What are the guidelines in the ATP III report on management of low HDL cholesterol (hypoalphalipoproteinemia)?

Updated: May 21, 2021
  • Author: Vibhuti N Singh, MD, MPH, FACC, FSCAI; Chief Editor: George T Griffing, MD  more...
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Most individuals are diagnosed with hypoalphalipoproteinemia (HA) based on the results of a routine lipid profile measurement. This finding of a low high-density lipoprotein (HDL) cholesterol level can be useful as an independent factor in assessing coronary artery disease (CAD) risk and further management. Guidelines in the ATP III report emphasized the importance of HDL cholesterol; the level of HDL considered to be a significant risk factor was changed from less than 35 mg/dL to less than 40 mg/dL. [3, 4, 5, 6, 29]

The basic purpose of the management of HA and related lipid abnormalities is to reduce the risk of atherosclerosis, which is the main mechanism of increased morbidity and mortality. With regard to HA, the ATP III report stated, "Low HDL cholesterol is a strong independent predictor of CHD [coronary heart disease]. In ATP III, low HDL cholesterol is defined categorically as a level < 40 mg/dL, a change from the level of < 35 mg/dL in ATP II [1993]. In the present guidelines, low HDL cholesterol both modifies the goal for LDL-lowering therapy and is used as a risk factor to estimate 10-year risk for CHD." [3, 4, 5, 6]

The document also reported that there are several causes of low HDL cholesterol levels and that a number of these—including type II diabetes, overweight, obesity, elevated triglycerides (TGs), and a lack of physical activity—are associated with insulin resistance. The study also cited cigarette smoking, a very high carbohydrate intake (>60% of calories), and certain agents (such as progestational drugs, anabolic steroids, and beta blockers) as causes of low HDL levels.

  • Follow an appropriate management strategy. The ATP III report did not provide a specific level to which a low HDL concentration should be raised. According to the study's executive summary, "Although clinical trial results suggest that raising HDL will reduce risk, the evidence is insufficient to specify a goal of therapy. Furthermore, currently available drugs do not robustly raise HDL cholesterol." The panel stated that low HDL levels should be managed in the following manner:

    • Reducing low-density lipoprotein (LDL) levels is the primary goal.

    • Metabolic syndrome is the second target. According to the ATP III executive summary, "After the LDL goal has been reached, emphasis shifts to weight reduction and increased physical activity (when the metabolic syndrome is present)." Metabolic syndrome is diagnosed in patients with at least 3 of the following risk factors:

      • Abdominal obesity, with a waist circumference of over 35 inches (females) or above 40 inches (males)

      • TG levels of 15 mg/dL or greater

      • HDL cholesterol levels of below 40 mg/dL (males) or less than 50 mg/dL (females)

      • Blood pressure at or above 130 mm Hg systolic and greater than or equal to 85 mm Hg diastolic

      • Fasting glucose levels at or above 110 mg/dL

    • An association between low HDL and hypertriglyceridemia requires attention. The ATP III reported, "When a low HDL cholesterol is associated with high triglycerides (200-499 mg/dL), secondary priority goes to achieving the non-HDL cholesterol goal." For example:

      • In the patients with established CHD or a CHD risk equivalent (10-year risk for CHD >20%), the LDL goal is under 100 mg/dL, and the goal for non-HDL cholesterol (LDL plus very–low-density lipoprotein [VLDL]) is below 130 mg/dL.

      • In persons with multiple (2+) risk factors and 10-year risk of equal to or less than 20%, the LDL goal is < 130 mg/dL, while the non-HDL goal is < 160 mg/dL.

      • In persons with 0-1 risk factor, the LDL goal is < 160 mg/dL, and that for the non-HDL is < 190 mg/dL.

    • Managing isolated low HDL cholesterol is also important. According to the ATP III, if a patient's TG levels are below 200 mg/dL (isolated low HDL cholesterol), the administration of drugs that increase HDL (fibrates or nicotinic acid) can be considered. Statins have only a modest effect. Treatment for isolated low HDL cholesterol is provided mainly to patients with CHD and CHD risk equivalents.

  • Identify patients whose diet is very low in fat. A low HDL cholesterol level in this setting is rarely associated with an increased risk for premature CHD.

  • Identify and correct secondary factors. Instruct patients who smoke to stop smoking, tell persons who are overweight to manage their weight, and encourage individuals who are sedentary to engage in regular exercise. Whenever possible, eliminate medications associated with low HDL cholesterol levels. Control diabetes optimally, and aggressively treat LDL cholesterol, regardless of HDL cholesterol levels.

  • Consider estrogen replacement therapy for postmenopausal women, because this can substantially raise HDL cholesterol levels.

  • It is unclear whether pharmacologic agents should be used to raise the HDL cholesterol level in otherwise healthy persons, because no published clinical trials are available that demonstrate a benefit. Nonetheless, individuals at high risk require further assessment for CHD risk, with an evaluation that includes a family history, measurements of apo and lipoprotein Lp(a), and electron beam CT scanning.

    • Niacin is the most effective agent currently available. However, many patients with isolated HA do not respond well to niacin. Most patients who receive niacin also have high LDL cholesterol levels that are being managed pharmacologically, and niacin is added to raise their HDL cholesterol level if it is low.

    • Gemfibrozil and fenofibrate modestly raise the HDL cholesterol level. They are most effective in the setting of concomitant hypertriglyceridemia.

    • Statins only mildly raise HDL cholesterol levels. They are not recommended for this purpose alone.

    • Alcohol tends to raise some HDL subfractions. However, no clinical trial data are available to demonstrate any positive role for raising HDL levels with alcohol in order to reduce cardiovascular events in patients with CHD.

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