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KEY FEATURES

ESSENTIALS OF DIAGNOSIS

  • Elevated plasma levels of low-density lipoprotein (LDL)

  • Reduced plasma levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A

  • Elevated plasma levels of triglyceride

  • Skin xanthomas

GENERAL CONSIDERATIONS

  • Cholesterol and triglycerides are insoluble in water and are transported in plasma by lipoproteins

  • Apolipoprotein A carries LDL; the combination is called lipoprotein (a) or Lp(a), which is highly correlated with the development of atherosclerosis

  • LDL cholesterol can enter cells by way of apo-B-100 and by phosphoprotein proprotein convertase subtilisin/kexin 9 (PCSK9)

  • Cells can manufacture LDL cholesterol by a rate-limiting step that involves HMG-CoA reductase

  • Oxidation of LDL in subintimal macrophages in vascular endothelium leads to the formation of foam cells lining the arterial wall, leading to cholesterol plaque

  • The liver plays a role in removing LDL from the blood via the LDL receptor

  • HDL cholesterol exerts a protective effect by removing cholesterol from the circulation and returning it to the liver via a process involving cholesterol ester transfer protein (CETP)

  • Hyperlipidemia may be primary or the result of other diseases such as diabetes, hypothyroidism, renal failure, or alcoholism

  • In a minority of cases, elevated LDL levels are caused by genetic disorders that can be associated with very high levels of LDL and early-onset cardiovascular disease

CLINICAL PRESENTATION

SYMPTOMS AND SIGNS

  • Usually asymptomatic

  • Very high triglyceride levels can cause acute pancreatitis

PHYSICAL EXAM FINDINGS

  • Eruptive xanthomas are present if triglycerides are high

  • Tendon xanthomas and tuberous xanthomas are characteristic of familial hypercholesterolemia

  • Palmer and tuboeruptive xanthomas are seen in familial dysbetalipoproteinemia

  • Xanthelasmas are nonspecific and can be found in persons with normal lipids

DIFFERENTIAL DIAGNOSIS

  • Hypothyroidism increases LDL cholesterol

  • Nonfasting state increases triglycerides

  • Diabetes increases triglycerides, reduces HDL cholesterol

  • Alcohol increases triglycerides

  • Oral contraceptives increase triglycerides

  • Nephrotic syndrome increases LDL cholesterol and triglycerides

  • Renal failure increases LDL cholesterol and triglycerides

  • Primary biliary cirrhosis increases LDL cholesterol

  • Acute hepatitis increases triglycerides

  • Obesity increases triglycerides

  • Cigarette smoking decreases HDL

  • Commonly used drugs such as thiazide diuretics, beta blockers, and statins can affect lipid plasma levels. Also, antiretroviral agents can cause lipodystrophy and early atherosclerosis

DIAGNOSTIC EVALUATION

LABORATORY TESTS

  • Total cholesterol, LDL and HDL cholesterol, and triglycerides make up the standard lipid panel used for screening purposes and should be performed in men > age 35 and women > age 45 years

  • Selected tests for potential secondary causes should be considered, but especially for thyroid, liver, and renal function

TREATMENT

CARDIOLOGY REFERRAL

  • Suspected cardiovascular disease

MEDICATIONS

  • Bile acid sequestrants: cholestyramine, colestipol, colesevelam—reduce LDL

  • Intestinal endothelium blockers: ezetimibe 10 mg/day PO—reduce LDL

  • Fibric acid derivatives: gemfibrozil, fenofibrate—reduce triglycerides and increase HDL

  • Nicotinic ...

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