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.

This quiz covers the basics of dyslipidemia, including its diagnosis, treatment, and management. It also discusses specific topics such as low HDL, hyperlipidemia in pregnancy, and hypertriglyceridemia.