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A 56-year-old male is referred for lipid management after undergoing 3-vessel bypass grafting. Fasting lipid panel on atorvastatin (Lipitor) 10 mg daily revealed total cholesterol 137 mg/dL, HDL cholesterol 25 mg/dL, LDL cholesterol 92 mg/dL, and triglycerides 98 mg/dL. The patient reports his HDL has historically been <30 mg/dL. The patient's brother also has been diagnosed with CAD and low HDL cholesterol. Medical history is notable for hypertension. The patient is a nonsmoker.

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1. What is the patient's most likely lipid disorder?

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2. What is the next appropriate step in lipid management?

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Answers

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  1. Familial hypoalphalipoproteinemia.

  2. Adjust atorvastatin or add an additional cholesterol-lowering agent to achieve LDL cholesterol <70 mg/dL.

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Obesity, metabolic syndrome, physical inactivity, tobacco, diabetes mellitus, hypertriglyceridemia, and certain medications (eg, androgens, progestins, beta-blockers, and benzodiazepines) are potential causes of low HDL cholesterol. However, genetic factors also play an important role for some patients. Isolated low HDL cholesterol is defined as HDL cholesterol levels <40 mg/dL in the absence of hypertriglyceridemia, and a genetic disorder of HDL metabolism should be considered.

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Familial hypoalphalipoproteinemia is an autosomal dominant disorder characterized by HDL cholesterol less than the 10th percentile for men (<30 mg/dL) and 15th percentile for women (<40 mg/dL) and increased risk of premature cardiovascular disease. It is an autosomal dominant disorder with gene frequency approximately 1:400. The underlying metabolic defect leading to low HDL cholesterol remains unknown, although approximately half of cases can be linked to the apo-AI/CIII/AIV/AV gene locus on chromosome 11. The diagnosis is suggested in this patient's case by persistently low HDL cholesterol and early CAD and first-degree relative with both cardiovascular disease and low HDL. Other hereditary causes of low HDL cholesterol are presented in Table 55-1.

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Table Graphic Jump Location
Table 55-1. Hereditary HDL Cholesterol Disorders
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Treatment

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Prospective studies in several countries provide convincing evidence for an inverse association between HDL cholesterol level and cardiovascular risk. An important change in ATP III is redefining low HDL cholesterol as <40 mg/dL. HDL cholesterol is important in CAD risk stratification. It is 1 of the 5 non–LDL cholesterol risk factors and an important component of the Framingham Risk Score. Low HDL cholesterol also moves patients with established CAD from the high-risk to very-high-risk category and reduces LDL cholesterol treatment target to <70 mg/dL.

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The mechanisms by which low HDL cholesterol leads to atherosclerosis and cardiovascular disease are not fully understood. HDL promotes efflux of cholesterol from foam cells in atherosclerotic lesions, and diminished reverse cholesterol transport from arterial vasculature to liver may be a key factor. Low HDL levels also tend to occur with other atherogenic risks such as hypertriglyceridemia, elevated remnant lipoprotein levels, increased levels of small, dense LDL, and insulin resistance. Low HDL often occurs in the setting of hypertriglyceridemia and metabolic syndrome. Management of these conditions may result in a secondary improvement of HDL cholesterol levels.

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There is no formal ATP III treatment target for low HDL level. Although clinical trial data suggest that raising HDL cholesterol will reduce cardiovascular risk, currently available evidence is not sufficient to specify a therapeutic target for HDL. ATP III guidelines emphasize lifestyle modifications ...

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