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INTRODUCTION

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  • Dyslipidemia is defined as elevated total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides; low high-density lipoprotein (HDL) cholesterol; or a combination of these abnormalities.

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PATHOPHYSIOLOGY

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  • Cholesterol, triglycerides, and phospholipids are transported in blood as complexes of lipids and proteins (lipoproteins). Elevated total and LDL cholesterol and reduced HDL cholesterol are associated with development of coronary heart disease (CHD).

  • Risk factors such as oxidized LDL, mechanical injury to endothelium, and excessive homocysteine can lead to endothelial dysfunction and cellular interactions culminating in atherosclerosis. Eventual clinical outcomes may include angina, myocardial infarction (MI), arrhythmias, stroke, peripheral arterial disease, abdominal aortic aneurysm, and sudden death.

  • Atherosclerotic lesions arise from transport and retention of plasma LDL through the endothelial cell layer into the extracellular matrix of the subendothelial space. Once in the artery wall, LDL is chemically modified through oxidation and nonenzymatic glycation. Mildly oxidized LDL recruits monocytes into the artery wall, which transform into macrophages that accelerate LDL oxidation. Oxidized LDL provokes an inflammatory response mediated by chemoattractants and cytokines.

  • Repeated injury and repair within an atherosclerotic plaque eventually lead to a fibrous cap protecting the underlying core of lipids, collagen, calcium, and inflammatory cells. Maintenance of the fibrous plaque is critical to prevent plaque rupture and coronary thrombosis.

  • Primary or genetic lipoprotein disorders are classified into six categories: I (chylomicrons), IIa (LDL), IIb (LDL + very-low-density lipoprotein [VLDL]), III (intermediate-density lipoprotein), IV (VLDL), and V (VLDL + chylomicrons). Secondary forms of dyslipidemia also exist, and several drug classes may elevate cholesterol levels (eg, progestins, thiazide diuretics, glucocorticoids, β-blockers, isotretinoin, protease inhibitors, cyclosporine, mirtazapine, and sirolimus).

  • The primary defect in familial hypercholesterolemia is inability to bind LDL to the LDL receptor (LDL-R). This leads to a lack of LDL degradation by cells and unregulated biosynthesis of cholesterol.

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CLINICAL PRESENTATION

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  • Most patients are asymptomatic for many years. Symptomatic patients may complain of chest pain, palpitations, sweating, anxiety, shortness of breath, or abdominal pain. They may also experience difficulty with speech or movement or loss of consciousness.

  • Depending on the lipoprotein abnormality, signs on physical examination may include cutaneous xanthomas, peripheral polyneuropathy, high blood pressure, and increased body mass index or waist size.

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DIAGNOSIS

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  • Measure fasting (preferred) lipoprotein profile (total cholesterol, LDL, HDL, and triglycerides) in all adults 20 years of age or older at least once every 5 years.

  • Measure plasma cholesterol, triglyceride, and HDL levels after a 12-hour fast because triglycerides may be elevated in nonfasting individuals; total cholesterol is only modestly affected by fasting.

  • Two determinations, 1 to 8 weeks apart are recommended to minimize variability and obtain a reliable baseline. If the total cholesterol is greater than 200 mg/dL (>5.17 mmol/L), a second determination is recommended, and if the values are greater than 30 mg/dL (>0.78 mmol/L) apart, use the average of three values.

  • History and physical examination should assess: (1) presence ...

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