-
1.
Coronary artery calcium scoring: an evidence-based guide for primary care physicians.
Cheong, BYC, Wilson, JM, Spann, SJ, Pettigrew, RI, Preventza, OA, Muthupillai, R
Journal of internal medicine. 2021;(3):309-324
-
-
Free full text
-
Abstract
Primary care physicians often must decide whether statin therapy would be appropriate (in addition to lifestyle modification) for managing asymptomatic individuals with borderline or intermediate risk for developing atherosclerotic cardiovascular disease (ASCVD), as assessed on the basis of traditional risk factors. In appropriate subjects, a simple, noninvasive measurement of coronary artery calcium can help clarify risk. Coronary atherosclerosis is a chronic inflammatory disease, with atherosclerotic plaque formation involving intimal inflammation and repeated cycles of erosion and fibrosis, healing and calcification. Atherosclerotic plaque formation represents the prognostic link between risk factors and future clinical events. The presence of coronary artery calcification is almost exclusively an indication of coronary artery disease, except in certain metabolic conditions. Coronary artery calcification can be detected and quantified in a matter of seconds by noncontrast electrocardiogram-gated low-dose X-ray computed tomography (coronary artery calcium scoring [CACS]). Since the publication of the seminal work by Dr. Arthur Agatston in 1990, a wealth of CACS-based prognostic data has been reported. In addition, recent guidelines from various professional societies conclude that CACS may be considered as a tool for reclassifying risk for atherosclerotic cardiovascular disease in patients otherwise assessed to have intermediate risk, so as to more accurately inform decisions about possible statin therapy in addition to lifestyle modification as primary preventive therapy. In this review, we provide an overview of CACS, from acquisition to interpretation, and summarize the scientific evidence for and the appropriate use of CACS as put forth in current clinical guidelines.
-
2.
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.
-
3.
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
-
-
Free full text
-
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.
-
4.
Coronary artery calcium scoring in individuals at risk for coronary artery disease: current status and future perspectives.
Vonder, M, van der Aalst, CM, de Koning, HJ
The British journal of radiology. 2020;(1113):20190880
-
-
Free full text
-
Abstract
The aim of this review is to provide clinicians with an overview of the role of coronary artery calcium (CAC) scoring across the spectrum ranging from asymptomatic individuals to chronic chest pain patients. We will briefly introduce the technical background of CAC scoring, summarize the major guidelines per type of patient at risk and discuss latest research with respect to CAC. Finally, the reader should be able to determine when CAC scoring is indicated or may be of added value.
-
5.
Cardiovascular Risk Heterogeneity in Adults with Diabetes: Selective Use of Coronary Artery Calcium in Statin Use Decision-making.
Sarkar, S, Orimoloye, OA, Nass, CM, Blumenthal, RS, Martin, SS
Journal of general internal medicine. 2019;(11):2643-2647
-
-
Free full text
-
Abstract
Current American College of Cardiology/American Heart Association and American Diabetes Association guidelines recommend statin therapy for all patients with diabetes between the ages of 40 and 75, including those without cardiovascular disease (CVD). While diabetes is a major CVD risk factor, not all patients with diabetes have an equal risk of CVD. Thus, a more risk-based approach warrants consideration when recommending statin therapy for the primary prevention of CVD. Coronary artery calcium (CAC) is a noninvasive imaging modality that can help risk stratify patients with diabetes for future CVD events. CAC has been extensively studied in large cohorts such as the Multi-Ethnic Study of Atherosclerosis and found to outperform other novel risk stratification tools including carotid intima-media thickness. Moreover, a CAC score of 0 has been shown to be useful in downgrading the estimated risk of a CVD event in patients with diabetes and an intermediate Pooled Cohort Equation score. As clinicians weigh the recommendation for a lifelong therapy and the problem of statin nonadherence and patients weigh concerns about adverse effects of statins, the decision to initiate statin therapy in patients with diabetes is ideally a shared one between patients and providers, and CAC could facilitate this discussion.
-
6.
Tissue Non-Specific Alkaline Phosphatase and Vascular Calcification: A Potential Therapeutic Target.
Azpiazu, D, Gonzalo, S, Villa-Bellosta, R
Current cardiology reviews. 2019;(2):91-95
-
-
Free full text
-
Abstract
Vascular calcification is a pathologic phenomenon consisting of calcium phosphate crystal deposition in the vascular walls. Vascular calcification has been found to be a risk factor for cardiovascular diseases, due to its correlation with cardiovascular events and mortality, and it has been associated with aging, diabetes, and chronic kidney disease. Studies of vascular calcification have focused on phosphate homeostasis, primarily on the important role of hyperphosphatemia. Moreover, vascular calcification has been associated with loss of plasma pyrophosphate, one of the main inhibitors of calcification, thus indicating the importance of the phosphate/pyrophosphate ratio. Extracellular pyrophosphate can be synthesized from extracellular ATP by ecto-nucleotide pyrophosphatase/ phosphodiesterase, whereas pyrophosphate is hydrolyzed to phosphate by tissuenonspecific alkaline phosphatase, contributing to the formation of hydroxyapatite crystals. Over the last decade, vascular calcification has been the subject of numerous reviews and studies, which have revealed new agents and activities that may aid in explaining the complex physiology of this condition. This review summarizes current knowledge about alkaline phosphatase and its role in the process of vascular calcification as a key regulator of the phosphate/pyrophosphate ratio.
-
7.
Role of Vascular Smooth Muscle Cell Phenotypic Switching and Calcification in Aortic Aneurysm Formation.
Petsophonsakul, P, Furmanik, M, Forsythe, R, Dweck, M, Schurink, GW, Natour, E, Reutelingsperger, C, Jacobs, M, Mees, B, Schurgers, L
Arteriosclerosis, thrombosis, and vascular biology. 2019;(7):1351-1368
-
-
Free full text
-
Abstract
Aortic aneurysm is a vascular disease whereby the ECM (extracellular matrix) of a blood vessel degenerates, leading to dilation and eventually vessel wall rupture. Recently, it was shown that calcification of the vessel wall is involved in both the initiation and progression of aneurysms. Changes in aortic wall structure that lead to aneurysm formation and vascular calcification are actively mediated by vascular smooth muscle cells. Vascular smooth muscle cells in a healthy vessel wall are termed contractile as they maintain vascular tone and remain quiescent. However, in pathological conditions they can dedifferentiate into a synthetic phenotype, whereby they secrete extracellular vesicles, proliferate, and migrate to repair injury. This process is called phenotypic switching and is often the first step in vascular pathology. Additionally, healthy vascular smooth muscle cells synthesize VKDPs (vitamin K-dependent proteins), which are involved in inhibition of vascular calcification. The metabolism of these proteins is known to be disrupted in vascular pathologies. In this review, we summarize the current literature on vascular smooth muscle cell phenotypic switching and vascular calcification in relation to aneurysm. Moreover, we address the role of vitamin K and VKDPs that are involved in vascular calcification and aneurysm. Visual Overview- An online visual overview is available for this article.
-
8.
Role of pyrophosphate in vascular calcification in chronic kidney disease.
Azpiazu, D, Gonzalo, S, González-Parra, E, Egido, J, Villa-Bellosta, R
Nefrologia. 2018;(3):250-257
Abstract
Vascular calcification is a pathology characterized by the deposition of calcium-phosphate in cardiovascular structures, mainly in the form of hydroxyapatite crystals, resulting in ectopic calcification. It is correlated with increased risk of cardiovascular disease and myocardial infarction in diabetic patients and in those with chronic kidney disease (CKD). Vascular smooth muscle cells are sensitive to changes in inorganic phosphate (Pi) levels. They are able to adapt and modify some of their functions and promote changes which trigger calcification. Pi is regulated by parathyroid hormone and 1,25-dihydroxyvitamin D. Changes in the transport of Pi are the primary factor responsible for the regulation of Pi homeostasis and the calcification process. Synthesis of calcification inhibitors is the main mechanism by which cells are able to prevent vascular calcification. Extracellular pyrophosphate (PPi) is a potent endogenous inhibitor of calcium-phosphate deposition both in vivo and in vitro. Patients with CKD show lower levels of PPi and increased activity of the enzyme alkaline phosphatase. Numerous enzymes implicated in the metabolism of PPi have been associated with vascular calcifications. PPi is synthesized from extracellular ATP by nucleotide pyrophosphatase/phosphodiesterase from extracellular ATP hydrolysis. PPi is hydrolyzed into Pi by tissue-nonspecific alkaline phosphatase. ATP can be hydrolyzed to Pi via the ectonucleoside triphosphate diphosphohydrolase family. All these enzymes must be in balance, thereby preventing calcifications. However, diseases like CKD or diabetes induce alterations in their levels. Administration of PPi could open up new treatment options for these patients.
-
9.
Arterial ageing: from endothelial dysfunction to vascular calcification.
Tesauro, M, Mauriello, A, Rovella, V, Annicchiarico-Petruzzelli, M, Cardillo, C, Melino, G, Di Daniele, N
Journal of internal medicine. 2017;(5):471-482
-
-
Free full text
-
Abstract
Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed.
-
10.
CT calcium scoring. History, current status and outlook.
Sandfort, V, Bluemke, DA
Diagnostic and interventional imaging. 2017;(1):3-10
Abstract
Cardiovascular risk assessment has assumed a prominent role in the course of preventive care of all adults. Traditionally cardiovascular risk assessment has been performed using risk factors including gender, age, smoking history, lipid status, diabetes status, and family history. Increasingly, imaging has been deployed to directly detect coronary atherosclerotic disease. Quantification of coronary calcium (e.g., Agatston method, calcium mass and volume) is readily detected using helical CT scanners. Large multicenter cohort studies have enabled a better understanding of the relevance of coronary calcium detection. The purpose of this review is to review the methods for quantification of coronary artery calcium, as well as to present current and future perspectives on calcium scoring for cardiovascular risk stratification.