Along with proteins and carbohydrates, lipids play an integral role in maintaining cell function and sustaining life. Lipids are a family of water-insoluble organic compounds that includes fats, oils, sterols, and triglycerides. Cholesterols and phospholipids are the building blocks for the cell wall and the plasma membrane, respectively. Triglycerides are made of fatty acids, which can be utilized for energy production.

Given that the human body is primarily aqueous and lipids are water-insoluble, lipids are transported via a unique lipoprotein family. This consists of a water-soluble outer coat with nonpolar lipid coat. Apolipoproteins are proteins that help in this transport system (Figure 2-1).

Briefly, there are two major sources for lipids in the body: diet and hepatic production. The chylomicrons deliver lipids from dietary fat to the plasma, and the very low-density lipoproteins (VLDLs) transport lipids from the hepatic production of lipids to the body (Figure 2-2). Lipoprotein lipase breaks down the VLDL to low-density lipoprotein (LDL), which is internalized by the cells to provide fatty acid for cell function and energy (Figure 2-3). Cholesteryl ester transfer protein (CETP) permits exchange of triglycerides and cholesteryl esters from VLDL to high-density lipoprotein (HDL), allowing for reverse cholesterol transport via the HDL system (Figure 2-4).

LIPID DISORDERS

Hyperlipidemia is a condition in which there are abnormally elevated levels of lipids or lipoproteins in the blood. They can be divided into primary or secondary causes. Primary hyperlipidemia is typically due to a genetic cause, whereas secondary hyperlipidemia usually occurs as a result of a systemic disorder, such as diabetes mellitus. The types of familial hyperlipidemia are categorized by the Fredrickson classification (Table 2-1).

Type IIa familial hyperlipidemia is due to mutations in the gene encoding the LDL receptor, which is essential for the transport and metabolism of cholesterol. The human LDL receptor gene is located on chromosome 19 and there are more than 900 known mutations. Those who are heterozygous tend to have a 2- to 3-fold increase in plasma cholesterol whereas those who are homozygous will have a 5- to 6-fold elevation.

Common findings include xanthomas, xanthelasmas, corneal arcus, and premature atherosclerosis. In all types of type IIa familial hyperlipidemia, there is a decrease of clearance of LDL, which in turn causes a larger proportion of plasma LDL. Patients with familial hyperlipidemia have been shown to be associated with increased atherosclerotic coronary artery disease and premature death.

Mutations in the apolipoprotein B-100 (APOB) gene and the gene encoding for proprotein convertase subtilisin/kexin type 9 (PCSK9) can cause a clinical familial hyperlipidemia phenotype.

Secondary causes of hyperlipidemia include diabetes, hypothyroidism, nephrotic syndrome, hepatitis, and HIV. In diabetes, insulin resistance and subsequent hyperinsulinemia cause a characteristic increase in plasma triglycerides and a lowering of HDL. Certain medications such as steroids, oral contraceptives, and thiazide diuretics can also affect lipid levels. Some potentially modifiable causes of hypercholesterolemia are excessive alcohol consumption, cigarette smoking, and obesity.

MANAGEMENT

The revised 2013 ACC/AHA guidelines on lipid management have changed the landscape of lipid management.¹ Firstly, risk calculators that are gender- and race-specific have been proposed (Table 2-2). Secondly, the guidelines focus on statins as the mainstay for treatment. Statins have been classified as moderate- and high-intensity statins (Figure 2-5). Four groups of patients have been identified to benefit from treatment (Figure 2-6). Although the major criticism is overestimation of risk, there have been ongoing efforts to validate this scoring system.