Dyslipidemia 2024 PDF

1  2 Lecture Reading Material Required reading: DiPiro J, Talbert RL, Yee G, Matzke G, Wells B, Posey LM. Pharmacotherapy: A Pathophysiologic Approach, 12th Ed. McGraw Hill; 2023 Recommended reading: 2018 ACC...

1  2 Lecture Reading Material Required reading: DiPiro J, Talbert RL, Yee G, Matzke G, Wells B, Posey LM. Pharmacotherapy: A Pathophysiologic Approach, 12th Ed. McGraw Hill; 2023 Recommended reading: 2018 ACC/AHA Guideline on the management of blood cholesterol. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of American College of Cardiology 2018. 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. Journal of American College of Cardiology 2017. Objectives 1. Describe the role of cholesterol and lipoproteins in the development of ASCVD 2. Recommend lifestyle modifications for patients with elevated dyslipidemia 3. Describe the mechanism of action, pharmacologic properties, and side effects of the anti-dyslipidemic drugs 4. Design a patient specific treatment regimen for the management of dyslipidemia Background Cholesterol, triglycerides, and phospholipids are the major lipids that combine with proteins to be transported as complexes of lipid and proteins known as lipoproteins. Lipoproteins carriers : Responsible for transporting cholesterol, TG, and phospholipids throughout the body Vary in characteristics depending on the amount of cholesterol, TG, and apolipoproteins. There are four types of lipoproteins: chylomicrons, VLDL, LDL, and HDL Pharmacotherapy: A Pathophysiologic Approach, 12e  5 Background Cont, Cholesterol: o A lipid molecule that is biosynthesized (primarily in the liver) or obtained through diet o An essential component of animal cell membranes and used in the biosynthesis of steroid hormones and bile acids. Triglycerides o Three fatty acids esterified to a glycerol molecule found in all lipoproteins but primarily chylomicrons and (VLDL); used as an energy source Apolipoproteins: o Are essential components of lipoproteins, responsible for assembly, secretion, and binding to receptors or cell surfaces. They transport lipids from absorption sites to their intended sites. Pharmacotherapy: A Pathophysiologic Approach, 12e  LIPOPROTEIN METABOLISM AND TRANSPORT Citation: Chapter 32 Dyslipidemia, DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition; 2023. Available at: https://accesspharmacy.mhmedical.com/content.aspx?bookid=3097&sectionid=267225800 Accessed: September 11, 2023 Copyright © 2023 McGraw-Hill Education. All rights reserved  LIPOPROTEIN METABOLISM AND TRANSPORT Citation: Chapter 32 Dyslipidemia, DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition; 2023. Available at: https://accesspharmacy.mhmedical.com/content.aspx?bookid=3097&sectionid=267225800 Accessed: September 11, 2023 Copyright © 2023 McGraw-Hill Education. All rights reserved Lipoprotein structure Lipoprotein structure, which contains variable amounts of core cholesterol esters and triglycerides and have varying numbers and types of surface apolipoproteins. Citation: Chapter 32 Dyslipidemia, DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition; 2023. Available at: https://accesspharmacy.mhmedical.com/content.aspx?bookid=3097&sectionid=267225800 Accessed: September 11, 2023 Copyright © 2023 McGraw-Hill Education. All rights reserved Background Chylomicrons: transport dietary fat around the body and deliver lipids and TGs to tissues in need. Very-low-density lipoproteins (VLDL): is the primary carrier of triglycerides (TG) in the circulation. VLDL transports lipids and TGs to tissues for energy or storage. Intermediate-density lipoproteins (IDL): when VLDL is transported across lipase, which changes the VLDL to. IDL can then be converted to LDL Low-density lipoproteins (LDL): is mainly responsible for transporting cholesterol to body tissues, which is needed for hormone production and cell membrane integrity. High-density lipoproteins (HDL): picks up excess cholesterol and returns it to the liver, with the full HDL containing the cholesterol binding to scavenger receptors. Pharmacotherapy: A Pathophysiologic Approach, 12e  Figure 2 Lipoprotein types and structures. Representative description of typical diameter, content and apolipoprotein... Cardiovasc Res, Volume 118, Issue 3, February 2022, Pages 716–731, https://doi.org/10.1093/cvr/cvab017 The content of this slide may be subject to copyright: please see the slide notes for details.  11 lipoprotein cholesterol and metabolism Watch these YouTube videos to learn about cholesterol basics as well as the physiology of lipoprotein cholesterol and metabolism: Cholesterol Good and Bad (https://tinyurl.com/yx6a5ufj) by the US National Library of Medicine Physiology of Lipoprotein Metabolism (https://tinyurl.com/pwo856o ) by National Heart, Lung, and Blood Institute Background Cont,. Apolipoprotein B containing lipoproteins (non-HDL): make up the lipid- delivery pathway. ApoB acts as a ligand for LDL receptors, which allows the delivery of cholesterol into the cells, removing cholesterol from the blood ApoB-containing lipoproteins include: Chylomicron, very low density lipoproteins (VLDL), intermediate-density lipoproteins, lLDLs, and lipoprotein(a) [Lp(a)] Retention of ApoB-containing lipoproteins in the subendothelial is the primary cause and initiator of atherosclerosis 🡪 “atherogenic lipoproteins” LDL is the dominant form of atherogenic cholesterol (>90%) Pharmacotherapy: A Pathophysiologic Approach, 12e Background Cont, Apolipoprotein A-1 containing lipoproteins (HDL): : does not contain ApoB A key participant in reverse cholesterol transport, which moves cholesterol from peripheral tissues back to the liver ApoA-1 containing lipoproteins include: High-density lipoprotein cholesterol (HDL-C) Non-HDL represents all potentially atherogenic cholesterol and is calculated by subtracting HDL-C from TC Pharmacotherapy: A Pathophysiologic Approach, 12e  14 Pathophysiology Resources Video 292e–2 Plaque instability. Video 292e–3 Lipoprotein menagerie. Video 292e–4 Formation and complication of atherosclerotic plaques. Video 292e–5 Atherogenesis. Video 292e–6 Metabolic syndrome. Go to English Databases Select Access Pharmacy Videos under multimedia section  15 Cholesterol and Atherosclerosis ▪ Primary initiator of atherosclerosis is elevation and retention of ApoB-containing lipoproteins in the subendothelial layer ▪ Atherosclerosis begins with endothelial damage and dysfunction o Damage results from chronic endothelial injury from hypertension, diabetes, inflammation, tobacco, etc. o ↑ in number of LDL particles that can permeate through the vascular wall and accumulate o Trapped by cellular matrix in vascular intima o LDL is taken up via scavenger receptors on macrophages resulting in foam-cell formation o Smooth muscle cells begin to migrate into the lesion and encapsulate the newly formed plaque forming the fibrous plaque o Atherosclerotic plaques can lead to occlusion or rupture causing acute ASCVD events ▪ Clinical Atherosclerotic Cardiovascular Disease (ASCVD) = history of acute coronary syndromes (ACS), myocardial infarction (MI), stable or unstable angina, coronary or arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral arterial disease (PAD)  Pathogenesis of Atherosclerotic Cardiovascular Disease Citation: Chapter 32 Dyslipidemia, DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition; 2023. Available at: https://accesspharmacy.mhmedical.com/content.aspx?bookid=3097&sectionid=267225800 Accessed: September 11, 2023 Copyright © 2023 McGraw-Hill Education. All rights reserved  17 Atherogenic Cascade Atherosclerosis progression Background Cont, Abnormalities of plasma lipoproteins: o Can result in a predisposition to coronary, cerebrovascular, and peripheral vascular arterial disease o Constitutes one of the major risk factors for coronary heart disease (CHD) o Evidence had linked elevated total & LDL cholesterol & reduced HDL to the development of CHD Pharmacotherapy: A Pathophysiologic Approach, 12e  EPIDEMIOLOGY Dyslipidemia: ↑ total cholesterol, ↑ in LDL cholesterol, ↑ in triglycerides or ↓ HDL cholesterol or some combination of these abnormalities o Based on estimates from the AHA: o 49% of American adults > 20 years have total cholesterol levels of ≥ 200 mg/dL (5.17 mmol/L) o In 2011, CHD caused one in every seven deaths in the United States o About 1/3 of treated patients are achieving their LDL goal o < 20% of CHD patients are at their LDL goal A 2017 study investigating the cardiovascular risk factors burden in Saudi Arabia found that dyslipidemia was the most prevalent risk factor (68.6%) Pharmacotherapy: A Pathophysiologic Approach, 12e Ahmed et al, J Saudi Heart Assoc, 2017  20 Etiology Primary or familial dyslipidemias Genetic defects resulting in hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and disorders of HDLC 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 LDLC to LDLC receptors. This leads to lack of LDLC degradation by cells and unregulated biosynthesis of cholesterol. Pharmacotherapy: A Pathophysiologic Approach, 12e Secondary or Acquired Dyslipidemias Cause Increase LDL-C Increase TG Medications Glucocorticoids, Oral estrogens, amiodarone, diuretics, glucocorticoids, bile acid cyclosporine sequestrants, protease inhibitors, retinoic acid, anabolic steroids, immunosuppressive drugs (cyclosporine, tacrolimus, sirolimus), atypical antipsychotics, tamoxifen, raloxifene, β-blockers, thiazides Dietary influences Saturated or trans fats, Very high-fat diets, high weight gain, anorexia carbohydrate intake (refined), excess alcohol, weight gain Disease states and Nephrotic syndrome, biliary Poorly controlled diabetes, medical conditions obstruction, hypothyroidism, obesity, hypothyroidism, obesity, pregnancy, nephrotic pregnancy syndrome, chronic renal failure, lipodystrophies Clinical presentation & diagnosis o Most patients are asymptomatic for many years o Physical findings None to abdominal pain, pancreatitis (TG > 500), xanthelasma and corneal arcus (LDL > 250 mg/dL) o Laboratory tests ↑ in total cholesterol, LDL, triglycerides, apolipoprotein B, and high sensitivity C-reactive protein (hsCRP), ↓ HDL Pharmacotherapy: A Pathophysiologic Approach, 12e Measurement of cholesterol Initial measurement of the lipid profile: o To assess ASCVD risk and should be done in all adults 20 years and older who are not on lipid therapy (at least every 5 years) o To document baseline cholesterol values LDL-C (Friedewald equation) = (TC) – (TG/5) – (HDL-C) LDL-C (Martin-Hopkins equation) =TC-HDL-C-TG/adjustable factor Non-HDL = (TC) – (HDL-C) Martin-Hopkins equation has demonstrated improved estimation of LDL-C compared to Friedewald equation Pharmacotherapy principles & practice, 6e Measurement of cholesterol Cont, Fasting vs. Non-fasting Measurement o Generally fasting and non-fasting measurements can be used for ASCVD risk assessment o Initial fasting measurement is recommended in individuals with FH of premature ASCVD or genetic hyperlipidemia o If the initial non-fasting profile shows TG > 400 mg/dL, a repeat fasting measurement is recommended o Non-HDL can be assessed accurately irrespectivePharmacotherapy of fastingprinciples state& practice, 6e  25 Treatment Guidelines  26 Desired Outcome ◻ Reduce the risk first or recurrent events such as MI, angina, heart failure, or ischemic stroke or other forms of peripheral arterial disease such as carotid stenosis or abdominal aortic aneurysm Classification of cholesterol & triglyceride levels Total Cholesterol (TC)