Abstract:
BACKGROUND:CSL112 is a new formulation of human apolipoprotein A-I (apoA-I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double-blind, multicenter, dose-ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease. METHODS AND RESULTS:Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2-hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug-related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA-I plasma concentration and measures of the ability of serum to promote cholesterol efflux from cells ex vivo. Of 45 patients randomized, 7, 12, and 14 received 1.7-, 3.4-, and 6.8-g CSL112, respectively, and 11 received placebo. There were no clinically significant elevations (>3× upper limit of normal) in alanine aminotransferase or aspartate aminotransferase. Adverse events were nonserious and mild and occurred in 5 (71%), 5 (41%), and 6 (43%) patients in the CSL112 1.7-, 3.4-, and 6.8-g groups, respectively, compared with 3 (27%) placebo patients. The imbalance in adverse events was attributable to vessel puncture/infusion-site bruising. CSL112 resulted in rapid (T(max)≈2 hours) and dose-dependent increases in apoA-I (145% increase in the 6.8-g group) and total cholesterol efflux (up to 3.1-fold higher than placebo) (P<0.001). CONCLUSIONS:CSL112 infusion was well tolerated in patients with stable atherosclerotic disease. CSL112 immediately raised apoA-I levels and caused a rapid and marked increase in the capacity of serum to efflux cholesterol. This potential novel approach for the treatment of atherosclerosis warrants further investigation. CLINICAL TRIAL REGISTRATION:URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01499420.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Tricoci P,D'Andrea DM,Gurbel PA,Yao Z,Cuchel M,Winston B,Schott R,Weiss R,Blazing MA,Cannon L,Bailey A,Angiolillo DJ,Gille A,Shear CL,Wright SD,Alexander JHdoi
10.1161/JAHA.115.002171subject
Has Abstractpub_date
2015-08-25 00:00:00pages
e002171issue
8issn
2047-9980pii
JAHA.115.002171journal_volume
4pub_type
杂志文章,多中心研究,随机对照试验abstract::Background Hyperhomocysteinemia is a risk factor for ischemic stroke; however, a targeted treatment strategy is lacking partly because of limited understanding of the causal role of homocysteine in cerebrovascular pathogenesis. Methods and Results In a genetic model of cystathionine beta synthase (CBS) deficiency, we ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.013368
更新日期:2020-02-18 00:00:00
abstract::Background Atherosclerotic vertebrobasilar disease is a significant etiology of posterior circulation stroke. The prospective observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated that distal hemodynamic status is a robust predictor of subsequent ve...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.016406
更新日期:2020-06-16 00:00:00
abstract::Background Programs targeting the standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, smoking) are critical to tackling coronary heart disease at a community level. However, myocardial infarction in SMuRF-less individuals is not uncommon. This study uses 2 se...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.013296
更新日期:2019-11-05 00:00:00
abstract::Background Many patients use opioids for nonmalignant pain, and opioid use in the general population has been associated with poor long-term outcomes. The use of high-risk medications, including opioid analgesics, may increase the risk of unplanned healthcare utilization. Methods and Results We performed a nested eval...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.010664
更新日期:2019-02-05 00:00:00
abstract:BACKGROUND:Neuregulin-1β (NRG-1β) is a growth factor critical for cardiac development and repair with therapeutic potential for heart failure. We previously showed that the glial growth factor 2 (GGF2) isoform of NRG-1β improves cardiac function in rodents after myocardial infarction (MI), but its efficacy in a large a...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.113.000773
更新日期:2014-10-23 00:00:00
abstract::Background Hyperkalemia can be harmful, but the effect of correcting hyperkalemia is sparsely studied. We used nationwide data to examine hyperkalemia follow-up in patients with hypertension. Methods and Results We identified 7620 patients with hypertension, who had the first plasma potassium measurement ≥4.7 mmol/L (...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.017087
更新日期:2020-12-15 00:00:00
abstract::Background Age-related changes in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age-related increases in blood pressure, but few genetic loci have been identified. We examined the role of mitochondrial genomic variation in blood pressure by sequencin...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.118.010009
更新日期:2018-09-18 00:00:00
abstract:BACKGROUND:Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed by a genetic risk score (GRS) are predictors of CHD risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways. METHODS AND RESULTS:Total effects of self-report...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.005254
更新日期:2017-03-20 00:00:00
abstract:BACKGROUND:Higher circulatory corin in patients with cardiac diseases is associated with improved cardiovascular outcomes, and chronic cardiac dysfunction is a well-known cause of progressive renal dysfunction. This study aimed to determine the role of serum corin in predicting short-term and long-term renal outcomes a...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.008157
更新日期:2018-05-04 00:00:00
abstract::Background Noninvasive cardiac tests, including exercise treadmill tests (ETTs), are commonly utilized in the evaluation of patients in the emergency department with suspected acute coronary syndrome. However, there are ongoing debates on their clinical utility and cost-effectiveness. It is important to be able to use...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.014940
更新日期:2020-03-03 00:00:00
abstract::Background Past reports suggested that total-body irradiation at 0.5 to 1.0 Gy could be responsible for atherosclerosis. Peripheral artery disease ( PAD ) is a manifestation of systematic atherosclerosis. Whether the consequences of a low-to-moderate dose of radiation include increased risk of PAD remains to be determ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.008921
更新日期:2018-12-04 00:00:00
abstract:BACKGROUND:Timely reperfusion after ST-elevation myocardial infarction (STEMI) improves survival. Guidelines recommend primary percutaneous coronary intervention (PPCI) within 90 minutes of arrival at a PCI-capable hospital. The alternative is fibrinolysis within 30 minutes for those in those for whom timely transfer t...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004113
更新日期:2016-10-06 00:00:00
abstract::Background Obesity is a precursor to heart failure with preserved ejection fraction. Biomarkers that identify preclinical metabolic heart disease ( MHD ) in young obese patients would help identify high-risk individuals for heart failure prevention strategies. We assessed the predictive value of GAL3 (galectin-3), FST...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.011100
更新日期:2019-04-02 00:00:00
abstract::Background Early discontinuation of P2Y12 antagonists post-percutaneous coronary intervention may increase risk of stent thrombosis or nonstent recurrent myocardial infarction. Our aims were to (1) analyze the early discontinuation rate of P2Y12 antagonists post-percutaneous coronary intervention, (2) explore factors ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012812
更新日期:2019-11-05 00:00:00
abstract:BACKGROUND:Clinical symptoms are part of the risk stratification approaches used in the emergency department (ED) to evaluate patients with suspected acute coronary syndromes (ACS). The objective of this study was to determine the sensitivity, specificity, and predictive value of 13 symptoms for a discharge diagnosis o...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.113.000586
更新日期:2014-04-02 00:00:00
abstract:BACKGROUND:Healthcare resources vary geographically, but associations between hospital-based resources and acute stroke quality and outcomes remain unclear. METHODS AND RESULTS:Using Get With The Guidelines-Stroke and Dartmouth Atlas of Health Care data, we examined associations between healthcare resource availabilit...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.116.003813
更新日期:2017-02-03 00:00:00
abstract:BACKGROUND:Cardiovascular disease is the leading cause of death in the United States, making improving cardiovascular health a key population health goal. As part of efforts to achieve this, the American Heart Association has developed the first comprehensive cardiovascular health index (CVHI). Our objective was to inv...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.001650
更新日期:2015-09-22 00:00:00
abstract:BACKGROUND:Microvascular injury (MVI) after primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) is a major determinant of adverse clinical outcome. Experimental data indicate an impact of hypercholesterolemia on MVI; however, there is a lack of clinical studies confirming this rela...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006957
更新日期:2017-10-10 00:00:00
abstract:BACKGROUND:Coronary heart disease and peripheral arterial disease (PAD) affect different vascular territories. Supplementing baseline findings with assays from stored serum, we compared their 20-year predictors. METHODS AND RESULTS:We randomly recruited 15 737 disease-free men and women aged 30 to 75 years across Scot...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.117.005967
更新日期:2017-09-18 00:00:00
abstract::Background Little attention has been paid to the importance of sex in the long-term prognosis of patients undergoing cardiac surgery. Methods and Results We conducted a retrospective cohort study of Ontario residents, aged ≥40 years, who underwent coronary artery bypass grafting (CABG) and/or aortic, mitral, or tricus...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
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更新日期:2016-11-23 00:00:00
abstract::Background Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations within the dystrophin gene. DMD is characterized by progressive skeletal muscle degeneration and atrophy and progressive cardiomyopathy. It has been observed the severity of cardiomyopathy varies in patients with DMD. Methods ...
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pub_type: 杂志文章
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更新日期:2020-10-20 00:00:00
abstract::Background Impaired heart rate variability (HRV) is associated with increased mortality in sinus rhythm. However, HRV has not been systematically assessed in patients with atrial fibrillation (AF). We hypothesized that parameters of HRV may be predictive of cardiovascular death in patients with AF. Methods and Results...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.016075
更新日期:2020-08-04 00:00:00
abstract::Background In this nationwide study, we used the unique Danish registries to estimate the risk of suicide and deliberate self-harm in patients with congenital heart disease (CHD). Methods and Results We identified all Danish citizens receiving a diagnosis of CHD between 1977 and 2007. As a reference cohort, we randoml...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.015735
更新日期:2020-05-18 00:00:00
abstract:BACKGROUND:A high consumption of omega-3 long-chain polyunsaturated fatty acids, and particularly docosahexaenoic acid (DHA), has been suggested to reduce the risk of cardiovascular disease (CVD). However, while DHA supplementation may have benefits for secondary prevention, few studies have investigated the role of DH...
journal_title:Journal of the American Heart Association
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/JAHA.113.000283
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:This study aimed to determine the relationship of statin therapy and cardiovascular risk factors to changes in atherosclerosis in the carotid artery. METHODS AND RESULTS:Carotid magnetic resonance imaging was used to evaluate 106 hyperlipidemic participants at baseline and after 12 months of 3-hydroxy-3-met...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003621
更新日期:2016-07-13 00:00:00
abstract::Background The overall goal of this longitudinal study was to determine if the Black population has decreased myocardial function, which has the potential to lead to the early development of congestive heart failure, compared with the White population. Methods and Results A total of 673 subjects were evaluated over a ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.015612
更新日期:2021-01-18 00:00:00
abstract:BACKGROUND:Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. We assessed the impact of quercetin on BP through a systematic review and meta-analysis of available randomized controlled t...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,meta分析,评审
doi:10.1161/JAHA.115.002713
更新日期:2016-07-12 00:00:00
abstract:BACKGROUND:Diabetes is associated with coronary arteriolar endothelial dysfunction. We investigated the role of the small/intermediate (SK(Ca)/IK(Ca)) conductance of calcium-activated potassium channels in diabetes-related endothelial dysfunction. METHODS AND RESULTS:Coronary arterioles (80 to 150 μm in diameter) were...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
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更新日期:2015-08-24 00:00:00