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INTRODUCTION

ESSENTIALS OF DIAGNOSIS

  • Serum cholesterol values greater than ideal for the prevention of atherosclerotic cardiovascular disease (ASCVD).

  • Optimum values vary with the risk status of the individual patient.

GENERAL CONSIDERATIONS

The Framingham Heart Study firmly established an epidemiologic link between elevated serum cholesterol and an increased risk of morbidity and mortality from ASCVD. Although the benefits of lowering cholesterol were assumed for many years, not until 2001 had enough evidence accumulated to show unequivocal benefits from using lifestyle and pharmacologic therapy to lower serum cholesterol. Evidence in support of using statin agents is particularly strong and has revolutionized the treatment of dyslipidemias.

The efficacy of lipid reduction for the secondary prevention of ASCVD (reducing further disease-related morbidity in those with manifest disease) is supported by multiple trials and is appropriate in all patients with ASCVD. The efficacy of primary prevention (reducing the risk of disease occurrence in those without overt cardiovascular disease) is now supported even in patients at a low risk of ASCVD by the 10-year Framingham risk assessment (available at http://hp2010.nhlbihin.net/atpiii/calculator.asp).

The National Cholesterol Education Program (NCEP), Adult Treatment Panel (ATP) III released guidelines in 2001. New integrated guidelines for cardiovascular disease reduction were released at the end of 2013. These guidelines emphasize aggressive treatment of dyslipidemias and other cardiovascular risk factors with the intensity of treatment titrated to the patients risk status.

PATHOGENESIS

Serum cholesterol is carried by three major lipoproteins: high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL). Most clinical laboratories measure the total cholesterol, total triglycerides (TG), and the HDL fraction.

The triglyceride fraction, and to a lesser extent the HDL level, vary considerably depending on the fasting status of the patient. The NCEP/ATP III guidelines recommend that only fasting measurements including total cholesterol, triglycerides, HDL cholesterol, and a LDL cholesterol be used to guide management decisions.

Different populations have different median cholesterol values. For example, Asian populations tend to have total cholesterol values 20–30% lower than those of populations living in Europe or the United States. It is important to recognize that unlike a serum sodium electrolyte value, there is no normal cholesterol value. Instead, there are cholesterol values that predict higher morbidity and mortality from ASCVD if left untreated, and lower cholesterol values that correlate with less likelihood of cardiovascular disease.

Atherosclerosis is an inflammatory disease in which cells and mediators participate at every stage of atherogenesis from the earliest fatty streak to the most advanced fibrous lesion. Elevated glucose, increased blood pressure, and inhaled cigarette byproducts can trigger inflammation. However, one of the key factors triggering this inflammation is oxidized LDL. When LDL is taken up by macrophages, it triggers the release of inflammatory mediators, which can lead to thickening and/or rupture of plaque lining the arterial walls. Ruptured or unstable plaques ...

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