Maximizing the benefits of cholesterol-lowering drugs Purpose of review Drugs to lower LDL-C levels are very widely used. In this brief review, I will use selected recent studies to delineate several important principles that provide a rationale for how to maximize the benefits of using LDL-C lowering drugs to reduce cardiovascular disease. The focus will be on using statins, ezetimibe, and PCSK9 monoclonal antibodies as recent studies have predominantly utilized these agents. Recent findings The key principles to consider when using LDL-C-lowering drugs to reduce cardiovascular disease are: the lower the LDL-C the better; the sooner and the longer one lowers LDL-C the better; the higher the risk of cardiovascular disease the greater the absolute benefit; the higher the baseline LDL-C the greater the absolute benefit; and compared with the benefits of cholesterol-lowering drugs on reducing cardiovascular disease the risk of side effects is very modest. Summary Understanding and employing these key concepts in caring for patients will allow one to use cholesterol-lowering drugs wisely to maximize the reduction of cardiovascular events. Correspondence to Kenneth R. Feingold, MD, Department of Medicine, University of California, San Francisco, CA 94121, USA. Tel: +1 415 302 8463; e-mail: kenneth.feingold@ucsf.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Trained immunity and atherosclerotic cardiovascular disease Purpose of review The two major challenges in cardiovascular medicine are to refine risk prediction and to improve pharmacological prevention and treatment. The concept of innate immune memory, which is called trained immunity, has the potential to improve clinical practice in these regards. Recent findings Monocytes and macrophages have the capability to develop a long-term proinflammatory and proatherogenic phenotype after brief exposure to inflammatory stimuli, such as oxidized low-density lipoprotein particles. This innate immune memory develops because of rewiring of intracellular metabolic pathways and epigenetic reprogramming of histone modifications. The persistence of circulating hyperresponsive monocytes in vivo is explained by the fact that training occurs in myeloid progenitor cells in the bone marrow. Several recent studies reported the presence of monocytes with a trained immune phenotype in patients with established atherosclerosis, and in patients with an increased risk for atherosclerosis because of dyslipoproteinemia. Summary In monocytes and their bone marrow progenitors, metabolic and epigenetic reprogramming can induce trained immunity, which might contribute to the persistent nonresolving inflammation that characterizes atherosclerosis. These pathways offer exciting novel drug targets to improve the prevention and treatment of cardiovascular disease. Correspondence to Niels P. Riksen, Professor of Vascular Medicine, Department of Internal Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, the Netherlands. Tel: +31 24 3618819; fax: +31 24 3616519; e-mail: niels.riksen@radboudumc.nl Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.