Abstract:
BACKGROUND:Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition, and cardiovascular risk reduction remains undefined. METHODS:Lp(a) was measured in 25 096 patients in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a randomized trial of evolocumab versus placebo in patients with established atherosclerotic cardiovascular disease (median follow-up, 2.2 years). Cox models were used to assess the independent prognostic value of Lp(a) and the efficacy of evolocumab for coronary risk reduction by baseline Lp(a) concentration. RESULTS:The median (interquartile range) baseline Lp(a) concentration was 37 (13-165) nmol/L. In the placebo arm, patients with baseline Lp(a) in the highest quartile had a higher risk of coronary heart disease death, myocardial infarction, or urgent revascularization (adjusted hazard ratio quartile 4: quartile 1, 1.22; 95% CI, 1.01-1.48) independent of low-density lipoprotein cholesterol. At 48 weeks, evolocumab significantly reduced Lp(a) by a median (interquartile range) of 26.9% (6.2%-46.7%). The percent change in Lp(a) and low-density lipoprotein cholesterol at 48 weeks in patients taking evolocumab was moderately positively correlated ( r=0.37; 95% CI, 0.36-0.39; P<0.001). Evolocumab reduced the risk of coronary heart disease death, myocardial infarction, or urgent revascularization by 23% (hazard ratio, 0.77; 95% CI, 0.67-0.88) in patients with a baseline Lp(a) >median, and by 7% (hazard ratio, 0.93; 95% CI, 0.80-1.08; P interaction=0.07) in those ≤median. Coupled with the higher baseline risk, the absolute risk reductions, and number needed to treat over 3 years were 2.49% and 40 versus 0.95% and 105, respectively. CONCLUSIONS:Higher levels of Lp(a) are associated with an increased risk of cardiovascular events in patients with established cardiovascular disease irrespective of low-density lipoprotein cholesterol. Evolocumab significantly reduced Lp(a) levels, and patients with higher baseline Lp(a) levels experienced greater absolute reductions in Lp(a) and tended to derive greater coronary benefit from PCSK9 inhibition. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.
journal_name
Circulationjournal_title
Circulationauthors
O'Donoghue ML,Fazio S,Giugliano RP,Stroes ESG,Kanevsky E,Gouni-Berthold I,Im K,Lira Pineda A,Wasserman SM,Češka R,Ezhov MV,Jukema JW,Jensen HK,Tokgözoğlu SL,Mach F,Huber K,Sever PS,Keech AC,Pedersen TR,Sabatine MSdoi
10.1161/CIRCULATIONAHA.118.037184subject
Has Abstractpub_date
2019-03-19 00:00:00pages
1483-1492issue
12eissn
0009-7322issn
1524-4539journal_volume
139pub_type
杂志文章,随机对照试验相关文献
CIRCULATION文献大全abstract:BACKGROUND:Myocardium irreversibly injured by ischemic stress must be efficiently repaired to maintain tissue integrity and contractile performance. Macrophages play critical roles in this process. These cells transform across a spectrum of phenotypes to accomplish diverse functions ranging from mediating the initial i...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.117.031046
更新日期:2018-06-12 00:00:00
abstract:BACKGROUND:Apoptosis in human atherosclerotic coronary plaques possibly causes plaque destabilization by contributing to the weakening and breaking down of the fibrous cap. We tested the hypothesis that apoptosis is quantitatively increased in unstable atherosclerotic plaques. METHODS AND RESULTS:We analyzed the expre...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000142865.04816.89
更新日期:2004-09-28 00:00:00
abstract::We evaluated the effects of selective activation of H1 receptors on coronary hemodynamics in 16 patients divided into two groups: group A, 11 patients with atypical angina or valvular heart disease and normal coronary arteries, and group B, five patients with spontaneous angina, four of whom had significant (greater t...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.73.6.1175
更新日期:1986-06-01 00:00:00
abstract::Current automatic implantable cardioverter-defibrillators detect tachyarrhythmias primarily by rate-only algorithms and cannot adequately distinguish hemodynamically stable from unstable tachyarrhythmias. The responses of right atrial (mean) and right ventricular pressures (mean, systolic, diastolic, and pulse) to 64 ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.82.2.394
更新日期:1990-08-01 00:00:00
abstract:BACKGROUND:The introduction of limited approaches to the heart and the avoidance of cardiopulmonary bypass (CPB) aim to reduce the invasiveness of CABG by decreasing the systemic release of inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8, as well as the anti-inflammatory ...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/01.cir.102.suppl_3.iii-95
更新日期:2000-11-07 00:00:00
abstract:BACKGROUND:BET (bromodomain and extraterminal) epigenetic reader proteins, in particular BRD4 (bromodomain-containing protein 4), have emerged as potential therapeutic targets in a number of pathological conditions, including cancer and cardiovascular disease. Small-molecule BET protein inhibitors such as JQ1 have demo...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.120.047239
更新日期:2020-12-15 00:00:00
abstract:BACKGROUND:Although autonomic imbalance is known to be characteristics of patients with clinically overt symptomatic congestive heart failure, it is currently unknown whether this autonomic response arises early in the course of left ventricular dysfunction or is restricted to the later stages of circulatory failure. ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.92.3.555
更新日期:1995-08-01 00:00:00
abstract:BACKGROUND:High blood pressure (BP) is a known risk factor for mobility and cognitive impairment in older adults. This study tested the association of cumulative BP exposure from young adulthood to midlife with gait and cognitive function in midlife. Furthermore, we tested whether these associations were modified by ce...
journal_title:Circulation
pub_type: 杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.119.042502
更新日期:2020-03-03 00:00:00
abstract:BACKGROUND:Trends in cardiovascular mortality across Europe demonstrate significant geographical variation, and an understanding of these trends has a central role in global public health. METHODS AND RESULTS:Ischemic heart disease and cerebrovascular disease age-standardized death rates (as per International Classifi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.115.018931
更新日期:2016-05-17 00:00:00
abstract:BACKGROUND:The clinical significance and pathophysiological mechanisms of reverse redistribution on stress-redistribution thallium-201 myocardial scintigraphy in patients with chronic coronary artery disease are unclear. Recent studies have shown that thallium-201 reinjection is a useful technique for the detection of ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.88.4.1736
更新日期:1993-10-01 00:00:00
abstract:BACKGROUND:Treatment of aortocaval fistulae (ACFs) by open surgery is known to be a high-risk procedure. In this experimental study, we developed a percutaneous model of ACF to test a new nonsurgical method of treatment of ACF using endovascular stent grafts. METHODS AND RESULTS:An ACF was created percutaneously in ei...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.94.1.108
更新日期:1996-07-01 00:00:00
abstract::Variations in the frequency of complex ventricular arrhythmias were evaluated by consecutive 24-hour long-term electrocardiographic recordings over 4 days using a two-channel recorder and computer-assisted analysis system with a weighted relative mean error of 7.5 +/ 5% (SD). Twenty patients (mean age 58 +/- 9 years ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.61.4.690
更新日期:1980-04-01 00:00:00
abstract:BACKGROUND:Observational studies have shown better survival in patients undergoing coronary artery bypass grafting (CABG) with 2 arterial grafts compared with 1. However, whether a third arterial graft is associated with incremental benefit remains uncertain. We sought to analyze the outcomes of 3 versus 2 arterial gra...
journal_title:Circulation
pub_type: 杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.118.034464
更新日期:2018-11-06 00:00:00
abstract::The effect of prolonged intense endurance exercise training on exertional hypotension was investigated in 16 patients with coronary artery disease who had a 10 mm Hg or greater fall in systolic blood pressure (SBP) during progressive exercise testing. Training consisted of walking, running, or cycling at 50% to 60% of...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.76.3.548
更新日期:1987-09-01 00:00:00
abstract:BACKGROUND:Previous studies have established that bone marrow-derived endothelial progenitor cells (EPCs) are present in the systemic circulation. In the current study, we investigated the hypothesis that gene transfer can be used to achieve phenotypic modulation of EPCs. METHODS AND RESULTS:In vitro, ex vivo murine v...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc0602.103673
更新日期:2002-02-12 00:00:00
abstract::This review defines the substantial pediatric morbidity from tobacco use, including health effects on the cardiovascular system, the respiratory system, the fetus and newborn, and risk-taking behaviors of adolescents. More recent research suggests effects may extend to other areas, including reports that cigarette smo...
journal_title:Circulation
pub_type: 杂志文章,评审
doi:10.1161/01.cir.90.5.2581
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND:Bias in studies of preventive medications can occur when healthier patients are more likely to initiate and adhere to therapy than less healthy patients. We sought evidence of this bias by examining associations between statin exposure and various outcomes that should not be causally affected by statin expos...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.824151
更新日期:2009-04-21 00:00:00
abstract::Although a family history of ischemic heart disease is a well-accepted risk factor for cardiovascular disease, only three prospective studies--all in men--have examined the predictive strength of a positive family history after adjusting for other heart disease risk factors. The present analysis is based on a 9 year f...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.69.6.1065
更新日期:1984-06-01 00:00:00
abstract:BACKGROUND:During ischemia, the intracellular calcium and inorganic phosphate (P(i)) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial r...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc3501.095485
更新日期:2001-09-04 00:00:00
abstract::Scanning and transmission electron microscopic studies were made of: 1) 15 glutaraldehyde-treated porcine valvular heterografts that had been implanted in patients for periods of time ranging from 2 days to 76 months; 2) unimplanted, commercially processed porcine aortic valves; and 3) unprocessed porcine aortic valve...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1978-09-01 00:00:00
abstract::In 526 patients undergoing a first percutaneous transluminal coronary angioplasty (PTCA) of a single native vessel, we studied the influence of length and eccentricity of the lesion on complications and primary success. Long stenoses (greater than or equal to 5 mm, n = 153) did not differ from short stenoses (less tha...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.67.3.497
更新日期:1983-03-01 00:00:00
abstract:BACKGROUND:Although the American Heart Association/American College of Sports Medicine's Preparticipation Questionnaire (AAPQ) is a recommended preexercise cardiovascular screening tool, it has never been systematically evaluated. The purpose of this research is to provide preliminary evidence of its effectiveness amon...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.113.004160
更新日期:2014-03-11 00:00:00
abstract::From January 1968 to June 1975 tricuspid regurgitation was encountered in 238 patients of a total of 1074 patients undergoing operations on the mitral valve. During this time tricuspid annuloplasty (TA) was performed in 137 patients and the tricuspid valve was replaced (TVR) in 101 patients. Comparison of hospital mor...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1976-12-01 00:00:00
abstract:BACKGROUND:We hypothesized that during demand ischemia, abnormal perfusion will precede abnormal function, the spatial extent of perfusion abnormality will be greater than that of functional abnormality, and the spatiotemporal disparity between abnormal perfusion and abnormal function will be more marked in the presenc...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc0802.104326
更新日期:2002-02-26 00:00:00
abstract:BACKGROUND:Functional mitral regurgitation (MR) is caused by systolic traction on the mitral leaflets related to ventricular distortion. Little is known about whether chronic tethering causes the mitral leaflet area to adapt to the geometric needs imposed by tethering, in part because of inability to reconstruct leafle...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.107.749440
更新日期:2008-08-19 00:00:00
abstract:BACKGROUND:Failure to differentiate supraventricular from ventricular arrhythmias is the most frequent cause of inappropriate implantable cardioverter-defibrillator therapies. Although a sudden-onset criterion is available to differentiate sustained monomorphic ventricular tachycardias (SMVTs) and sinus tachycardias (S...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.98.7.671
更新日期:1998-08-18 00:00:00
abstract:BACKGROUND:Controversy exists as to whether off-pump CABG with local occlusion results in clinically significant myocardial ischemia during the occlusion period. This study was undertaken to delineate the effects of transient local coronary artery occlusion on regional systolic function. METHODS AND RESULTS:Eight cons...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.100.suppl_2.ii-125
更新日期:1999-11-09 00:00:00
abstract:BACKGROUND:Alpha-linolenic acid may protect against cardiovascular disease. We examined the association between adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction (MI) in a population-based case-control study in Costa Rica. METHODS AND RESULTS:The 482 case patients with a first nonfatal acute...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000058165.81208.C6
更新日期:2003-04-01 00:00:00
abstract::We studied regional myocardial perfusion by scintigraphic computer-assisted analysis of initial distribution, washout rates, and residual activity of 133Xe injected into the left coronary artery of four patients with normal arteriograms and 14 patients with coronary stenosis. At rest, residual activity in poststenotic...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.55.3.423
更新日期:1977-03-01 00:00:00
abstract:BACKGROUND:Thirteen of 14 epidemiological studies have shown an increased risk of approximately 20% for coronary heart disease (CHD) for never-smokers exposed to environmental tobacco smoke (ETS), but this association remains controversial. If true, ETS might account for an estimated 35,000 to 40,000 heart disease deat...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.94.4.622
更新日期:1996-08-15 00:00:00