Cholesterol and Cardiovascular Health Quiz
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Questions and Answers

What is the primary risk factor for coronary heart disease related to plasma cholesterol levels?

  • Stable plasma cholesterol concentrations
  • Elevated plasma LDL-cholesterol levels (correct)
  • Decreased plasma triglycerides
  • High HDL-cholesterol levels

Which type of studies provide unequivocal evidence of the relationship between coronary atherosclerosis and plasma cholesterol concentrations?

  • Qualitative reviews
  • Animal studies
  • Epidemiological studies (correct)
  • Case studies

What is NOT one of the major sources of cholesterol in the human body?

  • Bacterial fermentation (correct)
  • Transport via lipoprotein particles
  • Synthesis in the liver
  • Dietary intake

What key feature enables lipoprotein particles to transport cholesterol in the blood?

<p>Their protein composition (D)</p> Signup and view all the answers

Which of the following pathways is NOT involved in cholesterol transport and metabolism?

<p>Direct absorption pathway (A)</p> Signup and view all the answers

Which class of drugs is primarily used to lower plasma cholesterol levels?

<p>Statins (D)</p> Signup and view all the answers

What is the main mechanism of action of plasma cholesterol-lowering agents?

<p>Stimulate LDL receptor synthesis in the liver (D)</p> Signup and view all the answers

Which of the following statements about the relationship between cholesterol and cardiovascular disease (CVD) is correct?

<p>Both high LDL and low HDL cholesterol are risk factors for CVD. (C)</p> Signup and view all the answers

What is the primary role of cholesterol in the human body?

<p>Required for the synthesis of cell membranes and steroid hormones (B)</p> Signup and view all the answers

Which of the following is NOT a source of cholesterol in the human body?

<p>Synthesis in the pancreas (D)</p> Signup and view all the answers

How are cholesterol and related lipids transported in the bloodstream?

<p>In soluble lipoprotein particles (C)</p> Signup and view all the answers

Which apolipoprotein is primarily involved in mediating the uptake of remnant particles?

<p>ApoE (A)</p> Signup and view all the answers

What function does ApoB-100 serve in lipid metabolism?

<p>It acts as a ligand for the LDL receptor (C)</p> Signup and view all the answers

Which statement correctly describes apolipoproteins?

<p>They serve multiple roles including enzyme activation and lipoprotein transport (D)</p> Signup and view all the answers

What component makes up the inner core of lipoprotein particles?

<p>Triglycerides and cholesterol esters (B)</p> Signup and view all the answers

Where in the body is cholesterol synthesized endogenously?

<p>Liver and intestines (B)</p> Signup and view all the answers

What is the primary function of bile acids in relation to cholesterol?

<p>To facilitate the absorption of dietary fats (D)</p> Signup and view all the answers

Which lipoprotein carrier is found in chylomicrons?

<p>ApoB-48 (A)</p> Signup and view all the answers

What is the primary mechanism by which statins lower LDL-C levels?

<p>Inhibit HMG-CoA reductase (A)</p> Signup and view all the answers

Fibrates primarily exert their effects by activating which receptor?

<p>PPAR-α receptor (D)</p> Signup and view all the answers

What effect do fibrates have on triglyceride levels?

<p>Decrease by 20-50% (D)</p> Signup and view all the answers

Which of the following is an adverse effect associated with nicotinic acid?

<p>Flushing (D)</p> Signup and view all the answers

How does ezetimibe function to regulate cholesterol levels?

<p>Blocks intestinal absorption of cholesterol (D)</p> Signup and view all the answers

Which class of drugs increases LDL-C clearance from circulation through the inhibition of PCSK9?

<p>PCSK9 inhibitors (A)</p> Signup and view all the answers

What is a common adverse effect of both statins and nicotinic acid?

<p>Myopathy (D)</p> Signup and view all the answers

Which of the following best describes the role of bempedoic acid in lipid regulation?

<p>Inhibits ATP-citrate lyase to reduce LDL-C levels (B)</p> Signup and view all the answers

Which drug class is primarily responsible for reducing plasma triglyceride levels through mediating effects on VLDL?

<p>Fibrates (C)</p> Signup and view all the answers

What effect does mipomersen have on cholesterol regulation?

<p>Reduces synthesis of apoB-100 (D)</p> Signup and view all the answers

Statins have secondary beneficial effects that include all EXCEPT which of the following?

<p>Reducing hepatic triglyceride synthesis (B)</p> Signup and view all the answers

Which adverse effect is commonly associated with the use of statins?

<p>Rhabdomyolysis (B)</p> Signup and view all the answers

Which of the following statements regarding PCSK9 is TRUE?

<p>It targets LDL receptors for degradation. (C)</p> Signup and view all the answers

How does lomitapide function in lipid regulation?

<p>Reduces hepatic VLDL production (A)</p> Signup and view all the answers

What is the primary function of ApoC-II in the lipid metabolism process?

<p>Activates lipoprotein lipase (D)</p> Signup and view all the answers

Which pathway is responsible for the transport of dietary cholesterol and triglycerides from the intestine into the bloodstream?

<p>Exogenous (Intestinal) Pathway (D)</p> Signup and view all the answers

What component is mainly responsible for the formation of mature HDL from nascent HDL?

<p>Lecithin-cholesterol acyltransferase (LCAT) (C)</p> Signup and view all the answers

The remnants of chylomicrons are removed from the plasma primarily through which receptor in the liver?

<p>Remnant receptor (LRP) (D)</p> Signup and view all the answers

What is the consequence of bile acid sequestrants on hepatic cholesterol levels?

<p>Decrease hepatic cholesterol levels (A)</p> Signup and view all the answers

Which agent is primarily involved in the hydrolysis of triglycerides in chylomicrons?

<p>Lipoprotein lipase (LPL) (A)</p> Signup and view all the answers

What role does ApoA-I play in the metabolism of HDL particles?

<p>Activates lecithin:cholesterol acyltransferase (C)</p> Signup and view all the answers

Which process is involved in returning excess cholesterol from peripheral tissues to the liver?

<p>Reverse cholesterol transport (B)</p> Signup and view all the answers

How do VLDL particles contribute to lipid metabolism?

<p>Undergo hydrolysis by lipoprotein lipase (B)</p> Signup and view all the answers

What primarily initiates the absorption of dietary cholesterol in enterocytes?

<p>Niemann-Pick C1-Like 1 (NPC1L1) transporter (D)</p> Signup and view all the answers

Which lipoprotein class is considered potentially pro-atherogenic?

<p>LDL (B)</p> Signup and view all the answers

What effect do bile acid sequestrants have on triglyceride levels?

<p>Cause a moderate increase in triglyceride levels (A)</p> Signup and view all the answers

How does cholesterol get esterified in enterocytes post absorption?

<p>Through acyl-coenzyme A:cholesterol acyltransferase (ACAT) (D)</p> Signup and view all the answers

What is the consequence of hepatic lipase action on intermediate-density lipoproteins (IDL)?

<p>Converts IDL to LDL-C (B)</p> Signup and view all the answers

What condition is NOT categorized as a type of cardiovascular disease?

<p>Muscle Strain (B)</p> Signup and view all the answers

What is the primary aim when optimizing lipids in a patient?

<p>To reduce the risk of developing cardiovascular disease (A)</p> Signup and view all the answers

Which of the following statements about lipids is accurate?

<p>Lipids are involved in synthesizing cell membranes. (A)</p> Signup and view all the answers

Which of the following is a key understanding related to QRISK assessments?

<p>QRISK assessments should be explained to a patient. (B)</p> Signup and view all the answers

What is a common condition associated with atherosclerosis?

<p>Coronary Heart Disease (B)</p> Signup and view all the answers

Which of the following best describes the term 'lipoproteins'?

<p>Complexes that transport lipids through the bloodstream. (C)</p> Signup and view all the answers

What is NOT a strategy for reducing the risk of cardiovascular disease?

<p>Increasing saturated fat intake (D)</p> Signup and view all the answers

Which statement is false regarding cardiovascular disease prevention?

<p>Preventive strategies are only for high-risk individuals. (B)</p> Signup and view all the answers

In which scenario would a patient be indicated for secondary prevention due to severe hypercholesterolaemia?

<p>Very high-risk patient with LDL-C &gt; 3.5mmol/L (B)</p> Signup and view all the answers

What characterizes a very high-risk patient concerning cardiovascular events?

<p>Presence of recurrent cardiovascular events (C)</p> Signup and view all the answers

What could be the likely outcome for a patient with normal U&Es, LFTs, TFTs, HbA1c, and urine:albumin but elevated LDL-C of 4.4mmol/L?

<p>They may be indicated for secondary prevention. (B)</p> Signup and view all the answers

Which of the following factors contributes to classifying a patient as high risk for hypercholesterolaemia?

<p>Recent coronary revascularisation procedures (D)</p> Signup and view all the answers

Which lipid profile result indicates a need for further evaluation or treatment in a patient with optimal lifestyle and no family history of elevated cholesterol?

<p>LDL Cholesterol: 4.4mmol/L (C)</p> Signup and view all the answers

What is the primary purpose of atorvastatin in primary prevention?

<p>To lower non-HDL cholesterol levels (D)</p> Signup and view all the answers

What is the recommended monitoring period before repeating a lipid panel for patients on atorvastatin?

<p>Three months (D)</p> Signup and view all the answers

What should be assessed prior to initiating atorvastatin treatment?

<p>Full lipid profile (B)</p> Signup and view all the answers

If a patient on atorvastatin experiences elevated liver function tests, when should the tests be repeated?

<p>In 1 month (B)</p> Signup and view all the answers

What is a key lifestyle modification encouraged alongside atorvastatin therapy?

<p>Moderation of alcohol consumption (A)</p> Signup and view all the answers

How often should liver function tests be monitored once atorvastatin treatment has stabilized?

<p>Annually (D)</p> Signup and view all the answers

What is the primary role of triglycerides in the body?

<p>To store energy (D)</p> Signup and view all the answers

What action should be taken if a patient's creatine kinase level is over 5 times the upper limit during atorvastatin treatment?

<p>Discontinue atorvastatin treatment (C)</p> Signup and view all the answers

Which component is assessed in a standard lipid profile?

<p>Total cholesterol including both 'good' and 'bad' (B)</p> Signup and view all the answers

What is the target percentage reduction in non-HDL cholesterol when on atorvastatin?

<p>40% (D)</p> Signup and view all the answers

In the context of patient assessment, what does a QRISK score above 10% indicate?

<p>Requires treatment for primary prevention (C)</p> Signup and view all the answers

What factors could potentially impact the accuracy of QRISK assessment?

<p>All aspects of patient history and current health (B)</p> Signup and view all the answers

Which of the following best describes cholesterol's role in the body?

<p>Essential for cell membrane structure and hormone production (B)</p> Signup and view all the answers

At what point might a QRISK assessment need to be reset?

<p>Every time you use the assessment tool (B)</p> Signup and view all the answers

What is the significance of a cholesterol: HDL ratio of 5?

<p>It suggests an unhealthy balance between good and bad cholesterol (C)</p> Signup and view all the answers

Which of the following health conditions is NOT mentioned as a factor influencing cholesterol levels?

<p>Hypertension (A)</p> Signup and view all the answers

What should be done if a patient on atorvastatin 80mg does not achieve a 40% reduction in lipids?

<p>Add ezetimibe 10mg once daily (D)</p> Signup and view all the answers

What is a significant side effect associated with statin use that warrants discontinuation of the drug?

<p>Muscle-related problems (D)</p> Signup and view all the answers

What is the recommended action when a patient taking rosuvastatin is prescribed clarithromycin?

<p>Discontinue rosuvastatin temporarily (B)</p> Signup and view all the answers

What should be monitored during statin therapy to assess lipid control?

<p>Lipid levels should be checked every three months (D)</p> Signup and view all the answers

Which statement is true regarding statin administration and sleep disturbances?

<p>Simvastatin should be taken at night due to its short half-life (C)</p> Signup and view all the answers

Which adverse effect is most commonly shared between statins and ezetimibe?

<p>Myalgia (B)</p> Signup and view all the answers

What monitoring is critical for patients on statins to prevent toxicity?

<p>Routine liver function tests (B)</p> Signup and view all the answers

What action is recommended if a patient experiences muscle pain while on statin therapy?

<p>Reduce the dose and re-introduce gradually (D)</p> Signup and view all the answers

What is the recommended dosage of atorvastatin for patients with established cardiovascular disease?

<p>80mg (A)</p> Signup and view all the answers

Inclisiran is licensed for which group of patients?

<p>Patients with an LDL-C above 2.6mmol/L despite statins and ezetimibe (B)</p> Signup and view all the answers

What is the primary goal of high-dose statin therapy in secondary prevention?

<p>Reduce LDL-C levels effectively (D)</p> Signup and view all the answers

Which action is necessary for patients undergoing treatment with injectable PCSK9 inhibitors?

<p>Initiated by specialist lipid clinics (A)</p> Signup and view all the answers

What is a key component of discussing ASCVD risk reduction with patients?

<p>Understanding patient's beliefs about their health (C)</p> Signup and view all the answers

Which of the following treatments might be considered if non-HDL-C levels exceed 2.6mmol/L after statin therapy?

<p>Initiate inclisiran or monoclonal antibodies (A)</p> Signup and view all the answers

What monitoring is emphasized for patients on lipid-modifying therapy?

<p>Regular checks for liver function and cholesterol levels (C)</p> Signup and view all the answers

What is a consequence of drug interactions with grapefruit juice for patients on certain lipid-lowering medications?

<p>Potentially increased drug levels leading to side effects (C)</p> Signup and view all the answers

What is a critical component of a shared management plan for patients at risk of ASCVD?

<p>Collaborating with patients on lifestyle and medication choices (C)</p> Signup and view all the answers

Flashcards

Cholesterol & CVD

Atherosclerosis and coronary events are strongly connected to the amount of cholesterol in the blood. This relationship has been confirmed through various studies.

What is LDL-cholesterol?

It is a major risk factor for coronary heart disease. High levels of this type of cholesterol in the blood are directly linked to heart problems.

Major Studies Linking Cholesterol and CVD

The Framingham Heart Study and the MRFIT are two major studies that have provided substantial evidence linking cholesterol levels to heart disease.

How Do Genetic Studies Support the Link?

Genetic disorders that cause extremely high cholesterol levels can be powerful evidence of the link between cholesterol and CVD.

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What is Cholesterol?

This type of cholesterol is essential for many bodily functions but must be transported carefully. Too much of it can lead to major health problems.

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What is Cholesterol Metabolism?

It's a complex process involving various particles that transport cholesterol throughout the body. Understanding this process helps us develop effective strategies for managing cholesterol levels.

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What are Plasma Lipid Lowering Agents?

They function to help manage cholesterol levels in the blood. These drugs play a crucial role in preventing and managing heart disease.

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Key Types of Cholesterol Lowering Agents

These drugs are designed to specifically target and reduce cholesterol levels in the blood. They are a vital part of treating and preventing cardiovascular disease.

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Cholesterol

A type of lipid that is essential for cell membranes, steroid hormone synthesis, and bile acid production.

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Exogenous Cholesterol

Cholesterol derived from the diet, typically found in foods like eggs and shellfish.

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Endogenous Cholesterol

Cholesterol synthesized within the body, primarily in the liver, intestines, ovaries and adrenal glands.

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Endogenous Cholesterol Synthesis

A process where the body produces cholesterol de novo, meaning from scratch, using various enzymes and precursors.

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Lipoprotein Particles

Water-insoluble molecules, like cholesterol and triglycerides, that are transported in the bloodstream in a water-soluble package.

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Hydrophobic Core

The core of a lipoprotein particle, composed of fats like cholesterol esters and triglycerides.

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Hydrophilic Coat

The outer layer of a lipoprotein particle, composed of a hydrophilic shell made of proteins, phospholipids, and cholesterol.

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Apolipoproteins (Apo)

Proteins associated with lipoproteins, essential for their assembly, transport, and function.

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Lipoprotein Classification

Classification of lipoproteins based on their density, size, and protein composition.

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Low-Density Lipoprotein (LDL)

A major type of lipoprotein that carries cholesterol from the liver to cells throughout the body.

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Intestinal Cholesterol Absorption

The process by which dietary and biliary cholesterol are absorbed into the intestinal wall, esterified, and packaged into chylomicrons for transport.

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ApoE

A protein that binds to chylomicron remnants and facilitates their uptake by the liver.

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Lipoprotein Lipase (LPL)

Lipoprotein lipase (LPL) is an enzyme that hydrolyzes triglycerides in chylomicrons and VLDL, releasing free fatty acids that can be utilized for energy or stored as fat.

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VLDL (Very Low-Density Lipoprotein)

A type of lipoprotein that carries triglycerides and cholesterol from the liver to peripheral tissues.

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LDL (Low-Density Lipoprotein)

A type of lipoprotein that carries cholesterol from the liver to peripheral tissues. It is considered the 'bad cholesterol' because high levels are associated with an increased risk of heart disease.

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HDL (High-Density Lipoprotein)

A type of lipoprotein that scavenges excess cholesterol from peripheral tissues and transports it back to the liver, a process known as reverse cholesterol transport.

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Reverse Cholesterol Transport

The process of transporting cholesterol from peripheral tissues back to the liver by HDL particles.

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ApoA-I

A protein found in HDL that activates the enzyme lecithin:cholesterol acyltransferase (LCAT), crucial for the process of reverse cholesterol transport.

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Niemann-Pick C1-Like 1 (NPC1L1)

A transporter protein located in the intestinal wall that facilitates the absorption of cholesterol into enterocytes.

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Lecithin:Cholesterol Acyltransferase (LCAT)

An enzyme that converts free cholesterol to cholesteryl ester, a more stable and transportable form, within HDL particles during reverse cholesterol transport.

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Scavenger Receptor, Class B, Type 1 (SR-B1)

A transporter protein that mediates the uptake of cholesteryl ester from HDL into the liver.

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ApoC-II

A protein found in chylomicrons and VLDL, which activates lipoprotein lipase (LPL) and plays a critical role in lipid metabolism.

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ApoC-III

A protein found in chylomicrons, VLDL and HDL, which may inhibit the action of lipoprotein lipase (LPL).

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ApoB-100

A protein found in chylomicrons and VLDL, which facilitates the uptake of chylomicron remnants by the liver.

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Hepatic Lipase (HL)

An enzyme that converts intermediate-density lipoprotein (IDL) to low-density lipoprotein (LDL).

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Exogenous Lipid Pathway

The process of lipid metabolism that starts in the intestine and involves the absorption, packaging, and transport of dietary lipids, primarily in the form of triglycerides.

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Endogenous Lipid Pathway

The process of lipid metabolism that starts in the liver and involves the synthesis, packaging and transport of lipids, such as triglycerides and cholesterol.

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Statins

A group of drugs that lower cholesterol levels in the blood by inhibiting the enzyme HMG-CoA reductase, which is responsible for cholesterol synthesis in the liver.

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Nicotinic Acid

Decrease the production of triglycerides, which are a type of fat found in the blood. Common side effect: flushing (redness and warmth of the skin).

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Ezetimibe

A type of drug that blocks the absorption of cholesterol from the intestines, reducing the amount of cholesterol that reaches the liver.

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PCSK9

A protein in the body that binds to the LDL receptor and targets it for degradation. Reducing PCSK9 levels increases the number of LDL receptors and leads to lower LDL cholesterol.

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PCSK9 inhibitors

A type of drug that inhibits the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) which helps lower LDL cholesterol.

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Selective Cholesterol absorption Inhibitors

A class of drugs that reduce the amount of cholesterol in the blood by blocking the absorption of dietary cholesterol in the intestine.

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HMG-CoA reductase Inhibitors

A group of drugs that reduce the amount of cholesterol in the blood by inhibiting the enzyme HMG-CoA reductase, which is involved in cholesterol synthesis in the liver.

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NSAIDs

A group of drugs that are mainly used for treating pain and inflammation.

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Warfarin

A type of drug that is used to prevent blood clots by interfering with the process of blood clotting.

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GIT disturbances

Drugs that cause disturbances in the digestive system, often causing nausea, vomiting, dyspepsia, bloating, flatulence, constipation, and cramping.

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Thiazide diuretics

A type of drug that increases the excretion of sodium and water by the kidneys, leading to a decrease in blood pressure.

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Digoxin

A drug that increases the force of heart contractions and slows down heart rate, improving overall blood flow.

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Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Drugs that are mainly used for treating pain and inflammation by acting as anti-inflammatory and analgesic agents.

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Warfarin

A type of drug that is used to prevent blood clots by inhibiting the production of vitamin K-dependent clotting factors.

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Digoxin

A drug that is used to treat heart failure by increasing the force of heart contractions and slowing down heart rate.

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What is Cardiovascular Disease?

A condition affecting the heart that can include Coronary Heart Disease (CHD), Stroke and Transient Ischaemic Attack (TIA), Peripheral Arterial Disease (PAD) and more, all caused by atherosclerosis.

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What is Atherosclerosis?

A process where fatty deposits build up in the arteries, narrowing them and impeding blood flow.

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What are Lipids?

A generic term referring to various types of fats used in cell membranes and transported as lipoproteins.

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What is Primary Prevention of CVD?

Measures involving lifestyle changes and medications aimed at reducing the risk of developing cardiovascular disease.

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What is Secondary Prevention of CVD?

Measures used to decrease the chance of recurrent cardiovascular events in individuals who have already experienced a heart event.

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What is a QRISK assessment?

A tool used to assess the ten-year risk of developing cardiovascular disease in individuals. It considers multiple risk factors.

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What are other CVD conditions?

Refers to a group of conditions impacting the heart that include Heart Failure, Atrial Fibrillation (AF), and Hypertension.

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Why optimize lipids?

Measures taken to optimize blood lipid levels to minimize the risk of developing or recurring coronary heart disease.

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What are triglycerides?

Triglycerides are lipids made of glycerol and fatty acids, serving as the body's primary energy storage.

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What does a lipid profile measure?

A standard lipid profile checks total cholesterol, including both 'good' and 'bad' cholesterol.

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Why is high cholesterol a risk factor for heart disease?

High cholesterol levels are associated with heart problems, especially in those with other risk factors like diabetes, smoking, and high blood pressure.

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What is primary prevention in heart disease?

Primary prevention aims to reduce the risk of heart disease in individuals who haven't already had it.

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What is QRISK3?

QRISK3 is an online tool that helps assess a person's 10-year risk of having a heart attack or stroke.

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What happens after a QRISK3 assessment?

An action plan for primary prevention is developed based on the QRISK3 score and patient factors.

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What are some primary prevention treatments for heart disease?

Treatment for primary prevention includes lifestyle changes and medications to lower cholesterol levels and blood pressure.

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High Risk Patient with High LDL-C

A condition where a patient has a high risk of cardiovascular disease (CVD) and their LDL cholesterol is above 4 mmol/L. This signals a need for secondary prevention measures to lower their risk of further heart problems.

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Very High Risk Patient with High LDL-C

A patient with a very high risk of cardiovascular disease (CVD) and their LDL cholesterol is above 3.5 mmol/L. This requires immediate and aggressive interventions to reduce their risk of future heart events.

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Familial Hypercholesterolaemia

A condition characterized by extremely high levels of total cholesterol in the bloodstream, often inherited genetically. This significantly increases the risk of developing cardiovascular disease (CVD) and requires special management strategies to prevent heart problems.

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Hypotriglyceridaemia

A condition where the levels of triglycerides in the blood are abnormally low. This may be indicative of underlying medical conditions or nutritional deficiencies, requiring further investigation and potential treatment to address the root cause.

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Lipid Profile

A comprehensive blood test that assesses the levels of different types of cholesterol in the blood. This is crucial for understanding a patient's risk for cardiovascular disease and guiding treatment strategies.

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Atorvastatin

A high-intensity statin used as the first-line treatment for primary prevention of cardiovascular disease, typically prescribed at a dosage of 20mg once daily.

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Primary Prevention of CVD

Measures taken to prevent the development of cardiovascular disease in individuals without pre-existing heart conditions.

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Statin Monitoring

The process of monitoring a statin's effectiveness and potential side effects after it has been initiated.

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Full Lipid Profile

A common blood test that assesses the levels of various lipids in the blood, including cholesterol and triglycerides.

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Creatine Kinase

A blood test that measures the levels of creatine kinase, an enzyme found predominantly in muscle tissue. It can be elevated in muscle damage or injury.

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Liver Function Deranged

An increase in liver enzyme levels, potentially indicating liver damage or inflammation. Elevated levels can be a side effect of statins and require monitoring.

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Secondary Prevention of CVD

A measure taken to prevent the recurrence of cardiovascular events in individuals who have already experienced a heart attack, stroke, or other cardiovascular event.

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40% Reduction in Non-HDL Cholesterol

The recommended target for reduction in non-HDL cholesterol levels following three months of atorvastatin treatment. A 40% reduction helps decrease heart disease risk.

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What are high-dose statins?

These powerful drugs help lower cholesterol levels in people who have already had a heart attack or stroke.

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What are PCSK9 inhibitors?

A treatment option that can be used for people who need additional help lowering their cholesterol after taking the maximum dose of statins.

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What is ezetimibe?

A type of medication that helps lower cholesterol levels in the blood by reducing the amount of cholesterol absorbed by the body.

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What is inclisiran?

This treatment involves injections that help reduce cholesterol levels in the blood by targeting a specific protein called PCSK9.

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What is Atorvastatin?

A specific type of statin drug that is often used for secondary prevention of cardiovascular disease.

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What is shared management in ASCVD risk reduction?

The process of working with a patient to understand their individual needs and develop a management plan for their cardiovascular health.

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What are statins?

A type of medication that helps lower cholesterol levels in the blood by inhibiting the production of a specific enzyme in the liver.

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What is Enzyme Inhibition?

The process of inhibiting an enzyme's activity by binding to its active site, preventing the enzyme from performing its normal function. This can lead to an increase in substrate concentration and possible toxicity.

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What is myopathy?

A side effect of statins that involves muscle pain and weakness. It can be serious and may require discontinuing the statin treatment.

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What are sleep disturbances?

A type of adverse effect of statins that can cause sleep disturbances. Some statins need to be taken at night due to their short half-life.

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What is key statin counselling?

A key counselling point for statins is to explain their purpose and benefits in a clear and easy-to-understand way. Use patient-friendly language that they can relate to.

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What are statin interactions?

When someone is taking statins and also taking other medications that can interact with statins, it's crucial to adjust the dosage or switch to a different statin to avoid potential problems.

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What are food interactions with statins?

Grapefruit juice can interact with statins, potentially increasing their levels in the body and causing side effects. It's important to avoid grapefruit juice while taking statins.

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Study Notes

MPharm Programme: Plasma Lipid (Cholesterol) Transport & Metabolism

  • This week's programme focuses on plasma lipid (cholesterol) transport and metabolism.
  • The lecturer is Dr G Boachie-Ansah, with contact details provided.
  • The course material covers cardiovascular disease (CVD) pathogenesis, cholesterol metabolism and transport, and current plasma lipid-lowering drugs and their mechanisms of action.

General Outline of Lecture

  • The established role of cholesterol in cardiovascular disease (CVD) pathogenesis.
  • General overview of cholesterol metabolism and transport in the human body.
  • Available plasma lipid-lowering drugs and their mechanisms of action.

Learning Outcomes

  • Students should be able to describe the evidence base for cholesterol's central role in CVD pathogenesis.
  • Students should be able to describe the structure of lipoprotein particles and their cholesterol transport in the blood.
  • Students should be able to describe the sources of cholesterol and the three pathways of cholesterol transport and metabolism.
  • Students should be able to name the major classes of plasma cholesterol-lowering agents and describe their mechanisms of action.

Plasma Cholesterol & CVD Risk

  • Elevated plasma LDL-cholesterol levels are a major risk factor for coronary heart disease.
  • Strong relationship between coronary atherosclerosis, coronary events, and plasma cholesterol concentrations, supported by epidemiological and genetic studies, as well as experimental and clinical trials.
  • Management of plasma cholesterol levels is a crucial component of cardiovascular disease prevention.

Why Do Humans Need Cholesterol?

  • Cholesterol is crucial for synthesizing cell membranes, stabilizing and transporting functions.
  • Also required for steroid hormones (e.g., adrenal and sex hormones).
  • It's a component for bile acids, facilitating the gastrointestinal absorption of dietary fat.

Major Sources of Cholesterol

  • Exogenous: Dietary intake (e.g., eggs, shellfish).
  • Endogenous: De novo synthesis in various organs and tissues (e.g., liver, intestines, ovaries, adrenals).

Cholesterol Transport

  • Cholesterol and related lipids are insoluble in water, requiring transport as water-soluble lipoprotein particles.
  • Lipoproteins have a hydrophobic core (e.g., cholesterol, cholesterol esters, triglycerides, free fatty acids) and a hydrophilic coat (apolipoproteins, phospholipids, cholesterol).

Apolipoproteins

  • Multiple isoforms (ApoA, ApoB, ApoC, ApoE,etc).
  • Key functions: lipoprotein assembly and transport in the blood, maintenance of lipoprotein structural integrity, enzyme activation and inhibition, and cellular receptor binding.

Classification of Lipoproteins

  • Lipoproteins are classified based on their density (e.g. Chylomicrons, VLDL, IDL, LDL, HDL)
  • Each class has specific lipid compositions and apolipoproteins with different functions. A table gives the source and key components of these lipoproteins.

Pathways of Plasma Lipid Transport and Metabolism

  • Three major pathways: exogenous (intestinal), endogenous (hepatic), and reverse cholesterol transport.
  • These pathways are co-ordinated by the liver to maintain a balance of major lipid classes.

Exogenous (Intestinal) Pathway

  • Dietary & biliary cholesterol is absorbed into enterocytes via NPC1L1 transporter.
  • Absorbed cholesterol is esterified by ACAT.
  • Esterified cholesterol packaged into chylomicrons (CMs) by MTP.
  • Triglycerides in CMs leave the intestine via lymphatics, enter the bloodstream.
  • Endothelial lipoprotein lipase (LPL) hydrolyzes triglycerides in CMs releasing free fatty acids (FFAs) utilised for energy or stored as fat.
  • Chylomicron remnants are removed by the liver via apoE binding to the LRP or LDL receptor (LDLR).
  • This pathway is mainly for dietary lipids.

Endogenous (Hepatic) Pathway

  • Cholesterol synthesis and transport in the liver.
  • Chylomicron remnants are taken up by hepatocytes.
  • They are re-packaged into VLDL particles to transport endogenous lipids.
  • Triglycerides in VLDL are hydrolyzed by LPL releasing FFAs for energy or storage.
  • IDL formed.
  • IDL taken up by liver or converted into LDL.
  • LDL carries cholesterol to peripheral tissues.
  • Excess LDL cholesterol is removed from the circulation by the liver, either directly or indirectly through exchange with other lipoproteins.

Reverse Cholesterol Transport

  • Excess LDL-C from peripheral cells is returned to the liver via HDL pathway.
  • Nascent HDL picks up cholesterol from the cells.
  • LCAT converts cholesterol to cholesteryl ester (CE) forming mature HDL.
  • HDL transports CE to the liver.
  • Direct (SR-B1) and indirect (CETP) mechanisms are used for HDL cholesterol transport to the liver.

Lipoprotein Classes and Atherogenesis

  • ApoB-containing lipoproteins (chylomicrons, VLDL, LDL) are potentially pro-atherogenic.
  • ApoA-I-containing lipoproteins (HDL) are potentially anti-atherogenic.

Plasma Lipid Regulating Drugs

  • First Generation Agents

    • Bile acid sequestrants: non-absorbable resins (e.g., colestyramine, colesevelam) bind bile acids decreasing enterohepatic cycling, leading to increased hepatic cholesterol uptake and lowering LDL-C (15-30%), and modestly increasing HDL-C (3-5%). Adverse effects include GI disturbances and drug interactions (e.g., inhibits absorption of fat-soluble vitamins and some drugs).
    • Fibric acid derivatives: (e.g., fenofibrate, gemfibrozil) increase lipoprotein lipase activity leading to TG hydrolysis and VLDL elimination, and they increase HDL activity. Adverse effects include drug interactions (e.g., statins → risk of myositis, and warfarin → ↑ anticoagulant effect) and GI disturbances (e.g., nausea, vomiting, dyspepsia, bloating, flatulence, constipation, cramping), and CNS effects (e.g., fatigue, headaches).
    • Nicotinic Acid: (e.g., nicotinic acid, acipimox) reduces FFA mobilization, lowers TG synthesis and VLDL secretion lowering plasma LDL. Adverse effects include drug interactions (e.g., vasodilators → ↑ risk of hypotension, and statins → ↑ risk of myositis), flushing, and hepatotoxicity.

  • Second Generation Agents

    • Statins: (e.g., lovastatin, simvastatin, pravastatin, atorvastatin, fluvastatin) inhibit HMG-CoA reductase, reducing hepatic cholesterol synthesis, and increasing LDL receptors resulting in clearing cholesterol from circulation. May have other benefits, such as anti-inflammatory effects. Potential for myalgia, myopathy, or rhabdomyolysis.
    • Selective cholesterol absorption inhibitors (e.g., ezetimibe) inhibit intestinal cholesterol absorption into enterocytes, leading to reduced intestinal delivery to the liver.

  • Newer Agents

    • PCSK9 inhibitors: (e.g., alirocumab, evolocumab) bind and inhibit PCSK9, increase recycling and expression of hepatic LDL receptors, and thus increase LDL clearance, resulting in lower plasma LDL-C (~50-60%).
    • RNA interferences: (e.g., inclisiran) are small RNA molecules that target mRNA translation for PCSK9, thus lowering the synthesis of PCSK9, increasing LDL receptor recycling and expression, leading to a reduction in plasma LDL (~LDL-C 50-60%).
    • Apolipoprotein B inhibitors: (e.g., mipomersen) reduce LDL cholesterol through a reduction in apoB-100 synthesis and VLDL production. Adverse effects may include decreased uptake, cleavage, and degradation of mRNA.
    • ATP-citrate lyase (ACL) inhibitors (e.g., bempedoic acid): target ATP-citrate lyase, ultimately reducing hepatic cholesterol biosynthesis.
    • Microsomal triglyceride transfer protein (MTP) inhibitors (e.g., lomitapide): reduce VLDL production.
  • Zodda D et al. (2018). Treatment Strategy for Dyslipidemia in Cardiovascular Disease Prevention: Focus on Old and New Drugs. Pharmacy 6(1), 10. doi: 10.3390/pharmacy6010010.

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Test your knowledge on cholesterol's role in coronary heart disease and cardiovascular health. This quiz covers major sources of cholesterol, pathways of transport, and the impact of drugs on cholesterol levels. Understand the complex relationship between cholesterol and heart-related conditions.

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