The Impact of the Apolipoprotein E Genotype on Cardiovascular Disease and Cognitive Disorders.

Apolipoprotein E (ApoE) plays a critical role in cholesterol transport and protection against the development of atherosclerotic cardiovascular disease (ASCVD). Humans have 3 prevalent isoforms of ApoE: apolipoprotein E2 (ApoE2), apolipoprotein E3 (ApoE3), and apolipoprotein E4 (ApoE4). The E4 allele has been associated with higher ASCVD risk. While E4 patients do have higher cholesterol levels, they do not have enough to account for the substantially elevated ASCVD risk relative to E2 and E3 patients. ASCVD risk calculators would underestimate the true effect of E4 if the difference was caused entirely by a difference in cholesterol level. This article reviews the function of ApoE in atherosclerosis, and how each isoform functions differently. We review what is known about the molecular mechanisms through which ApoE prevents endothelial dysfunction and damage, how ApoE stimulates macrophage efflux of cholesterol from atherogenic lesions, and the ways in which ApoE decreases inflammation throughout atherosclerosis. The impact of ApoE on Alzheimer's disease and a discussion of why it is possibly unrelated to ASCVD prevention are included. Clinical applications to hyperlipidemia management and ASCVD prevention in specific patient populations are discussed.

The Impact of Long COVID-19 on the Cardiovascular System.

Long coronavirus disease (COVID) is the development or persistence of symptoms after an acute SARS-CoV-2 (COVID-19) infection. Fewer patients are developing acute COVID-19 infections, but patients with long COVID continue to have alarming long-term sequelae. Many cardiac magnetic resonance imaging studies show significant changes in cardiac structure after a COVID-19 infection, suggestive of an increased burden of many cardiovascular diseases, notably myocarditis. The pathophysiology of COVID-19 requires viral binding to angiotensin-converting enzyme 2 protein receptors throughout the body, which are upregulated by inflammation. Consequently, the numerous preexisting conditions that worsen or prolong inflammation enhance this binding and have differing effects on patients based on their unique immune systems. These pathophysiological changes drive long COVID cardiac sequelae such as inappropriate sinus tachycardia, postural orthostatic tachycardia, and other types of orthostatic intolerance. Increased screening for long COVID and low-risk interventions such as exercise regimens could alleviate the suffering endured by patients with long COVID. Many studies such as the Researching COVID to Enhance Recovery Initiative (RECOVER) trials at the National Institutes of Health are exploring potential treatments for long COVID patients.

Clinical Management of Patients With Stable Ischemic Heart Disease.

Ischemic heart disease is considered stable, if patients are asymptomatic or have well controlled symptoms. Based on the pretest probability, noninvasive imaging tests are performed to rule out the disease, and coronary computed tomography angiography being the first line. Invasive coronary angiography remains the gold standard method for diagnosing coronary artery disease. In patients with stable coronary artery disease, comorbidities such as hyperlipidemia, hypertension, and diabetes should be optimized. For patients with persistent anginal symptoms even with optimized medical therapy, coronary revascularization with percutaneous coronary intervention can be considered. Coronary artery bypass grafting may be more beneficial for patients who has stable coronary artery disease with left main disease and/or left ventricular dysfunction and/or multivessel disease; however, treatment should be individualized to the overall clinical picture.

Use of the DASH Diet and Coronary Artery Disease.

Initial dietary approach to stop hypertension (DASH) diet feeding trials showed blood pressure (BP)-lowering effects that corresponded to higher degrees of concordance with the diet. These results popularized the idea that adherence to a DASH diet could reduce coronary artery disease (CAD) risk for patients. Recent evidence shows that the impact of DASH on CAD incidence and risk is less clear. While many studies show that the DASH diet impacts CAD risk factors, others suggest that these effects do not remain when important confounders are controlled. Also, the evidence from meta-analyses that the DASH diet impacts incident CAD is still inconclusive. Reassessment of the DASH diet, and the search for an ideal diet to prevent CAD will require a better understanding of the mechanisms through which the DASH diet works. Proposed mechanisms for its benefit include preventing inflammation and atherosclerosis progression as well as providing a heathy balance of dietary sodium and potassium intake.

Epitope characterization of anti-drug antibodies-a tool for discovery and health: an overview of the necessity of early epitope characterization to avoid anti-drug antibodies and promote patient health.

Introduction: The market for monoclonal antibody (mAb) therapies is growing rapidly as the pharmaceutical industry expands its development across a broad spectrum of diseases. Unfortunately, as shown in the recent failure of bococizumab by Pfizer, these treatments often stimulate the formation of problematic anti-drug antibodies (ADAs). ADAs can cause side effects and limit efficacy for many patients. To increase efficacy and decrease safety concerns from ADAs, immunogenicity characterization is needed early in the drug development process. Here, we present emerging techniques that hold promise to improve ADA assays and their potential applications to pharmaceutical development and personalized medicine.Areas covered: This manuscript outlines the importance of epitope characterization to better understand immunogenicity and describes a strategy for using this information in treating patients taking mAb therapies.Expert opinion: We propose using high-information assays to characterize epitopes to help mAb therapy engineering and potentially improve individual patient outcomes. To understand this, we will discuss three different aspects of ADAs: (1) the problem of ADAs and what is currently being done about them, (2) the current state of epitope characterization and how it is being utilized, and (3) how early epitope characterization can advance drug discovery and improve outcomes for patients taking mAb therapies.