Hyperlipidemia : Pathophysiology, Diagnosis, And Treatment
Hyperlipidemia is defined as an elevation of one or more of the following: cholesterol, cholesterol esters, phospholipids, or triglycerides. Hyperlipoproteinemia describes an increased concentration of the lipoprotein macromolecules that transport lipids in the plasma.
Pathophysiology of Hyperlipidemia :
Cholesterol, triglycerides, and phospholipids are transported in the bloodstream as complexes of lipid and proteins known as lipoproteins. Elevated total and low-density lipoprotein (LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol are associated with the development of coronary heart disease (CHD).
Atherosclerotic lesions are thought to arise from transport and retention of plasma LDL through the endothelial cell layer into the extracellular matrix of the subendothelial space. Once in the artery wall, LDL is chemically modified through oxidation and nonenzymatic glycation. Mildly oxidized LDL then recruits monocytes into the artery wall. These monocytes then become transformed into macrophages that accelerate LDL oxidation.
The extent of oxidation and the inflammatory response are under genetic control, and primary or genetic lipoprotein disorders are classified into six categories for the phenotypic description of hyperlipidemia. The types and corresponding lipoprotein elevations include the following: I (chylomicrons), IIa (LDL), IIb (LDL + very low density lipoprotein, or VLDL), III (intermediate-density lipoprotein, or IDL); IV (VLDL), and V (VLDL + chylomicrons). Secondary forms of hyperlipidemia also exist, and several drug classes may elevate lipid levels (e.g., progestins, thiazide diuretics, glucocorticoids, Î² blockers, isotretinoin, protease inhibitors, cyclosporine, mirtazapine, sirolimus).
Diagnosis of Hyperlipidemia :
A fasting lipoprotein profile (FLP) including total cholesterol, LDL, HDL, and triglycerides should be measured in all adults 20 years of age or older at least once every 5 years.
Measurement of plasma cholesterol (which is about 3% lower than serum determinations), triglyceride, and HDL levels after a 12-hour or longer fast is important, because triglycerides may be elevated in nonfasted individuals; total cholesterol is only modestly affected by fasting.
Two determinations, 1 to 8 weeks apart, with the patient on a stable diet and weight, and in the absence of acute illness, are recommended to minimize variability and to obtain a reliable baseline. If the total cholesterol is greater than 200 mg/dL, a second determination is recommended, and if the values are more than 30 mg/dL apart, the average of three values should be used.
After a lipid abnormality is confirmed, major components of the evaluation are the history (including age, gender, and, if female, menstrual and estrogen replacement status), physical examination, and laboratory investigations.
Because total cholesterol is composed of cholesterol derived from LDL, VLDL, and HDL, determination of HDL is useful when total plasma cholesterol is elevated. HDL may be elevated by moderate alcohol ingestion (fewer than two drinks per day), physical exercise, smoking cessation, weight loss, oral contraceptives, phenytoin, and terbutaline. HDL may be lowered by smoking, obesity, a sedentary lifestyle, and drugs such as Î² blockers.
In patients with borderline-high blood cholesterol (200 to 239 mg/dL), assessment of risk factors is needed to more clearly define disease risk.
There are three categories of risk that modify the goals and modalities of LDL-lowering therapy. The highest risk category is having known CHD or CHD risk equivalents; the risk for major coronary events is equal to or greater than that for established CHD (i.e., more than 20% per 10 years, or 2% per year). The intermediate category includes two or more risk factors, in which the 10-year risk for CHD is 20% or less. The lowest risk category is persons with zero to one risk factor, which is usually associated with a 10-year risk of CHD of less than 10%.
TLCs (Therapeutic Lifestyle Changes) are begun on the first visit and include dietary therapy, weight reduction, and increased physical activity. Inducing a weight loss of 10% should be discussed with patients who are overweight. In general, physical activity of moderate intensity 30 minutes a day for most days of the week should be encouraged. All patients should be counseled to stop smoking and to meet the Seventh Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines for control of hypertension
The objectives of dietary therapy are to progressively decrease the intake of total fat, saturated fat, and cholesterol and to achieve a desirable body weight .
Fish oil supplementation has a fairly large effect in reducing triglycerides and VLDL cholesterol, but it either has no effect on total and LDL cholesterol or may cause elevations in these fractions.
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