Hyperlipoproteinemia occurs when there is too much lipid (fat) in the blood. Shorter terms that mean the same thing are hyperlipidemia and hyperlipemia. Dyslipidemia refers to a redistribution of cholesterol from one place to another that increases the risk of vascular disease without increasing the total amount of cholesterol. When more precise terms are needed, hypercholesterolemia and hypertriglyceridemia are used.
It is commonly known that oil and water do not mix unless another substance like a detergent is added. Yet the body needs to transport both lipids (fats) and water-based blood within a single circulatory system. There must be a way to mix the two, so that essential fatty nutrients can be transported in the blood and so that fatty waste products can be carried away from tissues. The solution is to combine the lipids with protein to form water-soluble packages that can be transported in the blood.
These packages of fats are called lipoproteins. They are a complex mixture of triglycerides, cholesterol, phospholipids and special proteins. Some of these chemicals are fatty nutrients absorbed from the intestines on their way to being made part of the body. Cholesterol is a waste product on its way out of the body through the liver, the bile, and ultimately the bowel for excretion. The proteins and phospholipids make the packages water-soluble.
There are five different sizes of these chemical packages. Each package needs all four chemicals in it to hold everything in solution. They differ in how much of each they contain. If blood serum is spun very rapidly in an ultracentrifuge, these five packages will layer out according to their density. They have, therefore, been named according to their densities—high-density lipoproteins (HDL), low-density lipoproteins (LDL), intermediate-density lipoproteins (IDL), very low density lipoproteins (VLDL), and chylomicrons. Only the HDLs and the LDLs will be discussed in the rest of this article.
If there is not enough detergent in the laundry, the oily stains will remain in the clothes. In the same way, if the balance of chemicals in these packages is not right, cholesterol will stay in tissues rather than being excreted from the body. What is even worse, if the chemical composition of these packages changes, the cholesterol can fall out of the blood and stay where it lands. On the other hand, a different change in the balance can remove cholesterol from tissues where there is too much. This appears to be exactly what is going on in atherosclerosis. The lesions contain lots of cholesterol.
The LDLs are overloaded with cholesterol. A minor change in the other chemicals in this package will leave cholesterol behind. The HDLs have a third to a half as much cholesterol. They seem to be able to pick up cholesterol left behind by the LDLs. It seems that atherosclerosis begins with tiny tears at stressed places in the walls of the arteries. Low density lipoproteins from the blood enter these tears, where their chemistry changes enough to leave cholesterol behind. The cholesterol causes irritation; the body responds with inflammation; damage and scarring follow. Eventually the artery gets so diseased blood cannot flow through it. Strokes and heart attacks are the result.
But if there are lots of HDLs in the blood, the cholesterol is rapidly picked up and not allowed to cause problems. Women before menopause have estrogen (the female hormone), which encourages the formation of HDLs. This is the reason they have so little vascular disease, and why they rapidly catch up to men after menopause, when estrogen levels fall. Replacement of estrogen after menopause has been prescribed to for protection through the later years. However, in 2003, the Women's Health Initiative, a large clinical trial involving postmenopausal women, was halted in July 2002 because of the many detrimental effects of combined estrogen and progesterone therapy (called hormone replacement therapy ). Among the effects was increased risk of heart disease, sometimes within the first year of use.
Cholesterol is the root of the problem, but like any other root it cannot just be eliminated. Ninety percent of the cholesterol in the body is created there as a waste product of necessary processes. The solution lies in getting it out to the body without clogging the arteries.
Of course the story is much more complex. The body has dozens of chemical processes that make up, break down, and reconfigure all these chemicals. It is these processes that are the targets of intervention in the effort to cure vascular disease.
Near the dawn of concern over cholesterol and vascular disease a family of hereditary diseases was identified, all of which produced abnormal quantities of blood fats. These diseases were called dyslipoproteinemias and came in both too many and too little varieties. The hyperlipoproteinemias found their way into five categories, depending on which chemical was in excess.
- Type 1 has a pure elevation of triglycerides in the chylomicron fraction. These people sometimes get pancreatitis and abdominal pains, but they do not seem to have an increase in vascular disease.
- Type 2 appears in two distinct genetic patterns and a third category, which is by far the most important kind, because everyone is at risk for it. All Type 2s have elevated cholesterol. Some have elevated triglycerides also. The familial (genetic) versions of Type 2 often develop xanthomas, which are yellow fatty deposits under the skin of the knuckles, elbows, buttocks or heels. They also may have xanthelasmas, smaller yellow patches on the eyelids.
- Type 3 appears in one in 10,000 people and elevates both triglycerides and cholesterol with consequent vascular disease. In 2003, researchers discovered the molecular mechanism that contributes to high triglycerides in those with this type of hyperlipopoproteinemia.
- Type 4 elevates only triglycerides and does not increase the risk of vascular disease.
- Type 5 is similar to Type 1.
- Dyslipidemia refers to a normal amount of cholesterol that is mostly in LDLs, where it causes problems.
All but Type 2 are rare and of interest primarily because they give insight into the chemistry of blood fats.
In addition to the above genetic causes of blood fat disorders, a number of acquired conditions can raise lipoprotein levels.
- Diabetes mellitus, because it alters the way the body handles its energy needs, and also affects the way it handles fats. The result is elevated triglycerides and reduced HDL cholesterol. This effect is amplified by obesity.
- Hypothyroidism is a common cause of lipid abnormalities. The thyroid hormone affects the rate of many chemical processes in the body, including the clearing of fats from the blood. The consequence usually is an elevation of cholesterol.
- Kidney disease affects the blood's proteins and consequently the composition of the fat packages. It usually raises the LDLs.
- Liver disease, depending on its stage and severity, can raise or lower any of the blood fats.
- Alcohol raises triglycerides. In moderate amounts (if they are very moderate) it raises HDLs and can be beneficial.
- Cigarette smoking lowers HDL cholesterol, as does malnutrition and obesity.
Certain medications elevate blood fat levels. Because some of these medications are used to treat heart disease, it has been necessary to reevaluate their usefulness:
- Thiazides, water pills used to treat high blood pressure, can raise both cholesterol and triglycerides.
- Beta-blockers, another class of medication used to treat high blood pressure, cortisone-like drugs, and estrogen can raise triglycerides.
- Progesterone, the pregnancy hormone, raises cholesterol.
Not all of these effects are necessarily bad, nor are they necessarily even significant. For instance, estrogen is clearly beneficial. Each effect must be considered in the overall goal of treatment.
Causes and symptoms
A combination of heredity and diet is responsible for the majority of fat disorders. It is not so much the cholesterol in the diet that is the problem, because that accounts for only 10% of the body's store. It is the other fats in the diet that alter the way the body handles its cholesterol. There is a convincing relation between fats in the diet and the incidence of atherosclerosis. The guilty fats are mostly the animal fats, but palm and coconut oil also are harmful. These fats are called saturated fats for the chemical reason that most of their carbon atoms have as many hydrogen atoms attached as they can accommodate. More important than the kind of fat is the amount of fat. For many people, fat is half of their diet. One-fifth to one-fourth is a much healthier fraction, the rest of the diet being made up of complex carbohydrates and protein.
This disease is silent for decades, until the first episode of heart disease or stroke.
It would be easier if simple cholesterol and triglyceride tests were all it took to assess the risk of atherosclerosis. But the important information is which package the cholesterol is in—the LDLs or the HDLs. That takes a more elaborate testing process. To complicate matters further, the amount of fats in the blood varies greatly in relation to the last meal—how long ago it was and what kind of food was eaten. A true estimate of the risk comes from several tests several weeks apart, each done after at least twelve hours of fasting.
Diet and lifestyle change are the primary focus for most cholesterol problems. It is a mistake to think that a pill will reverse the effects of a bad diet, obesity, smoking, excess alcohol, stress, and inactivity. Reducing the amount of fat in the diet by at least half is the most important move to make. Much of the food eaten to satisfy a "sweet tooth" is higher in fat than in sugar. A switch away from saturated fats is the next step, but the rush to polyunsaturated fats was ill-conceived. These, particularly the hydrogenated fats in margarine, have problems of their own. They raise the risk of cancer and are considered more dangerous than animal fat by many experts. Theory supports population studies that suggest monounsaturated olive oil may be the healthiest of all.
There was a tremendous push at the end of the 20th century to use lipid-lowering medications. The most popular and most expensive agents, the "statins," hinder the body's production of cholesterol and sometimes damage the liver as a side effect. Their full name is 3-hydroxy-3-methylglutarylcoemzyme A (HMG-CoA) reductase inhibitors. Their generic names are cervistatin, fluvastatin, lovastatin, pravastatin, simvastatin, and the newest and most powerful to date, rosuvastatin. Studies show that these drugs lower cholesterol. Only recently, though, has any evidence appeared that this affects health and longevity. Earlier studies showed, in fact, an increased death rate among users of the first class of lipid-altering agents—the fibric acid derivatives. The chain of events connecting raised HDL and lowered LDL cholesterol to longer, healthier lives is still to be forged.
High-tech methods of rapidly reducing very high blood fat levels are performed for those rare disorders that require it. There are resins that bind cholesterol in the intestines. They taste awful, feel like glue and routinely cause gas, bloating, and constipation. For acute cases, there is a filtering system that takes fats directly out of the blood.
Niacin (nicotinic acid) lowers cholesterol effectively and was the first medication proven to improve overall life expectancy. It also can be liver toxic, and the usual formulation causes a hot flash in many people. This can be overcome by taking a couple of aspirins 30 minutes before the niacin, or by taking a special preparation called "flush free," "inositol-bound" or inositol hexanicotinate.
Omega-3 oil is a special kind found mostly in certain kinds of fish. It is beneficial in lowering cholesterol. An herbal alternative called guggulipid, Commiphora mukul, an extract of an Indian plant, has been touted as working the same way as the expensive and liver toxic cholesterol-lowering medications. However, a 2003 clinical trial found that the supplement did not meet these claims. In fact, guggul did not lower total cholesterol, LDL cholesterol, or triglycerides. Most patients tolerated the supplement, but some developed a hypersensitivity rash.
To lower cholesterol, naturopathic medicine, traditional Chinese medicine, and ayurvedic medicine may be considered. Some herbal therapies include alfalfa (Medicago sativa ), Asian ginseng (Panax ginseng ), and fenugreek (Trigonella foenum-graecum ). Garlic (Allium sativum ) and onions are also reported to have cholesterol-lowering effects. In naturopathic medicine, the liver is considered to be an organ that needs cleansing and rebalancing. The liver often is treated with a botanical formula that will act as a bitter to stimulate bile flow in the liver. Before initiating alternative therapies, medical consultation is strongly advised.
The prognosis is good for Type 1 hyperlipoproteinemia with treatment; without treatment, death may result. For Type 2 the prognosis is poor even with treatment. The prognosis for type 3 is good when the prescribed diet is strictly followed. For types 4 and 5 the prognosis is uncertain, due to the risk of developing premature coronary artery disease and pancreatitis, respectively.
Genetic inheritance cannot be changed, but its effects may be modified with proper treatment. Family members of an individual with hyperlipoproteinemia should consider having their blood lipids assessed. The sooner any problems are identified, the better the chances of limiting or preventing the associated health risks. Anyone with a family history of disorders leading to hyperlipoproteinemia also may benefit from genetic testing and counseling to assist them in making reproductive decisions.
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Dowhower Karpa, Kelly. "New Statin Said to be More Powerful than Others." Drug Topics 147, no. 17 (September 1, 2003): 27.
"Herbal Extract Not Effective in Treating High Cholesterol." Drug Week August 29, 2003: 197.
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Inherited High Cholesterol Foundation. 410 Chipeta Way, Room 167, Salt Lake City, UT 84104. (888) 244-2465.
Atherosclerosis— Hardening of the arteries due to fat (cholesterol) deposits in their walls. Also known as arteriosclerosis.
Genetic— Refers to the genes and characteristics inherited from parents.
Inflammation— The body's response to irritation, by releasing chemicals that attack germs and tissues and also repair the damage done.
Lesion— Localized disease or damage.
Pancreatitis— Inflammation of the pancreas.
Serum— The liquid part of blood, from which all the cells have been removed.