pathophysiology of hyperlipidemia
Hyperlipidemia is a blood disorder characterized by elevations in blood cholesterol levels. The term is often used synonymously with dyslipidemia and hypercholesterolemia.
Hyperlipidemia is one of the major contributing risk factors in the development of coronary heart disease (CHD). It is estimated that approximately 12.6 million people in the United States have CHI), with approximately 530.000 deaths each year (National Heart. Lung and Blood Institute, 2002). In addition. approximately $112 billion is spent each year on healthcare expenditures and lost productivity secondary to CHD.
Informed estimates indicate that approximately 105 million adults aged 20 and older have total cholesterol levels above 200 mg/dL (50.7%). and 37 million ( 18.3% have levels above 240 mg/dL (American Heart Association. 2003). less than half of the patients eligible for lipid-lowering therapy receive it. and only about one third are at their low-density lipoprotein (LDL) cholesterol goal (Expert Panel. National Cholesterol Educatio Program. In addition, approximately 50% of patients discontinue therapy within 6 months of initiating treatment, with only 30% to 40% remaining on
after 12 months.
Multiple large studies have shown that reducing elevated cholesterol levels reduces morbidity and mortality rates in patients with and without existing CHD. Advances in CHD therapies. including treatment of high cholesterol levels and preventive measures such as aspirin and beta-blocker therapy in patients with previous myocardial infarction (MI). have reduced mortality associated with acute Ml and have improved long-term survival in patients after MI (Pearson & Swan, 1996). As a result of these advances, deaths from cardiovascular disease have decreased by approximately 50% since the early 1980s. although cardiovascular disease still remains the leading cause of death in the United States.
hyperlipidemia causes :
In hyperlipidemia. serum cholesterol levels may be elevated as a result Of an increased level Of any of the lipoproteins(see section on Pathophysiology: Lipoproteins and Lipid Metabolism). The mechanisms for hyperlipidemia appear to be genetic (primary) and environmental (secondary). In fact, the most common cause of hyperlipidemia (95% Of all those with hyperlipidemia) is a combination of genetic and environmental factors.
Some individuals are genetically predisposed to elevated cholesterol levels. They may inherit defective genes that lead to abnormalities in the synthesis or breakdown Of cholesterol. These may include abnormalities in LDL receptors and mutations in apolipoproteins that lead to increased production of cholesterol or decreased clearance Of cholesterol from the bloodstream (see section on Pathophysiology:
Lipoproteins and Lipid Metabolism).
Secondary factors may include medications (eg, beta blockers and oral contraceptives). concomitant disease states or other conditions (eg, diabetes mellitus and pregnancy), diets high in fat and cholesterol. lack of exercise. obesity. and smoking.
The major plasma lipids are cholesterol, triglycerides, and phospholipids. Cholesterol is a naturally occurring substance that is required by body to synthesize bile acids and steroid hormones and to maintain the integrity of cell membranes. Although cholesterol is found predominantly in the cells, approximately 7% circulates in serum. It is this serum cholesterol that is implicated in atherosclerosis. Triglycerides are made up of free fatty and glycerol and serve as an important source Of stored energy. Phospholipids are essential for cell function and lipid transport. Because these lipids are insoluble in plasma, they are surrounded by special fat-carrying
proteins, called lipoproteins, for transport in blood.
Lipoproteins are produced in the liver and intestines, but endogenous production of lipoproteins occurs primarily in the liver. Lipoproteins consist of a hydrophobic (water-insoluble) inner core made of cholesterol and triglycerides and a hydrophilic (water-soluble) outer surface composed Of apolipoproteins and phospholipids. Apolipoproteins are specialized proteins that identify specific receptors to which the lipoprotein will bind. They are thought to play a role in the development or prevention of hyperlipidemia because they control the interaction and metabolism of the lipoproteins.
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