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Chapter 32: Dyslipidemia

Dave L. Dixon; Daniel M. Riche; Michael S. Kelly

KEY CONCEPTS

KEY CONCEPTS

  • image Lipid abnormalities increase the risk of atherosclerotic cardiovascular disease (ASCVD) which includes ischemic coronary heart disease, ischemic stroke, and peripheral arterial disease.

  • image Low-density-lipoprotein cholesterol (LDL-C) is the primary target to reduce the risk of ASCVD events.

  • image Genetic abnormalities and environmental factors are involved in the development of dyslipidemia.

  • image Therapeutic lifestyle change is the first-line therapy for any lipoprotein disorder.

  • image 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 ASCVD.

  • image Statins are the drug of choice for dyslipidemia because they significantly lower LDL-C and the risk of ASCVD events, and are generally well tolerated.

  • image If statin monotherapy is insufficient, patients may be treated with evidence-based combination therapy but should be monitored closely for drug-drug interactions.

  • image Reducing total cholesterol and LDL-C reduces CHD and total mortality.

  • image Lipid-lowering therapies that reduce ASCVD event rates are cost-effective.

  • image 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) modulating therapies can be used as add-on therapy or in lieu of statin therapy in select high-risk patients.

BEYOND THE BOOK

BEYOND THE BOOK

Watch these YouTube videos to learn about cholesterol basics as well as the physiology of lipoprotein cholesterol and metabolism:

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. 32-1).1,2

FIGURE 32-1

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.)

An illustration shows the process of intestinal cholesterol absorption and transportation. Inside the intestinal lumen into the brush border, diet and bile lead to the production of luminal cholesterol. This leads to micellar cholesterol and other sterols. FA is present inside the intestinal lumen. Inside the enterocyte, FA of the intestinal lumen becomes TG. Micellar cholesterol in the intestinal lumen becomes cholesterol due to the NPC1L1 transporter. The cholesterol becomes CE. The cholesterol also becomes fecal cholesterol in the intestinal lumen with the help of ABC G5 or G8. TG, CE, and Apo B-48 of enterocyte lead to Apo B-48 inside the lymph. Apo B-48 consists of TG and CE which help in the process of lipolysis and delivery to the liver.
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There are three major classes of lipoproteins in the serum. These include low-density lipoproteins (LDL), high-density lipoproteins (HDL), ...

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