Some people have low HDLC (< 35 mg/dL) and another abnormalities of lipid metabolism. These disorders are called "dyslipidemia" or "dyslipoproteinemia," and are most likely caused by genetic defects compounded by bad diets (severe obesity can cause some of these problems). Dyslipidemia is elevation of plasma cholesterol and/or TGs or a low HDL level that contributes to the development of atherosclerosis. Causes may be primary (genetic) or secondary. Diagnosis is by measuring plasma levels of total cholesterol, TGs, and individual lipoproteins. Treatment is dietary changes, exercise, and lipid-lowering drugs.
Dyslipidemia currently affects approximately 10% of the global population. There is an increasing prevalence and medical need for lipid-modifying drugs in obese and type 2 diabetic patients. A high proportion of type 2 diabetic patients have abnormal concentrations of lipoproteins. In the US, Japan and Europe there are more than 240 million people with abnormal lipoprotein levels. Of these, more than 55 million have low high density lipoprotein (HDL) and/or high triglyceride levels.
There is no natural cutoff between normal and abnormal lipid levels because lipid measurements are continuous. A linear relation probably exists between lipid levels and cardiovascular risk, so many people with “normal” cholesterol levels benefit from achieving still lower levels. Consequently, there are no numeric definitions of dyslipidemia; the term is applied to lipid levels for which treatment has proven beneficial. Proof of benefit is strongest for lowering elevated LDL levels; it is less strong for lowering elevated TG and increasing low HDL levels, in part because elevated TG and low HDL levels are more predictive of cardiovascular risk in women than in men.
This colored scanning electron micrograph of a coronary artery cross section shows atherosclerosis, with fatty plaque (in yellow). A
diet high in cholesterol can reduce blood flow
and lead to clots or blockages.
Dyslipidemias were traditionally classified by patterns of elevation in lipids and lipoproteins. A more practical system categorizes dyslipidemias as primary or secondary and characterizes them by increases in cholesterol only (pure or isolated hypercholesterolemia), increases in TGs only (pure or isolated hypertriglyceridemia), or increases in both cholesterol and TGs (mixed or combined hyperlipidemias). This system does not take into account specific lipoprotein abnormalities (eg, low HDL or high LDL) that may contribute to disease despite normal cholesterol and TG levels.
Primary causes are single or multiple genetic mutations that result in either overproduction or defective clearance of TG and LDL cholesterol, or in underproduction or excessive clearance of HDL . Primary lipid disorders are suspected when a patient has physical signs of dyslipidemia (see Lipid Disorders: Symptoms and Signs), onset of premature atherosclerotic disease (< 60 yr), a family history of atherosclerotic disease, or serum cholesterol > 240 mg/dL (> 6.2 mmol/L). Primary disorders, the most common cause of dyslipidemia in children, do not cause a large percentage of cases in adults. The names of many reflect an old nomenclature in which lipoproteins were detected and distinguished by how they separated into α (HDL) and β (LDL) bands on electrophoretic gels.
Secondary causes contribute to most cases of dyslipidemia in adults. The most important secondary cause in developed countries is a sedentary lifestyle with excessive dietary intake of saturated fat, cholesterol, and trans fatty acids (TFAs). TFAs are polyunsaturated fatty acids to which hydrogen atoms have been added; they are commonly used in many processed foods and are as atherogenic as saturated fat. Other common secondary causes include diabetes mellitus, alcohol overuse, chronic renal insufficiency and/or failure, hypothyroidism, primary biliary cirrhosis and other cholestatic liver diseases, and drugs, such as thiazides, β-blockers, retinoids, highly active antiretroviral agents, estrogen and progestins, and glucocorticoids.
Diabetes is an especially significant secondary cause because patients tend to have an atherogenic combination of high TGs; high small, dense LDL fractions; and low HDLs (diabetic dyslipidemia, hypertriglyceridemic hyperapo B). Patients with type 2 diabetes are especially at risk. The combination may be a consequence of obesity and/or poor control of diabetes, which may increase circulating FFAs, leading to increased hepatic VLDL production. TG-rich VLDL then transfers TG and cholesterol to LDL and HDL, promoting formation of TG-rich, small, dense LDL and clearance of TG-rich HDL. Diabetic dyslipidemia is often exacerbated by the increased caloric intake and physical inactivity that characterize the lifestyles of some patients with type 2 diabetes. Women with diabetes may be at special risk for cardiac disease from this form.
Symptoms and Signs
Dyslipidemia itself causes no symptoms but can lead to symptomatic vascular disease, including coronary artery disease and peripheral arterial disease. High TGs (> 1000 mg/dL [> 11.3 mmol/L]) can cause acute pancreatitis. High levels of LDL can cause eyelid xanthelasmas; arcus corneae; and tendinous xanthomas found at the Achilles, elbow, and knee tendons and over metacarpophalangeal joints. Patients with the homozygous form of familial hypercholesterolemia may have the above findings plus planar or cutaneous xanthomas. Patients with severe elevations of TGs can have eruptive xanthomas over the trunk, back, elbows, buttocks, knees, hands, and feet. Patients with the rare dysbetalipoproteinemia can have palmar and tuberous xanthomas.
Severe hypertriglyceridemia (> 2000 mg/dL [> 22.6 mmol/L]) can give retinal arteries and veins a creamy white appearance (lipemia retinalis). Extremely high lipid levels also give a lactescent (milky) appearance to blood plasma.
When you are diagnosed with a genetic disorder of lipid metabolism, you will need to follow a very strict and complex diet, and you may also have to take drugs. This is a situation where you must be seen by a lipids specialist like Dr. Tapp rather than a general physician. Because each of these disorders is fairly unique and manifests differently in different patients, you need to work with your health provider to develop the optimal plan. Treatment involves a combination of different strategies:
- Weight loss. This is the most important strategy for overweight people
- Diet low in calories, high in nutrients, essential fats. Adequate in vitamins and minerals
- Combination of drugs
Drugs come in several categories, Each category is particularly useful for a specific type of disorder. Some help increase HDL and decrease TGs; others lower LDL and total cholesterol. A doctor needs to spend considerable time analyzing your problem to determine the cause of your lipid abnormality and the best types of drugs for your condition.
Once a decision is made about the types of drugs to be used, one needs to decide the specific drug within each type and the dose. These decisions involve more subtle aspects of each person’s condition. Sometimes one must try a drug for a while, and then change to a different type to see which one works better and has fewer side effects. Alternatively, changing drugs may minimize side effects.
A combination of drugs may allow a doctor to prescribe lower doses of individual drugs, thereby decreasing the risk of side effects. Remember: Each drug has side effects, and many of the long term side effects cannot be known because each person has different genes and likely responds differently to each drug.
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