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.

Subcutaneous Furosemide: A Novel to Euvolemia.

Furoscix, a subcutaneous pH-neutral formulation of furosemide, obtained US Food and Drug Administration approval in October 2022 for adult patients with New York Heart Association class II and class III chronic heart failure. This approval marks an anticipated potential shift in the traditional management of decongestive therapy in chronic heart failure patients from the confines of the hospital to more accessible outpatient or home-based care. In this review, we will summarize existing evidence regarding the use of subcutaneous furosemide in comparison to both oral and intravenous formulations, highlighting the demonstrable benefits of its application in both outpatient and inpatient settings, and also discuss several factors that may limit its use.

Genetic Problems, Diagnosis, and Cardiovascular Manifestations of Loeys-Dietz Syndrome.

Loeys-Dietz Syndrome (LDS) is an autosomal dominant connective tissue disorder with multisystem involvement of wide spectrum, found to be associated with transforming growth factor-ß pathway. LDS is characterized by craniofacial, skeletal, cutaneous, vascular abnormalities along with aortic aneurysm and aortic dissection contributing to mortality and morbidity at a young age. Therefore, timely diagnosis and intervention in patients with LDS is vital. Several gene mutations have been described as contributing factors of LDS, causing widespread and aggressive vascular disease. Based on these gene mutations, 5 types of LDS have been described so far. Besides aortic aneurysm and dissection, some of the other cardiac manifestations of LDS involve cardiomyopathy, valvular abnormality, atrial fibrillation, patent ductus arteriosus, atrial septal defects, etc. Routine imaging of patients' vasculatures and aggressive medical and surgical management are key factors in managing patients with LDS.