Preventive Therapies in Peripheral Arterial Disease.

Atherosclerosis, while initially deemed a bland proliferative process, is now recognized as a multifactorial-lipoprotein-mediated inflammation-driven pathway. With the rising incidence of atherosclerotic disease of the lower extremity arteries, the healthcare burden and clinical morbidity and mortality due to peripheral artery disease (PAD) are currently escalating. With a healthcare cost burden of over 21 billion USD and 200 million patients afflicted worldwide, accurate knowledge regarding the pathophysiology, presentation, and diagnosis of the disease is crucial. The role of lipoproteins and their remnants in atherosclerotic vessel occlusion and plaque formation and progression has been long established. This review paper discusses the epidemiology, pathophysiology, and presentation of PAD. PAD has been repeatedly noted to portend to poor cardiovascular and limb outcomes. We discuss major therapeutic avenues for the prevention of major cardiovascular adverse events and major limb adverse events in patients with PAD.

New Drugs and Therapies in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension is a chronic, progressive disorder of the pulmonary vasculature with associated pulmonary and cardiac remodeling. PAH was a uniformly fatal disease until the late 1970s, but with the advent of targeted therapies, the life expectancy of patients with PAH has now considerably improved. Despite these advances, PAH inevitably remains a progressive disease with significant morbidity and mortality. Thus, there is still an unmet need for the development of new drugs and other interventional therapies for the treatment of PAH. One shortcoming of currently approved vasodilator therapies is that they do not target or reverse the underlying pathogenesis of the disease process itself. A large body of evidence has evolved in the past two decades clarifying the role of genetics, dysregulation of growth factors, inflammatory pathways, mitochondrial dysfunction, DNA damage, sex hormones, neurohormonal pathways, and iron deficiency in the pathogenesis of PAH. This review focuses on newer targets and drugs that modify these pathways as well as novel interventional therapies in PAH.

Molecular Pathways in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension is a multifactorial, chronic disease process that leads to pulmonary arterial endothelial dysfunction and smooth muscular hypertrophy, resulting in impaired pliability and hemodynamics of the pulmonary vascular system, and consequent right ventricular dysfunction. Existing treatments target limited pathways with only modest improvement in disease morbidity, and little or no improvement in mortality. Ongoing research has focused on the molecular basis of pulmonary arterial hypertension and is going to be important in the discovery of new treatments and genetic pathways involved. This review focuses on the molecular pathogenesis of pulmonary arterial hypertension.

Role of Lipid-Lowering Therapy in Peripheral Artery Disease.

Atherosclerosis is a multifactorial, lipoprotein-driven condition that leads to plaque formation within the arterial tree, leading to subsequent arterial stenosis and thrombosis that accounts for a large burden of cardiovascular morbidity and mortality globally. Atherosclerosis of the lower extremities is called peripheral artery disease and is a major cause of loss in mobility, amputation, and critical limb ischemia. Peripheral artery disease is a common condition with a gamut of clinical manifestations that affects an estimated 10 million people in the United States of America and 200 million people worldwide. The role of apolipoprotein B-containing lipoproteins, such as LDL and remnant lipoproteins in the development and progression of atherosclerosis, is well-established. The focus of this paper is to review existing data on lipid-lowering therapies in lower extremity atherosclerotic peripheral artery disease.