Advances in targeting LDL cholesterol: PCSK9 inhibitors and beyond.

There is a direct relationship between the duration and level of exposure to low density lipoprotein cholesterol (LDL-C) levels over one's lifespan and cardiovascular events. Early treatment to lower elevated LDL-C is crucial for better outcomes with multiple therapies currently available to reduce atherogenic lipoproteins. Statins remain the foundation of LDL-C lowering therapy as one of the most cost-effective drugs to reduce atherosclerotic events (ASCVD) and mortality.

A system approach to improving guideline-directed therapy for cardio-renal-metabolic conditions: The "beyond diabetes" initiative.

Objective: Despite demonstrating improvements in cardiovascular disease, kidney disease, and survival outcomes, guideline-directed antihyperglycemic medications such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like-peptide-1 receptor agonists (GLP1-RA), are underutilized. Many obstacles constrain their use including lack of systematic provider and patient education, concern for medication side effects, and patient affordability.

Methods: We designed a multimodality, systems-based approach to address these challenges with the goal of increasing medication utilization across the largest healthcare system in New York State.

Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association.

The objective of this scientific statement is to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive low-density lipoprotein cholesterol lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke. The writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize existing evidence and to identify gaps in current knowledge. Although some retrospective, case control, and prospective longitudinal studies suggest that statins and low-density lipoprotein cholesterol lowering are associated with cognitive impairment or dementia, the preponderance of observational studies and data from randomized trials do not support this conclusion.

De novo ulcerative colitis and Takotsubo cardiomyopathy following sleeve gastrectomy.

The increasing prevalence of severe obesity is a major public health concern. Bariatric surgery is an important treatment option for severe obesity due to its long-term sustained result. Multiple studies have shown that patients have an increased risk of developing inflammatory bowel disease following bariatric surgery.

Implementation of Novel Lipid Therapies in a Refractory Heterozygous Familial Hypercholesterolemia Patient With Atherosclerotic Disease.

Compound heterozygous familial hypercholesterolemia patients are phenotypically similar to homozygous familial hypercholesterolemia patients, present with significant elevations of low-density lipoprotein cholesterol, and are at risk of cardiovascular disease. Although new treatment options are emerging, the stepwise approach to the use of different therapies has not been well described. ().

Comparison of Methods to Estimate Low-Density Lipoprotein Cholesterol in Patients With High Triglyceride Levels.

Importance: Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or greater, laboratories reflexively perform direct LDL-C (dLDL-C) measurement. The use of direct chemical LDL-C assays and estimation of LDL-C via the National Institutes of Health Sampson equation are not well validated, and data on the accuracy of LDL-C estimation at higher triglyceride levels are limited.

Objective: To compare an extended Martin/Hopkins equation for triglyceride values of 400 to 799 mg/dL with the Friedewald and Sampson equations.

Early use of PCSK9 inhibitor therapy after heart transplantation from a hepatitis C virus positive donor.

Although statin therapy is a primary treatment to prevent cardiac allograft vasculopathy (CAV), its use may be delayed due to pharmacologic interactions in the early post-transplant period among heart transplant (HT) recipients with hepatitis C virus positive (HCV+) donors. Further examination of the possible benefits of early, nonstatin lipid-lowering therapies (LLT), such as PCSK9 inhibitors (PCSK9i), among this specific subset of transplant recipients is therefore becoming increasingly important. We report a 60-year-old man who received a HT from a HCV+ donor for end-stage ischemic cardiomyopathy.

Primary and Novel Lipid-Lowering Therapies to Reduce Risk in Patients With Peripheral Arterial Disease.

Purpose Of Review: The diagnosis of peripheral arterial disease (PAD) is a high-risk marker for accelerated atherosclerotic cardiovascular disease (ASCVD) and is associated with substantial morbidity and mortality. In addition to common, modifiable cardiovascular disease risk factors that contribute to PAD, which include hypertension, diabetes mellitus, and smoking, an elevation in concentrations of serum atherogenic lipoproteins (lipids) is an increasingly recognized contributor to premature atherosclerosis.

Recent Findings: The recognition and inclusion of PAD as a marker of higher-cardiovascular risk demonstrates the need to aggressively reduce elevations in atherogenic lipoproteins, particularly low-density-lipoprotein cholesterol.

PCSK9 inhibition in patients with heart transplantation: A case series.

PCSK9 inhibitors are potent low-density lipoprotein cholesterol-lowering medications. There is a lack of data regarding safety and efficacy of PCSK9 inhibitors in cardiac transplant patients. In this case series, we provide data supporting the low-density lipoprotein-lowering efficacy and short-term safety of PCSK9 inhibitors in three cardiac transplant patients.

Three-dimensional echocardiography demonstrates a skewered left ventricular thrombus in a patient with a heart transplant.

A left ventricular (LV) false tendon is a frequently visualized structure in echocardiography with unclear clinical significance. We present the case of a false tendon serving as a nidus for thrombus in a post-orthotopic heart transplantation patient. Three-dimensional transthoracic echocardiography (3DTTE) was utilized to visualize a LV mass and facilitate its identification as a thrombus as well as the surrounding structures.

Utilization of and Adherence to Guideline-Recommended Lipid-Lowering Therapy After Acute Coronary Syndrome: Opportunities for Improvement.

In addition to aggressive lifestyle and nonlipid risk factor modification, statin therapy improves cardiovascular disease outcomes following acute coronary syndromes. Despite established benefits of treatment, contemporary registries reveal substantial underutilization of and nonadherence to statin therapy for secondary prevention. In randomized controlled trials investigating statin therapy, including moderate-intensity statin plus ezetimibe therapy, rates of nonadherence are reported in up to 40% of subjects.

Fibrotic atrial cardiomyopathy, atrial fibrillation, and thromboembolism: mechanistic links and clinical inferences.

The association of atrial fibrillation (AF) with ischemic stroke has long been recognized; yet, the pathogenic mechanisms underlying this relationship are incompletely understood. Clinical schemas, such as the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score, incompletely account for thromboembolic risk, and emerging evidence suggests that stroke can occur in patients with AF even after sinus rhythm is restored. Atrial fibrosis correlates with both the persistence and burden of AF, and gadolinium-enhanced magnetic resonance imaging is gaining utility for detection and quantification of the fibrotic substrate, but methodological challenges limit its use.

Dilemmas in end-stage heart failure.

Heart failure (HF), a complex clinical syndrome due to structural or functional disorder of the heart, is a major global health issue, with a prevalence of over 5.8 million in the USA alone, and over 23 million worldwide. As a leading cause of hospitalizations among patients aged 65 years or older, HF is a major consumer of healthcare resources, creating a substantial strain on the healthcare system.

Mechanisms of myocardial ischemia-reperfusion injury and the cytoprotective role of minocycline: scope and limitations.

Deep insight into the complex mechanisms of myocardial ischemia-reperfusion injury has been attained in the past years. Minocycline is a second-generation tetracycline with US FDA approval for clinical use in various infections. Lately, several noninfectious cytoprotective activities of minocycline have been discovered as well.

Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease.

Triglycerides represent 1 component of a heterogeneous pool of triglyceride-rich lipoproteins (TGRLs). The reliance on triglycerides or TGRLs as cardiovascular disease (CVD) risk biomarkers prompted investigations into therapies that lower plasma triglycerides as a means to reduce CVD events. Genetic studies identified TGRL components and pathways involved in their synthesis and metabolism.

Effect of β-blocker cessation on chronotropic incompetence and exercise tolerance in patients with advanced heart failure.

Background: Chronotropic incompetence is defined as the inability to reach 80% of heart rate (HR) reserve or 80% of the maximally predicted HR during exercise. The presence of chronotropic incompetence is associated with reduced peak oxygen consumption, and rate-responsive pacing therapy is under investigation to improve exercise capacity in heart failure (HF). However, uncertainty exists about whether chronotropic incompetence and reduced exercise tolerance in HF are attributable to β-blockade.

Metabolic abnormalities in adults with cystic fibrosis.

Background And Objective: Survival of patients with cystic fibrosis (CF) has improved, resulting in increased exposure of patients to cardiovascular risk factors. Diabetes mellitus is common in patients with CF; however, less is known about lipid abnormalities in this population. In this study, the prevalence of lipid abnormalities was investigated in a contemporary population of adults with CF.

beta-catenin/TCF/Lef controls a differentiation-associated transcriptional program in renal epithelial progenitors.

In the embryonic kidney, progenitors in the metanephric mesenchyme differentiate into specialized renal epithelia in a defined sequence characterized by the formation of cellular aggregates, conversion into polarized epithelia and segmentation along a proximal-distal axis. This sequence is reiterated throughout renal development to generate nephrons. Here, we identify global transcriptional programs associated with epithelial differentiation utilizing an organ culture model of rat metanephric mesenchymal differentiation, which recapitulates the hallmarks of epithelialization in vivo in a synchronized rather than reiterative fashion.

Dissecting stages of mesenchymal-to-epithelial conversion during kidney development.

During embryonic development, the structures of the nephron from the glomerulus to distal tubule derive from the metanephric mesenchyme. The mesenchymal cells change their cell type and produce highly organized epithelia under the influence of signals from the ureteric bud. The morphological sequence of this conversion includes the formation of a corona of mesenchymal cells surrounding the tips of the ureteric bud, followed by the development of a pre-tubular aggregate, which evolves into preliminary forms of the segmented nephron.