BLOOD LIPIDS

Lipids are fatty organic compounds or particles in the body that are poorly soluble in water and generally feel greasy to the touch. The most important lipids in the blood are fatty acids, cholesterol, cholesterol esters (cholesterol attached to a fatty acid), triglycerides (three fatty acids attached to a three-carbon glycerol), and phospholipids, such as lecithin.

Cholesterol esters and triglycerides are hydrophobic and do not dissolve in water. They are thus carried through the bloodstream in particles called lipoproteins—complex particles with the less water-soluble cholesterol esters and triglycerides on the inside and the more water-soluble free cholesterol, phospholipids, and apoproteins on the surface.

Lipoproteins are clinically named by their location in a density gradient, which is discerned by placing them in a ultracentrifuge for twenty-four hours. In order of increasing density, lipoproteins include: chylomicrons, very low-density lipo-protein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL; see Figure 1). The least dense particles—the chylomicrons, VLDL, and IDL particles—mostly contain triglycerides, and when severely elevated they can make the plasma look milky. The more dense particles—LDL and HDL—contain more water-soluble cholesterol esters, and no triglycerine, and thus, when elevated, they are visually undetectable in the plasma.

Through long-term studies of large populations, the particles associated with increasing atherosclerosis (a buildup of fatty cholesterol-filled plaques in the arteries that can lead to heart attacks, strokes, and gangrene) are LDL, IDL, and small breakdown remnants of VLDL and chylomicrons. Large amounts of HDL are associated with protection from atherosclerosis, thus the designation of cholesterol in these particles as healthy, or "good," cholesterol. The cholesterol in LDL particles, because of its strong association with atherosclerosis, has been designated as lousy or "bad" cholesterol and has been targeted as the most important lipid for people to lower. Since two-thirds of the total cholesterol in the blood stream is LDL cholesterol, high levels of total cholesterol, which thus generally reflect this LDL cholesterol, are associated with an increased risk of atherosclerosis.

A lipid profile is the clinical blood test which measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. The most common way lipid risk for atherosclerosis is interpreted on a lipid profile is the total cholesterol/HDL cholesterol ratio. For heart attack prevention the TC/HDLC ratio should be less than 4.5 to 1 (ideally less than 4.0).

Each lipoprotein has proteins on its surface called apoproteins (or apolipoproteins). These are designated by letters and numbers; for example, there is predominantly apoprotein apo AI on HDL; apo B100 on LDL, VLDL, and IDL; and apo B48 on chylomicrons. Thus, apo B100 represents particles associated with risk for atherosclerosis and Apo AI with particles associated with protection. The apo B/apo AI ratio has been used to determine atherosclerotic risk, though it seems to be no better in predicting risk than the TC/HDLC ratio. Lipoprotein "little a," written as lipoprotein (a) or Lp(a), is an LDL particle with an apoprotein (a) attached; in some populations increased Lp(a) increases risk for atherosclerosis in persons with increased LDL cholesterol levels.

Extreme elevations of LDL cholesterol usually occurs in families for genetic reasons, but can be

Figure 1

Lipoproteins
Name	Relative size	Main ingredients	Function	Risk for CHD
SOURCE: Courtesy of author.
Chylomicrons	Very large	Triglycerides	Carry dietary fatty acids from intestine to liver, muscle, and fat cells	Low
Very low-density lipoproteins (VLDL)	Large	Triglycerides	Carry fatty acids from liver to muscle for energy, and to fat for storage	Medium
Low density lipoproteins (LDL)	Medium	Cholesterol	Carry cholesterol throughout body, including to glands for making steroid hormones	High
High density lipoproteins (HDL)	Small	Cholesterol	Carries cholesterol from inside body to liver for excretion in bile	Protective

increased in individuals and populations by diet as well. LDL cholesterol levels may be elevated by consumption of saturated fatty acids (found in animal fats, dairy fats, and palm oil); partially hydrogenated fats such as vegetable shortening (found in fried fast-food products, pastries, and certain snacks such as potato chips); and cholesterol in the diet from too many egg yolks, meats, liver, or a high intake of squid or shrimp. Hypothyroidism or certain types of kidney failure may also elevate LDL cholesterol. Medications that reduce LDL cholesterol include statins (HMG CoA reductase inhibitors), a popular group of medications that inhibit an important enzyme in cholesterol synthesis; bile acid binders, which waste bile salts in stools, forcing the liver to make new bile salts from cholesterol; and niacin (vitamin B3).

Triglycerides, elevation of which has been associated with increased coronary heart disease, are increased mostly by genetic factors, but also by excess abdominal fat; excess simple sugar intake as found in table sugar, fruit juices, cold drinks; estrogens; glucocorticoids (cortisone-like agents); excess alcohol intake; and insulin resistance and diabetes. Triglycerides may be lowered by weight loss; increased exercise; reduction of simple sugars and excess carbohydrates in the diet; control of blood glucose in persons with diabetes; fibric acid medications (gemfibrozil, fenofibrate); niacin; and fish oils (in high doses).

Low HDL cholesterol, which increases risk for coronary heart disease, is most often caused by genetic factors, but can also be lowered by smoking; abdominal obesity; inactivity; insulin resistance and diabetes; and androgen (male hormone) ingestion. HDL cholesterol may be raised by smoking cessation; substantial increases in physical activity; maintained weight loss; mild to moderate alcohol consumption; reducing elevated triglyceride levels; postmenopausal estrogen usage; moderate to high doses of niacin; fibric acid medications; statins; and bile acid binders.