Cardiovascular disease Flashcards
What is the burden of cardiovascular disease?
2nd and 3rd leading cause of death in Canada (number 1 is malignancy) - 1st and 2nd worldwide. Incidence decreasing in developed countries. Overall global burden to double in next few decades.
What is Atherosclerosis?
Atherosclerosis is a systemic disease affecting large and medium-sized arteries.
- It is characterised by the formation of atheromas (fibrofatty plaques) which narrow (stenose) the artery lumens resulting in blood-flow reduction (ischemia) and subsequent damage or necrosis to the “downstream” organs. Results in end-organ damage (symptomatic disease) - acute or chronic
-> (intima = most inner layer of vessel, then media, then adventitia - have tunica before each name)
-> Overtime intima is thickened because of atherosclerosis - expands and takes over the other layers of the vessels.
-> Vessel becomes hardened due to deposition of cholesterol and fibrosis. Plaques are calcified - difficult to cut.
-> May cause thrombosis - stroke
-> Atheroma (fibrofatty plaque) - fibrous cap (smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastic, proteoglycans, neovascularization) - necrotic centre (cell debris, cholesterol crystals, foam cells, calcium) + media
-> Complications of atherosclerosis account for more than half of all deaths in the Western world.
Describe the pathogenesis of atherosclerosis
- Plaques develop as a result of a chronic inflammatory reaction to various forms of injury/ insult to the endothelium - “response to injury hypothesis”.
- The earliest pathological lesion is called a fatty-streak. Some of these slowly progress and develop into the mature atherosclerotic lesion, the fibro-fatty plaque.
- The “response in injury hypothesis” explains plaque development as a chronic inflammatory response resulting from injury to the endothelial lining of the artery. Many of the atherosclerotic risk factors act by contributing to some form of endothelial damage. This “damage” results in endothelial dysfunction, allowing for platelets and monocytes (macrophages) to adhere to the lining. These elements release various growth factors and cytokines, which cause recruitment and migration of smooth muscle cells and fibroblasts into the endothelium. Collagen is produced. Macrophages also engulf lipid and cholesterol derived from the blood. The end result is a raised plaque, with both fibrous and fatty elements, which narrows the vessel lumen.
What are the risk factors of Atherosclerosis? modifiable vs non-modifiable?
- Can be separated by major/ minor, modifiable / non-modifiable. When there are multiple risk factors present, risk is multiplied, not added.
-> Major / modifiable = hyperlipidemia, hypertension, cigarette smoking, and diabetes mellitus. - The “big three” major risk factors are:
1. smoking
2. hypertension
-> “silent killer” / asymptomatic, underdiagnosed, undertreated
3. elevated blood cholesterol (hyperlipidemia)
-> cholesterol transported by lipoproteins. LDL (low density lipoprotein) = “bad” cholesterol. HDL (high density lipoprotein) = “good” cholesterol. Blood levels are determined by genetic influence. Pharmacological treatment is sometimes necessary - change in lifestyle or diet may improve. - An important feature of all three is that they are potentially modifiable (can be improved through prevention or treatment). Diabetes mellitus is also a major risk factor, modifiable with treatment.
-> Diabetes mellitus = strong risk factor, mechanism of contribution multifactorial - associated with hyperlipidemia, predisposition of clot formation, risk of coronary artery disease is doubled, risk of gangrene - Non-modifiable risk factors include- age (older = more at risk), sex (premenopausal women at lower risk but catch up to men after menopause - men usually at more risk - estrogen has protective effect - testosterone also has protective effect to a lesser degree - these hormones are only protective in own gender - e.g. can’t give males estrogen to protect) family history, ethnicity
- Other factors, potentially modifiable- obesity (associated with hypertension), lower socioeconomic class, type “A” personality/ stress, elevated blood homocysteine level - substances present in blood, multiple effects on blood vessels - toxic on endothelium, unfavourable on lipids (can be treated with vitamin B).
What are the major sites of atherosclerotic ischemic injury as well as the manifestations there?
- Heart - causing angina pectoris, myocardial infarction, chronic heart failure, sudden cardiac death
- Brain - ischemic stroke (infarct), may get hemorrhage
- Extremities - claudication (ischemic type pain in extremity, usually associated with stenosis of vessels - e.g. lower leg arteries), gangrene (often complete blockage of vessels by stenosis - causes necrosis) - diabetes is high risk factor for this
- Kidneys - chronic kidney/ renal failure
- Note that many patients may have coexisting atherosclerotic disease in more than one organ system
Describe coronary atherosclerosis
The heart itself requires a large supply of oxygen and nutrients. It receives its blood supply via the coronary arteries which originate from the aorta just beyond the aortic valve. There are three major branches; the left anterior descending (LAD) branch and the left circumflex branch supply the anterior and lateral portions of the left ventricle respectively, and the right coronary artery (RCA) supplies the right ventricle and the posterior wall of the left ventricle. These are medium-sized arteries, and therefore susceptible to atherosclerosis. Coronary atherosclerosis begins early in life (20s) and is slowly progressive. It does not become manifest clinically with symptoms until later in life when there is reduction in blood flow of a magnitude which can potentially cause ischemic damage (necrosis) of heart muscle. This degree of flow reduction does not occur until there is about a 70% reduction in the area of the coronary artery lumen (there is a large “safety margin” of flow)
What is the epidemiology of atherosclerosis/ ischemic heart disease?
In Western society, the mortality rate of IHD (ischemic heart disease) has been declining since the 1960’s but it remains the leading cause of death. However, the rate has been steadily increasing in developing countries (due partly to increasing life expectancy and also to acquiring bad “western” lifestyle habits) and therefore the overall global burden of IHD is on the rise.
What is Angina Pectoris?
Angina is chest pain which is the result of myocardial ischemia, and this blood flow reduction is usually due to coronary atherosclerosis.
- there is usually at least one coronary artery with a fixed severe stenosis although vasospasm (muscular constriction of the vessel wall) can further contribute to the narrowing. The pain is usually described as “crushing, tightness or heaviness”. By definition, the resultant myocardial ischemia is of insufficient duration and magnitude to result in actual death (necrosis) of the downstream heart muscle. Angina is often precipitated by events that increase myocardial blood flow demand such as exercise or stress. Episodes usually resolve with rest or medications (nitroglycerine).
- Exertional ischemic pain resolves before necrosis occurs (cardiac pain)
-> Necrosis can occur in cardiac muscle after half an hour of ischemia - less than that and it may recover. - Often during times where there is a higher demand for oxygen - exercise or stress -> pain - pain resolves with rest or medication.
- Unstable angina can herald impending infarction - at higher risk for myocardial infarct
What is myocardial infarction?
- Ischemic necrosis of hear/ cardiact muscle
- Muscle begins to die after about 30 minutes of ischemia (if shorter - changes are reversible)
- Diagnosis made by symptoms (angina type pain), ECG changes and cardiac enzyme rise
- Often precipitated by coronary thrombosis (90% of cases). Occlusive (completely blocks blood flow) vs. non-occlusive (incomplete blockage)
What is the pathogenesis, diagnosis and treatment of myocardial infarction?
Pathogenesis
- If myocardium is ischemic for about 30-40 minutes, it begins to die, and the result is a myocardial infarct (MI). It is therefore important to seek prompt medical attention when an anginal episode does not resolve within this time period.
- Most MI’s are precipitated by formation of a thrombus on the luminal surface of a coronary artery plaque, causing complete or near-complete occlusion of the vessel (the thrombus is the “straw that breaks the camel’s back”).
Treatment:
- thrombolytic drugs (“clotbusters”) which are highly effective in re-establishing coronary blood flow and either preventing or reducing infarction. These drugs must be administered promptly, again emphasizing the importance of early diagnosis & treatment.
- Early treatment very important - must be given before the muscle dies
- Other treatments include percutaneous transluminal coronary angioplasty (dilatation of a stenosis by inflation of a balloon catheter) or coronary artery bypass surgery. (both of these treatments can also be given for unstable angina to prevent infarction)
Diagnosis:
- clinical symptoms - prolonged “angina-like” chest pain, often radiating to jaw or left arm, associated nausea and sweating
- changes on the electrocardiogram (ECG) which can indicate heart muscle injury
- Measuring elevated levels of cardiac enzymes such as troponins and cardiac muscle creatine kinase. These substances are specific to heart muscle and they leak into the blood when heart muscle cells are injured and dying
What are the morphological and histological features of myocardial infarction?
- MIs most often involve the left ventricle (it works much harder than the right ventricle and therefore demands much more blood flow)
- The affected area usually corresponds to the territory supplied by the narrowed “culprit” coronary artery. Therefore, blockages of the LAD result in anterior wall infarcts, left circumflex artery blockages infarct the lateral LV wall and RCA blockages infarct the posterior LV wall.
- Infarct size is variable; prognosis is worse for larger lesions
- If an infarct involves the full thickness of the wall, it is termed transmural
- If it involves only the inner half of the wall (the furthest “downstream” muscle), it is termed subendocardial
- Infarcts heal by a process of scarring; muscle does not regenerate. Therefore, infarcted muscle is “lost” to the heart which has to rely on its remaining muscle to keep it functioning
- Healing starts with removal of the dead muscle. This requires the digestive proteolytic and phagocytic action of neutrophils and macrophages.
- This is followed by ingrowth of fibroblasts which produce and lay down collagen which forms the bulk of the scar
- Scar is usually well-developed after 2 months
- Microscopic - cardiomyocytes become necrotic, dense, lose their nuclei
What are the complications of myocardial infarction?
Early:
1. Dysrhythmias: disturbances in the electrical rhythm of the heart. Infarcted muscle can interfere with the normal conduction of electrical impulses through the heart. These can be serious and potentially fatal and often require either drugs or electrical pacemakers.
- Arrhythmias: while dysrhythmias just mean that the heartbeat is irregular - arrhythmias mean that the heart rate is too fast or too slow. Very common. Can happen at any time - most common cause of death from ischemic injury.
- Congestive heart failure/cardiogenic shock: if too much muscle is infarcted and the remaining living muscle cannot meet the demands required of the heart, the result is “back-up” congestion of blood in the lungs (congestive heart failure) and inadequate forward flow of blood to the body (cardiogenic shock)
-> In both cases the heart is not able to pump blood. Cardiogenic shock = organ damage. Congestive heart failure = backflow of blood in venous circulation - get congestion in lungs - results in generalized edema. - Ventricular rupture (cardiac rupture): sometimes the infarcted zone cannot hold together and the heart wall ruptures, causing acute hemorrhage into the sac around the heart which in turn compresses the heart (cardiac tamponade) and is almost always fatal - usually a few days after myocardial infarct
-> If ruptures - blood flows in pericardial space - heart cannot pump - life threatening - may lead to cardiac tamponade.
-> Cardiac tamponade is a medical emergency that takes place when abnormal amounts of fluid accumulate in the pericardial sac compressing the heart and leading to a decrease in cardiac output and shock. - Pericarditis (inflammation of the heart surface) can be either an early (acute) or late complication. - fibrin on surface of the heart
- Sudden death
Late:
1. Aneurysm (balloon-like bulge of arterial wall) -> An end-stage scar from a large transmural infarct can weaken and bulge, forming an aneurysm of the LV wall.
- Congestive heart failure can be a chronic condition
What are the therapeutic strategies for myocardial infarction?
Medical / preventative:
- Risk factor reduction
- Anti-hypertensives
- Lipid lowering agents
- Thrombolytics - must use promptly
Surgical / interventional
- Coronary artery bypass
-> For coronary arteries with stenosis (larger segment - significant) and cannot use angioplasty. Often use vessels behind sternum - left internal mammary artery, radial arteries, arteries in legs
-> Coronary artery bypass surgery creates a new path for blood to flow around a blocked or partially blocked artery in the heart. The surgery involves taking a healthy blood vessel from the chest or leg area. The vessel is connected below the blocked heart artery. The new pathway improves blood flow to the heart muscle.
- Angioplasty - for early myocardial infarct, and angina
-> Through the skin - guided wire with balloon and stent in balloon - when balloon is inflated the stent crushes plaque, and keeps vessel open - then balloon deflated and removed but stent remains
-> Sometimes have dissolvable stent - so that it is gone after a few months for example
Describe hypertension. What is blood pressure? Arterial blood pressure curve?
BP is measured as two numbers:
- the top number is systolic-the BP during contraction of the heart (normal = 120)
- the bottom number is diastolic-while the heart is relaxing and filling up for the next beat (normal = 80) - longer phase - considered “more important” - longer = more important, heart has more exposure during this time.
- hypertension is generally accepted as BP of 140/90 and greater - either of those parameters, meaning 140/80 still hypertensive, and so is 130/90.
Arterial blood pressure curve:
- Highest pressure in arteries - lowest in right atrium
- Pulse pressure: difference between systolic and diastolic pressure.
- Mean pressure = average arterial pressure during single cardiac cycle (determined by many factors - venous pressure, etc.). Mean pressure is perfusion pressure = pressure the heart needs to sustain in order for an organ to be perfused. - below that organs will experience ischemia
- Both systolic and diastolic pressure decrease as they go through smaller arteries/ vessels - keeps decreasing as it gets closer to right atrium
- Have to overcome resistance
-> Arterials contract and diameter gets smaller -> resistance gets higher - a way to keep blood pressure consistent
- about 25% of population is hypertensive
- only about 50% of hypertensive Canadians know they are hypertensive
- only 16% of hypertensive Canadians have adequate blood pressure control
- Continuous variable, bell-curve distribution
- BP is multifactorial, determined by combination of genetic and environmental influences
- Poor awareness - inadequate treatment - inadequate control
Describe BP regulation
Depends on two major factors - cardiac output and peripheral vascular resistance
*BP = cardiac output x peripheral vascular resistance
- Cardiac output depends on heart rate and stroke volume (volume pumped with each contraction)
*Cardiac output = heart rate x stroke volume
- Peripheral resistance is controlled by the balance of constricting and dilating humoral and neural factors on blood vessels (eg. Epinephrine is a vasoconstrictor)
-> Vasoconstricting factors vs vasodilating factors
- The kidney plays a very important role in BP regulation
-> Sensing a drop in BP, the kidney will release the hormone renin which in turn activates the vasoconstrictor angiotensin
-> Renin-angiotensin feedback loop
- Kidney senses drop, secretes renin - renin substrate acts on angiotensin - converts from 1 to 2. Angiotensin 2 causes vasoconstriction as well as acts to produce/ synthesise aldosterone - which increases sodium retention. All of this increases the blood pressure. Once blood pressure is back to acceptable level - feedback to kidney to stop the loop.
- The kidney also controls the body’s sodium balance which in turn influences the blood volume
