The complete blood count and cardiovascular disease: analyses across six cohorts of 23,370 adults.

Background: The complete blood count (CBC) is one of the most commonly performed laboratory studies. Although studies have found associations between the CBC and cardiovascular disease (CVD), there is limited contemporary information regarding the relationship between the CBC and traditional risk factors and their joint association with CVD endpoints.

Objective: We sought to define the relationships between the CBC and traditional CVD risk factors and their joint association with CVD endpoints in diverse adult populations.

Impact of Social Determinants of Health and Lifestyle on Association Between Lipoprotein(a) and Cardiovascular Events.

Background: In European cohorts, healthier lifestyle either attenuated or associated with lower cardiovascular risk despite elevated lipoprotein(a) [Lp(a)].

Objectives: The purpose of this study was to test if social determinants of health (SDOH) and Life's Simple 7 (LS7) scores impact the association of Lp(a) with cardiovascular events in U.S.

Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening.

An elevated level of lipoprotein(a), or Lp(a), in the bloodstream has been causally linked to the development of atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Steady state levels of circulating lipoproteins are modulated by their rate of clearance, but the identity of the Lp(a) uptake receptor(s) has been controversial. In this study, we performed a genome-scale CRISPR screen to functionally interrogate all potential Lp(a) uptake regulators in HuH7 cells.

Inhibition of PCSK9 with evolocumab modulates lipoproteins and monocyte activation in high-risk ASCVD subjects.

Background: Mechanistic studies suggest that proprotein convertase subtilisin/kexin type 9 inhibitors can modulate inflammation.

Methods: Double-blind, placebo-controlled trial randomized 41 ASCVD subjects with type 2 diabetes with microalbuminuria and LDL-C level >70 mg/dL on maximum tolerated statin therapy received subcutaneous evolocumab 420 mg every 4 weeks or matching placebo. The primary outcomes were change in circulating immune cell transcriptional response, lipoproteins and blood viscosity at 2 weeks and 12 weeks.

The Impact of Social Determinants of Health and Lifestyle on the Association of Lipoprotein(a) with Myocardial Infarction and Stroke.

Background: In European cohorts, a higher Mediterranean diet or Life's Simple 7 (LS7) score abolished or attenuated the risk associated with increasing Lipoprotein(a) [Lp(a)] on cardiovascular outcomes. This is unstudied in US cohorts. The impact of social determinants of health (SDOH) on the association of Lp(a) with cardiovascular outcomes remains unstudied.

Incident CHD and ischemic stroke associated with lipoprotein(a) by levels of Factor VIII and inflammation.

Background: Inflammation and coagulation may contribute to the increased risk for atherosclerotic cardiovascular disease (ASCVD) associated with high lipoprotein(a). The association of lipoprotein(a) with ASCVD is stronger in individuals with high versus low high-sensitivity C-reactive protein (hs-CRP), a marker of inflammation.

Objectives: Determine the association of lipoprotein(a) with incident ASCVD by levels of coagulation Factor VIII controlling for hs-CRP.

Association of blood viscosity and device-free days among hospitalized patients with COVID-19.

Background: Increased estimated whole blood viscosity (eWBV) predicts higher mortality in patients hospitalized for coronavirus disease 2019 (COVID-19). This study assesses whether eWBV is an early predictor of non-fatal outcomes among patients hospitalized for acute COVID-19 infection.

Methods: This retrospective cohort study included 9278 hospitalized COVID-19 patients diagnosed within 48 h of admission between February 27, 2020 to November 20, 2021 within the Mount Sinai Health System in New York City.

Clinical Trial Design for Lipoprotein(a)-Lowering Therapies: JACC Focus Seminar 2/3.

Lipoprotein(a) [Lp(a)] is a source of residual risk in patients with atherosclerotic cardiovascular disease (ASCVD). Clinical trials of fully human monoclonal antibodies targeting proprotein convertase subtilisin kexin 9 have shown that reductions in Lp(a) concentrations may be a predictor of event reduction with this class of cholesterol-lowering therapy. With the advent of selective therapies targeting Lp(a) such as antisense oligonucleotides, small-interfering RNA-based therapies, and gene editing, lowering of Lp(a) may lead to reduction in ASCVD.

Glycocalyx Disruption Triggers Human Monocyte Activation in Acute Heart Failure Syndromes.

Purpose: Acute heart failure (AHF) syndromes manifest increased inflammation and vascular dysfunction; however, mechanisms that integrate the two in AHF remain largely unknown. The glycocalyx (GAC) is a sugar-based shell that envelops all mammalian cells. Much GAC research has focused on its role in vascular responses, with comparatively little known about how the GAC regulates immune cell function.

Association of Blood Viscosity With Mortality Among Patients Hospitalized With COVID-19.

Background: Coronavirus disease-2019 (COVID-19) is characterized by a dysfunctional immune response and abnormal blood rheology that contribute to endothelial dysfunction and thrombotic complications. Whole blood viscosity (WBV) is a clinically validated measure of blood rheology and an established predictor of cardiovascular risk. We hypothesize that increased WBV is associated with mortality among patients hospitalized with COVID-19.

Blood hyperviscosity in acute and recent COVID-19 infection.

Background: Elevated estimated blood viscosity (EBV), derived from hematocrit and globulins, is associated with thrombotic complications, organ failure, and higher mortality in COVID-19 patients. Although informative, EBV does not account for cellular interactions or fibrinogen.

Objective: Investigate whether patients with acute and recent COVID-19 have altered whole blood viscosity (WBV) when measured at both high and low shear rates using in vitro blood samples from patients.

Repurposing low-dose naltrexone for the prevention and treatment of immunothrombosis in COVID-19.

Coronavirus disease 2019 (COVID-19) is characterized by striking dysregulation of the immune system, with evidence of hyperinflammation, an impaired induction of interferons, and delayed adaptive immune responses. In addition to dysfunctional immune responses, thrombosis is a hallmark of severe COVID-19. Because traditional anticoagulation strategies are associated with increased bleeding, novel strategies that address both the immune and thrombotic dysfunction associated with COVID-19 would be of tremendous benefit.

Immune-Mediated Glycocalyx Remodeling in Hospitalized COVID-19 Patients.

Purpose: Vascular and immune dysfunction are hallmarks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections and coronavirus disease 2019 (COVID-19). Although our understanding of the pathogenesis of COVID-19 has rapidly evolved, much of the focus has been on the immune mechanisms underlying COVID-19. In addition to immune dysfunction, vascular injury is also associated with COVID-19 and is a major driver of clinical deterioration in SARS-CoV-2 infections.

Efficacy of Statin Therapy in Patients with Hospital Admission for COVID-19.

Purpose: COVID-19 is characterized by dysfunctional immune responses and metabolic derangements, which in some, lead to multi-organ failure and death. Statins are foundational lipid-lowering therapeutics for cardiovascular disease and also possess beneficial immune-modulating properties. Because of these immune-modulating properties, some have suggested their use in COVID-19.

Inactivation of Interleukin-4 Receptor α Signaling in Myeloid Cells Protects Mice From Angiotensin II/High Salt-Induced Cardiovascular Dysfunction Through Suppression of Fibrotic Remodeling.

Background Hypertension-induced cardiovascular remodeling is characterized by chronic low-grade inflammation. Interleukin-4 receptor α (IL-4Rα) signaling is importantly involved in cardiovascular remodeling, however, the target cell type(s) is unclear. Here, we investigated the role of myeloid-specific IL-4Rα signaling in cardiovascular remodeling induced by angiotensin II and high salt.

Potential repurposing of the HDAC inhibitor valproic acid for patients with COVID-19.

There is a need for therapeutic approaches to prevent and mitigate the effects of Coronavirus Disease (2019) (COVID-19). The histone deacetylase (HDAC) inhibitor valproic acid, which has been available for the therapy of epilepsy for many years, is a drug that could be repurposed for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This article will review the reasons to consider valproic acid as a potential therapeutic to prevent severe COVID-19.

Myeloid interleukin-4 receptor α is essential in postmyocardial infarction healing by regulating inflammation and fibrotic remodeling.

Interleukin-4 receptor α (IL4Rα) signaling plays an important role in cardiac remodeling during myocardial infarction (MI). However, the target cell type(s) of IL4Rα signaling during this remodeling remains unclear. Here, we investigated the contribution of endogenous myeloid-specific IL4Rα signaling in cardiac remodeling post-MI.