Abstract:
:There is now overwhelming evidence to support lowering LDL-c (low-density lipoprotein cholesterol) to reduce cardiovascular morbidity and mortality. Statins are a class of drugs frequently prescribed to lower cholesterol. However, in spite of their wide-spread use, discontinuation and nonadherence remains a major gap in both the primary and secondary prevention of atherosclerotic cardiovascular disease. The major reason for statin discontinuation is because of the development of statin-associated muscle symptoms, but a range of other statin-induced side effects also exist. Although the mechanisms behind these side effects have not been fully elucidated, there is an urgent need to identify those at increased risk of developing side effects as well as provide alternative treatment strategies. In this article, we review the mechanisms and clinical importance of statin toxicity and focus on the evaluation and management of statin-associated muscle symptoms.
journal_name
Circ Resjournal_title
Circulation researchauthors
Ward NC,Watts GF,Eckel RHdoi
10.1161/CIRCRESAHA.118.312782subject
Has Abstractpub_date
2019-01-18 00:00:00pages
328-350issue
2eissn
0009-7330issn
1524-4571journal_volume
124pub_type
杂志文章,评审abstract::The global prevalence of overweight and obesity has risen substantially over the past 4 decades and is accompanied by an increasing burden of cardiovascular risk factors such as hypertension. Metabolic surgery is the most effective method to treat obesity and may further improve associated conditions. Although most re...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.313320
更新日期:2019-03-29 00:00:00
abstract::To investigate the possible contributions of cardiac volume overload and cardiac sympathetic hyperactivity in the effects of sodium on cardiac mass, we evaluated the effects of treatment with saline (1%) and deoxycorticosterone acetate + saline (DOCA/saline) for 10 days and 3 and 6 weeks on ventricular anatomy and int...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.3.745
更新日期:1991-03-01 00:00:00
abstract::Myocardial responses to acute ischemia/reperfusion and to chronic ischemic conditions have been studied extensively at all levels of organization. These include subcellular (eg, mitochondria in vitro); intact, large animal models (eg, swine with chronic coronary stenosis); as well as human subjects. Investigations in ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.307898
更新日期:2017-03-31 00:00:00
abstract::Confocal imaging was used to study the influence of cytosolic ATP on the properties of spontaneous Ca(2+) sparks in permeabilized ventricular myocytes. Cells were perfused with mock intracellular solutions containing fluo 3. Reducing [ATP] to <0.5 mmol/L decreased the frequency but increased the amplitude of spontaneo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1801.096264
更新日期:2001-09-14 00:00:00
abstract::T-wave alternans (TWA), an ABAB oscillation, has been postulated as the initial pattern in a stepwise progression to higher-order oscillations, culminating in sudden arrhythmic death. The present study is the first to provide experimental evidence to support this intriguing concept. Epicardial and endocardial ECGs fro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000038887.17976.33
更新日期:2002-10-18 00:00:00
abstract::As described in earlier reviews in this series on the molecular basis of hypertrophic cardiomyopathy (HCM), HCM is one of the archetypal monogenic cardiovascular disorders to be understood at the molecular level. Twenty years after the discovery of the first HCM disease gene, genetic studies still confirm that HCM is ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.242974
更新日期:2011-06-24 00:00:00
abstract::Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle leng...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.1.182
更新日期:1985-07-01 00:00:00
abstract::Previous studies have shown that cardiac endothelial cells release substances that influence myocardial contraction. Since PO2 is an important stimulus that modulates endothelial function, we investigated the effects of acute moderate hypoxia and reoxygenation on the release of cardioactive factors by endothelial cell...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.5.688
更新日期:1997-05-01 00:00:00
abstract::Accumulation of plasminogen activator inhibitor type 1 (PAI-1) in the arterial wall may accelerate atherogenesis by inhibiting fibrinolysis, diminishing proteolysis of extracellular matrix proteins, or modifying migration of vascular smooth muscle cells. Increased intramural expression of the PAI-1 gene is induced by ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.4.671
更新日期:1993-10-01 00:00:00
abstract::The impact of vanadate on the Na,K-ATPase system in the vascular smooth muscle cell is poorly understood. The present study describes the kinetics of the effect of vanadate on Na,K-ATPase and the Na-K pump in in vitro grown rat VSMC's. Vanadate interaction with the Na,K-ATPase system in vascular smooth muscle cells wa...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.53.2.186
更新日期:1983-08-01 00:00:00
abstract::Endothelial cells isolated from bovine aortas without prior treatment with enzymes were cultured in RPMI 1640 medium containing 17% fetal calf serum and antibiotics. The endothelial cells at confluency (7 days) were similar to endothelium in situ or to freshly isolated endothelial cells from blood vessels as seen by l...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.799
更新日期:1975-06-01 00:00:00
abstract:BACKGROUND:Myocyte contractile dysfunction occurs in pathological remodeling in association with abnormalities in calcium regulation. Mice with cardiac myocyte-specific overexpression of Galphaq develop progressive left ventricular failure associated with myocyte contractile dysfunction and calcium dysregulation. OBJE...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.217570
更新日期:2010-07-23 00:00:00
abstract:RATIONALE:Hypoxia followed by reoxygenation promotes inflammation by activating nuclear factor κB transcription factors in endothelial cells (ECs). This process involves modification of the signaling intermediary tumor necrosis factor receptor-associated factor 6 with polyubiquitin chains. Thus, cellular mechanisms tha...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.300119
更新日期:2013-06-07 00:00:00
abstract::We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Con...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.3.881
更新日期:1991-09-01 00:00:00
abstract::Cyclic nucleotides are known to modify voltage-gated (L-type) Ca2+ channel activity in vascular smooth muscle cells, but the exact mechanism(s) underlying these effects is not well defined. The purpose of the present study was to investigate the modulatory role of the cAMP- and cGMP-dependent protein kinase (PKA and P...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.5.557
更新日期:1998-03-23 00:00:00
abstract::Proteases of the plasminogen activator (PA) and matrix metalloproteinase (MMP) system play an important role in smooth muscle cell (SMC) migration and neointima formation after vascular injury. Inhibition of either PAs or MMPs has previously been shown to result in decreased neointima formation in vivo. To inhibit bot...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000041418.51906.57
更新日期:2002-11-15 00:00:00
abstract::Postnatal development of the mammalian heart is associated with changes in the population of isoforms of the thin filament proteins. We correlated the change in thin filament proteins, which occur in rabbit hearts between 5 days and 22 days of age, with changes in Ca2+ dependence of myofibrillar ATPase activity, force...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1204
更新日期:1990-05-01 00:00:00
abstract:RATIONALE:Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE:To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressur...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.304846
更新日期:2015-02-13 00:00:00
abstract::C-reactive protein (CRP), a characteristic inflammatory marker, is a powerful predictor of cardiovascular events. Recent data suggest that CRP may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) is a newly identified endotheli...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000147309.54227.42
更新日期:2004-10-29 00:00:00
abstract::The role of contracture in the manifestation of calcium paradox-induced damage was examined using 2,3-butanedione monoxime (BDM) to inhibit myofibrillar activity. Calcium and sodium gain, loss of intracellular components, and changes in structure were monitored. If 30 mM BDM was added at the time of calcium repletion ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.4.560
更新日期:1987-10-01 00:00:00
abstract::The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate was used to probe the role of protein kinase-C in the modulation of alpha-adrenergic receptor-coupled calcium efflux in cultured vascular smooth muscle cells derived from rabbit aorta. Exposure of cells to 12-O-tetradecanoyl phorbol-13-acetate for 6 minutes cause...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.3.393
更新日期:1986-03-01 00:00:00
abstract::Heart failure is associated with death of cardiomyocytes leading to loss of contractility. Previous studies using membrane-targeted Akt (myristolated-Akt), an enzyme involved in antiapoptotic signaling, showed inhibition of cell death and prevention of pathogenesis induced by cardiomyopathic stimuli. However, recent s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000124394.01180.BE
更新日期:2004-04-16 00:00:00
abstract:RATIONALE:Upregulation of endothelial vascular cell adhesion molecule (VCAM)-1 and the subsequent increase in monocyte recruitment constitute critical events in atherogenesis. We have recently shown that in human coronary artery endothelial cells (HCAECs) regulated expression of VCAM-1 depends, to a significant extent,...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.213314
更新日期:2010-05-14 00:00:00
abstract:RATIONALE:Cardiac myocyte-specific deletion of either glycogen synthase kinase (GSK)-3α and GSK-3β leads to cardiac protection after myocardial infarction, suggesting that deletion of both isoforms may provide synergistic protection. This is an important consideration because of the fact that all GSK-3-targeted drugs, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308544
更新日期:2016-04-15 00:00:00
abstract::To determine the mechanical factors affecting regional segmental motion after acute coronary occlusion, we studied seven conscious dogs, instrumented with sonomicrometers. Loading conditions were changed by the withdrawal of 500 ml of blood and the transfusion of 800 ml of blood. To express segmental motion, percent s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.2.209
更新日期:1986-02-01 00:00:00
abstract::We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosol...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000262653.84850.8b
更新日期:2007-04-13 00:00:00
abstract::Although coronary artery spasm has been implicated as an important cause of myocardial ischemia in humans, an animal model of reversible segmental coronary constriction has not been described. To provoke coronary spasm in open-chest dogs, selected vasoconstricting agents adsorbed to viscous ion exchange gels were appl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.4.423
更新日期:1983-04-01 00:00:00
abstract:RATIONALE:Abdominal aortic aneurysms (AAAs) are characterized by pathological remodeling of the aortic wall. Although both increased Krüppel-like factor 5 (KLF5) expression and macrophage infiltration have been implicated in vascular remodeling, the role of KLF5 in macrophage infiltration and AAA formation remains uncl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.310367
更新日期:2017-03-03 00:00:00
abstract:RATIONALE:The dramatic upregulation of αvβ3-integrin that occurs in the vasculature during tumor growth has long suggested that the endothelial expression of this molecule is an ideal target for antiangiogenic therapy to treat cancer. This discovery led to the development of small-molecule inhibitors directed against α...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.301591
更新日期:2014-01-03 00:00:00
abstract::Focal ectopic activity in cardiac tissue is a key factor in the initiation and perpetuation of tachyarrhythmias. Because myofibroblasts as present in fibrotic remodeled myocardia and infarct scars depolarize cardiomyocytes by heterocellular electrotonic interactions via gap junctions in vitro, we investigated using st...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.160549
更新日期:2007-10-12 00:00:00