Hyperlipidemia (Lipid Disorders)

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 ...