Critical appraisal of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia

Niacin is a B-complex vitamin which has been used for decades for the management of mixed dyslipidemias and primary hypercholesterolemia. It decreases the risk of cardiovascular events either when used as a monotherapy or in combination with other lipid lowering medications. However, a major limitation to its use is niacin-induced flushing occurring even with the extended-release formulations. Laropiprant, a selective prostaglandin-2 receptor inhibitor, specifically targets the cascade of events causing the flushing. It has been recently used in combination with extended-release niacin. This article will review the early experience with this combination with focus on efficacy, safety, tolerability and current place in therapy. Early data are promising and suggest that more patients in clinical practice will benefit from niacin combined with laropiprant. Ongoing clinical trials will provide a better insight on the long-term safety of the drug and its efficacy for reducing cardiovascular events

Characterizing 15 Years of Saharan-like, Dry, Well-Mixed Air Layers in North Africa

The Saharan Air Layer (SAL) is a dry, well-mixed layer (WML) of warm and sometimes dusty air of nearly constant water vapor mixing ratio generated by the intense surface heating and strong, dry convection in the Sahara Desert, which has notable downstream impacts on the surface energy balance, organized convective system development, seasonal precipitation, and air quality. Characterizing both WMLs and SALs from the existing rawinsonde network has proven challenging because of its sparseness and inconsistent data reporting. Spurred on by this challenge, we previously created a detection methodology and supporting software to automate the identification and characterization of WMLs from multiple data sources including rawinsondes, remote sensing platforms, and model products. We applied our algorithm to each dataset at both its native and at a common (most coarse data product) vertical resolution to detect WMLs and their characteristics (temperature, mixing ratio, AOD, etc.) at each of the 53 rawinsonde launch sites in north Africa

PCSK9 inhibitors and reduction in cardiovascular events: Current evidence and future perspectives

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in low-density lipoprotein (LDL) metabolism. Pharmacological PCSK9 inhibitors have been developed as a novel approach to treating dyslipidemia. This article reviews the spectrum of evidence implicating the role of PCSK9 in lipid metabolism and the clinical impact of PCSK9 inhibitors on lipid parameters and cardiovascular risk. Biochemical and genomic studies have established the role that PCSK9 plays in lipid metabolism and potential protection from cardiovascular disease observed in the setting of PCSK9 deficiency. This led to the development of inhibitory monoclonal antibodies (evolocumab, alirocumab) that produce dose-dependent lowering of LDL cholesterol up to 60%, with evidence of regression and stabilization of coronary atherosclerosis (GLAGOV, HUYGENS, PACMAN-AMI) and reduction in cardiovascular risk in large clinical outcomes trials (FOURIER, ODYSSEY Outcomes). More recent developments have witnessed alternative approaches to PCSK9 inhibition such as RNA interference (inclisiran), vaccines, and gene editing, which are currently undergoing clinical evaluation. PCSK9 inhibition has emerged as an important component of treatment approaches to lowering LDL cholesterol and plays an increasing role in preventive strategies

Plasma Myeloperoxidase Predicts Incident Cardiovascular Risks in Stable Patients Undergoing Medical Management for Coronary Artery Disease

BACKGROUND: Myeloperoxidase (MPO) concentrations predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but the prognostic role of MPO in stable patients with known atherosclerotic burden is unclear. METHODS: We examined plasma MPO concentrations and their relationship with prevalent significant coronary artery disease (defined as \u3e50% stenosis in any coronary vessel) and incident major adverse cardiovascular events (MACEs), including death, myocardial infarction, and stroke, in a 3-year prospective follow-up study of 1895 patients undergoing elective coronary angiography. RESULTS: The median plasma MPO concentration was 101 pmol/L (interquartile range 68–187 pmol/L). Patients with plasma MPO concentrations \u3e322 pmol/L (14.6% of population) had increased risk of developing future MACEs [hazard ratio (HR) 1.78, 95% CI 1.33–2.37, P \u3c 0.001], and MPO as a single variable predictor of MACE showed an area under the ROC curve of 0.67. After adjusting for traditional cardiac risk factors, creatinine clearance, B-type natriuretic peptide, and high-sensitivity C-reactive protein (hsCRP), increased MPO concentrations remained significantly associated with incident MACEs over the ensuing 3-year period (HR 1.71; 95% CI 1.27–2.30, P \u3c 0.001). In patients with increased hsCRP, MPO ≤322 pmol/L was associated with lower event rates than observed with MPO \u3e322 pmol/L. CONCLUSIONS: Plasma MPO concentrations provide independent prognostic value for the prediction of long-term incident MACEs in a stable, medically managed patient population with coronary artery disease. In individuals with increased hsCRP concentrations, we observed lower risk of incident MACEs when concomitant MPO concentrations were low vs when MPO concentrations were high

Plasma Myeloperoxidase Predicts Incident Cardiovascular Risks in Stable Patients Undergoing Medical Management for Coronary Artery Disease

BACKGROUND: Myeloperoxidase (MPO) concentrations predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but the prognostic role of MPO in stable patients with known atherosclerotic burden is unclear. METHODS: We examined plasma MPO concentrations and their relationship with prevalent significant coronary artery disease (defined as \u3e50% stenosis in any coronary vessel) and incident major adverse cardiovascular events (MACEs), including death, myocardial infarction, and stroke, in a 3-year prospective follow-up study of 1895 patients undergoing elective coronary angiography. RESULTS: The median plasma MPO concentration was 101 pmol/L (interquartile range 68–187 pmol/L). Patients with plasma MPO concentrations \u3e322 pmol/L (14.6% of population) had increased risk of developing future MACEs [hazard ratio (HR) 1.78, 95% CI 1.33–2.37, P \u3c 0.001], and MPO as a single variable predictor of MACE showed an area under the ROC curve of 0.67. After adjusting for traditional cardiac risk factors, creatinine clearance, B-type natriuretic peptide, and high-sensitivity C-reactive protein (hsCRP), increased MPO concentrations remained significantly associated with incident MACEs over the ensuing 3-year period (HR 1.71; 95% CI 1.27–2.30, P \u3c 0.001). In patients with increased hsCRP, MPO ≤322 pmol/L was associated with lower event rates than observed with MPO \u3e322 pmol/L. CONCLUSIONS: Plasma MPO concentrations provide independent prognostic value for the prediction of long-term incident MACEs in a stable, medically managed patient population with coronary artery disease. In individuals with increased hsCRP concentrations, we observed lower risk of incident MACEs when concomitant MPO concentrations were low vs when MPO concentrations were high

Achievement of combined goals of low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol with three different statins: Results from VOYAGER

AbstractBackgroundGuidelines suggest that the combination of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) is the most clinically relevant goal for lipid-lowering treatments.MethodsData from VOYAGER, an individual patient data meta-analysis including 32,258 patients from 37 clinical trials, was used to determine the percentage of patients reaching combined goals of LDL-C and non-HDL-C following treatment with simvastatin, atorvastatin, or rosuvastatin. Paired comparisons were made between each dose of rosuvastatin and the same or higher doses of simvastatin and atorvastatin.ResultsEach dose of rosuvastatin brought significantly more patients to the combined goal of LDL-C < 100 mg/dL and non-HDL-C < 130 mg/dL than the same or double dose of atorvastatin; atorvastatin 80 mg was significantly superior to rosuvastatin 10 mg (all p < 0.001). Each dose of rosuvastatin helped significantly more patients reach the combined goal than any dose of simvastatin (all p < 0.001), except for rosuvastatin 10 mg versus simvastatin 80 mg (non-significant). Also, each dose of rosuvastatin helped significantly more patients to reach the combined goal of LDL-C < 70 mg/dL and non-HDL-C < 100 mg/dL than the same or double dose of atorvastatin (all p < 0.001). Every dose of rosuvastatin was significantly superior to all doses of simvastatin (all p ≤ 0.020), except for rosuvastatin 10 mg versus simvastatin 40 mg and 80 mg (non-significant).ConclusionsPhysicians' choice of statin and dose is important in helping patients achieve the combined LDL-C and non-HDL-C goals recommended in established guidelines

Influence of Bulk Microphysics Schemes upon Weather Research and Forecasting (WRF) Version 3.6.1 Nor'easter Simulations

This study evaluated the impact of five single- or double-moment bulk microphysics schemes (BMPSs) on Weather Research and Forecasting model (WRF) simulations of seven intense wintertime cyclones impacting the mid-Atlantic United States; 5-day long WRF simulations were initialized roughly 24 hours prior to the onset of coastal cyclogenesis off the North Carolina coastline. In all, 35 model simulations (five BMPSs and seven cases) were run and their associated microphysics-related storm properties (hydrometer mixing ratios, precipitation, and radar reflectivity) were evaluated against model analysis and available gridded radar and ground-based precipitation products. Inter-BMPS comparisons of column-integrated mixing ratios and mixing ratio profiles reveal little variability in non-frozen hydrometeor species due to their shared programming heritage, yet their assumptions concerning snow and graupel intercepts, ice supersaturation, snow and graupel density maps, and terminal velocities led to considerable variability in both simulated frozen hydrometeor species and radar reflectivity. WRF-simulated precipitation fields exhibit minor spatiotemporal variability amongst BMPSs, yet their spatial extent is largely conserved. Compared to ground-based precipitation data, WRF simulations demonstrate low-to-moderate (0.217 to 0.414) threat scores and a rainfall distribution shifted toward higher values. Finally, an analysis of WRF and gridded radar reflectivity data via contoured frequency with altitude (CFAD) diagrams reveals notable variability amongst BMPSs, where better performing schemes favored lower graupel mixing ratios and better underlying aggregation assumptions

Relationship Between Atheroma Regression and Change in Lumen Size After Infusion of Apolipoprotein A-I Milano

ObjectivesThe aim of this study was to determine the relationship between atheroma regression and arterial wall remodeling.BackgroundInfusion of reconstituted high-density lipoprotein (rHDL) containing recombinant apolipoprotein A-I Milano (AIM) has been reported to promote rapid regression of coronary atherosclerosis. The current study analyzed intravascular ultrasound (IVUS) to define the changes that take place in the arterial wall that accompanied atheroma regression in this study.MethodsForty-seven patients, ages 30 to 75 years, after an acute coronary syndrome were randomized to receive five weekly infusions of placebo or rHDL containing either low- or high-dose AIM. External elastic membrane (EEM) and lumen volumes were compared between coronary IVUS studies at baseline and follow-up.ResultsIn comparison with baseline, infusion of rHDL was associated with a 4.6% reduction in EEM volume. Lumen volume did not change. In 10-mm arterial subsegments with the greatest plaque burden at baseline, atheroma volume regressed by 10.9% with a similar reduction in EEM volume but with no change in lumen size. In contrast, EEM and atheroma volume did not change in the 10-mm segments containing the least plaque burden. The reduction in EEM in the most diseased segments was only apparent in subjects who underwent plaque regression. Reduction in EEM volume correlated with the decreased atheroma volume (r = 0.62), but there was no correlation between change in lumen size and change in plaque volume.ConclusionsRemodeling of the arterial wall is a focal and heterogeneous process. After infusion of rHDL containing AIM, regression of coronary atherosclerosis is accompanied by reverse remodeling of the EEM, resulting in no change in luminal dimensions