A5065063579- Lipoproteins and Cardiovascular Health
- Health Systems, Economic Evaluations, Quality of Life
- Antiplatelet Therapy and Cardiovascular Diseases
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Pharmaceutical Economics and Policy
- Cardiac Imaging and Diagnostics
- Cardiovascular Function and Risk Factors
- Diabetes Treatment and Management
- Acute Myocardial Infarction Research
- Cancer, Lipids, and Metabolism
- Atherosclerosis and Cardiovascular Diseases
- Peroxisome Proliferator-Activated Receptors
- Advanced MRI Techniques and Applications
- Protein Degradation and Inhibitors
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiac Ischemia and Reperfusion
- Coronary Interventions and Diagnostics
- Cardiac electrophysiology and arrhythmias
- Computational Drug Discovery Methods
- Hemodynamic Monitoring and Therapy
- Cardiac, Anesthesia and Surgical Outcomes
- Metabolism, Diabetes, and Cancer
- Pulmonary Hypertension Research and Treatments
- Cardiovascular Disease and Adiposity
- Adipose Tissue and Metabolism
University of Colorado Denver
2016-2025
Center for Innovation
2025
University of Colorado Anschutz Medical Campus
2004-2024
VA Eastern Colorado Health Care System
2020-2024
Northwestern University
2023-2024
Nuffield Health
2024
Rocky Mountain MS Center
2019-2024
National Health and Medical Research Council
2024
University of Colorado Health
2003-2023
Université Paris Cité
2012-2023
Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic cardiovascular events. We sought to determine whether alirocumab, a human monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9), would improve outcomes after in patients receiving high-intensity statin therapy.We conducted multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 1 12 months earlier, low-density lipoprotein (LDL) cholesterol level of least 70 mg...
Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators B2][3] Previous trials excluded patients who had experienced recent unstable angina or acute myocardial infarction (MI).However, it is within the early period after an coronary syndrome (ACS) that experience highest rate of death and recurrent ischemic events. 4,5o date, has not been determined whether initiation treatment a statin soon ACS can reduce occurrence these events.Recent studies indicate statins have...
In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk coronary heart disease events. However, whether raising HDL therapeutically reduces cardiovascular remains uncertain. Inhibition cholesteryl ester transfer protein (CETP) raises and might therefore improve outcomes.We randomly assigned 15,871 patients who had recent acute syndrome to receive the CETP inhibitor dalcetrapib, at dose 600 mg daily, or placebo, in addition...
Patients with ischemic stroke or transient attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a factor and myocardial infarction raised the possibility that pioglitazone, which improves sensitivity, might benefit patients cerebrovascular disease.
Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or patients with stable angina, the effect of on markedly heightened inflammation is unknown.We measured C-reactive protein (CRP), serum amyloid A (SAA), interleukin 6 (IL-6) 2402 subjects enrolled Myocardial Ischemia Reduction Aggressive Cholesterol Lowering (MIRACL) study. Subjects unstable angina non-Q-wave myocardial infarction were...
Following acute coronary syndrome (ACS), the risk for future cardiovascular events is high and related to levels of low-density lipoprotein cholesterol (LDL-C) even within setting intensive statin treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor expression circulating LDL-C. Antibodies PCSK9 can produce substantial sustained reductions The ODYSSEY Outcomes trial tests hypothesis that treatment with alirocumab, a fully human monoclonal antibody PCSK9,...
Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C).A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes LDL-C independently predicted major adverse events (MACE).One to 12 months after ACS, 18,924 on high-intensity...
<h3>Importance</h3> Secretory phospholipase A<sub>2</sub>(sPLA<sub>2</sub>) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA<sub>2</sub>inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect cardiovascular outcomes is unknown. <h3>Objective</h3> To determine the of sPLA<sub>2</sub>inhibition with outcomes. <h3>Design, Setting, Participants</h3> A double-blind, randomized, multicenter trial at 362 academic community...
No therapy directed against diabetes has been shown to unequivocally reduce the excess risk of cardiovascular complications. Aleglitazar is a dual agonist peroxisome proliferator-activated receptors with insulin-sensitizing and glucose-lowering actions favorable effects on lipid profiles.To determine whether addition aleglitazar standard medical reduces morbidity mortality among patients type 2 mellitus recent acute coronary syndrome (ACS).AleCardio was phase 3, multicenter, randomized,...
Background: Alirocumab, an antibody that blocks PCSK9 (proprotein convertase subtilisin/kexin type 9), was associated with reduced major adverse cardiovascular events (MACE) and death in the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After Acute Coronary Syndrome During Treatment With Alirocumab). In this study, higher baseline levels low-density lipoprotein cholesterol (LDL-C) predicted greater benefit from alirocumab treatment. Recent studies indicate high polygenic risk...
<h3>Importance</h3>The effectiveness of perioperative β-blockade in patients undergoing noncardiac surgery remains controversial.<h3>Objective</h3>To determine the associations early exposure to β-blockers with 30-day postoperative outcome surgery.<h3>Design, Setting, and Patients</h3>A retrospective cohort analysis evaluating on day or following major among a population-based sample 136 745 who were 1:1 matched propensity scores (37 805 pairs) treated at 104 VA medical centers from January...
Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) death. The impact lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined.This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks MACEs...
Abstract Aims Lipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial patients recent acute coronary syndrome (ACS), proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), compared placebo. This post hoc analysis determined whether baseline levels alirocumab-induced...
Patients with acute coronary syndrome are at risk for peripheral artery disease (PAD) events and venous thromboembolism (VTE). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors reduce lipoprotein(a) low-density lipoprotein cholesterol (LDL-C) levels. Our objective was to ascertain whether inhibition reduces the of PAD or VTE after syndrome, if such effects related levels LDL-C.This a prespecified analysis ODYSSEY OUTCOMES randomized clinical trial (Evaluation Cardiovascular...
Abstract Background Inclisiran, an siRNA administered twice-yearly, significantly reduced LDL cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a lower risk of cardiovascular (CV) events is not yet established. Methods and results Patient-level, pooled analysis ORION-9, −10 −11, included patients heterozygous familial hypercholesterolaemia, atherosclerotic CV disease (ASCVD), or ASCVD equivalent on maximally tolerated statin-therapy, randomized...
Abstract Aims Patients often require combination therapies to achieve LDL cholesterol (LDL-C) targets for the primary prevention of atherosclerotic cardiovascular disease. This study investigates effect inclisiran, a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 production, in patients with elevated LDL-C despite statins. Methods and results pre-specified analysis placebo-controlled, randomized ORION-11 trial included 203 individuals at...
Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk diabetes, but less is known about size or timing this effect, who at greatest risk. We aimed to address these gaps in knowledge through analysis individual participant large, long-term, randomised, double-blind therapy.
Data describing the long-term efficacy and tolerability of inclisiran are limited. This was explored in ORION-8, an open-label extension preceding Phase 2 3 placebo-controlled trials.
Importance Elevated lipoprotein(a) increases the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. Objective To evaluate effects zerlasiran, a small-interfering RNA targeting hepatic synthesis apolipoprotein(a), on serum concentration. Design, Setting, Participants A multicenter trial in patients with stable ASCVD concentrations greater than or equal to 125 nmol/L at 26 sites Europe South Africa between January 3, 2023, April 27, last follow-up July 1, 2024....
Background— Oxidized phospholipids (OxPL) are present within atherosclerotic plaques and bound by lipoprotein (a) [Lp(a)] in plasma. This study evaluated the impact of atorvastatin on oxidized LDL (OxLDL) patients with acute coronary syndromes (ACS). Methods Results— OxLDL-E06 (OxPL content apolipoprotein B-100 [apoB] detected antibody E06), apoB-100 immune complexes (apoB-IC), OxLDL autoantibodies, Lp(a) levels were measured 2341 at baseline after 16 weeks treatment 80 mg/d or placebo. The...
This report describes the effect of intensive cholesterol lowering with atorvastatin on incidence nonfatal stroke, a secondary end point, in randomized, placebo-controlled trial patients unstable angina or non-Q-wave myocardial infarction. The primary composite death, infarction, resuscitated cardiac arrest, recurrent symptomatic ischemia objective evidence requiring emergency rehospitalization, was reduced from 17.4% placebo group to 14.8% over 16 weeks (P=0.048).Strokes were adjudicated by...