Impact of In-Hospital PCSK9 Inhibition on Myocardial Inflammation After Myocardial Infarction: A Randomized Clinical Trial.

In a randomized trial with 55 participants from the EVACS (Evolocumab in Acute Coronary Syndrome) trials, patients with non-ST-segment elevation myocardial infarction (MI) or ST-segment elevation MI received a single dose of evolocumab or placebo, with myocardial inflammation assessed via F-fluorodeoxyglucose positron emission tomography scans at baseline and at 30 days. Evolocumab significantly reduced inflammation (SUV) compared with placebo. PCSK9 levels at 30 days correlated with SUV, and higher SUV was linked to increased end-systolic volume at 6 months.

Vericiguat prevents high glucose-mediated impaired vascular smooth muscle cGMP production and vasorelaxation.

Normal endothelial cell dependent vascular smooth muscle cell function is mediated by nitric oxide (NO), which stimulates soluble guanylyl cyclase (sGC) production of the second messenger cyclic guanosine monophosphate (cGMP) leading to increased protein kinase G (PKG) activity and vascular smooth muscle relaxation. NO bioavailability is impaired in high glucose (HG). We tested the hypothesis that the sGC sensitizer vericiguat reverses HG-mediated decreased sGC activity in two experimental models, human aortic vascular smooth muscle cells (HVSMCs) and isolated mouse aortic rings.

Peroxisome Proliferator-Activated Receptor Gamma Regulates Interleukin-6-Induced Lipoprotein (a) Gene Expression in Human HepG2 Cells.

Lipoprotein(a) [Lp(a)] is a risk factor for coronary disease. Although levels are primarily genetically determined, data from patients with inflammatory diseases indicate that the inflammatory milieu is associated with increased Lp(a) levels. Lp(a) is synthesized in the liver and the LPA gene promoter contains an interleukin-6 (IL-6) responsive binding site, but the regulatory steps linking inflammation with hepatic Lp(a) synthesis are not well clarified.

Intra-individual variability in lipoprotein(a): the value of a repeat measure for reclassifying individuals at intermediate risk.

Aims: Lipoprotein(a) [Lp(a)] levels are predominantly genetically determined and repeat measurements are generally considered unlikely to be clinically useful. However, the temporal variation of Lp(a) is not well characterized. Our aim was to determine the intra-individual variability of Lp(a) and whether a repeated measure reclassified Lp(a)-specific cardiovascular risk using the European Atherosclerosis Society (EAS) consensus statement risk categories.

VERICIGUAT RESCUES CYCLIC GUANOSINE MONOPHOSPHATE PRODUCTION IN HUMAN AORTIC VASCULAR SMOOTH MUSCLE CELLS AND AUGMENTS VASORELAXATION IN AORTIC RINGS EXPOSED TO HIGH GLUCOSE.

Background: Normal endothelial cell dependent vascular smooth muscle cell function is mediated by nitric oxide (NO), which stimulates soluble guanylyl cyclase (sGC) production of the second messenger, cyclic guanosine monophosphate (cGMP) leading to increased protein kinase G (PKG) activity and vascular smooth muscle relaxation. NO bioavailability is impaired in inflammatory settings, such as high glucose (HG). We examined whether the direct sGC sensitizer/stimulator vericiguat, augments cGMP production in human vascular smooth muscle cells (HVSMC) exposed to high glucose and explored its effect on vasorelaxation.

Emerging clinical role of proprotein convertase subtilisin/kexin type 9 inhibition-Part two: Current and emerging concepts in the clinical use of PCSK9 inhibition.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a novel class of drugs with cardioprotective effects through their lipid-lowering effects.

Objective: This review aims to discuss existing and novel strategies of PCSK9 inhibition, providing an overview of established randomized controlled trials and ongoing outcome trials that assess the efficacy and long-term safety of PCSK9 inhibitors. It also explores the evolving role of PCSK9 beyond lipid metabolism and outlines the pleiotropic actions of PCSK9 inhibition in various disorders and future directions including novel strategies to target PCSK9.

Emerging clinical role of proprotein convertase subtilisin/kexin type 9 inhibition-Part one: Pleiotropic pro-atherosclerotic effects of PCSK9.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in lipid metabolism, but recent evidence suggests that it may have broader implications due to its diverse tissue expression.

Objective: This review aims to explore the multifaceted functions of PCSK9, highlighting its pro-atherosclerotic effects, including its impact on circulating lipoprotein variables, non-low-density lipoprotein receptors, and various cell types involved in atherosclerotic plaque development.

Conclusions: PCSK9 exhibits diverse roles beyond lipid metabolism, potentially contributing to atherosclerosis through multiple pathways.

Homocysteine modifies the association of coronary stenosis and HIV infection in an inner city African American population.

Background And Aims: People with HIV (PWH) whose disease is controlled on anti-retroviral regimens remain at an increased risk for coronary artery disease (CAD). Traditional cardiovascular risk factors do not fully explain the residual risk in PWH suggesting contributions from nontraditional factors. Homocysteine (Hcy) may be one of these as prior work in adults without HIV demonstrate that Hcy may impair endothelial function by decreasing the availability of nitric oxide, promoting the development of atherosclerosis.

Coronary artery endothelial function and aging in people with HIV and HIV-negative individuals.

Coronary artery disease (CAD) is a common comorbidity in people with human immunodeficiency virus (HIV) (PWH) and impaired coronary endothelial function (CEF) plays a central role in the pathogenesis of CAD. Age-related impaired CEF among PWH, however, is not well characterized. We investigated the association between CEF and age in males and females with and without HIV using 3-T magnetic resonance imaging (MRI).

Platelet activation and endothelial dysfunction biomarkers in acute coronary syndrome: the impact of PCSK9 inhibition.

Aims: Platelet activation and endothelial dysfunction contribute to adverse outcomes in patients with acute coronary syndromes (ACS). The goals of this study were to assess the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on markers of platelet activation and endothelial dysfunction in ACS patients and the interaction among PCSK9, platelets, and endothelial cells (ECs) on left internal mammary artery (LIMA) vascular endothelium using specimens obtained during coronary artery bypass surgery (CABG).

Methods And Results: Acute coronary syndromes patients enrolled in the Evolocumab in ACS trials were randomized to placebo or a single dose of 420 mg evolocumab within 24 h of hospitalization.

Novel Diagnostic Imaging Approach for Patients With Spontaneous Coronary Artery Dissection: The Utility of 18 F-FDG PET Imaging.

Spontaneous coronary artery dissection (SCAD) is an underdiagnosed etiology of acute coronary syndrome in women. Accurate diagnosis remains challenging but is imperative for treatment and prevention. We show here the utility of 18 F-FDG PET imaging in SCAD diagnosis.

Lipoprotein(a) concentrations in acute myocardial infarction patients are not indicative of levels at six month follow-up.

Aims: Lipoprotein(a) [Lp(a)] levels are generally constant throughout an individual's lifetime, and current guidelines recommend that a single measurement is sufficient to assess the risk of coronary artery disease (CAD). However, it is unclear whether a single measurement of Lp(a) in individuals with acute myocardial infarction (MI) is indicative of the Lp(a) level six months following the event.

Methods And Results: Lp(a) levels were obtained from individuals with non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI) ( = 99) within 24 h of hospital admission and after six months, who were enrolled in two randomized trials of evolocumab and placebo, and in individuals with NSTEMI or STEMI ( = 9) who enrolled in a small observation arm of the two protocols and did not receive study drug, but whose levels were obtained at the same time points.

The role of proprotein convertase subtillisin/kexin type 9 in placental salvage and lipid metabolism in women with preeclampsia.

Introduction: Preeclampsia is associated with decreased maternal low-density lipoprotein cholesterol (LDL-c), which is essential for fetal growth. The underlying mechanisms for decreased LDL-c in preeclampsia remain unknown. Proprotein convertase subtillisin/kexin type 9 (PCSK9) regulates serum LDL-c via LDL receptor (LDL-R) degradation.

Effect of Sex on Coronary Endothelial Dysfunction in People Living With HIV.

Background Impaired coronary endothelial function (CEF) predicts cardiovascular events and occurs in people living with HIV (PLWH). Women compared with men living with HIV have worse cardiovascular outcomes, but prior CEF studies included few women. The authors aimed to compare CEF in women with HIV versus without HIV, investigate sex differences in CEF and PCSK9 (proprotein convertase subtilisin/kexin type 9) (a proinflammatory biomarker), and evaluate whether increased serum levels of PCSK9 are associated with CEF in PLWH.

The Trajectory of Lipoprotein(a) During the Peri- and Early Postinfarction Period and the Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition.

Lipoprotein(a), or Lp(a), levels and the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on Lp(a) during the peri-infarction and early postinfarction period are not well characterized. This study aimed to describe the trajectory of Lp(a), as well as the effect of PCSK9 inhibition on that trajectory during the peri-infarction and early postinfarction period. Lp(a) levels were obtained within 24 hours of hospital admission as well as within 24 hours of hospital discharge and at 30 days from 74 participants who presented with a NSTEMI (troponin I >5 ng/ml) or with a STEMI and were enrolled in 2 randomized, double-blind trials of evolocumab and placebo (Evolocumab in Acute Coronary Syndrome [EVACS I]; ClinicalTrials.