Therapy 1: Dyslipidemia

Background and Introduction

• Cholesterol, triglycerides, and phospholipids are the major lipids in the body.
• Cholesterol plays a central role in the pathogenesis of atherosclerosis.
• Lipids are transported by lipoprotein particles in the plasma.
• Atherogenesis i/s a progressive process initiated by the migration of LDL-C into vessel walls, leading to endothelial cell dysfunction and a prothrombotic state.

Lipid Abnormalities and Clinical Outcomes

• Lipid abnormalities increase the risk of coronary heart disease (CHD), cerebrovascular disease (CVA), and peripheral arterial disease (PAD), collectively known as atherosclerotic cardiovascular disease (ASCVD).
• Elevated blood levels of lipoproteins, including cholesterol, triglycerides, and phospholipids, define hyperlipidemia.
• Lipoprotein abnormalities, including elevated total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG), and reduced high-density lipoprotein (HDL), are characteristic of dyslipidemia.

Lipoprotein Disorders

• Primary dyslipidemia includes genetic defects resulting in hypercholesterolemia, hypertriglyceridemia, and disorders of HDL-C metabolism, with an increased risk of premature ASCVD.
• Familial hypercholesterolemia (FH) is a primary dyslipidemia characterized by the inability to bind LDL-C to LDL-C receptors, leading to unregulated biosynthesis of cholesterol.

Secondary Dyslipidemia

• Secondary dyslipidemias should be initially managed by correcting underlying abnormalities when possible.
• Certain drug classes and habits, such as excessive alcohol use, weight gain, and intake of carbohydrates or saturated fat, can affect lipid levels.
• Specific drugs, including thiazide diuretics, progestins, glucocorticoids, sirolimus, β-blockers, isotretinoin, and cyclosporine, can also impact lipid levels.

Effects of Drugs on Plasma Lipids

• Thiazide diuretics can increase cholesterol by 5-7% initially and 0-3% later, and triglycerides by 30-50%.
• Loop diuretics have no effect on cholesterol or triglycerides, but may decrease HDL-C by 10-15%.
• Non-selective β-blockers can increase triglycerides by 20-50% and decrease HDL-C by 10-15%.
• Selective β-blockers have a lesser effect on lipids compared to non-selective β-blockers.
• α-Blocking agents can decrease cholesterol by 0-10% and increase HDL-C by 0-15%.
• Oral contraceptives can increase cholesterol by 5-20% and triglycerides by 10-45%, and may also increase HDL-C.
• Glucocorticoids can increase cholesterol by 5-10% and triglycerides by 15-20%.
• Ethanol can increase triglycerides by up to 50% and HDL-C.
• Isotretinoin can increase cholesterol by 5-20% and triglycerides by 50-60%, and decrease HDL-C by 10-15%.
• Cyclosporine can increase cholesterol by 15-20% but has no effect on triglycerides or HDL-C.

Clinical Presentation and Diagnosis

• Most patients with dyslipidemia are asymptomatic for years before developing ASCVD, which may produce symptoms such as chest pain, palpitations, sweating, anxiety, and shortness of breath.
• Measure fasting lipoprotein profile, including total cholesterol, LDL-C, HDL-C, and triglycerides, in all adults 20 years of age or older at least once every 5 years.
• Laboratory tests may show elevated total cholesterol, LDL-C, triglycerides, apo-lipoprotein B, and high sensitivity C-reactive protein, as well as low HDL-C.
• Calculate 10-year ASCVD risk in primary prevention situations using the ACC/AHA ASCVD Risk Estimator.