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.

High-Risk Pulmonary Hypertension Does Not Worsen Outcomes in Heart Transplantation.

Pulmonary hypertension (PH) is a relative contraindication to heart transplantation (HT). Multiple studies showed increased mortality in patients with PH. Advances in care may have led to improved outcomes in the modern era. We analyzed patients who underwent HT at our institution between 2014 and 2018. We divided patients into 2 groups based on the presence of high-risk PH defined as either pulmonary vascular resistance >3 Wood units or transpulmonary gradient >15 mm Hg. The primary outcome was survival. Secondary outcomes were post-HT morbidity and changes in hemodynamics. Subsequently, we analyzed national trends of single organ HT recipients with a high-risk PH between 1994 and 2018 from the United Network for Organ Sharing registry. Of 98 patients who underwent HT at our center, 32% had PH. In patients without and with PH, the survival was 100% at 30 days, 87%, and 81% at 3 years (p = 0.96). In both groups, pulmonary vascular resistance and trans-pulmonary gradient decreased after HT. Nationwide data revealed 30-day survival without and with PH at 97% and 98% (p = 0.47) and 3-year survival at 86% and 87% (p = 0.84), respectively, in 2018. The proportion of recipients with PH decreased from 25% in 1994 to 19% in 2018. Recipients of HT with and without high-risk PH had similar early and late mortality in a single-center and nationwide analysis. PH improved immediately after transplant. The United Network for Organ Sharing registry analysis demonstrates continued improvement in survival in patients with PH in the modern era, whereas the relative percentage of recipients with PH decreased over time.

Cardiovascular complications of diabetes.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is the ninth leading cause of mortality globally, and the prevalence continues to rise. Among individuals with T2DM, over two-thirds of deaths are caused by the cardiovascular complications of diabetes. These complications include atherosclerosis, coronary artery disease, nephropathy, stroke, thromboembolism, peripheral vascular disease. They have been long studied, and there are several theories as to the pathophysiology of how diabetes leads to these complications. The least understood mechanism is the pathophysiology linking diabetes to heart failure. AREAS COVERED: This review focuses on the mechanisms of how T2DM leads to the aforementioned complications, particularly highlighting the development of heart failure. An extensive literature review of novel therapeutic options targeting the cardiovascular effects of T2DM was completed and summarized in this review. EXPERT OPINION: This review finds that most studies to date have focused on the atherosclerotic vascular complications of diabetes. The pathophysiology between T2DM and heart failure is even less understood. Currently therapies that aim to decrease the risk of heart failure in diabetes are sparse. More research is required in order to better understand the changes at a cellular level and subsequently help providers to choose therapeutics that better target cardiovascular complications.

A "Grave" Case of Mitral Regurgitation: Cardio-Obstetric Approach to Severe Mitral Regurgitation With Cardiogenic Shock.

A 26-year-old woman presented at 26 weeks of pregnancy with severe mitral regurgitation (MR) and cardiogenic shock in the setting of profound hyperthyroidism. An intra-aortic balloon pump was placed, and surgical intervention was considered. However, with management of thyrotoxicosis and delivery, complete resolution of MR and cardiogenic shock was achieved. (Level of Difficulty: Intermediate.).

Impact of Body Mass Index on Mortality in Hospitalized Patients With Hypertrophic Cardiomyopathy.

Although obesity is associated with increased phenotypic expression in patients with hypertrophic cardiomyopathy (HC), the effect of body mass index (BMI) on in-hospital mortality in hospitalized patients with HC has not been established. We evaluated the National Inpatient Sample in the United States to identify all adults with HC hospitalized for cardiac illnesses between 2008 and 2017. Using International Classification of Diseases codes, the study cohort was stratified into underweight (BMI ≤19.9 kg/m2), normal weight (BMI 20.0 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2), class I (BMI 30.0 to 34.9 kg/m2), class II (BMI 35.0 to 39.9 kg/m2), and class III (BMI ≥40.0 kg/m2) obesity. Multiple logistic regression analysis was used to analyze the independent association of various BMI categories and mortality. The study included a total of 2,392,325 hospitalizations (mean age-66.1 ± 12.2 years; 42.0% female). The patients with class III obesity (adjusted mortality rate [AMR] 3.3%, adjusted odds ratio [AOR] 1.53, 95% confidence interval [CI] 1.29 to 1.82, p <0.001) and underweight patients (AMR 4.4%, AOR 2.07, 95% CI 1.74-2.46, p <0.001) had higher in-hospital mortality whereas overweight patients (AMR 1.6%, AOR 0.26, 95% CI 0.19 to 0.34, p <0.001), patients with class I obesity (AMR 0.8%, AOR 0.35, 95% CI 0.27 to 0.45, p <0.001) and patients with class II obesity (AMR 0.8%, AOR 0.34, 95% CI 0.26 to 0.45, p <0.001) had lower mortality compared with patients with normal BMI (AMR 2.9%). In conclusion, BMI has a nonlinear U-shaped relation with in-hospital mortality in patients with HC. The patients who were underweight and morbidly obese had significantly higher mortality, whereas those patients with overweight, class I, and class II obesity had lower mortality than normal BMI.

Coronary Intravascular Lithotripsy.

Coronary artery calcification is strongly associated with adverse cardiac events and can impede the success of percutaneous coronary intervention (PCI) due to challenges with delivery of equipment and expansion of stents. Current treatment modalities for mitigation of coronary calcification have limitations and inherent risk of complications. Coronary intravascular lithotripsy (IVL) is a novel technique to modify coronary artery calcification via acoustic pressure waves. IVL utilizes an easy-to-use device, which does not require a steep learning curve. Prospective studies have shown this technique to be safe and effective and can be used to adequately modify calcified coronary stenoses in preparation for PCI and stent deployment and optimization. IVL has unique features that can be used alone or as an adjunctive therapy to other available calcium modification tools. As compared to the currently established modalities of calcium modification, IVL has the potential to facilitate successful PCI with fewer serious procedural complications. In this review article, we discuss the importance of coronary artery calcification, the role of IVL, its mechanism, the current clinical data behind its use and future directions. Overall, coronary IVL is a promising technology for the treatment of severely calcified coronary stenoses, with a need for, long-term clinical outcome data of IVL-facilitated PCI.