Lecture 3: CVD and Risk

Question 1

What are cardiovascular diseases (CVDs)?

Answer 1

Class of disorders that affect the heart, blood vessels (arteries, veins, capillaries), or both.

Question 2

What are some common types of CVDs?

Answer 2

1. Coronary heart disease (CHD):
   
   • Buildup of fatty plaques inside the coronary arteries, leading to a condition called atherosclerosis.
   • Can result in the thickening of artery walls and may partially or completely occlude blood flow.
   • CHD can cause conditions like myocardial infarction (heart attack) and angina (chest pain).
2. Cerebrovascular disease:
   
   • Cerebrovascular disease affects the blood vessels supplying the brain.
   • It can lead to strokes, which occur when blood flow to a part of the brain is blocked, causing brain cells to die.
   • Strokes can be ischemic (due to a blockage) or hemorrhagic (due to bleeding into the brain).
3. Hypertensive heart disease:
   
   • Characterized by an increase in blood pressure (hypertension), which can put strain on the heart and increase the risk of developing other cardiovascular conditions, such as CHD.
4. Peripheral arterial disease (PAD):
   
   • PAD affects the arteries in the limbs, particularly the legs.
   • Reduced blood flow to the extremities, leading to symptoms like leg pain, cramping, and impaired circulation.
5. Rheumatic heart disease:
   
   • Bacterial infection, often originating from untreated strep throat or scarlet fever.
   • Can result in damage to the heart valves and inflammation of the heart muscle.
6. Deep vein thrombosis (DVT) and pulmonary embolism (PE):
   
   • DVT occurs when a blood clot forms in a deep vein, usually in the legs.
   • If a clot breaks loose and travels to the lungs, it can cause a potentially life-threatening condition called pulmonary embolism.

Question 3

What is atherosclerosis and its role in cardiovascular disease (CVD)?

Answer 3

• Key precursor to many cardiovascular diseases (CVDs).
• Thickening of artery walls due to the accumulation of inflammatory cells and the formation of atheromas, which are lipid-rich plaques within the arterial walls.
• Atheromas reduce the arterial lumen, impairing blood flow and causing perfusion loss to tissues supplied by the affected arteries.
• Results in loss of arterial elasticity, increasing the likelihood of plaque rupture and subsequent hemorrhage.
• Plaque rupture can trigger the activation of platelets, leading to the formation of blood clots (thrombus), which can obstruct blood flow and cause conditions like strokes or myocardial infarctions (heart attacks).

Question 4

Risk Factors for Atherosclerosis

Answer 4

• Age: Risk increases with age.
• Sex: More prevalent in males than females.
• Genetics: Family history plays a role.
• Lifestyle factors:
  
  • Smoking
  • Hypertension
  • Diabetes
  • Insulin resistance
  • Hyperlipidemia (elevated cholesterol and LDL)
  • Hypercoagulable states
  • Hyperhomocysteinemia
• Stress and personality traits
• Exercise habits
• Dietary patterns
• Obesity
• Infections

Question 5

What are the major classes of lipoproteins involved in lipid transport within the cardiovascular system?

Answer 5

The major classes of lipoproteins are Chylomicrons, VLDL, IDL, HDL, and Lipoprotein A.

Question 6

How do lipoproteins interact with different tissues in the body, and what role do apolipoproteins play in this process?

Answer 6

• Lipoproteins interact with tissues through signaling molecules and apolipoproteins.\
• Apolipoproteins act as cell surface receptors, directing lipoproteins to specific tissue receptors and mediating enzymatic reactions.
  
  • This allows various reactions, such as fat deposition and energy utilization, to occur in different parts of the body.

Question 7

What are some key lipoproteins involved in lipid transport within the cardiovascular system?

Answer 7

Key lipoproteins include LDL (Low-Density Lipoprotein), Lipoprotein A, and HDL (High-Density Lipoprotein).

Question 8

What role does Apolipoprotein E play, and how is it associated with certain health conditions

Answer 8

Apolipoprotein E is associated with Alzheimer’s disease (AD) and dementia. It is involved in lipid metabolism and can serve as a biomarker for these conditions.

Question 9

What is the primary function of chylomicrons in lipid transport within the body?

Answer 9

Chylomicrons primarily carry lipids from the intestine to the bloodstream.

Question 10

How do VLDL, IDL, and LDL differ in terms of their composition and function?

Answer 10

• VLDL (Very Low-Density Lipoprotein) transports triglycerides synthesized in the liver to peripheral tissues, while IDL (Intermediate-Density Lipoprotein) is an intermediate form between VLDL and LDL.
• LDL primarily carries cholesterol to cells. These lipoproteins differ in size, lipid content, and the specific apolipoproteins present on their surfaces.

Question 11

What role do LPa and SD-LDL play in cardiovascular disease

Answer 11

Associated with cardiovascular disease. They are characterized by their composition, size, and association with atherosclerosis and other cardiovascular conditions.

Question 12

Explain the exogenous lipid transport pathway.

Answer 12

• Dietary fat and triglycerides are transported into chylomicrons (CM).
• Initially, nascent chylomicrons (nCM) are formed and interact with various apolipoproteins to become mature CM.
• Lipoprotein lipase cleaves the triglycerides carried by CM, releasing free fatty acids (FFA) for tissue utilization.
• Remnants of CM are taken up by the liver and removed from circulation.
• CM carry exogenous lipids to various tissues, where lipoprotein lipase releases FFAs for utilization.

Question 13

Q: Describe the endogenous lipid pathway

Answer 13

• The liver produces LDL containing cholesterol and triglycerides.
• LDL is transported to peripheral tissues.
• Interactions with HDL allow for the acquisition of apolipoproteins.
• In tissues, lipoprotein lipase (LPL) cleaves triglycerides to release free fatty acids (FFA) for utilization or storage in adipocytes.
• Intermediate-density lipoproteins (IDL) are cleared by the liver.
• Remaining lipoproteins are metabolized further to produce LDL, which is subsequently taken up by the liver.

Question 14

Describe the process of reverse cholesterol transport involving HDL.

Answer 14

HDL is produced in the liver and intestines to form mature particles.
Interactions occur to pick up various apolipoproteins.
HDL picks up cholesterol from capillaries and transports it around the body.
Some cholesterol is used for the synthesis of steroid hormones, such as in the ovaries.
Cholesterol is removed by endocytosis in the liver.
Dysregulation of this process can lead to disorders like hyperlipidemia (excess lipids in the bloodstream).

Question 15

What are the characteristics and potential complications of atherosclerosis?

Answer 15

• Atherosclerosis primarily affects medium to large arteries due to higher pressures.
• Characteristics include lipid deposition in the intima, smooth muscle and extracellular matrix proliferation, and the formation of a protruding fibrous plaque.
• It can remain asymptomatic until the vessel lumen is significantly narrowed, leading to ischemia (reduced blood supply) and resulting in symptoms like chest pain during exertion.
• Complications may arise from sudden occlusion due to plaque rupture and thrombosis, leading to events like myocardial infarction (heart attack), weakened vessel walls resulting in aneurysms, or blood clots breaking loose and causing embolisms.

Question 16

What are the underlying mechanisms of atherosclerosis?

Answer 16

• Lipid Hypothesis: Increased plasma lipids, especially cholesterol, are associated with cardiovascular disease (CVD).
• Response to Injury Hypothesis: Endothelial cell dysfunction, possibly due to factors like high blood pressure, lack of exercise, or stress, triggers the formation of atherosclerotic plaques.
• Inflammation Hypothesis: A more recent theory that combines the concepts of endothelial injury and lipid accumulation, emphasizing the role of inflammation in atherosclerosis development.
• Neoplasia: Abnormal proliferation of smooth muscle cells contributes to the formation of plaques.
• Prostaglandins: Imbalance between prostacyclin and thromboxane levels can influence thrombus formation, exacerbating atherosclerosis.
• Thrombosis: Formation of blood clots is a central event in the formation of atherosclerotic plaques.

Question 17

Describe the normal progression of atherosclerosis.

Answer 17

• Collagen exposure beneath the epithelial cell layer activates platelets and initiates an inflammatory response.
• The intima (inner layer of blood vessels) protrudes into the lumen of the vessel.
• Smooth muscle cells proliferate in response to injury or inflammation.
• Macrophages accumulate at the site of injury, often filled with lipids. These lipid-laden macrophages are known as foam cells.
• LDL infiltrate the vessel wall and become trapped within the developing plaque, contributing to foam cell formation.
• ECM accumulation, including collagen and proteoglycans, contributing to plaque formation.
• The initial stage of atherosclerosis, characterized by the accumulation of lipid-laden foam cells and extracellular matrix components, is known as a fatty streak.

Question 18

What are the key features of advanced atherosclerosis?

Answer 18

• Fatty streaks, initially consisting of lipid-laden foam cells, begin to accumulate various cells and extracellular matrix components.
• ECM proliferation within the fatty streak.
• Smooth muscle breakdown, leading to structural changes in the blood vessel.
• Cells within the plaque may undergo atrophy, resulting in decreased flexibility of the blood vessel.
• Lipids accumulate within the plaque, originating from macrophages and the degradation of lipoproteins. This leads to the formation of a lipid-rich core.
• Foam cells, macrophages engorged with lipids, are prominent within the plaque.
• ECM increase, contributing to plaque stability.
• ECM forms a fibrous cap on top of the plaque, providing structural support.
• The plaque releases various compounds that affect the extracellular matrix and surrounding tissues.
• Thrombus (blood clot) formation may occur, leading to occlusion of the blood vessel.

Question 19

What are the complications of atherosclerosis?

Answer 19

• Calcium deposition increases vessel wall rigidity.
• Can lead to thrombus formation, hemorrhage, embolization, and vessel weakening.
• Surrounding vessels may grow to bypass blockages.

Question 20

What determines the vulnerability of plaques to rupture?

Answer 20

• Plaque composition, not size.
• Plaques with large lipid cores, thin fibrous caps, and inflammatory cells are more prone to rupture.
• Coronary arteries are particularly vulnerable, even if not completely occluded.

Question 21

What lifestyle changes can be implemented to address cardiovascular risk factors?

Answer 21

Lifestyle changes include addressing obesity and smoking habits.

Question 22

What are some pharmacological interventions for managing cardiovascular risk factors?

Answer 22

• Hypertension: ACE inhibitors.
• High cholesterol: Statins.
• Thrombus formation: Antiplatelet drugs like low-dose aspirin and clopidogrel.

Question 23

What are some surgical interventions for cardiovascular conditions?

Answer 23

• Coronary artery bypass grafting for myocardial infarction.
• Carotid endarterectomy for stroke prevention.

Question 24

What is the mechanism of action of statins?

Answer 24

Statins, also known as HMG-CoA reductase inhibitors, limit the synthesis of mevalonate, a precursor of cholesterol.
They significantly reduce cholesterol synthesis in hepatocytes, leading to decreased levels of LDL cholesterol in the bloodstream.

Question 25

How do statins affect LDL clearance from circulation?

Answer 25

Statins increase the expression of LDL receptors (LDLR) on cell surfaces, facilitating the clearance of LDL cholesterol from the bloodstream.

Question 26

What is the role of Apo B-100 in cholesterol metabolism, and how do statins affect its synthesis?

Answer 26

Apo B-100 is an apolipoprotein associated with LDL particles, which is involved in transporting cholesterol to tissues. Statins inhibit the synthesis of Apo B-100, thereby reducing the production of LDL particles.

Question 27

Which statin is commonly prescribed and known for its effectiveness?

Answer 27

Atorvastatin is a commonly prescribed statin known for its efficacy in reducing LDL cholesterol levels.

Question 28

What is the observed effect of statins on the likelihood of diabetes?

Answer 28

• Statins have been associated with a 9% increased risk of diabetes.
• This increase is not significantly different from the control group.

Question 29

How do statins affect BMI and LDL levels?

Answer 29

Statins do not significantly affect Body Mass Index (BMI) or LDL cholesterol levels.

Question 30

While statins reduce the risk of coronary events, is this risk completely abolished?

Answer 30

• Statins reduce the risk of coronary events but do not completely abolish it.
• Despite statin therapy, 60-70% of major cardiovascular events may still occur.

Question 31

What is the controversy surrounding statins?

Answer 31

• There is controversy surrounding statins due to their widespread prescription and concerns about certain side effects.
• The benefits and potential risks of statin therapy are subjects of ongoing debate.