Chapter 31: Dyslipidemia

Dave L. Dixon; Daniel M. Riche

CHAPTER SUMMARY FROM THE PHARMACOTHERAPY HANDBOOK

For the Chapter in the Schwinghammer, Handbook (not Wells Handbook anymore) please go to Chapter 8, Dyslipidemia.

KEY CONCEPTS

Lipid abnormalities increase the risk for coronary heart disease (CHD) and cerebrovascular morbidity and mortality.
Low-density-lipoprotein cholesterol (LDL-C) is the primary target for lipid-lowering therapy.
Genetic abnormalities and environmental factors are involved in the development of dyslipidemia.
Therapeutic lifestyle change is first-line therapy for any lipoprotein disorder.
If therapeutic lifestyle changes are insufficient, lipid-lowering agents should be chosen based on which lipid is at an undesirable level and the degree to which it is expected to increase the risk of atherosclerotic cardiovascular disase (ASCVD).
Statins are the drugs of choice for dyslipidemia because of potency and cost-effectiveness.
If statin monotherapy is insufficient, patients may be treated with evidence-based combination therapy but should be monitored closely for drug–drug interactions.
Reducing total cholesterol and LDL-C reduces CHD and total mortality.
Lipid-lowering therapies that reduce ASCVD event rates are cost-effective.
Several novel medications including antisense oligonucleotide inhibitors of apoB, microsomal triglyceride transport protein inhibitors, adenosine triphosphate-citrate lyase (ACL) inhibitors, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can be used as add-on therapy or in lieu of statin therapy in select high-risk populations.

PRECLASS ACTIVITY

Preclass Engaged Learning Activity

Watch these YouTube videos to learn about cholesterol basics as well as the physiology of lipoprotein cholesterol and metabolism:
- Cholesterol Good and Bad (https://tinyurl.com/yx6a5ufj) by the US National Library of Medicine
- Physiology of Lipoprotein Cholesterol (https://tinyurl.com/hcy239y) by Armando Hasudungan
- Physiology of Lipoprotein Metabolism (https://tinyurl.com/pwo856o) by National Heart, Blood, Lung Institute

INTRODUCTION

Cholesterol, triglycerides, and phospholipids are the major lipids that combine with proteins to be transported as complexes of lipid and proteins known as lipoproteins. Lipids, such as cholesterol and triglycerides, are insoluble in plasma, which is why the lipoproteins are required for transportation (Fig. 31-1).^1,2

FIGURE 31-1

Intestinal cholesterol absorption and transportation. Cholesterol from food and bile enters the gut lumen and is emulsified by bile acids into micelles. Micelles bind to intestinal enterocytes and cholesterol, and other sterols are transported from the micelles to the enterocytes by sterol transporters. Triglycerides (TG) synthesized by absorbed fatty acids (FA) are incorporated into chylomicrons. Chylomicrons are released into lymphatic circulation and converted to chylomicron remnants (by losing triglyceride), and are then taken up by hepatic LDL-receptor–related protein. (Apo, apolipoprotein; ABC, ATP-binding cassette; CE, cholesterol ester; FA, fatty acid; NPC1L1, Niemann-Pick C1-Like1 protein; TG, triglyceride.) (Reproduced, with permission, from Chisholm-Burns MA, Schwinghammer TL, Malone PM, Kolesar JM, Bookstaver PB, Lee KC, eds. Pharmacotherapy Principles & Practice. 5th ed. New York: McGraw-Hill; 2019.)