular ultrasound.
Kataoka, Y, Wolski, K, Uno, K, Puri, R, Tuzcu, EM, Nissen, SE, Nicholls, SJ
Journal of the American College of Cardiology. 2012;(18):1592-7
Abstract
OBJECTIVES The purpose of this study was to determine atheroma progression in patients with spotty calcification. BACKGROUND Although extensively calcified atherosclerotic lesions have been proposed to be clinically quiescent, the presence of spotty calcification within plaque has been reported to be associated with an increased incidence of ischemic cardiovascular events. The relationship between spotty calcification and disease progression has not been investigated. METHODS A total of 1,347 stable patients with angiographic coronary artery disease underwent serial evaluation of atheroma burden with intravascular ultrasound imaging. Patients with spotty calcification were identified based on the presence of lesions (1 to 4 mm in length) containing an arc of calcification of <90°. Clinical characteristics and disease progression were compared between patients with spotty calcification (n = 922) and those with no calcification (n = 425). RESULTS Patients with spotty calcification were older (age 56 years vs. 54 years; p = 0.001), more likely to be male (68% vs. 54%; p = 0.01), and have a history of diabetes mellitus (30% vs. 24%; p = 0.01) and myocardial infarction (28% vs. 20%; p = 0.004), and have lower on-treatment high-density lipoprotein cholesterol levels (48 ± 16 mg/dl vs. 51 ± 17 mg/dl; p = 0.001). Patients with spotty calcification demonstrated a greater percent atheroma volume (PAV) (36.0 ± 7.6% vs. 29.0 ± 8.5%; p < 0.001) and total atheroma volume (174.6 ± 71.9 mm(3) vs. 133.9 ± 64.9 mm(3); p < 0.001). On serial evaluation, spotty calcification was associated with greater progression of PAV (+0.43 ± 0.07% vs. +0.02 ± 0.11%; p = 0.002). Although intensive low-density lipoprotein cholesterol and blood pressure lowering therapy slowed disease progression, these efficacies were attenuated in patients with spotty calcification. CONCLUSIONS The presence of spotty calcification is associated with more extensive and diffuse coronary atherosclerosis and accelerated disease progression despite use of medical therapies.
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Abdominal aortic calcification detected on lateral spine images from a bone densitometer predicts incident myocardial infarction or stroke in older women.
Schousboe, JT, Taylor, BC, Kiel, DP, Ensrud, KE, Wilson, KE, McCloskey, EV
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2008;(3):409-16
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UNLABELLED Among a cohort of elderly women, abdominal aortic calcification scored on baseline lateral spine densitometric images intended for vertebral fracture assessment was associated with subsequent myocardial infarction or stroke over a median 4-yr period, independent of clinical cardiovascular disease risk factors. INTRODUCTION Cardiovascular disease (CVD) risk among older women is not adequately captured by traditional CVD risk factors. Lateral spine images obtained on bone densitometers for vertebral fracture assessment (VFA) can detect abdominal aortic calcification (AAC), an important marker of subclinical CVD. Our objective was to estimate the association between AAC scored on VFA images and subsequent myocardial infarction (MI) or stroke in elderly women. MATERIALS AND METHODS Among participants in a randomized controlled trial (women; age > 75 yr) of clodronate versus placebo, those who sustained an MI or stroke during the median 4-yr follow-up study period were selected as cases (n = 408), and 408 controls were randomly selected from the remainder of the parent study population. Baseline VFA images were scored for AAC with a previously validated 24-point scale and a newer, simpler 8-point scale. RESULTS The OR of incident MI or stroke for those in the middle and top tertiles, respectively, compared with the bottom tertile of AAC score were 1.14 (95% CI, 0.79-1.66) and 1.74 (95% CI, 1.19-2.56) for the 24-point scale and 1.42 (95% CI, 0.98-2.05) and 1.77 (95% CI, 1.22-2.55) for the 8-point scale, adjusted for age, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, blood pressure, smoking, renal function, health status, and baseline diagnoses of diabetes mellitus, hypertension, angina, and prior stroke. CONCLUSIONS AAC scored on VFA images is independently associated with incident MI or stroke. Because bone densitometry is indicated for all women > or = 65 yr of age, VFA imaging offers an opportunity to capture this CVD risk factor in postmenopausal women undergoing bone densitometry at very little additional cost.
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The interscan variation of CT coronary artery calcification score: analysis of the Calcium Acetate Renagel Comparison (CARE)-2 study.
Budoff, MJ, Kessler, P, Gao, YL, Qunibi, W, Moustafa, M, Mao, SS
Academic radiology. 2008;(1):58-61
Abstract
RATIONALE AND OBJECTIVES In the Calcium Acetate Renagel Evaluation (CARE)-2 study, the effects of calcium acetate plus atorvastatin (Lipitor) on the progression of coronary artery calcifications (CACs) are evaluated versus those of Renagel, monitored using dual electron beam tomography (EBT) scans (two scans at study initiation and two at follow up). The aim of this study is to estimate the interscan variation for the Agatston score and for the volume score determined in patients with end-stage renal disease (ESRD) in the CARE-2 study. MATERIALS AND METHODS CAC score and volume were measured at study initiation in 463 ESRD subjects (mean age: 59.4 +/- 12.5 years, 48.3% female). All patients underwent dual scanning using an EBT, as first scan of two needed to measure the progression of CAC when treated with sevelamer (Renagel) compared with calcium acetate with or without atorvastatin. All scans in all participants were completed by using an EBT system (GE Imatron, South San Francisco, CA). Interscan variability was defined by the following formula: abs (scan A - scan B) / (0.5 x scan A + 0.5 x scan B) x 100%, where A and B denote the first and second scan, respectively, of the dual scan procedure performed before treatment. We evaluated the reproducibility of the cutpoints commonly used for calcium scores clinically, namely 1-30, 31-100, 101-400, and >400. RESULTS The CAC interscan variability was 11.8% using the Agatston score and 10.3% using the volume score. The reproducibility was then assessed using cutpoints 1-30, 31-100, 101-400, and >400. Agatston score variability for the four subgroups was 61.3%, 23%, 16.1%, and 8.2%, respectively (mean variability, 11.8%). Volume score variability was 60.0%, 14.4%, 14.6%, and 7.7%, respectively (mean variability, 10.3%). The correlation coefficient for scan A to scan B goes up significantly with increasing calcium scores and reaches 0.99 for scores greater than 400 (P < .0001). CONCLUSION Interscan variability was sufficiently small for patients with calcium scores greater than 30. Our study thus demonstrates a sufficient reproducibility of the calcium score using EBT. This score allows for accurate serial assessment of these patients and for comparing different therapies.
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The effect of intensive glycemic treatment on coronary artery calcification in type 1 diabetic participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study.
Cleary, PA, Orchard, TJ, Genuth, S, Wong, ND, Detrano, R, Backlund, JY, Zinman, B, Jacobson, A, Sun, W, Lachin, JM, et al
Diabetes. 2006;(12):3556-65
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The Epidemiology of Diabetes Interventions and Complications (EDIC) study, an observational follow-up of the Diabetes Control and Complications Trial (DCCT) type 1 diabetes cohort, measured coronary artery calcification (CAC), an index of atherosclerosis, with computed tomography (CT) in 1,205 EDIC patients at approximately 7-9 years after the end of the DCCT. We examined the influence of the 6.5 years of prior conventional versus intensive diabetes treatment during the DCCT, as well as the effects of cardiovascular disease risk factors, on CAC. The prevalences of CAC >0 and >200 Agatston units were 31.0 and 8.5%, respectively. Compared with the conventional treatment group, the intensive group had significantly lower geometric mean CAC scores and a lower prevalence of CAC >0 in the primary retinopathy prevention cohort, but not in the secondary intervention cohort, and a lower prevalence of CAC >200 in the combined cohorts. Waist-to-hip ratio, smoking, hypertension, and hypercholesterolemia, before or at the time of CT, were significantly associated with CAC in univariate and multivariate analyses. CAC was associated with mean HbA(1c) (A1C) levels before enrollment, during the DCCT, and during the EDIC study. Prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced levels of A1C during the DCCT.
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Progressive coronary calcification despite intensive lipid-lowering treatment: a randomised controlled trial.
Houslay, ES, Cowell, SJ, Prescott, RJ, Reid, J, Burton, J, Northridge, DB, Boon, NA, Newby, DE, ,
Heart (British Cardiac Society). 2006;(9):1207-12
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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.
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Aggressive versus moderate lipid-lowering therapy in hypercholesterolemic postmenopausal women: Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES).
Raggi, P, Davidson, M, Callister, TQ, Welty, FK, Bachmann, GA, Hecht, H, Rumberger, JA
Circulation. 2005;(4):563-71
Abstract
BACKGROUND Women have been underrepresented in statin trials, and few data exist on the effectiveness and safety of statins in this gender. We used sequential electron-beam tomography (EBT) scanning to quantify changes in coronary artery calcium (CAC) as a measure of atherosclerosis burden in patients treated with statins. METHODS AND RESULTS In a double-blind, multicenter trial, we randomized 615 hyperlipidemic, postmenopausal women to intensive (atorvastatin 80 mg/d) and moderate (pravastatin 40 mg/d) lipid-lowering therapy. Patients also submitted to 2 EBT scans at a 12-month interval (mean interval 344+/-55 days) to measure percent change in total and single-artery calcium volume score (CVS) from baseline. Of the 615 randomized women, 475 completed the study. Mean+/-SD percent LDL reductions were 46.6%+/-19.9% and 24.5%+/-18.5 in the intensive and moderate treatment arms, respectively (P<0.0001), and National Cholesterol Education Program Adult Treatment Panel III LDL goal was reached in 85.3% and 58.8% of women, respectively (P<0.0001). The total CVS% change was similar in the 2 treatment groups (median 15.1% and 14.3%, respectively; P=NS), and single-artery CVS% changes and absolute changes were also similar (P=NS). In both arms, there was a trend toward a greater CVS progression in patients with prior cardiovascular disease, diabetes mellitus, and hypertension, whereas hormone replacement therapy had no effect on progression. CONCLUSIONS In postmenopausal women, intensive statin therapy for 1 year caused a greater LDL reduction than moderate therapy but did not result in less progression of coronary calcification. The limitations of this study (too short a follow-up period and the absence of a placebo group) precluded determination of whether progression of CVS was slowed in both arms or neither arm compared with the natural history of the disease.
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The effects of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients.
Chertow, GM, Raggi, P, McCarthy, JT, Schulman, G, Silberzweig, J, Kuhlik, A, Goodman, WG, Boulay, A, Burke, SK, Toto, RD
American journal of nephrology. 2003;(5):307-14
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BACKGROUND We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated. METHODS To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year. RESULTS The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate -2.5 +/- 1.8 mg/dl vs. sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium > or =10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 +/- 2.1 g/day - equivalent to 1.2 +/- 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 +/- 350, median change +20, p = 0.002) and aorta (mean change 181 +/- 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects. CONCLUSION Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.
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Continuous probabilistic prediction of angiographically significant coronary artery disease using electron beam tomography.
Budoff, MJ, Diamond, GA, Raggi, P, Arad, Y, Guerci, AD, Callister, TQ, Berman, D
Circulation. 2002;(15):1791-6
Abstract
BACKGROUND We sought to incorporate electron beam tomography-derived calcium scores in a model for prediction of angiographically significant coronary artery disease (CAD). Such a model could greatly facilitate clinical triage in symptomatic patients with no known CAD. METHODS AND RESULTS We examined 1851 patients with suspected CAD who underwent coronary angiography for clinical indications. An electron beam tomographic scan was performed in all patients. Total per-patient calcium scores and separate scores for the major coronary arteries were added to logistic regression models to calculate a posterior probability of the severity and extent of angiographic disease. These models were designed to be continuous, adjusted for age and sex, corrected for verification bias, and independently validated in terms of their incremental diagnostic accuracy. The overall sensitivity was 95%, and specificity was 66% for coronary calcium to predict obstructive disease on angiography. With calcium scores >20, >80, and >100, the sensitivity to predict stenosis decreased to 90%, 79%, and 76%, whereas the specificity increased to 58%, 72%, and 75%, respectively. The logistic regression model exhibited excellent discrimination (receiver operating characteristic curve area, 0.842+/-0.023) and calibration (chi2 goodness of fit, 8.95; P=0.442). CONCLUSIONS Electron beam tomographic calcium scanning provides incremental and independent power in predicting the severity and extent of angiographically significant CAD in symptomatic patients, in conjunction with pretest probability of disease. This algorithm is most useful when applied to an intermediate-risk population.