Artery Calcification In Patients Research Articles

Association of Matrix Metalloproteinases with Coronary Artery Calcification in Patients with CHD

This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary heart disease (CHD) and 36 without CHD. Blood and samples of coronary arteries obtained as a result of endarterectomy were examined. Serum levels of metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13 were determined by multiplex analysis. In blood vessel samples, MMP-1, MMP-3, MMP-7, and MMP-9 were determined by enzyme immunoassay; MMP-9 expression was evaluated by immunohistochemistry. Patients with CHD had higher serum levels of MMP-1, MMP-7, and MMP-12. Blood levels of MMP-1 and MMP-3 were associated with calcium levels, MMP-9 with osteoprotegerin and osteonectin, MMP-7 and MMP-10 with osteoprotegerin, MMP-12 with osteocalcin, and MMP-13 with osteopontin. Calcified plaques had higher levels of MMP-1 and MMP-9 compared to plaques without calcification. The relative risk of coronary arteries calcification was associated with MMP-9, which is confirmed by the results of immunohistochemistry. The results obtained indicate the participation of some MMPs, and especially MMP-9, in the calcification processes. The study can serve as a basis for the further study of the possibility of using MMP-1, MMP-7 and MMP-12 as potential biomarkers of CHD.

Positive Association of Leptin and Artery Calcification of Lower Extremity in Patients With Type 2 Diabetes Mellitus: A Pilot Study.

ObjectiveWe aimed to explore the role and possible mechanism of leptin in lower-extremity artery calcification in patients with type 2 diabetes mellitus (T2DM).MethodsWe recruited 59 male patients with T2DM and 39 non-diabetic male participants. All participants underwent computed tomography scan of lower-extremity arteries. The calcification scores (CSs) were analyzed by standardized software. Plasma leptin level was determined by radioimmunoassay kits. Human vascular smooth muscle cells (VSMCs) calcification model was established by beta-glycerophosphate and calcium chlorideinduction. Calcium deposition and mineralization were measured by the o-cresolphthalein complexone method and Alizarin Red staining. The mRNA expression of bone morphogenic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and osteopontin (OPN) was determined by quantitative RT-PCR. The protein levels of BMP2, Runx2, α-smooth muscle actin (α-SMA) and (p)-Akt was determined by Western-blot analysis, and α-SMA was also measured by immunofluorescence analysis.ResultsCompared with controls, patients with T2DM showed higher median calcification score in lower-extremity artery [286.50 (IQR 83.41, 1082.00) vs 68.66 (3.41, 141.30), p<0.01]. Plasma leptin level was higher in patients with calcification score ≥300 than ≥100 (252.67 ± 98.57 vs 189.38 ± 44.19 pg/ml, p<0.05). Compared with calcification medium, intracellular calcium content was significantly increased in VSMCs treated by leptin (200, 400 and 800 ng/ml) combined with calcification medium [11.99 ± 3.63, 15.18 ± 4.55, and 24.14 ± 5.85 mg/ml, respectively, vs 7.27 ± 1.54 mg/ml, all p<0.01]. Compared with calcification medium, Alizarin Red staining showed calcium disposition was more obvious, and the mRNA level of BMP2, Runx2 and OCN was significantly increased, and immunofluorescence and Western blot analysis showed that the expression of α-SMA was downregulated in VSMCs treated by leptin (400 ng/ml) combined with calcification medium, respectively. Compared with calcification medium, the protein level of BMP2 and Runx2 was upregulated in VSMCs treated by leptin (400 ng/ml) combined with calcification medium. Moreover, blocking PI3K/Akt signaling pathway can decrease the protein expression of BMP2 and Runx2 in VSMCs treated by leptin (400 ng/ml) combined with calcification medium.ConclusionsLeptin promoted lower-extremity artery calcification of T2DM by upregulating the expression of BMP2 and Runx2, and regulating phenotypic switch of VSMCs via PI3K/Akt signaling pathway.

Incremental prognostic value of visually estimated coronary artery calcium in patients undergoing positron emission tomography imaging

ObjectiveVisually estimated coronary artery calcium (VECAC) from chest CT or attenuation correction (AC)/CT obtained during positron emission tomography (PET)–myocardial perfusion imaging (MPI) is feasible. Our aim was to determine the...

Association of Plasma MiRNA-204 and the Presence and Severity of Coronary Artery Calcification in Patients With Type 2 Diabetes.

We investigated the association between plasma microRNA (miR)-204 and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus (T2DM). We consecutively enrolled 179 individuals with T2DM who underwent coronary computed tomography at Anzhen Hospital from January 2015 to September 2016. The CAC score (CACS) was expressed in Agatston units and >10 Hounsfield units were defined as CAC-positive status. Significant CAC was observed in 98 (54.7%) patients. Plasma miR-204 levels (relative expression) were significantly lower in patients with significant CAC than controls (1.001 ± 0.100 vs 0.634 ± 0.211, P < .001). Plasma miR-204 levels were also negatively correlated with the glycosylated hemoglobin A1c (HbA1c) level (r = -0.702, P < .001), CACS (r = -0.710, P < .001), and the United Kingdom Prospective Diabetes Study (UKPDS) score (r = -0.355, P < .001). After multivariate logistic analyses, plasma miR-204 levels were still significantly and independently associated with the presence of CAC (odds ratio = 0.103, CI = 0.018-0.583, P < .001) after adjustment for conventional risk factors. Receiver operating characteristic curve analysis showed that plasma miR-204 levels can predict the severity and extent of CAC, and the specificity was higher than that of the traditional risk factors UKPDS score and HbA1c. In conclusion, the downregulation of miR-204 was independently associated with CAC in patients with T2DM.

Histopathological assessment of radial artery calcification in patients with end-stage kidney disease

Background A comprehensive understanding of vascular calcification pathology is significant for the development of cardiovascular disease therapy in high-risk populations. This cross-sectional study aimed to evaluate the prevalence and characteristics of radial artery calcification (RAC) and to identify the factors that are associated with RAC in end-stage kidney disease (ESKD). Methods Detailed medical histories of 180 patients with ESKD were recorded. Fragments of the radial artery obtained during the creation of arteriovenous fistula for hemodialysis access were stained with alizarin red S. Results Calcification was localized in the arterial media layer. The prevalence of positive calcification staining in the radial arteries was 21.1% (n = 38). Patients with RAC had a higher glycated hemoglobin level (p < 0.01), higher prevalence of dialysis duration >5 years (p = 0.022), and diabetes mellitus (p < 0.01) than those without RAC. Multiple logistic regression models showed dialysis duration >5 years (odds ratio [OR], 9.864; 95% confidence interval [CI], 2.666–36.502; p < 0.01) and diabetes mellitus (OR, 12.689; 95% CI, 2.796–34.597; p < 0.01) were independent risk factors for RAC in patients with ESKD. Patients with dialysis duration >5 years had a higher prevalence of RAC (p = 0.012) than those with dialysis duration ≤5 years. Patients with diabetes mellitus had a higher prevalence of RAC (p < 0.01) than those without diabetes mellitus. Patients with diabetes mellitus ≥15 years had a higher prevalence of RAC (p = 0.042) than those with diabetes mellitus <15 years. Radial artery calcification level showed a significantly positive correlation with dialysis duration (p < 0.05), diabetes mellitus duration (p < 0.01), HbA1c level (p < 0.01) and Calcium level (p < 0.01). Conclusions In patients with ESKD, dialysis duration >5 years and diabetes predict RAC. Thus, the combination of prolonged dialysis and hyperglycemic conditions exerts a synergistic effect on RAC.

Diagnostic value of fibroblast growth factor 23 for abdominal aortic calcification in Indonesian hemodialysis patients.

Objective:Homeostasis of serum phosphorus and calcitriol level is regulated mainly by fibroblast growth factor 23 (FGF23). Studies show that elevated serum FGF23 level was significantly associated with aortic calcification severity, peripheral blood vessels, and a higher score of coronary artery calcification in patients undergoing hemodialysis. We did this cross-sectional study to determine the FGF23 diagnostic value for abdominal aortic calcification in Indonesian hemodialysis patients.Materials and Methods:This study included seventy-five, chronic hemodialysis patients. An enzyme-linked immunosorbent assay method was used to measure serum intact FGF23 level, and abdominal aortic calcification was detected by lateral lumbar X-ray. The diagnostic value of FGF23 was analyzed using receiver operating characteristic (ROC) curves.Results:fifty-one (68.0%) patients had abdominal aortic calcification (AAC). Serum intact FGF23 level ranged from 217 to 950 pg/mL with a median level of 328 pg/mL. The FGF23 levels in the serum of patients with AAC were significantly higher than those without AAC (P < 0.001). The best cutoff point was 277 pg/mL. The calculated area under the ROC curves was 0.959 (95% confidence interval, 0.912–1.00); sensitivity was 94.0% and specificity was 84.0% (P < 0.001).Conclusion:serum intact FGF23 level may be proposed as a proper tool for abdominal aortic calcification in Indonesian hemodialysis patients.

Long-Term Prognosis of Moderate to Severe Coronary Artery Calcification in Patients Undergoing Percutaneous Coronary Intervention.

Moderate/severe coronary artery calcification (CAC) predicts worse clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). However, to date most studies have been modest in size and with limited follow-up. We aimed to assess the association between calcification severity and long-term clinical outcomes in a large cohort undergoing PCI. In total, 10,068 consecutive patients who underwent PCI at Fuwai Hospital were enrolled in this prospective observational study. Patients were categorized as none/mild or moderate/severe CAC according to the severity of the target lesion by visual assessment of coronary angiography. Major adverse cardiovascular events (MACE), a composite event of death, myocardial infarction and revascularization, at 5 years were assessed. None/mild CAC was observed in 8,229 (81.7%) patients, and moderate/severe CAC was observed in 1,839 (18.3%) patients. Patients with moderate/severe CAC had a significantly higher rate of 5-year unplanned revascularization (15.2% vs. 13.2%, P=0.022) and MACE (20.7% vs. 17.9%, P=0.005). After propensity score matching, the moderate/severe CAC group still had a higher rate of 5-year unplanned revascularization (15.2% vs. 12.6%, P=0.019). Cox regression analysis using clinically significant variables revealed moderate/severe calcification was independently associated with higher risk of 2-year unplanned target vessel revascularization (hazard ratio (HR)=1.287, 95% confidence interval (CI): 1.036-1.600, P=0.023) and MACE (HR=1.242, 95% CI: 1.039-1.484, P=0.017), but not 5-year unplanned revascularization and MACE. In patients undergoing PCI, moderate/severe coronary calcification increases the risk of long-term MACE.

Regional distribution and severity of arterial calcification in patients with chronic kidney disease stages 1\u20135: a cross-sectional study of the Copenhagen chronic kidney disease cohort

BackgroundPatients with chronic kidney disease (CKD) and arterial calcification are considered at increased risk of adverse cardiovascular outcomes. However, the optimal site for measurement of arterial calcification has not been determined. The primary aim of this study was to examine the pattern of arterial calcification in different stages of CKD.MethodsThis was an observational, cross-sectional study that included 580 individuals with CKD stages 1–5 (no dialysis) from the Copenhagen CKD Cohort. Calcification of the carotid, coronary and iliac arteries, thoracic and abdominal aorta was assessed using non-contrast multidetector computed tomography scans and quantified according to the Agatston method. Based on the distribution of Agatston scores in the selected arterial region, the subjects were divided into calcium score categories of 0 (no calcification), 1–100, 101–400 and > 400.ResultsParticipants with CKD stages 3–5 had the highest prevalence of calcification and the highest frequency of calcium scores > 400 in all arterial sites. Calcification in at least one arterial site was present in > 90% of patients with CKD stage 3. In all five CKD stages prevalence of calcification was greatest in both the thoracic and abdominal aorta, and in the iliac arteries. These arterial sites also showed the highest calcium scores. High calcium scores (> 400) in all five arterial regions were independently associated with prevalent cardiovascular disease. In multivariable analyses, after adjusting for cardiovascular risk factors, declining creatinine clearance was associated with increasing calcification of the coronary arteries (p = 0.012) and the thoracic aorta (p = 0.037) only.ConclusionsArterial calcification is highly prevalent throughout all five CKD stages and is most prominent in both the thoracic and abdominal aorta, and in the iliac arteries. Follow-up studies are needed to explore the potential of extracardiac calcification sites in prediction of cardiovascular events in the CKD population.

Evaluation of the Correlation between the rs4918 Polymorphism of AHSG Gene and Coronary Artery Calcification in Patients with Coronary Artery Disease

Objectives: Fetuin-A is a circulating calcification inhibitor that prevents coronary artery calcification (CAC) by increasing calcium phosphate solubility and inhibiting VSMC differentiation and apoptosis. In this study, we investigated the correlation between rs4918 and CAC in patients with coronary artery disease (CAD). Methods: Forty-two healthy individuals and eighty-one CAD patients were recruited in the present study. The CAC score (CACS) was measured by CT angiography and the genotype analysis of rs4918 single-nucleotide polymorphism SNP was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: The CACS was significantly higher in CAD patients compared to healthy individuals (p &lt; 0.001); however, there was no significant difference between the mean CACS in the presence and absence of rs4918 (p = 0.792). The mean calcium score of the left main coronary artery (LMCA) was significantly lower in carriers of the rs4918 allele (p = 0.036). The frequency of rs4918 SNP was almost similar in the control group and CAD patients (p = 0.846). Conclusions: in patients with CAD, we found no significant association between rs4918 SNP and CACS, indicating that carriers of this allele are not at increased risk of developing cardiovascular diseases compared with those without.

Association of apolipoprotein C3 with insulin resistance and coronary artery calcium in patients with type 1 diabetes

Apolipoprotein C3 (APOC3) is a risk factor for incident coronary artery disease in people with type 1 diabetes (T1D). The pathways that link elevated APOC3 levels to an increased risk of incident cardiovascular disease in people with T1D are not understood. To explore potential mechanisms, we investigated the association of APOC3 with insulin resistance and coronary artery calcium (CAC). In a random subcohort of participants with T1D from Coronary Artery Calcification in Type 1 Diabetes (n=134), serum APOC3, high-density lipoprotein (HDL)-associated APOC3, and retinol binding protein 4 (RBP4; a potential marker of insulin resistance) were measured by targeted mass spectrometry. We used linear regression to evaluate associations of serum APOC3 and HDL-APOC3 with APOB, non-HDL cholesterol, serum- and HDL-associated RBP4, and estimated insulin sensitivity and logistic regression to evaluate association with presence of CAC, adjusted for age, sex, and diabetes duration. Serum APOC3 correlated positively with APOB and non-HDL cholesterol and was associated with increased odds of CAC (odds ratio: 1.68, P=.024). Estimated insulin sensitivity was not associated with serum- or HDL-RBP4 but was negatively associated with serum APOC3 in men (ß estimate: -0.318, P=.0040) and decreased odds of CAC (odds ratio: 0.434, P=.0023). Serum APOC3 associates with increased insulin resistance and CAC in T1D.

Risk assessment of acute pulmonary embolism utilizing coronary artery calcifications in patients that have undergone CT pulmonary angiography and transthoracic echocardiography.

To evaluate the relation of coronary artery calcifications (CAC) on non-ECG-gated CT pulmonary angiography (CTPA) with short-term mortality in patients with acute pulmonary embolism (PE). We retrospectively included all in-patients between May 2007 and December 2014 with an ICD-9 code for acute PE and CTPA and transthoracic echocardiography available. CAC was qualitatively graded as absent, mild, moderate, or severe. Relations of CAC with overall and PE-related 30-day mortality were assessed using logistic regression analyses. The independence of those relations was assessed using a nested approach, first adjusting for age and gender, then for RV strain, peak troponin T, and cardiovascular risk factors for an overall model. Four hundred seventy-nine patients were included (63 ± 16 years, 52.8% women, 47.2% men). In total, 253 (52.8%) had CAC-mild: 143 (29.9%); moderate: 89 (18.6%); severe: 21 (4.4%). Overall mortality was 8.8% (n = 42) with higher mortality with any CAC (12.6% vs. 4.4% without; odds ratio [OR] 3.1 [95%CI 2.1-14.5]; p = 0.002). Mortality with severe (19.0%; OR 5.1 [95%CI 1.4-17.9]; p = 0.011), moderate (11.2%; OR 2.7 [95%CI 1.1-6.8]; p = 0.031), and mild CAC (12.6%; OR 3.1 [95%CI 1.4-6.9]; p = 0.006) was higher than without. OR adjusted for age and gender was 2.7 (95%CI 1.0-7.1; p = 0.050) and 2.6 (95%CI 0.9-7.1; p = 0.069) for the overall model. PE-related mortality was 4.0% (n = 19) with higher mortality with any CAC (5.9% vs. 1.8% without; OR 3.5 [95%CI 1.1-10.7]; p = 0.028). PE-related mortality with severe CAC was 9.5% (OR 5.8 [95%CI 1.0-34.0]; p = 0.049), with moderate CAC 6.7% (OR 4.0 [95%CI 1.1-14.6]; p = 0.033), and with mild 4.9% (OR 2.9 [95%CI 0.8-9.9]; p = 0.099). OR adjusted for age and gender was 4.2 (95%CI 0.9-20.7; p = 0.074) and 3.4 (95%CI 0.7-17.4; p = 0.141) for the overall model. Patients with sub-massive PE showed similar results. CAC is frequent in acute PE patients and associated with short-term mortality. Visual assessment of CAC may serve as an easy, readily available tool for early risk stratification in those patients. • Coronary artery calcification assessed on computed tomography pulmonary angiography is frequent in patients with acute pulmonary embolism. • Coronary artery calcification assessed on computed tomography pulmonary angiography is associated with 30-day overall and PE-related mortality in patients with acute pulmonary embolism. • Coronary artery calcification assessed on computed tomography pulmonary angiography may serve as an additional, easy readily available tool for early risk stratification in those patients.

Association of Bone Mineral Density and Coronary Artery Calcification in Patients with Osteopenia and Osteoporosis.

The aim of this study was to investigate the association between bone mineral density (BMD) and coronary artery calcification (CAC) in adults with osteopenia or osteoporosis. A retrospective medical review study was conducted in a regional hospital in southern Taiwan. Medical records of patients who underwent both a coronary computed tomography scan and a BMD measurement were identified. Multinomial logistic regression analyses were used to assess the association between BMD and CAC levels in patients with osteopenia or osteoporosis. Of the 246 patients, 119 were female and 42.3% had CAC. For patients with osteopenia, after adjusting for the significant factors of CAC, no significant association was observed between BMD with either moderate CAC (0 < CAC score ≤ 100) or high CAC (CAC score > 100). However, in patients with osteoporosis, after adjusting for the significant factors of CAC, BMD in the lumbar spine was inversely associated with moderate CAC (odds ratio = 0.38, p = 0.035). In conclusion, a lower BMD in the lumbar spine was associated with an increased risk of moderate CAC in patients with osteoporosis. It is crucial to take action to maintain bone health, particularly in those who already have osteoporosis, to reduce the risk of developing CAC and its associated morbidity and mortality.

Prevalence of basal ganglia and carotid artery calcifications in patients with permanent hypoparathyroidism after total thyroidectomy.

ObjectivePermanent hypoparathyroidism is an uncommon disease resulting most frequently from neck surgery. It has been associated with visceral calcifications but few studies have specifically this in patients with post-surgical hypoparathyroidism. The aim of the present study was to assess the prevalence of basal ganglia and carotid artery calcifications in patients with long-term post-thyroidectomy hypoparathyroidism compared with a control population.DesignCase–control study.MethodsA cross-sectional review comparing 29 consecutive patients with permanent postoperative hypoparathyroidism followed-up in a tertiary reference unit for Endocrine Surgery with a contemporary control group of 501 patients who had an emergency brain CT scan. Clinical variables and prevalence of basal ganglia and carotid artery calcifications were recorded.ResultsFrom a cohort of 46 patients diagnosed with permanent hypoparathyroidism, 29 were included in the study. The mean duration of disease was 9.2 ± 7 years. Age, diabetes, hypertension, smoking and dyslipidemia were similarly distributed in case and control groups. The prevalence of carotid artery and basal ganglia calcifications was 4 and 20 times more frequent in patients with permanent hypoparathyroidism, respectively. After propensity score matching of the 28 the female patients, 68 controls were matched for age and presence of cardiovascular factors. Cases showed a four-fold prevalence of basal ganglia calcifications, whereas that of carotid calcifications was similar between cases and controls.ConclusionA high prevalence of basal ganglia calcifications was observed in patients with post-surgical permanent hypoparathyroidism. It remains unclear whether carotid artery calcification may also be increased.

Associations of Serum Calciprotein Particle Size and Transformation Time With Arterial Calcification, Arterial Stiffness, and Mortality in Incident Hemodialysis Patients

Characteristics of the transformation of primary to secondary calciprotein particles (CPPs) in serum, including the size of secondary CPP (CPP2) aggregates and the time of transformation (T50), may be markers for arterial calcification in patients undergoing hemodialysis (HD). We examined the associations of CPP2 aggregate size and T50 with arterial calcification in incident HD patients. Prospective cohort study. Incident HD patients (n=402with available CPP2 measures and n=388with available T50 measures) from the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) Study PREDICTORS: Serum CPP2 size and T50 at baseline. Primary outcomes were baseline coronary artery and thoracic aorta calcifications. Exploratory outcomes included baseline arterial stiffness, measured by pulse wave velocity (PWV) and ankle brachial index, and longitudinally, repeat measures of PWV and all-cause mortality. Tobit regression, multiple linear regression, Poisson regression, linear mixed-effects regression, and Cox proportional hazards regression. Mean age was 55±13 years, 41% were women, 71% were Black, and 57% had diabetes mellitus. Baseline CPP2 size and T50 were correlated with baseline fetuin A level (r=-0.59 for CPP2 and 0.44 for T50; P<0.001 for both), but neither was associated with baseline measures of arterial calcification or arterial stiffness. Baseline CPP2 size and T50 were not associated with repeat measures of PWV. During a median follow-up of 3.5 (IQR, 1.7-6.2) years, larger CPP2 was associated with higher risk for mortality (HR, 1.17 [95% CI, 1.05-1.31] per 100nm larger CPP2 size) after adjusting for demographics and comorbid conditions, but there was no association between baseline T50 and risk for mortality. Possible imprecision in assays, small sample size, limited generalizability to incident HD populations with different racial composition, and residual confounding. In incident HD patients, neither CPP2 size nor T50 was associated with prevalent arterial calcification and stiffness. Larger CPP2 was associated with risk for mortality, but this finding needs to be confirmed in future studies.

Association between the high risk for obstructive sleep apnea and intracranial carotid artery calcification in patients with acute ischemic stroke.

Obstructive sleep apnea (OSA) is an independent risk factor for stroke. Furthermore, intracranial carotid artery calcification (ICAC) is a marker for subclinical atherosclerosis and future cardiovascular events. We investigated the association between the high risk for OSA and ICAC in patients with acute ischemic stroke. We retrospectively investigated 73 patients who were admitted to the hospital with acute ischemic stroke in the internal carotid artery (ICA) territory due to large-artery atherosclerosis. The risk for OSA was assessed using the Berlin Questionnaire, and patients were classified into low-risk (LR-OSA) and high-risk groups (HR-OSA). We compared the burden of ICAC between the two groups. Univariable and multivariable analyses were conducted to investigate the association of high risk for OSA with the presence of calcium in intracranial ICA. The HR-OSA group of 35 patients (48%) was significantly older and had a higher rate of hypertension and diabetes mellitus than the LR-OSA group. The HR-OSA group had more frequent ICAC (92% vs. 63%, p < 0.001), higher Agatston score (162.0 vs. 8.5, p < 0.001), and greater total volume of ICAC (261.2 mm3 vs. 20.1 mm3, p < 0.001) in the intracranial ICA. Presence of calcium in symptomatic intracranial ICA was positively correlated with age (odds ratio, OR, 1.432; 95% confidence interval, CI, 1.098-1.868) and HR-OSA (OR, 18.272; 95% CI, 0.500-668.401) in multivariable logistic regression analysis. This study showed that the presence of calcium in symptomatic intracranial ICA was related to high risk for OSA in patients with acute ischemic stroke.

P1283BASELINE CHARACTERISTICS IN THE “IPACK-HD” STUDY (INHIBIT PROGRESSION OF CORONARY ARTERY CALCIFICATION WITH VITAMIN K IN HEMODIALYSIS PATIENTS): A PHASE 2, MULTI-CENTRE, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PILOT TRIAL

Abstract Background and Aims The leading cause of mortality for patients with end-stage kidney disease (ESKD) is cardiovascular disease (CVD). This is due, in part, to vascular calcification (VC) where calcium becomes deposited within arterial walls causing narrowing of the arteries and altering their flexibility. Matrix Gla protein (MGP), a vitamin k-dependent protein, is a key local inhibitor of VC and becomes up-regulated adjacent to sites of calcification. There is a very high prevalence of vitamin K deficiency in patients across the chronic kidney disease (CKD) spectrum and vitamin K has been shown to prevent VC in experimental models. To date, no trial has examined whether vitamin K supplementation prevents the progression of coronary artery calcification in patients with ESKD, a group in which high risk has been established. The aim of the iPACK-HD pilot study is to determine whether a trial to determine whether vitamin K has a favourable effect on coronary artery calcium (CAC) scores in patients with ESKD is feasible. Method The iPACK-HD pilot trial is a phase 2 multi-centre, double-blind, randomized, placebo-controlled clinical trial conducted in three sites (Kingston, Ottawa and London) in Ontario, Canada. Adult patients with ESKD on chronic dialysis with a baseline CAC score of ≥30 Agatston units (AUs) are randomized to receive 10 mg of vitamin K1 or matching placebo administered post-hemodialysis 3x/week for a total of 12 months. Exclusions include medical conditions that require anticoagulation and a history of either coronary artery bypass, grafting or stenting. Randomization is stratified based on diabetes and study centre. Baseline CAC scores are determined by computed tomography (CT) and demographic and laboratory data at study entry are obtained by participant interview and medical chart review. Results A total of 85 participants are randomized into this trial. Baseline characteristics of trial participants are reported as mean ± SD, median [IQR], or %. The mean age is 63 ± 13 years. There are a higher proportion of males (57%) than females and whites (85%) compared to all other ethnicities. Forty-four percent of participants have diabetes and 77% have hypertension. Dialysis vintage is 0.9 [0.4,2.7] years. Most participants take calcium-based phosphate binders (89%) and over half of participants take an HMG-CoA reductase inhibitor (53%) or vitamin D (61%). Clinical laboratory values are presented in Table 1. Total median CAC and volume calcium scores are 587 [252,1416] AUs and 482 [206,1170] mm3, respectively. Sixty-five (76%) participants had a study exit CT scan performed upon completion of the study. Of 156 doses, a median of 150 [123,155] were received and 2 [1,6] were missed. Conclusion Participants in the iPACK-HD study have a high burden of calcification but are similar in baseline characteristics to the Canadian hemodialysis population. Loss to trial completion is 24%, but the most frequent reason is kidney transplantation. Adherence to study drug is very high with few reported side effects.

Prevalence of Coronary Artery Calcium in Patients With Atrial Fibrillation With and Without Cardiovascular Risk Factors

The burden of coronary artery atherosclerosis in patients with atrial fibrillation (AF) is unknown. We aimed to assess the coronary artery calcium (CAC) in AF patients. We retrospectively analyzed 324 consecutive patients with AF who had CT angiogram before AF ablation and their cardiovascular risk were prospectively collected. Mean age of the cohort was 66 years and 71% were male. The previous history of coronary artery disease (CAD) was present in 19% (n = 63) and CAC was positive in all. In patients without known CAD (n = 261), CAC was present in 70% (n = 182) with a comparable prevalence between men and women, which raised the prevalence of coronary atherosclerosis to 76% (n = 245) for the entire cohort. The median CAC score was 170 (range 1 to 6,157) and largely in multivessel distribution in patients without known CAD. Presence of CAC increased with an increasing number of cardiovascular risk factors. Nevertheless, CAC was present in 58% (n = 40) of patients without conventional cardiovascular risk factors. If CAC score >100 was considered as CAD equivalent as 10-year risk of incident atherosclerotic cardiovascular diseases is >7.5% it would have resulted in higher CAD prevalence of 52% and significant reclassification of CHA2DS2-VASc score in 41% of patients without known CAD. In conclusion, coronary calcium is highly prevalent in AF patients, including those without cardiovascular risk factors. Advanced CAC can potentially shift CHA2DS2-VASc score in many AF patients. Our findings suggest that characterizing CAC in AF may be clinically valuable in thromboembolic risk stratification and management of preventive cardiac therapies.

Heart dose and coronary artery calcification in patients receiving thoracic irradiation for lung cancer.

BackgroundThoracic irradiation (TIR) is associated with an increased risk of coronary artery disease (CAD) and coronary-related death. Lung cancer patients receive considerable doses of TIR, making them a high-risk population that may benefit from post-therapy surveillance. Coronary artery calcium (CAC) is a known biomarker of CAD development and may serve as a useful indicator of disease progression in this population. We hypothesized greater CAC progression in lung cancer patients subjected to higher whole heart radiation doses.MethodsCAC progression (pre- and >2 years post-TIR) from chest CT scans of lung cancer patients were evaluated. A 2:1 matched control population was established controlling for age, gender, race, and CT scan interval. Vessel-specific CAC presence, progression, and extension in pre- and post-interval CT studies was evaluated by two blinded reviewers using the ordinal method. Dosimetric treatment files were restored and contours of the whole heart and proximal left anterior descending artery (LAD) were created within existing plans to compute radiation doses (Pinnacle Treatment Planning Software). Binary logistic regression analysis identified factors predictive for CAC development. Multiple logistic regression analysis with hierarchal method was used to assess covariates.ResultsThirty-five patients and 65 controls (50% female) were evaluated; mean age 57 years, mean follow-up post-radiation 4.9±2.2 years. Average mean and maximum left anterior descending coronary artery (LAD) radiation doses were 19.9 Gy (95% CI, 14.1–25.7) and 30.7 Gy (95% CI, 23.8–37.5), respectively; 91.6% inter-observer variability. There was greater incidence of coronary calcification in irradiated patients (48.6% vs. 24.6%; P=0.01). In interval CT scans, a greater proportion of radiated patients demonstrated new coronary calcification (P=0.007) and extension within the LAD (P=0.003). Radiation exposure was the only independent predictor of new calcification (OR 3.1; 95% CI: 1.09–9.2).ConclusionsWe identified both an increase in the development and progression of CAC in lung cancer patients receiving TIR. Future studies utilizing alternative cancer populations and larger sample sizes are necessary to further correlate radiographic and dosimetric observations to cardiovascular events.

Vascular Calcification in Patients Undergoing Total Knee Arthroplasty: Frequency and Effects on the Surgery.

BackgroudThis study aims to investigate the frequency of distal femoral and popliteal arterial calcification and to evaluate the intraoperative and postoperative effects of arterial calcification in patients undergoing total knee arthroplasty using a tourniquet.MethodsThe records of 5,438 patients who had undergone primary total knee arthroplasty between January 2003 and January 2017 were retrospectively reviewed. We examined the preoperative radiographs of the knee from all patients for calcifications of the femoral and popliteal arteries. Vascular calcification was identified on preoperative radiographs in 223 cases. Intraoperative and postoperative complications were investigated among these patients. Postoperative complications were analyzed from the time of surgery to the last follow-up (minimum 1-year follow-up).ResultsVascular calcification of the arteries around the knee was found in 223 cases (4.1%). The mean patient age was 70.6 years in the non-calcification group and 73.8 years in the calcification group (p > 0.05). The calcification group was classified into medial, intimal, or mixed subgroups according to the morphology of calcification on preoperative radiographs. The medial type included 46 cases (20.6%); intimal type, 161 cases (72.2%); and mixed type, 16 cases (2.7%). There was no statistically significant difference in demographic and surgical data among the three groups. There were intraoperative complications in two cases in the medial type group, both of which involved tourniquet failure. There was also a postoperative complication in one case in the medial type group, which involved wound dehiscence at 2 weeks postoperatively. No other postoperative complications were identified during 1-year follow-up.ConclusionsDespite the presence of calcifications in the arteries around the knee, total knee arthroplasty (using a tourniquet) can be performed without serious complications.

Vitamin K Antagonist Use and Risk for Intracranial Carotid Artery Calcification in Patients With Intracerebral Hemorrhage

Background: Intracranial carotid artery calcification (ICAC) on computed tomography (CT) is a marker of atherosclerosis and an independent predictor of vascular events including stroke. While vitamin K antagonists (VKAs) are used to prevent embolic stroke, they have been shown to increase levels of both coronary and extracoronary artery calcification. This has not been studied for (intracranial) carotid arteries. The aim of this study is to investigate the association between VKA use and degree of ICAC. We tested our hypothesis in a cohort of patients with nontraumatic intracerebral hemorrhage (ICH) of which a substantial part used VKAs.Materials and Methods: We retrospectively semiquantified ICAC on brain unenhanced CT of consecutive adult patients with nontraumatic ICH. Assessment was performed blinded to clinical characteristics and status of VKA use. We used a 5-point visual scale and dichotomized degree of ICAC in low and high degree. Patient demographics, VKA use, duration of VKA treatment, as well as known risk factors for intracranial calcification were collected. Univariable and multivariable logistic regression analyses were performed to investigate the association between ICAC and VKA use.Results: Three hundred and seventy-six nontraumatic ICH patients were included of whom 77 were using VKAs (20.5%) with a median treatment duration of 35 months. Any degree of ICAC was detected in 289 patients (76.9%). Univariable analysis showed that a high degree of ICAC was significantly associated with older age [odds ratio (OR), 1.06, 95% confidence interval (CI), 1.03–1.08], hypertension (OR, 2.14; 95% CI, 1.27–3.62), diabetes mellitus (OR, 2.38; 95% CI, 1.27–4.49), and the use of VKAs (OR, 1.84; 95% CI, 1.06–3.20). In multivariable regression analysis, only older age was significantly associated with a higher degree of ICAC (OR, 1.05; 95% CI, 1.02–1.08), while VKA use was not (OR, 1.22; 95% CI, 0.67–2.24).Conclusions: Our findings do not support VKA use as an independent risk factor for higher ICAC degree in patients with ICH. We could not confirm the concerns about VKA use and intracranial carotid vascular calcification. We suggest further research in other cohorts with VKA users such as patients with ischemic stroke and atrial fibrillation.