Atherosclerosis
What is the risk of CVD in a pt over 30 y/o w/o CVD
50%
Involves the walls and smooth muscle of small arteries and arterioles 2 types: hyaline and hyperplastic D/t hypertension
Arteriolosclerosis
CVD is the leading cause of death in middle age and older adults Leading cause of death in developed countries Mortality appears to have decreased by 50% in the 90s and 2000s why
Because most people live after their first MI
most cases from ASVD: fatal or nonfatal myocardial infarction (MI), angina pectoris, and/or heart failure (HF)
CHD
Cardiac Output (CO) -> what is the calculation? Stroke Volume (SV) -> what is the most precise definition? What are the 3 major determinants of SV? What are three synonymous term for "Stretch on the ventricular fibers prior to contraction"?
CO = SV x HR CO = mL./min as SV is mL/beat and HR = beats/min EDV - ESV = SV measured in mL 3 determinants are preload, afterload and contractility Preload, LVEDV and LVEDP
Ischemic stroke - fatal or nonfatal (~60% of strokes from ASVD), transient ischemic attack (TIA), vascular dementia (10-20% of all cases of dementia are from cerebrovascular disease*)
CVD cerebrovascular disease
Describe phase 1 of the cardiac cycle
Cardiac Cycle: Phase 1 Atrial contraction Initiated by the P wave Causes the a-wave on the LAP tracing Normally accounts for 10% of ventricular filling... high heart rates as much as 40% b/c less time for passive filling After contraction the LVEDV is maximal (120ml) S4 is caused by vibration of a stiff ventricle during atrial contraction A fib w/o atrial kick can you have an S4? NO you cannot by definition, no atrial contraction vs a stiff ventricle because there is no atrial contraction
What is negative remodeling?
Constrictive, does narrow the lumen, thick fibrous cap more stable causes angina
Rupture prone
Coronary thin-cap fibroatheroma (TCFA). A TCFA containing a soft and destabilizing necrotic core devoid of supporting collagen and separated from the lumen only by a thin fibrous cap
What factors alter endothelial function?
DM Obesity High fat meal Look at these RF Improve it: Stop smoking, lower cholesterol, exercise, Mediterranean diet
What foams the necrotic core?
Death of foam cells, then the thin fibrous cap is d/t death of the smooth muscle
How do you see CAD on ultra sound?
Distance between the lumen-intima interface to media-adventitia interface. Thicker = disease. carotid intima media thickness
What causes atherosclerotic plaques?
Dyslipidemia oxidation of LDL Endothelial dysfunction Inflammatory and immunologic factors Plaque rupture and thrombosis
RF of ASCVD
Elevated uric acid level Psychosocial stress External stressors Reactions to stress (personality) Anxiety Sleep disturbances Elevated plasma homocysteine
Atheroma or Atheromatous plaque What does it look like
Fatty streak: Yellow things cholesterol Macrophages coming in to consume it T cells and collagen Fibrous cap forms over it which is smooth muscle The medium is down under the dotted line
Accumulating lipids and extracellular deposition Can be seen as early as childhood They then turn into plaques and lead to thrombotic occlusions later in life
Fatty streaks, the first sign of ASCVD
What is the positive remodeling phase of the plaque?
Growth of atheroma outwards (preserves the lumen) Vessel size increases Expansion of plaque and external elastic membrane UNSTABLE PLAQUE
What do you see in a mature plaque
Hemosiderin RBC break down, fibrin clot Calcium: slow erosion prone event they calcify Burden of calcification = burden of atherosclerosis
d/t proteins leaking into vessel walls Causes homogenous and eosinophilic arteriolar wall thickening with a narrow vessel lumen Associated w. HTN (high pressure forces proteins into the vessel walls) DM (glycosylation of BM makes vessel wall leaky)
Hyaline arteriolosclerosis Kidneys: Arteriolonephrosclerosis Lumen narrowed, thickened w/ pink hyaline
How does a plaque rupture
Increased inflammation -> infiltration with macrophages, activated T cells, DCs, mast cells AND reduced thickness of fibrous cap, increased neovascularity at plaque rupture. Matrix metalloproteinases and cysteine proteinases at site of rupture Cell death as trigger of rupture? "A continuous buildup of cytotoxic lipids in the plaque tissue activates a vicious process of cell death, inflammation, and degradation of the fibrous tissue resulting in weakening of the fibrous cap and plaque rupture."
What do you call the phase Between S1 and the ejection click? 2. Is the ejection click a typical heart sound? 3. What do you call the phase between S2 and the OS? 4. What does OS stand for? 5. Which valve is involved in the OS typically?
Isovolemic contraction No - usually do NOT hear valves open Isovolemic relaxation Opening Snap Mitral (RHD)
In what order are vessels affected in atherosclerosis?
Lower abdominal aorta Coronary arteries Popliteal arteries Internal carotid Circle of willis
What happens when the smooth muscle cells migrate through the internal elastic membrane and go into the expanding intima?
Make the ECM and are stimulated by cytokines from the macrophages Make the fibrous plaque/cap over the growing fatty streak Fibrofatty lesion: fibrous with fatty streak Supposed to stabilize the plaque so it doesn't become thrombotic: Smooth muscle dies, the fibrous plaque becomes thin
How do microthrombi form?
Microscopic breaks in endothelium Microthrombi w/ platelet exposed to BM Platelets then promote fibrosis Thrombin makes fibirn then we get SM migration and proliferation Then clot propegates occlusion happens they may have chronic problems, no issues until 70-80% blockage If acute and complete obstruction, and no collaterals, can be devastating. Acute syndromes from rupture usually occur when <50% of lumen is narrowed to start with.
Despite increases in longevity and decreases in age-specific death rates from CVD, CHD, and stroke since 1975 , CVD and its related complications remain highly prevalent and expensive to treat. Why is mortality down?
More people living with it
Involves the internal elastic membrane of the BV (media not intima) Calcification of the walls of muscular arteries Typically in 50+ pt Not usually significant b/c the lumen is not obstructed
Mönckeberg medial sclerosis
What are risk equivalents of CHD?
Non-coronary atherosclerosis DM CKD *Noncoronary atherosclerotic arterial disease includes patients with carotid artery disease, peripheral artery disease, or abdominal aortic aneurysm. Patients with any form of noncoronary atherosclerotic arterial disease have a 10-year risk of developing CHD that exceeds 20 percent.
Prevalence increases progressively with age, beginning after age 40 Sx: Intermittent claudication, walking impairment, presence of non-healing wounds; can present with buttock, hip, thigh, calf, or foot pain, alone or in combination. Buttock and hip: Aorto-iliac disease Thigh: Aorto-iliac or common femoral artery Upper two-thirds of the calf: Superficial femoral artery Lower one-third of the calf: Popliteal artery Foot claudication: Tibial or peroneal artery
PAD
intermittent claudication and critical limb ischemia
PAD/PVD Peripheral arterial/vascular disease
Apolipoprotein B containing lipoproteins of small dense LDL Collect in the intima and ECM where it binds Negative LDL interact w. positive intima proteoglycans Oxidative modifcations occur
Pathophysiology of ASCVD
What would positive look like in a cross section
Positive remodeling the external elastic membrane expands
The five leading modifiable risk factors (hypercholesterolemia, diabetes, hypertension, obesity, and smoking) are estimated to be responsible for > 50% of cardiovascular mortality. What is important about border line RFS?
Pts may only have borderline numebrs but 8% of CHD is in ppl w. borderline
Oxidized LDL depost in the endothelium Macrophages eat them Become foam cells Then what happens
Removal of lipid from macrophages is possible Monocytes, HDL cholesterol, apoptosis of macrophages Amount of lipid accumulating >> lipid being removed -> atheroma
What is the difference b/t the smoldering vs rupture prone
Smoldering: may have collaterals over time and not die Someone with like 50% with the thin cap and then boom clots they're dead, no collaterals there to help
focal neurologic symptoms that are sudden in onset and referable to the carotid artery distribution within the previous four to six months. TIAs Episodes of transient monocular blindness (Amaurosis fugax) Minor (non-disabling) ischemic strokes. Almost always come from the Internal carotid artery, where plaque builds just distal to the bifurcation of the CCA.
Symptomatic carotid disease
What do you see in erosion prone
Thick fibrous cap Thrombosis not caused by plaque rupture. Coronary artery containing a nonruptured plaque with mural thrombosis (Thr), so-called plaque erosion. The endothelium between the plaque and the thrombus is missing, but no other morphologic features characterize this type of thrombosed plaques and their vulnerable precursors. The plaque is rich in smooth muscle cells (smc), but not macrophages (mac), just beneath the thrombus.
Wide split RBBB Pulmonic stenosis Fixed split ASD Paradoxical splitting LBBB Aortic stenosis
Top: expiration split and now wider: why wider split to begin with? Pulmonary valve stenosis right bundle branch block can also slow the R ventricle Middle: fixed split S2 = ASD atrial septal defect Bottom: paradoxical splitting: pulmonic closed before the aortic: aortic valve stenosis or LBBB
What can happen with PAD
gangrene, necrosis etc
Things that cause alterations in circulating blood leads to issues especially when there is a vulnerable vessel leading to a state of hypercoaguability and hypofibrinolysis
hyperglycemia increased concentrations of LDL cholesterol tissue factor fibrinogen von Willebrand factor coagulation factor VII platelet microparticles
Fatty Streak (intimal xanthoma) Fibrous/fibromuscular Cap Intimal thickening Vasa vasorum Fibrous plaque Necrotic, lipid-rich core (fibroatheroma) Remodeling Thrombosis
plaques of atherosclerosis
Cardiovascular outcome is usually determined by the combination of multiple co-existing risk factors, rather than high levels of a single factor. How do reduce mortality?
prevention This graph shows the importance of the multiple combined RF
The fibrous cap is between the necrotic core and the lumen it is thin and can rupture This is a what
thin-cap fibroatheroma (TCFA
Nearly 1/2 of all middle-aged men and 1/3 of middle-aged women in the US will develop some manifestation of CHD in their lifetime. When does the risk increase
with age About 630,000 Americans die from heart disease each year—that's 1 in every 4 deaths.
When race, gender etc are accounted for, the risk of CVD decreases when
with lowered RF
CHD accounts for approximately how many cases of CVD?
1/3-1/2
What do we see on abdominal aortic aneurysm
Any reduction in intestinal blood flow: arterial occlusion (embolic or thrombotic), venous occlusion, or vasoconstriction Location: If small intestine = Mesenteric Ischemia If large intestine = Colonic Ischemia Acute (60-70% cases) or chronic Presentation: Acute - "abdominal pain out of proportion to the physical examination" If acute colonic ischemia, also have bloody diarrhea Chronic - pain after eating, less intense Abdominal aorta below renal arteries, aorta should not be huge like this one it should be thin and narrow, this is ectatic
abdominal aortic aneurysm (AAA) >> thoracic aorta extension to mesenteric ischemia and renal artery ASVD.
Aortic atherosclerosis
Hardening of the arteries General term for arterial wall thickening and loss of elasticity
Arteriosclerosis
What makes a plaque vulnerable for rupture?
Associated features include big plaque size, expansive (+) remodeling mitigating luminal obstruction (mild stenosis by angiography), neovascularization (angiogenesis), plaque hemorrhage, adventitial inflammation, and a spotty pattern of calcifications
Most frequent and clinically important pattern Involves the intima of large and moderate sized arterial walls
Atherosclerosis
patients over the age of 45 years usually involves the aortic orifice or the proximal main renal artery common in patients with diffuse atherosclerosis, can occur as an isolated renal lesion.
Atherosclerosis
Chronic inflammatory response d/t accumulation of lipids in arterial wall Causes multifocal intimal plaques over years and causes obstruction of blood flow Large and moderate sized arteries Elastic: aorta, carotid, iliac Muscular: coronary, popliteal Smoldering inflammation, heterogenous plaques, happen and low endothelial shear stress
Atherosclerosis Predilection sites are those that are characterized by low and oscillatory endothelial shear stress (bifurcations, inner wall of curvatures) and preexisting intimal thickenings
How does atheroslcerosis develop?
Atherosclerosis is responsible for almost all cases of coronary heart disease (CHD). This process is insidious, and begins with fatty streaks that are first seen in adolescence; these lesions progress into plaques in early adulthood, and culminate in thrombotic occlusions and coronary events typically seen in middle age and later life. These events can occur earlier in some of the more aggressive inherited dyslipidemias.
What is the most common congenital heart disease? What is the genetic form of transmission of this disease? Should first degree relatives be screened and if so, how? What is the second most common CHD? Transition to ACHD care should begin at what age?
Bicuspid AV Autosomal dominant; screen 1st degree relatives Yes - Echocardiogram VSD Age 12
Who has the highest and lowest CHD risk Member: Heart disease kills more than cancer
Blacks have the highest mortality male and female Lowest for CHD = Asian then American indians
generally used to refer to the pathologic process affecting the coronary arteries (usually atherosclerosis). It is sometimes used synonymously with CHD.
CAD coronary artery disease
includes the diagnoses of angina pectoris, myocardial infarction, silent myocardial ischemia, and CHD mortality that result from coronary artery disease.
CHD coronary heart disease
pathologic process (usually atherosclerosis) affecting the entire arterial circulation, not just the coronary arteries. Stroke, transient ischemic attacks, angina, myocardial infarction, mesenteric ischemia, claudication, and critical limb ischemia are manifestations
CVD cardio vascular disease
What does CAN-D stand for? What are the characteristics of CAN? What are 3 factors that help the body to Prevent orthostatic hypotension? What does POTS stand for?
Cardiac Autonomic Neuropathy in Diabetes 2. Heart rate variability Resting tachycardia (Not uncommon to have resting rates 100-130) Exercise intolerance Abnormal blood pressure regulation Orthostatic hypotension Healthy heart (increasing HR), vessels able to constrict, and adequate fluid in the blood vessels (hydration) Postural Orthostatic Tachycardic Syndrome
key role in initiation, progression, and destabilization of atherosclerotic plaques Variable function: Beneficial scavenger function - cleaning up intima for toxic lipid-rich waste products Or Destructive function - accelerate development of a destabilizing necrotic core and a rupture-prone fibrous cap
Foam cells
Hyperplasia of smooth muscle in the wall occurs in severe HTN Vessels show concentric laminated "onion-skin" thickened walls with lumen narrowing Can cause luminal obliteration
Hyperplastic arteriolosclerosis Hyperplasia = increase in the amount of tissue due to cell proliferation; physiological response to a specific stimulus Histologically, hypertension is associated with thickening of arterial walls caused by hyaline deposits and, in severe cases, by proliferation of smooth muscle cells and reduplication of basement membranes. Hyperplastic: hyperplasia of the smooth muscle of the wall Severe hypertension
What labs would we check when looking at ASCVD
LABS: CBC (esp HGB) Creatinine and electrolytes FBS and HGBA1C Urinalysis ECG Lipid panel (TC, TG, HDL, LDL, non-HDL) Liver enzymes CBC: why hemoglobin? High they can have sludge, or hemoglobin low they have poor oxygen carrying capacity Creatine: kidney disease FBS and A1 DM Urinalysis kidneys ECG
What casues cerebrovascular disease? Symptoms involve loss of neurological function in one or more regions determined by the section of cerebral or cerebellar tissue affected. If damage is temporary, "TIA"; if permanent, "stroke" or CVA.
Large vessel atherothrombotic Small vessel (lacunar) occlusion Cardio-aortic embolic Intracerebral hemorrhage Other (including cerebral mass, or dissections)Large vessel atherothrombotic Small vessel (lacunar) occlusion Cardio-aortic embolic Intracerebral hemorrhage Other (including cerebral mass, or dissections) Large vessel atherothrombotic Small vessel (lacunar) occlusion Cardio-aortic embolic Intracerebral hemorrhage Other (including cerebral mass, or dissections)
What would negative look like in a cross section
Negative the external elastic membrane gets smaller, thickening is internal not external
What is an erosion prone vulnerable plaque
No plaque rupture (or fibrous cap disruption) is seen. Abundance of smooth muscle cells and proteoglycan matrix and absence of surface endothelium (apoptotic loss) Without a prominent lipid core 25-40% of cases of sudden cardiac death In general, eroded plaques with thrombosis are scarcely calcified, rarely associated with expansive remodeling, and only sparsely inflamed
What are the 4 abnormalities in Tetralogy of Fallot?
RVOT obstruction Over-riding aorta VSD Right ventricular hypertrophy
Copper wiring and AV nicking of the fundus Diameter of the arterioles reduced and color appears less saturated
Retinal Arteriolosclerosis - in hypertension
What happens as total cholesterol goes up?
Risk of CVD increases
Rupture vs erosion prone plaques
Rupture prone: huge necrotic lipid core, fibrous cap is a tiny little thing Below: erosion prone: lipid core is tiny, cap is bigger than the core, less necrotic Can happen in the same pt close to each other
again what do you see in rupture prone
Ruptured coronary plaque with thrombosis. The thin cap is heavily inflamed, whereas the remainder of the plaque is not. Macrophages (asterisk) cluster in the cap next to the rupture site. The majority of the plaque consists of acellular lipid-rich core and hypocellular fibrosis and lipid pools.
Differentiate stenotic and ectatic
Stenotic/Occlusive Narrowing of a vessel Ectatic/Aneurysmal Distension or dilation of a vessel
How do atherosclerotic plaques progress?
Thickening -> fatty streak -> fibrous cap (D) NC = necrotic core and the cap is really thinning out Busts: now the material is available to the blood stream, platelets will clot (it is very prothrombotic) Narrowed vessel, necrotic core, thin cap, busted and now the platelets clot and the BV is occluded = MI/STROKE/PVD
Name one example of a congenital heart disease in each of the 4 categories.
Volume overload: ASD, VSD, PDA, AVSD Pressure overload: PS, AS, Coarctation Decreased PBF: TOF, Tricuspid atresia Increased PBF: TGA, HLHS, TAPVR, Truncus Acyanotic L to R extra volume coming over Increased pressure w/o deoxygenation: still oxygenating but a ton of pressure Cyanotic: decreased pulmonary blood flow Increased PBF increased pulmonary blood flow: no 180 = transposition
Symptomatic atherosclerotic disease most often involves the arteries supplying the heart, brain,
kidneys, and lower extremities. In descending order, the most extensively involved vessels are the lower abdominal aorta, the coronary arteries, the popliteal arteries, the internal carotid arteries, and the vessels of the circle of Willis. In humans, the abdominal aorta is typically involved to a much greater degree than the thoracic aorta. Vessels of the upper extremities are usually spared, as are the mesenteric and renal arteries, except at their ostia. Although most individuals tend to have a consistent degree of atherosclerotic burden in the affected vasculature, severity of disease in one arterial distribution does not always predict its severity in another.
What is the big deal with rupture vulnerable plaques?
~55-75% of symptomatic coronary thrombi are caused by plaque rupture (more in men than women). Prototype rupture-prone plaque: contains large and soft lipid-rich necrotic core covered by a thin and inflamed fibrous cap Contents of necrotic core of plaque are highly thrombogenic.
