Podcast
Questions and Answers
Which factor is considered nonmodifiable in the context of cardiovascular health?
Which factor is considered nonmodifiable in the context of cardiovascular health?
What role does inflammation play in atherosclerosis?
What role does inflammation play in atherosclerosis?
Which risk factor is associated with a higher likelihood of developing cardiovascular disease according to recent studies?
Which risk factor is associated with a higher likelihood of developing cardiovascular disease according to recent studies?
Which of the following is considered a modifiable risk factor for cardiovascular disease?
Which of the following is considered a modifiable risk factor for cardiovascular disease?
Signup and view all the answers
How does high cholesterol contribute to the risk of atherosclerotic cardiovascular disease (ASCVD)?
How does high cholesterol contribute to the risk of atherosclerotic cardiovascular disease (ASCVD)?
Signup and view all the answers
Which lifestyle choice is shown to have a critical impact on reducing the incidence of heart disease?
Which lifestyle choice is shown to have a critical impact on reducing the incidence of heart disease?
Signup and view all the answers
What percentage of patients enrolled in the study were men?
What percentage of patients enrolled in the study were men?
Signup and view all the answers
Which combination of risk factors is specifically highlighted as major contributors to ASCVD risk?
Which combination of risk factors is specifically highlighted as major contributors to ASCVD risk?
Signup and view all the answers
What is the primary lipid associated with increased risk for atherosclerosis?
What is the primary lipid associated with increased risk for atherosclerosis?
Signup and view all the answers
How does diabetes mellitus influence the risk of atherosclerosis?
How does diabetes mellitus influence the risk of atherosclerosis?
Signup and view all the answers
What effect does prolonged lower LDL-C have on the risk of ASCVD?
What effect does prolonged lower LDL-C have on the risk of ASCVD?
Signup and view all the answers
Which of the following risk factors doubles the death rate from ischemic heart disease?
Which of the following risk factors doubles the death rate from ischemic heart disease?
Signup and view all the answers
What percentage increase in ischemic heart disease is associated with hypertension?
What percentage increase in ischemic heart disease is associated with hypertension?
Signup and view all the answers
Which statement correctly differentiates genetic and environmental factors in ASCVD risk?
Which statement correctly differentiates genetic and environmental factors in ASCVD risk?
Signup and view all the answers
Which modifiable risk factor is associated with both hypercholesterolemia and increased risk of myocardial infarction?
Which modifiable risk factor is associated with both hypercholesterolemia and increased risk of myocardial infarction?
Signup and view all the answers
What role does the endothelium play in inflammation during atherosclerosis?
What role does the endothelium play in inflammation during atherosclerosis?
Signup and view all the answers
Which statement accurately describes endothelial dysfunction?
Which statement accurately describes endothelial dysfunction?
Signup and view all the answers
What determines the integrity of the endothelium?
What determines the integrity of the endothelium?
Signup and view all the answers
How do endothelial progenitor cells contribute to endothelial health?
How do endothelial progenitor cells contribute to endothelial health?
Signup and view all the answers
What is likely a consequence of prolonged exposure to cardiovascular risk factors?
What is likely a consequence of prolonged exposure to cardiovascular risk factors?
Signup and view all the answers
Why is the release of endothelin important in vascular function?
Why is the release of endothelin important in vascular function?
Signup and view all the answers
Which of the following is an impact of lifestyle choices on endothelial function?
Which of the following is an impact of lifestyle choices on endothelial function?
Signup and view all the answers
Which factors can lead to valuable endothelial activation?
Which factors can lead to valuable endothelial activation?
Signup and view all the answers
Study Notes
Atherosclerosis
- A chronic inflammatory condition
- Often develops silently until a severe stenosis or thrombosis happens
- A diffuse problem, so if PAD is present, check other vessels (coronary, brachiocephalic), and vice versa
- Control of risk factors is important to prevent rupture
### Endothelium
- Major regulator of vascular homeostasis
- Vasoprotective effects (vasodilation, reduction of smooth muscle growth, inflammation reduction)
- Largely mediated by nitric oxide, a potent endogenous vasodilator
- Inhibits oxidation of low-density lipoproteins
- Dysfunction/ Activation is linked to impaired endothelium-dependent vasodilation and atherosclerosis
### Endothelial Activation and Atherosclerosis
- Endothelial dysfunction is better viewed as endothelial activation
- Most cardiovascular risk factors activate molecular processes in the endothelium (chemokines, cytokines, and adhesion molecules) to target inflammation towards specific tissues
### Endothelial Injury and Repair
- Prolonged exposure to cardiovascular risk factors exhausts anti-inflammatory systems.
- Endothelial cells become dysfunctional and can be lost from circulation.
- Adjacent mature cells can replicate and repair lesions.
- Circulating endothelial progenitor cells are also an alternative repair mechanism.
Arterio-sclerosis
- General term for "arterial hardening"
- Changes in arterial wall leading to loss of elasticity
- Types:
- Atherosclerosis
- Monckeberg medial calcific sclerosis
- Arteriolosclerosis
Medial Calcific Sclerosis
- Calcifications in muscular arteries
- Usually seen in older than 50 years old
- Can be detected radiologically
- Does not narrow the vascular lumen
Arteriolosclerosis
- Affects small arteries and arterioles
- Types:
- Hyaline
- Hyperplastic
Atherosclerosis (Detailed)
- Clinically significant damage (intimal damage)
- Leading to atherosclerotic plaques that:
- Narrow the vascular lumen
- Influence hemodynamics/blood flow
- Weaken the tunica media
Atherosclerosis (Definition)
- Chronic inflammatory condition that can be converted into acute clinical events by plaque rupture and thrombosis.
- Primarily causes heart disease and stroke
- Accounts for ~50% of deaths in Westernized societies
Atherosclerotic Plaques (Frequent Locations)
- Elastic arteries (aorta, common carotid artery, iliac artery)
- Large and medium-sized muscular arteries serving legs and abdominal organs
- High-pressure arteries
- Branching points of arteries
Target Organs
- Heart
- Brain
- Kidney
- Leg
- Intestines
Coronary Heart Disease
- 90% of myocardial ischemia due to atherosclerosis of coronary arteries
- Ischemia is a dysbalance between oxygen supply vs metabolic demands
- More dangerous than hypoxemia
Pathogenesis of Coronary Heart Disease
- General factor: decreased blood perfusion in coronary arteries.
- Components:
- Atherosclerosis
- Thrombosis
- Thrombocyte aggregation
- Vasospasm
### Endothelial Activation and Atherosclerosis (Causes)
- Increased expression of inflammatory molecules
- Recruitment of immune cells
- Foam cell formation
### Endothelial Injury and Repair (Causes)
- Prolonged exposure to cardiovascular risk factors
- Leads to endothelial dysfunction, loss of integrity, and senescence
### Atherosclerosis (Causes)
- Non-modifiable: genetics, family history, increasing age, male gender.
- Modifiable: hyperlipidemia, hypertension, cigarette smoking, diabetes, inflammation
### Atherosclerosis (Modifiable Major Risk Factors)
- Hyperlipidemia (specifically hypercholesterolemia):
- Major risk factor
- Significant even without other risk factors
- Sufficient to initiate lesion development
### Additional Atherosclerosis Risk Factors
- Hypertension: ~60% increased risk of ischemic heart disease versus normotensive populations
- Cigarette Smoking
- Doubles the death rate for ischemic heart disease
- Especially with prolonged use
- Diabetes Mellitus
- Induces hypercholesterolemia
- Significantly increases risk of atherosclerosis
- Myocardial infarction occurs frequently in diabetics
Cholesterol (in atherosclerosis)
- LDL-C plays a causal role in atherosclerosis development.
### Atherosclerosis (Prolonged Lower LDL-C)
- Lower risk of ASCVD, even at low LDL levels
- Relative risk proportional to absolute change in LDL-C
- Significant benefit from even a small reduction
Fatty Streak Phase of Atherosclerosis
- Begins with dysfunctional endothelial cells and retention of apoB-containing lipoproteins (LDL, VLDL, apoE remnants) in subendothelial space.
- Retained lipoprotein modification (oxidation, glycation, enzymatic) activates endothelial cells
Activated Endothelial Cells
- Increased expression of monocyte adhesion molecules (selectins, VCAM-1) and chemoattractants (MCP-1)
- Prompts monocyte migration into the intima
- Differentiation into macrophages and foam cells
- Promote inflammatory signaling pathways in macrophage foam cells
### Blood Pressure (in Atherosclerosis)
- Raised blood pressure (BP) a major cause of ASCVD and HF
- Risk factors for CAD, HF, cerebrovascular disease, lower extremity arterial disease (LEAD), chronic kidney disease (CKD), and atrial fibrillation (AF).
- Lifetime blood pressure evolution different in men vs. women, potentially higher CVD risk at lower thresholds in women
Cigarette Smoking
- Responsible for 50% of deaths in smokers due to ASCVD
- Lifetime smokers have a significantly higher probability of dying from smoking
Diabetes Mellitus
- Type 1, Type 2, and prediabetes independent risk factors for ASCVD (about two-fold depending on the population)
- Higher risk of stroke, particularly in type 2 diabetes sufferers.
- Often associated with other ASCVD risk factors like dyslipidemia and hypertension.
Pathogenesis of Atherosclerosis
- "Response to Injury" hypothesis
- Chronic inflammatory and healing response to endothelial injury
- Lesion progression occurs from macrophage, T lymphocyte interaction, modified lipoproteins and the extracellular matrix.
Atherosclerosis (General Concepts)
- Endothelial injury/dysfunction (e.g. increased permeability, leukocyte adhesion, thrombosis).
- Accumulation of lipoproteins (LDL and oxidized forms) in vessel wall.
- Monocyte adhesion; migration into intima and transformation into macrophages and foam cells.
- Platelet adhesion.
Atherosclerosis (Ongoing Events)
- Factors released from activated platelets, macrophages, and vascular wall cells trigger smooth muscle recruitment
- SMC proliferation, ECM production
- Lipid accumulation within macrophages and smooth muscle cells
- Calcification of ECM and necrotic debris
Stages of Atherosclerosis
- Initial lesion ("fatty droplet")
- Fatty streak
- Imminent lesion
- Atheroma
- Fibroatheroma
- Complicated fibroatheroma
Descriptions of I/II Stages of Atherosclerosis
- I: Initial lesion/fatty droplet, occasional fat containing foam cells in the arterial intima
- II: Fatty streak, groups of macrophages mainly intracellular fat, few T lymphocytes, yellow streaks 1 cm x 1 mm
Description of III-V Atherosclerosis
- III: Imminent lesion: small aggregations of extracellular fat.
- IV: Atheroma: fatty core.
- V: Fibroatheroma: fatty core + fibrosis; calcinosis can develop
Components of V Stage of Atherosclerosis
- Cells: smooth muscle, macrophages, lymphocytes
- Extracellular matrix: collagen, elastic fibers, proteoglycans
- Intracellular and extracellular fat
- Surface- connective tissue + smooth muscle fibers
- Detritus/organic debris: Fats (mainly cholesterol), Fibrin, organized thrombi, plasma proteins, remnants of necrotic cells.
- In debris- foamy cells developing from macrophages and smooth muscle cells
Stable vs Unstable Atherosclerotic Plaque
- Stable: thick fibrotic cap, small lipid core
- Unstable: small fibrotic cap, thick lipid core with active inflammation
Complicated Plaque
- Thrombosis
- Rupture, ulceration, erosion
- Hemorrhage in the plaque
- Aneurysm
Consequences of Atherosclerotic Disease
- Heart: coronary heart disease
- Brain: acute or chronic ischemic brain disease
- Kidney: acute or chronic ischemic kidney damage, kidney infarction, chronic kidney insufficiency
- Intestines: acute or chronic ischemic intestinal disease
- Leg: gangrene, muscular atrophy, arterial ulcers
Acute Coronary Syndrome (ACS)
- STEMI (ST-segment elevation MI)
- With ST-segment elevation in ECG
- NON-STEMI (Non-ST-segment elevation MI)
- Without ST-segment elevation in ECG
- Most cases of acute MI are caused by atherothrombotic coronary artery disease involving rupture of a plaque (Types I)
- Many other events (Type 2 MI) cause an imbalance of demand and supply, resulting in acute MI
Myocardial Infarction
- Area of ischemic necrosis.
- Transmural (subepicardial) affects complete/almost complete thickness.
- Presentation as ACS STEMI (ST-segment elevation) MI.
- Subendocardial affects inner 1/3-1/2, and as ACS NON-STEMI (ST-segment not elevated) MI
Coronary Artery
- Epicardium and endocardium are parts of the coronary artery
- Atherosclerotic lesions are located in arteries flowing from epicardium to endocardium
Myocardial Infarction (Morphological Course)
- Coagulation necrosis (12-24 hrs after)
- Thin, hypereosinophilic necrotic fibres
- Nuclei disappear
- "Wavy" fibers
- Vacuolar degeneration in periphery
Myocardial Infarction (Morphological Course Details)
- Infiltration of macrophages (5-10 days post-occlusion)
- Granulation tissue (2nd-4th week post-occlusion)
- Scar formation (6 weeks post-occlusion)
Reperfusion
- Aim: to renew blood flow
- Ischemia lasting 15-20 minutes can be reversed, if reperfusion begins within 4 hours
Reperfusion-Induced Changes in Tissues
- Desirable changes - regress of ischemic ultrastructural changes
- Hemorrhage in necrotic areas
- Necrosis changes (contraction bands)
- Microvascular damage, endothelial swelling
- Activation of apoptosis
- Post-ischemic functional disturbances
Reperfusion Complications
- Reperfusion arrhythmia
- Hemorrhage in the myocardium
- Irreversible reperfusion lesion
- Microvascular damage
- Prolonged ischaemia
Myocardial Infarction (Complications)
- Loss of contractility
- Progression of infarction
- Disturbances of heart rate
- Pericarditis (Dressler syndrome)
- Mural thrombosis
- Aneurysm (possible thrombosis, embolism, or chronic heart insufficiency)
- Papillary muscle dysfunction (rare)
Sudden Cardiac Death
- Death from cardiac reason within 1 hour of symptoms
- Most causes are arrhythmias.
- Other underlying causes are possible
Aneurysms and Dissection
- Localized abnormal dilation of a blood vessel (or heart).
- Can be congenital or acquired.
- True aneurysm involves all layers of the arterial wall.
- Types include atherosclerotic and congenital vascular aneurysms
Aneurysms (Pathogenesis)
- Atherosclerosis (weakening of the wall)
- Ischemia of blood vessel wall
- Other factors:
- Dysproportionate collagen synthesis/destruction
- Increased activity of matrix metalloproteinases
- Decreased activity of TIMP (tissue inhibitors of matrix metalloproteinases)
- Decreased mechanical properties of connective tissue
Atherosclerotic Aortic Aneurysms
- Mostly located in abdominal aorta below ostia of renal arteries
- Develop in aortic arch or thoracic aorta
- Can involve inguinal arteries
- Severe atherosclerosis
- Features include ulcers or granulation tissue and thrombosis; saccular or fusiform.
- Reach diameter of 15 cm and length 25 cm
Aortic Aneurysms (Complications)
- Rupture into abdominal or retroperitoneal space with significant bleeding
- Compression of arterial branches
- Compression of organs
- Embolism
- Large aneurysms can resemble tumors
Stroke
- Hypoxia/ischemia
- Brain receives 15% resting cardiac output
- 20% of the body's oxygen consumption
- Inadequate blood flow occurs with reduction in perfusion pressure, small/large vessel obstruction and/ or hypotension
- Ischemic stroke: embolism
- Embolism to brain from various sources (mural thrombi, myocardial infarct, valvular disease, atrial fibrillation)
- Next in frequency: Thromboemboli from arteries (often atherosclerotic plaques in the carotids).
- Thrombotic occlusion of cerebral arteries occurs quickly from atherosclerotic plaques
- Inflammatory processes involve blood vessels, leading to luminal narrowing, occlusion, and cerebral infarcts
- Global cerebral hypoxia/ischemia = generalized reduction in cerebral perfusion (e.g. cardiac arrest, shock, hypotension) or reduced oxygen carrying capacity of blood (e.g. carbon monoxide poisoning).
Atherosclerotic Renal Artery Stenosis (ARAS)
- Narrowing of the renal arteries (RAS), primarily due to atherosclerosis.
- Accounts for ~90% of lesions obstructing blood flow, commonly involves the ostium and proximal one-third of the renal artery and sometimes adjacent aorta.
- Prevalence increases with age and traditional (modifiable) risk factors (hypertension ~1% -6%, compared to >30% in patients undergoing cardiac catheterization, and >50% in elderly with known atherosclerotic vascular disease).
- Progressive loss of renal mass and function
- In some subgroups, 60% obstruction leads to renal atrophy in 21% and 27% develop chronic renal failure within 6 years
Atherosclerotic Renal Artery Stenosis (ARAS) (Predictive Value)
- Associated with higher risk of adverse coronary events observed in clinical studies.
- Patients with ARAS, compared to those without, show greater incidence of hospitalization, myocardial infarction, and coronary revascularization.
- 4-year survival rate 65% in patients with ARAS vs 86% in those without ARAS, confirming significant risk associated.
- Complex mechanism of hypertension/cardiac morbidity in ARAS patients
Atherosclerotic Gastrointestinal Ischemia
- Splanchnic artery stenosis (up to 50% in celiac artery and 30% in superior/inferior mesenteric arteries) is observed at a higher rate in patients over 65.
- This rate is similar to that for lower extremities (14.5%) and coronary arteries (22%), highlighting a similar prevalence.
Chronic Splanchnic Syndrome
- Analysis of 376 patients, 97 had chronic splanchnic syndrome
- Excluded data for 90 patients due to incomplete data.
- Mean age 63 years, with 74% female.
- 59% patients had atherosclerotic disease in other vessels, 57% reported smoking, 53% hypercholesterolemia, 62% hypertension, 21% diabetes, & 21% increased bodyweight.
Chronic Splanchnic Syndrome (Risk Profile)
- Risk profile in splanchnic patients differs from other atherosclerotic diseases
- Lower presence of obesity, diabetes, hypertension, and hypercholesterolemia
- Reduced caloric intake may explain the observed differences between patients suffering this condition vs. that in general with atherosclerosis.
Peripheral Arterial Disease (PAD)
- Problem causing reduced blood flow, primarily in the arteries of legs and feet
- Often associated with atherosclerosis of abdominal aorta, iliac, and femoral arteries.
- Can be sudden (emboli of cardiac or atherosclerotic disease origin).
- Common at arterial branching points, where vessel branches have abrupt takeoff points.
Peripheral Arterial Disease (PAD) (Hemodynamic Consequences)
- Hemodynamic consequences based on the degree of arterial narrowing.
- 50% decrease in vessel diameter equal to ~75% loss of cross sectional area (considered flow-limiting).
- Narrowing or constriction shifts blood flow to parallel arteries. Distal perfusion, though maintained by collateral circulation, lacks the same level of flow as primary vessels.
Peripheral Arterial Disease (PAD) (Symptoms)
- Patients reach a point during walking where collateral circulation maxima out, thus perfusing lower extremity muscles, and pain/cramping/fatigue.
- Poor perfusion to nerves causes ischemic rest pain (localized and intractable/burning) and non-healing wounds and ulcers represent localized tissue loss.
- Gangrene (toes or complete forefoot) most severe presentations of tissue loss
Peripheral Arterial Disease (PAD) (Complications)
- Ischemia/Gangrene, Amputation
- Infection
- Ulceration
- Heart attack
- Stroke
- Blood clots
- Erectile Dysfunction
Take Home Message
- If one vascular region is damaged, check other vessels (e.g., coronary/encephalic). Atherosclerosis affects everything simultaneously. Gangrene requires assessing coronary and encephalic vessels to prevent MI/stroke. Control risk factors to prevent further issues.
Thank You
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on cardiovascular health and risk factors associated with atherosclerosis. This quiz covers nonmodifiable and modifiable risk factors, the impact of cholesterol, and the role of lifestyle choices in heart disease prevention. Assess your understanding of recent findings in cardiovascular disease research.
