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INTRODUCTION

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

PATHOPHYSIOLOGY

  • Cholesterol, triglycerides, and phospholipids are transported in blood as complexes of lipids and proteins (lipoproteins). Lipid abnormalities increase the risk of coronary, cerebrovascular, and peripheral arterial disease, collectively known as atherosclerotic cardiovascular disease (ASCVD).

  • Atherogenesis is a progressive process initiated by migration of LDL-C and remnant lipoprotein particles into vessel walls. These particles undergo oxidation and are taken up by macrophages, which induces endothelial cell dysfunction that reduces the ability of the endothelium to dilate the artery and causes a prothrombotic state. Unregulated uptake of cholesterol by macrophages leads to foam cell formation and the development of atherosclerotic plaques. Macrophages eventually produce and secrete matrix metalloproteinases, which degrade the collagen matrix of the plaques and cause them to be unstable.

  • 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. Potential clinical outcomes include angina, myocardial infarction (MI), arrhythmias, stroke, peripheral arterial disease, abdominal aortic aneurysm, and sudden death.

  • Primary dyslipidemias include genetic defects resulting in hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and disorders of HDL-C metabolism and an excess of lipoproteins. These disorders have an increased risk of premature ASCVD due to significant elevations in cholesterol levels. In homozygous and heterozygous familial hypercholesterolemia (FH), the primary defect is the inability to bind LDL-C to LDL-C receptors. This leads to lack of LDL-C degradation by cells and unregulated biosynthesis of cholesterol.

  • Secondary or acquired dyslipidemias can accompany genetic disorders and may be associated with diet (excessive alcohol use, anorexia, weight gain, excessive intake of carbohydrates or saturated fat), medications (eg, progestins, thiazide diuretics, glucocorticoids, β-blockers, isotretinoin, protease inhibitors, cyclosporine, mirtazapine, sirolimus), and comorbid conditions (eg, nephrotic syndrome, renal failure, hypothyroidism, obesity, diabetes).

CLINICAL PRESENTATION AND DIAGNOSIS

  • Most patients are asymptomatic for years before they develop ASCVD, which may produce symptoms including chest pain, palpitations, sweating, anxiety, shortness of breath, loss of consciousness, difficulty with speech or movement, or abdominal pain.

  • Perform a thorough medical history in patients presenting with dyslipidemia, including individual characteristics (age, race, gender, pregnancy), history of high-risk comorbid conditions (eg, hypertension, diabetes, peripheral arterial disease, coronary heart disease [CHD], chronic kidney disease [CKD], carotid artery stenosis), family history (eg, early-onset CHD), current medication and prior lipid-lowering medication use, lifestyle assessment (smoking status, exercise, diet, alcohol use), and ischemic symptoms.

  • Measure height, weight, BMI, and blood pressure. Physical signs may include eruptive xanthomas, peripheral polyneuropathy, increased blood pressure, and abdominal obesity.

  • Laboratory tests may show elevated TC, LDL-C, TG, apolipoprotein B, and high-sensitivity C-reactive protein (hsCRP); HDL-C may be low. Perform other baseline testing (eg, AST/ALT, TSH, glucose, serum ...

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