Optimizing sodium-glucose co-transporter 2 inhibitor use in patients with heart failure with reduced ejection fraction: A collaborative clinical practice statement.

Heart failure with reduced ejection fraction (HFrEF) is a debilitating disease that is associated with substantial morbidity, mortality, and societal costs. The past three decades have brought about significant advancements in the pharmacologic management of HFrEF, and a corresponding reduction in morbidity and mortality. However, the progress to improve clinical outcomes in real-world settings has stalled in recent years, largely due to underutilization of guideline directed medical therapies (GDMT). The discovery of significant cardio-renal protection from sodium-glucose co-transporter 2 inhibitors (SGLT2i) has ushered in a new treatment paradigm for HFrEF management with SGLT2i therapy becoming an essential component of GDMT. Our Preventive Cardiology and Heart Failure services have established an innovative, multi-disciplinary, collaborative protocol to optimize management of cardiovascular risk factors and facilitation SGLT2i use in patients with HFrEF. The goal of this collaboration is to enhance utilization and safety of SGLT2i for HFrEF management by circumventing medication access issues, the major obstacle to therapy initiation. Within this protocol, our heart failure providers identify patients for the addition of SGLT2i to a background of heart failure GDMT. The patient is then referred to preventive cardiology where the team performs a comprehensive cardiovascular risk assessment, optimizes cardiovascular risk factors, and initiates SGLT2i with an emphasis on medication access, cost minimization, and mitigation of potential side effects. The heart failure team assumes responsibility for modification of heart failure-based therapies, and the preventive team manages diabetes, lipid, and metabolic-based therapies. The patient is followed by both cardiology services in a structured fashion, comparing outcome measures at regular intervals and utilizing our patient registry and bio-repository. This clinical practice statement provides a detailed evidentiary review on the cardiovascular and renal benefits of SGLT2i, outlines the rational for creation of a collaborative protocol, details a structured program that may serve as a template for enhanced heart failure management in other health systems, and addresses challenges encountered and recommendations for use.

Progress and perspectives in plant sterol and plant stanol research.

Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking.

Emerging Treatments for Heterozygous and Homozygous Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal co-dominant disorder marked by extremely high low-density lipoprotein (LDL) cholesterol levels and concomitant premature vascular disease. FH is caused by mutations that most commonly affect three genes integrally involved in the LDL receptor's ability to clear LDL particles from the circulation. Primary intervention efforts to lower LDL cholesterol have centered on therapies that upregulate the LDL receptor. Unfortunately, most patients are insufficiently responsive to traditional LDL-lowering medications. This article focuses primarily on the clinical management of homozygous FH.

Competitive inhibition of carotenoid transport and tissue concentrations by high dose supplements of lutein, zeaxanthin and beta-carotene.

BACKGROUND: Carotenoids may interact differently in their absorption and transport in animals and humans. The simultaneous administration of large amounts of lutein, zeaxanthin and beta carotene would affect not only plasma values but also their concentrations in the retina and other tissues. OBJECTIVE: In this study, we investigated the transport, distribution and interactions of lutein, zeaxanthin and beta-carotene in the plasma, retina and other tissues of chicks fed supplements rich in lutein, zeaxanthin or beta-carotene. METHODS: Newly hatched male Leghorn chicks were randomly assigned to ten groups. One group provided baseline data (1-day-old group). The other groups were fed one of the following six diets for 14 or 28 days: high lutein diet; high zeaxanthin diet; three high beta-carotene supplemented diets and the control diet. Plasma and tissues including retina were analyzed for lutein and zeaxanthin and beta-carotene at baseline and at 14 and 28 days. RESULTS: All tissues had increased concentrations of lutein after the high lutein diet and had increased concentrations of zeaxanthin after the high zeaxanthin diet. After 28 days, the retinal concentrations of lutein and zeaxanthin in the chicks supplemented with lutein (27.2 mg/kg diet) and zeaxanthin (15.3 mg/kg diet) increased 128 and 116%, respectively, compared to the retinas of chicks fed the control diet (lutein 5.2 mg/kg and zeaxanthin 1.7 mg/kg). Lutein was decreased in plasma and other non-retinal tissues when the diet was supplemented with zeaxanthin; likewise, zeaxanthin was decreased in plasma and non-retinal tissues after the lutein supplement. Zeaxanthin increased in the retina after the high lutein supplement, and retinal lutein was maintained after the high zeaxanthin supplement. The high beta-carotene supplement increased the beta-carotene content of plasma and liver very little, and beta-carotene was not found in any other tissue in the chick, including the retina. More importantly, beta-carotene decreased the concentrations of both lutein and zeaxanthin in the plasma and most tissues, including the retina. CONCLUSION: High dose dietary supplementation of a single carotenoid may alter the assimilation of other carotenoids. The retina appears to have the capacity to preserve accumulation of lutein and zeaxanthin, but this capacity is diminished when intake of beta-carotene is high.