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1.
Carotid Artery Plaque Calcifications: Lessons From Histopathology to Diagnostic Imaging.
Saba, L, Nardi, V, Cau, R, Gupta, A, Kamel, H, Suri, JS, Balestrieri, A, Congiu, T, Butler, APH, Gieseg, S, et al
Stroke. 2022;(1):290-297
Abstract
The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.
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2.
Role of Coronary Artery Calcium Testing for Risk Assessment in Primary Prevention of Atherosclerotic Cardiovascular Disease: A Review.
Greenland, P, Lloyd-Jones, DM
JAMA cardiology. 2022;(2):219-224
Abstract
IMPORTANCE Current guidelines recommend a few different approaches to the use of coronary artery calcium (CAC) testing as a tool for risk assessment and decision-making regarding drug therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD). OBSERVATIONS Coronary artery calcium testing is not recommended for universal screening, particularly in patients at very low or high predicted risk for ASCVD, where its yield and utility for altering clinical decisions are limited. Use of CAC testing appears to be optimal when used in selected patients who are at intermediate or borderline risk of ASCVD as a sequential decision aid after initial quantitative risk assessment and consideration of individual patient risk-enhancing factors (eg, strong family history of premature ASCVD, chronic kidney disease). Although convincing clinical trials have not been completed, observational studies strongly suggest that, in those at intermediate risk, CAC testing can meaningfully reclassify risk and can support improved targeting of drug therapy to patients most likely to benefit. CONCLUSIONS AND RELEVANCE This narrative review summarizes the evidence available about the appropriate role of CAC testing for ASCVD risk assessment. Coronary artery calcium testing should be used selectively in patients who are at intermediate risk of ASCVD, when there is persistent uncertainty after performing standard risk assessment using traditional risk factors in a risk score, and after consideration of additional individual risk-enhancing factors. In these situations, the result of the CAC test can be helpful to clarify whether the patient's true risk is high enough to justify initiation of primary prevention medications, such as statins or aspirin.
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3.
Coronary artery calcium score: pivotal role as a predictor for detecting coronary artery disease in symptomatic patients.
Cherukuri, L, Birudaraju, D, Budoff, MJ
Coronary artery disease. 2021;(6):578-585
Abstract
Chest pain and dyspnea are common presentations for symptomatic individuals with suspected coronary artery disease (CAD) in the primary care office and cardiology clinics. However, it is imperative to properly diagnose who should undergo further evaluation for cardiac etiologies of chest pain, with either noninvasive or invasive imaging tests. The purpose of this review is to highlight the role of coronary artery calcium (CAC) score as a screening tool for symptomatic patients to detect CAD. The purpose of CAC scoring is to establish the presence and severity of coronary atherosclerosis that can play a vital role in symptomatic patients. The use of CAC testing in symptomatic patients has traditionally been limited due to fundamental concerns, including the occurrence of coronary calcification relatively late in the atherosclerotic process and high prevalence of CAC in the population. Further issue relates to its low specificity for obstructive CAD, as well as demonstration of significant ethnic variability in plaque composition and calcification patterns. CAC testing gained attention as an inexpensive, rapid, reproducible and a well-tolerated alternative to exclude CAD in symptomatic patients and defer further invasive imaging tests. This article will review the available literature in regard to the use of CAC in symptomatic populations.
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4.
Focused, low tube potential, coronary calcium assessment prior to coronary CT angiography: A prospective, randomized clinical trial.
Crimm, HA, Fergestrom, NM, Dye, C, Philip, C, Nguyen, BT, Villines, TC
Journal of cardiovascular computed tomography. 2021;(3):240-245
Abstract
BACKGROUND Coronary artery calcium (CAC) scanning is commonly performed before coronary CT angiography (CTA) based partly on its potential to influence CTA scan parameters. Encompassing the whole heart and performed at high tube potential (120 kVp), standard (Agatston) CAC scanning adds to patient radiation exposure. Most CAC exists in the proximal and mid coronary segments and is easily visualized at low kVp. METHODS We tested the impact of a modified calcium scan on coronary CTA acquisition decision-making and image quality in a randomized clinical trial. Providers documented planned CTA acquisition parameters prior to CAC scanning in a blinded manner. Standard Agatston CAC scans proceeded in typical fashion whereas modified scans utilized 80 kVp and reduced z-axis length focused on the proximal-to-mid coronary arteries. CTA providers reviewed the CAC burden then documented final acquisition parameters. RESULTS The study included 172 patients (48% female; mean age 59 ± 6.7). As planned, the calcium scan effective dose was significantly lower in the modified CAC scan group (0.14 vs. 0.74 mSv using a 0.014 k-factor or 0.26 vs. 1.38 mSv using a 0.026 k-factor; both p < 0.001). Initially selected CTA parameters were changed at an identical rate following visual CAC assessment (59%). There was no significant difference in coronary CTA image quality (median quality score = 4 in both groups, p = 0.26), noise (31.0 vs 31.4 HU; p = 0.81), or signal/noise ratio (17.9 vs 16.8; p = 0.26). CONCLUSIONS A low-kVp scan with focused field-of-view provides actionable information regarding the presence and severity of CAC prior to coronary CTA. Coronary CTA parameters based on patient variables are frequently modified after assessing CAC burden in the CTA suite. CLINICALTRIALS. GOV REGISTRATION NUMBER NCT02972242.
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5.
Interplay between gut microbiota, bone health and vascular calcification in chronic kidney disease.
Rodrigues, FG, Ormanji, MS, Heilberg, IP, Bakker, SJL, de Borst, MH
European journal of clinical investigation. 2021;(9):e13588
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Abstract
Deregulations in gut microbiota may play a role in vascular and bone disease in chronic kidney disease (CKD). As glomerular filtration rate declines, the colon becomes more important as a site of excretion of urea and uric acid, and an increased bacterial proteolytic fermentation alters the gut microbial balance. A diet with limited amounts of fibre, as well as certain medications (eg phosphate binders, iron supplementation, antibiotics) further contribute to changes in gut microbiota composition among CKD patients. At the same time, both vascular calcification and bone disease are common in patients with advanced kidney disease. This narrative review describes emerging evidence on gut dysbiosis, vascular calcification, bone demineralization and their interrelationship termed the 'gut-bone-vascular axis' in progressive CKD. The role of diet, gut microbial metabolites (ie indoxyl sulphate, p-cresyl sulphate, trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFA)), vitamin K deficiency, inflammatory cytokines and their impact on both bone health and vascular calcification are discussed. This framework may open up novel preventive and therapeutic approaches targeting the microbiome in an attempt to improve cardiovascular and bone health in CKD.
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Coronary artery calcium score and risk of cardiovascular events without established coronary artery disease: a systemic review and meta-analysis.
Abuzaid, A, Saad, M, Addoumieh, A, Ha, LD, Elbadawi, A, Mahmoud, AN, Elgendy, A, Abdelaziz, HK, Barakat, AF, Mentias, A, et al
Coronary artery disease. 2021;(4):317-328
Abstract
BACKGROUND Coronary artery calcium (CAC) is an indicator of atherosclerosis, and the CAC score is a useful noninvasive assessment of coronary artery disease. OBJECTIVE To compare the risk of cardiovascular outcomes in patients with CAC > 0 versus CAC = 0 in asymptomatic and symptomatic population in patients without an established diagnosis of coronary artery disease. METHODS A systematic search of electronic databases was conducted until January 2018 for any cohort study reporting cardiovascular events in patients with CAC > 0 compared with absence of CAC. RESULTS Forty-five studies were included with 192 080 asymptomatic 32 477 symptomatic patients. At mean follow-up of 11 years, CAC > 0 was associated with an increased risk of major adverse cardiovascular and cerebrovascular events (MACE) compared to a CAC = 0 in asymptomatic arm [pooled risk ratio (RR) 4.05, 95% confidence interval (CI) 2.91-5.63, P < 0.00001, I2 = 80%] and symptomatic arm (pooled RR 6.06, 95% CI 4.23-8.68, P < 0.00001, I2 = 69%). CAC > 0 was also associated with increased risk of all-cause mortality in symptomatic population (pooled RR 7.94, 95% CI 2.61-24.17, P < 0.00001, I2 = 85%) and in asymptomatic population CAC > 0 was associated with higher all-cause mortality (pooled RR 3.23, 95% CI 2.12-4.93, P < 0.00001, I2 = 94%). In symptomatic population, revascularization in CAC > 0 was higher (pooled RR 15, 95% CI 6.66-33.80, P < 0.00001, I2 = 72) compared with CAC = 0. Additionally, CAC > 0 was associated with more revascularization in asymptomatic population (pooled RR 5.34, 95% CI 2.06-13.85, P = 0.0006, I2 = 93). In subgroup analysis of asymptomatic population by gender, CAC > 0 was associated with higher MACE (RR 6.39, 95% CI 3.39-12.84, P < 0.00001). CONCLUSION Absence of CAC is associated with low risk of cardiovascular events compared with any CAC > 0 in both asymptomatic and symptomatic population without coronary artery disease.
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7.
Pathophysiology of Vascular Calcification and Bone Loss: Linked Disorders of Ageing?
Cannata-Andía, JB, Carrillo-López, N, Messina, OD, Hamdy, NAT, Panizo, S, Ferrari, SL, On Behalf Of The International Osteoporosis Foundation Iof Working Group On Bone And Cardiovascular Diseases,
Nutrients. 2021;(11)
Abstract
Vascular Calcification (VC), low bone mass and fragility fractures are frequently observed in ageing subjects. Although this clinical observation could be the mere coincidence of frequent age-dependent disorders, clinical and experimental data suggest that VC and bone loss could share pathophysiological mechanisms. Indeed, VC is an active process of calcium and phosphate precipitation that involves the transition of the vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Among the molecules involved in this process, parathyroid hormone (PTH) plays a key role acting through several mechanisms which includes the regulation of the RANK/RANKL/OPG system and the Wnt/ß-catenin pathway, the main pathways for bone resorption and bone formation, respectively. Furthermore, some microRNAs have been implicated as common regulators of bone metabolism, VC, left ventricle hypertrophy and myocardial fibrosis. Elucidating the common mechanisms between ageing; VC and bone loss could help to better understand the potential effects of osteoporosis drugs on the CV system.
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Safety and efficacy of coronary intravascular lithotripsy for calcified coronary arteries- a systematic review and meta-analysis.
Sattar, Y, Ullah, W, Mir, T, Biswas, S, Titus, A, Darmoch, F, Pacha, HM, Mohamed, MO, Kwok, CS, Fischman, DL, et al
Expert review of cardiovascular therapy. 2021;(1):89-98
Abstract
Objectives: Intravascular lithotripsy (IVL) clinical efficacy and safety in the treatment of calcified coronary artery disease (CAC) is not well known. We sought to assess IVL safety and efficacy in CAC. Methods: A comprehensive online databases search were performed to identify intravascular lithotripsy studies in patients with coronary artery disease. The primary outcome was IVL related change in the mean pre and post-procedural diameter of the coronary artery. Results: A total of 4 studies with 282 patients were included. The mean pre-IVL coronary diameter for all patients was 1.01 mm, while the mean post-IVL coronary diameter was 2.70 mm. The mean pre-post IVL diameter difference of coronary arteries on the pooled analysis was significantly lower by 4.08 mm (95% CI -4.94 to -3.30, p ≤ 0.00001). The Overall increase in the post-IVL lumen diameter was significantly higher than the pre-IVL diameter with a mean difference of -4.16 (95% CI -5.08 to -3.24, p = 0.000001). However, compared to pre-IVL, there was a significant reduction in the overall mean difference of luminal calcium angle after IVL of the stented coronary arteries (0.09, 95% CI 0.002-0.16, p = 0.01). Conclusion: Intravascular lithotripsy can offer a significant improvement in the vessel lumen to facilitate coronary stent delivery and deployments in severely calcified coronary arteries.
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User of angiotensin-converting-enzyme inhibitor and/or angiotensin II receptor blocker might be associated with vascular calcification in predialysis chronic kidney disease patients: a retrospective single-center observational study : ACEI/ARB and vascular calcification.
Takaori, K, Iwatani, H, Yamato, M, Ito, T
BMC nephrology. 2021;(1):7
Abstract
BACKGROUND Vascular calcification is a prominent feature in chronic kidney disease (CKD) and diabetes mellitus. A recent report suggests that angiotensin II is protective to vascular calcification. Therefore, we investigated the relationship between vascular calcification and use of angiotensin-converting-enzyme inhibitor (ACEI) and/or angiotensin II receptor blocker (ARB) from a cross-sectional view. METHODS A total of 121 predialysis CKD patients (age 71 ± 12 y; male 72; estimated glomerular filtration rate (eGFR) 20.2 (11.8 - 40.3) mL/min/1.73 m2) who underwent thoracoabdominal plain computed tomography scan were included in this study. The total vascular calcification volume (Calc) was calculated with a three-dimensional imaging software and standardized by body surface area (BSA). The relevance between log [Calc/BSA] and ACEI/ARB use was investigated by multivariate linear regression analyses with or without a time-duration factor of ACEI/ARB use. RESULTS The Calc/BSA was 5.62 (2.01 - 12.7) mL/m2 in 121 patients. In multivariate analyses adjusted with age, sex, ACEI/ARB and log [eGFR], ACEI/ARB use is significantly and positively associated with log [Calc/BSA] (β = 0.2781, p = 0.0007). Even after the adjustment by age, sex, log [eGFR], phosphate, diabetes mellitus, systolic blood pressure, warfarin, hypertension, dyslipidemia, low-density lipoprotein cholesterol, diuretics and ACEI/ARB, ACEI/ARB use is significantly and positively associated with log [Calc/BSA] (β = 0.1677, p = 0.0487). When 90 patients whose time-duration of ACEI/ARB use was clear in medical records were studied, a multivariate analysis adjusted with age, sex, log [eGFR], and ACEI/ARB duration factors showed that the longer use of ACEI/ARB more than 2 years was significantly, independently and positively associated with log [Calc/BSA] (β = 0.2864, p = 0.0060). CONCLUSIONS ACEI/ARB user was associated with vascular calcification in predialysis patients with low eGFR. Prospective studies with larger numbers of patients or more in vitro studies are needed to confirm whether this phenomenon is due to the use of ACEI/ARB itself, the underlying disease condition or the prescription bias.
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10.
Relationship between calcification, atherosclerosis and matrix proteins in the human aorta.
Kuzan, A, Wisniewski, J, Maksymowicz, K, Kobielarz, M, Gamian, A, Chwilkowska, A
Folia histochemica et cytobiologica. 2021;(1):8-21
Abstract
INTRODUCTION Extracellular matrix (ECM) proteins have been associated with atherosclerotic complications, such as plaque rupture, calcification and aneurysm. It is not clear what role different types of collagen play in the pathomechanism of atherosclerosis. The aim of the study was to analyze the content of elastin and major types of collagen in the aortic wall and how they associated are with course of atherosclerosis. MATERIAL AND METHODS In this work we present six biochemical parameters related to ECM proteins and collagen-specific amino acids (collagen type I, III, and IV, elastin, proline and hydroxyproline) analyzed in 106 patients' aortic wall specimens characterized by different degree of atherosclerosis. Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (LC/ESI-MS/MS), ELISA and immunohistochemical methods were used. The severity of atherosclerosis was assessed on the six-point scale of the American Heart Association, taking into account the number and location of foam cells, the presence of a fatty core, calcium deposits and other characteristic atherosclerotic features. RESULTS The results show that there is a relationship between the content of collagen-specific amino acids and development of atherosclerosis. The degree of atherosclerotic lesions was negatively correlated with the content of proline, hydroxyproline and the ratio of these two amino acids. Calcium deposits and surrounding tissue were compared and it was demonstrated that the ratio of type I collagen to type III collagen was higher in the aortic tissue than in aortic calcification areas, while the ratio of collagen type III to elastin was smaller in the artery than in the calcium deposits. CONCLUSIONS We suggest that increase in collagen type III presence in the calcification matrix may stem from disorders in the structure of the type I and III collagen fibers. These anomalous fibers are likely to favor accumulation of the calcium salts, an important feature of the process of atheromatosis.