• Serum cholesterol values greater than ideal for the prevention of atherosclerotic cardiovascular disease (ASCVD).
  
• Ideal values vary based on 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 the past decades has 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 in any patients at more than 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 and an update in July 2004. These guidelines emphasize aggressive treatment of dyslipidemias 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, varies 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 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 cholesterol values that correlate with less likelihood of cardiovascular disease if they are below certain levels.

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 by-products can trigger inflammation. But, 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 are responsible for clinical events such as myocardial infarction and stroke. Lipid lowering, whether by diet or medication, can therefore be thought of as an anti-inflammatory and plaque stabilizing therapy.

Clinical Findings

Symptoms and Signs

The majority of patients with dyslipidemias have no signs or symptoms of disease and is usually detected by routine laboratory screening in an asymptomatic individual. Rarely, patients with familial forms of hyperlipidemia may present with yellow xanthomas on the skin or in tendon bodies, especially the patellar tendon, Achilles tendon, and the extensor tendons of the hands.

There are a few associated conditions that can cause a secondary hyperlipidemia (Table 21-1). These conditions should be considered before lipid lowering therapy is begun or when the response to therapy is much less than predicted. In particular, poorly controlled diabetes and untreated hypothyroidism can lead to an elevation of serum lipids resistant to pharmacologic treatment.

Screening

The US Preventive Services Task Force (USPSTF) bases its screening recommendations on the age of the patient. It strongly recommends (rating A) routinely screening men 35 years and older and women 45 years of age and older for lipid disorders.

The USPSTF recommends (rating B) screening younger adults, (men 20-35 years of age and women 20-45 years of age), if they have other risk factors for coronary disease. They make no recommendation for or against screening in younger adults in the absence of known risk factors.

In contrast, the NCEP guidelines advise that screening should occur in adults aged 20 years or older with a fasting, lipid profile once every 5 years.

Screening children and adolescents is controversial and expert opinion recommends screening only those children older than 2 years of age with significant family histories of hypercholesterolemia or premature ASCVD.

Treatment

The current NCEP/ATP III treatment guidelines released on 15 May 2001 and the update from July 2004 are as rooted in evidence as possible. They are available online at www.nhlbi.nih.gov.

The NCEP/ATP III guidelines follow a 9-step process (Table 21-2). The first step begins after obtaining fasting lipoprotein levels. The profile is categorized based on the LDL, HDL, and total cholesterol values: