Week 1 Pathology HTN PAD ischemic heart disease Flashcards
(153 cards)
1
Q
What is the importance and equation for MAP? what is the usual cause for an increase in MAP
A
All physiology in body goes toward maintaining MAP.
MAP= COxSVR
or estimated as MAP is about equal to DP+ .33 Pulse Pressure (SBP-DBP)
Usually an increase in MAP is by increased SVR but CO can also cause it
2
Q
LO: define HTN, define shock
A
MAP below 60 is shock, above 105= HTN
**HTN is = to 140/90mmHg (if either number is equal to or greater)
3
Q
LO: When is SBP and DBP measured in relation to the cardiac cycle?
A
SBP measures the maximum pressure of cardiac cycle at end of systole
DBP is minimum pressure right before systole begins
4
Q
LO: Recognize and describe the molecular, cellular, and tissue pathology of HTN
A
Molecular- HTN induces changes in endothelial walls, turns on MLCK etc to get proliferation of smooth muscle
In essential HTN get hyaline arteriolosclerosis- glassy pink scar think wall with thin artery lumen
In malignant HTN get hyperplastic arterosclerosis- more layers than hyaline, and little area for blood to flow through
Also fibrinoid necrosis- damage arterial wall and endothelium and leaks plasma that congeals and clots
5
Q
LO: List the clinical outcomes associated with chronic HTN
A
There are two major complication from HTN: increased after load, arterial damage
6
Q
What are the consequences of increased after load from HTN?
A
Increased after load (end load against which the heart contracts to eject blood): heart must generate more pump, more contractility leading to systolic dysfunction, if over time the heart can’t keep up increased contractility and systolic dysfunction with LVH and diastolic dysfunction (can’t fill or relax properly) lead to heart failure.
Also the myocardium needs more O2 to keep up and can lead to myocardial ischemia or MI
7
Q
What are the consequences of arterial damage from HTN? what are the effects in coronary, cerebral, aorta vessels (larger vessels)
A
HTN increases pressure in endothelium to increase smooth muscle activity and creates damage- atheroscelosis: deposits in the vessels, can’t get as much blood into the vessels but need more
In coronary vessels this decreases myocardial O2 leading to myocardial ischemia and infarction
In cerebral vessels it can lead to ischemic stroke (clogging of vessels)
In aorta can lead to aneurysm and dissection
Large vessels clog up
8
Q
What are the effects HTN has in the smaller vessels?
what is effect in cerebral, renal, ophthalmic vessels
A
In smaller vessels HTN leads to weakened vessel walls
could affect aorta, small vessels break
in cerebral vessels in causes a hemmorhagic stroke (breaking of vessels)
in renal vessles in can lead to nephrosclerosis and renal failure
in opthalamic vessels it can lead to retionopathy
9
Q
What are examples of things that can raise BP other than increasing SVR
A
hyperthyoidism, secondary polycythemia, beriberi
10
Q
What are some symptoms of HTN?
A
headache, physical exam cardiac findings, vision changes, frothy urine
if left untreated HTN can reduce 15 years of life
11
Q
What are examples of things that can raise BP other than increasing SVR
A
hyperthyoidism, secondary polycythemia, beriberi, obstructive sleep apnea (baroreceptor sensitivity changes, RAA system effects endothelial dysfunction)
12
Q
What is the difference in primary and secondary HTN
A
Primary- don’t know what is causing it, genetics or something we don’t know yet
Secondary- something else in body is causing it and we know about it
13
Q
What are the signs, symptoms and effects of coarctation of aorta? What is a typical patient presenting with this look like?
A
A pinched aorta near aortic arch, occurs in younger patients M>F
Signs: Aterial HTN in UE with low BP in LE!!
Sign of 3 on CXR- literally looks like a 3 in aorta. creates resistance to flow
A cause of secondary HTN
14
Q
What are the effects and signs of salt hypersenstativty? who is more like to be effected?
A
salt sensativity is a common cause of secondary HTN in lots of people but blacks are more likely to have it
thought to be a MLCK or rho kinase mediated
kidneys can’t control fluids properly
15
Q
What is renal artery stenosis and its effects on HTN? What is the cause behind it?
A
Renal artery stenosis is the narrowing of one of the renal arteries, most often caused by atherosclerosis or fibromuscular dysplasia. This narrowing of the renal artery can impede blood flow to the target kidney, resulting in renovascular hypertension – a secondary type of high blood pressure. Possible complications of renal artery stenosis are chronic kidney disease and coronary artery disease.[1]
16
Q
What types of renal artery stenosis are there and who is effected
A
Renal artery stenosis is most often caused by atherosclerosis which causes the renal arteries to harden and narrow due to the build-up of plaque. This accounts for about 90% of cases with most of the rest due to fibromuscular dysplasia.[4]Fibromuscular dysplasia is the predominant cause in young patients, usually females under 40 years of age.[5]
In fibromuscular dysplasia see beads on a string appearance on angiogram
17
Q
What types of renal artery stenosis are there and who is effected
A
Renal artery stenosis is most often caused by atherosclerosis which causes the renal arteries to harden and narrow due to the build-up of plaque. This accounts for about 90% of cases with most of the rest due to fibromuscular dysplasia.[4]Fibromuscular dysplasia is the predominant cause in young patients, usually females under 40 years of age.[5]
In fibromuscular dysplasia see beads on a string appearance on angiogram. It is a increase in endothelial and smooth muscle growth of renal artery, kidney problems, kidney can’t measure blood properly after it
18
Q
what is glomerulonephritis and what is its effect?
A
It is an inflammation of the glomerulus- the filtering mechanism of the kidney, can’t excrete salt so excess water is retained and blood volume is expanded- SVR increases increasing BP
cause of secondary HTN
19
Q
How can a shift in the RAAS axis after BP and lead to HTN
A
RAAS= renin angiotensin aldosterone system
angiotensinogen made by liver, increased with estrogen so in 1% of girls on OC pills can increase BP
and some people just make more angiotensinogen leading to secondary HTN
Increased aldosterone increases salt retention, increase SVR increase BP
Increased Angiotensin II vasoconstricts to increase BP
20
Q
What are the 3 types of mineralocorticoid excess and how do they lead to HTN?
A
Mineralocorticoids are secreted from adrenal medulla glomerulosa and regulate salt in body
1) Conn syndrome- tumor in zona glomerulosa that releases excess aldosterone, sodium retention, SVR increases and increase BP
2) DOC hypersecretion- increased ACTH for any reason, hyper secrete deoxycortisone, retain sodium, SVR increase
3) glucocorticoid remediable aldosteronism- genes encoding aldosterone synthase and 11beta hydroxylase are linked in embryogenesis. ACTH causes hyper secretion of glucocorticoids and aldosterone, seen with severe HTN early in life, treated with glucocorticoids to suppress ACTH release - need to do properly or Cushings syndrome could occur with tx
21
Q
What are two classic examples of DOC hyper secretion in pediatric patients
A
17 alpha hydroxylase deficiency, congential adrenal hyperplasia
22
Q
What is another way to get mineralocorticoid excess via diet
A
many herbal supplements like licorice increase aldosterone when metabolized leading to secondary HTN
23
Q
What are three main effects of excess glucocorticoids?
A
Glucocorticoids are made in zona fasiculta of adrenal medulla, regulate blood sugar
3 effects of excess glucocorticoids are:
cushings syndrome, vascular effects of glucocorticoids, overwhelming of mineralocorticoid receptors
24
Q
Describe cause, effects, signs of Cushing’s syndrome
A
Cushing’s syndrome is due to excess glucocorticoids for any reason, most common reason is oral corticosteroids
From pituitary= Cushing disease
Glucocorticoids increase angiotensingoen release and increase HTN (from cortisol)
Presentation: moon face, high BP, red straie, central adiposity, thin arms and legs, red cheeks, buffalo hump, bruising, thin skin
25
How can excess catecholamines increase BP? what are symptoms and what is a tumor causing this called?
Increase in NE from adrenal medulla chromafin cells increases SBP and DBP
usually causes sustaine HTN but 15% of cases are episodic
Symptoms inculde palpitations, headache, glycosuria (glycogen in urine) and extreme SBP
Tumors causing excess catecholamines is called pheochromocytoma- too much NE released from medulla chromaffin cells
26
What is the most common mechanisms behind essential (primary) HTN? what are the main thoughts on how it is causes
Primary HTN- no identifiable cause
Natriuretic hormones- normally dump sodium into urine, there is a NP in blood called ouabain that causes Na to be lost in urine but Ca accumulates causing vascular smooth muscle contraction- digitalis like NP
Neurologic disorders- interruption of afferent input raises BP, evidence that chronic pressure on RVLM (pressor center of medulla) can cause HTN
NO- inhibit NO synthase will decrease NO and raise BP, can't relax endothelium as well
Metabolic syndrome- most important-
27
What is the most common mechanisms behind essential (primary) HTN? what are the main thoughts on how it is causes
Primary HTN- no identifiable cause
Natriuretic hormones- normally dump sodium into urine, there is a NP in blood called ouabain that causes Na to be lost in urine but Ca accumulates causing vascular smooth muscle contraction- digitalis like NP
Neurologic disorders- interruption of afferent input raises BP, evidence that chronic pressure on RVLM (pressor center of medulla) can cause HTN
NO- inhibit NO synthase will decrease NO and raise BP, can't relax endothelium as well
Metabolic syndrome- most important- distict entity of insulin resistance, hyper insulinemia, HLD, and obesity the characteristics. Tends to be in patients with essential HTN. Too much insulin and can't do anything with it but it may increases SNS activity, insulin may vasodilate
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1. Outline the risk factors and clinical presentation of PAD
Risk factorsSmoking- twice as likely to develop PAD as CAD
DM
HTN
Dyslipidemia
Atherosclerosis is a systemic illness, if have it one bed then good chance it is in lots of beds
Presentation
- Many are asymptomatic
- Many people get claudication, muscle cramp or pain with exertion bc can't match O2 demand with supply bc stenosis, relieved with rest and reproducible
- Critical limb ischemia- pain at rest, ulcers, gangrene from worse stenosis
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2. Understand the principles of ABI and Non-Invasive Flow Studies in diagnosing PAD
ABI= ankle-brachial index
Put BP cuffs on arms and ankles, BP should be about same in both beds, PAD affects LE more so get ration, if lower in ankles then lower ratio and decrease in blood flow to LE= PAD, very specific and sensitive
Segmental Pressures- measure brachial, thigh, calf, ankle pressures side to side and compare. A drop in 20mmHg going down or side to side is suggestive of PAD in that bed
or barely covered but can look at PVR- pulse volume recording in same spots. Plethysmography
30
3. Describe evidence-based therapy for PAD
Three prong approach to PAD tx
1) risk factor modification- smoking cessation, manage HTN and DM, high intensity statin
2) anti-platelet therapy- prevents MI CAD or strokes, no need to add clopidogrel with ASA, just ASA is fine
3) exercise program- promotes angiogenesis to make by pass circuits, significantly reduces claudication from PAD
31
4. Define acute aortic syndromes
Aortic dissection- tear in intima of aorta allowing access of blood into the media and formation of true and false lumens
Intramural hematoma- collection of blood in wall of aorta btn intima and media without an entry tear, "like a bruise"
Penetrating aortic ulcer- inflamed atherosclerotic plaque growth leading to a crater like outputting of aortic wall
Rapid aneurysm expansion- accelerated dilation of aorta that is associated with weakening of the vessel wall and impending rupture, if grows over 0.5cm per year is indication for fix
Aortic rupture- tear through entire wall of aorta causing hemorrhage into extravascular space, emergency or die
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5. Identify risk factors for aortic dissection and rupture
"What are the genetic vs acquired risk factors for acute aortic syndromes"
Acquired- HTN, cocaine/amphetamines, syphillis
Genetic- marfans (FBN1), EDS(type IIIcollagen), BAV (bicuspid aortic valve) is most common, aortic coarctation, LDS (TGFBR)
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6. Describe the approach to diagnosis of acute aortic syndromes
Hx, CTA or MRI, look at each card for the diseases
PAD dx with NIFS
34
What is the main difference btn TAA and AAA besides location?
Most AAA are atherosclerotic in nature. Most TAA are degenerative- with time and athersclerotic risk factors you can develop it but other factors lead to degeneration.
Degeneration is due to breakdown of ECM proteins and mechanical forces leading to cystic medial necrosis.
35
What is the main difference btn TAA and AAA besides location?
Most AAA are atherosclerotic in nature. Most TAA are degenerative- with time and atherosclerotic risk factors you can develop it but other factors lead to degeneration.
Degeneration is due to breakdown of ECM proteins and mechanical forces leading to cystic medial necrosis.
36
What are the types, causes, and risk factors for TAA?
Two types: descending (distal to lig arteriosum), most related to atherosclerosis
Ascending- proximal to lig arteriosum, related to bicuspid aortic valve (aortopathy- a genetic issue), connective tissue diseases (marfan, EDS, LDS), tertiary syphillis- causes inflammation leading to dilation
37
What are the genetic risk factors leading to TAA? What genes should we know
proximal/ascending TAA or more related to genetics.
Genetic factors: bicuspid aortic valve (aortopathy)= a genetic issue disrupting TAA and ECM proteins
Connetive tissue disorders: Marfan (FBN1 gene), Ehlers Danlos syndrome (type III collagen), Loeys-Dietz syndrome (autosomal dominant TGFBR mutation)
would want to check family members for genes too
38
Describe cystic medial necrosis. What is it associated with?
Cystic medial necrosis- mucoid material accumulation in media of aorta
associated with TAA (not AAA)
39
What are the types, causes, and risk factors for TAA?
Two types: descending (distal to lig arteriosum), most related to atherosclerosis
Ascending- proximal to lig arteriosum, related to bicuspid aortic valve (aortopathy- a genetic issue), connective tissue diseases (marfan, EDS, LDS), tertiary syphillis- causes inflammation leading to dilation
40
What size of aortic aneurysm is associated with increased risk of rupture? when do you try to treat?
Aortic size above 6cm is massive rise in risk for rupture or complicaitons. Try to catch at 5cm and fix.
41
Describe Marfan syndrome causes, inheritance, and presenation and related diseases
Marfans is a FBN1 mutation (fibrilin deficiency), accumulation of TGFb, AD inheritance
Presentation: Tall, long wingspan, ectopic lens, joint hyper mobility, Pecuts, scoliosis, spontaneous pneumothorax
Related to EDS (col3A) and LDS (TGFBR1/2)
42
What is an aortic dissection? and its pathophysiology
A tear in aortic intima from wall stress or degeneration of aortic media (non traumatic aortic dissection)
Blood passes into the aortic media separating it from media to create false lumen, propogates distal and proximal to tear, multiple tears possible
43
What are the types of aortic dissection? Where do they occur? Which is more serious? what arteries are involved?
Type A- usually occurs in right lateral wall of ascending aorta a few cm from aortic valve, usually spirals, can go in either direction, can involve RCA which could lead to R heart ischemia or into aortic annulus to get regurg
So Type A is more serious
Type B- beyond ligament arteriosum in descending aorta
44
How does aortic dissections present and what is diagnostic techniques
Presents with abrupt onset of severe chest pain radiating to the back, tearing sensation in chest, unequal b/l BP not a reliable dx tool
Negative D dimer rules out dissection
Rapid dx is with imaging and critical: CTA or TEE or MRI (slower)
45
What is an aortic intramural hematoma? What is possible mechanism? And how is it best dx?
Collection of blood in the aortic media without obvious dissection flap or entry tear
Could be from spontaneous hemmorhage from vaso versorum but not sure
Best dx with CTA with non contrast and contrast for comparison
Fresh hematoma suggests IMH (hemorrhage)
Tx: observe, don't usually dissect or rupture
46
What is the common approach to acute aortic dissections and then how do you treat the different types of dissections specifically? What do you give and what do you avoid
First want to decrease stress by decrease BP and HR (Iabetalol, nitroprusside) to prevent propagation of dissection- goal to get SBP 100-120 and HR<60bpm.
And then avoid vasodilators in dissections (hydralzine and nitroglycerin) bc don't want blood to pool on venous side
Type A: ascending, surgical emergency d/t risk of complications (stroke, MI, tamponade- bleeding into pericardium, aortic insufficiency)
Type B: in descending aorta, treat risk factors and prevent propagation medically, surgery considered with persistent pain from ongoing dissection, involvement of end organ vessels (ie. renal arteries), and extent of dissection, rupture, expansion, malperfusion, or marfans
47
How do you treat chronic dissections in both types? When to send to sx?
Type A: in acute all patients go but with chronic with dimension greater than 5.5cm, Marfan with greater than 4cm, increase in dimension > 1cm/year, severe aortic regard, symptoms of expansion or compression
Type B: max dimension 6cm or greater, increase in 1cm/year or greater, symptoms of expansion or compression
48
How can you get an aortic rupture? What is prognosis
From trauma, aneursym or dissection can predispose
Usually fatal
49
What are effects of HTN on the heart pathologically?
HTN can lead to cardiac hypertrophy- a compensatory increase in mass of LV.
50
1. Know the effect of systemic HTN on the heart including gross and microscopic findings.
HTN leads to cardiac hypertrophy via increased afterload on ventricle- typically concentric hypertrophy, a thick wall and small chamber volume. When limits of compensation are reached then may get cardiac decompensation with cardiac dilation. hypertrophy can lead to ventricular arythrmias and sudden cardiac death. An increase in preload leads to eccentric LVH.
Hypertrophic cells have an increased diameter with enlarged hyperchromatic and rectangular boxcar nuclei
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2. Know the effects of HTN on small arteries (hyaline and hyperplastic arteriolosclerosis) and their associations and clinical consequences.
In small arterioles HTN causes arteriosclerosis, hardening of small arteries. This leads to hyaline arteriosclerosis first- hyaline thickening with lumen narrowing from plasma protein leakage across injured endothelial cells and increased smooth muscle cell matrix synthesis in response to chronic hemodynamic stress. Hyaline= glassy, scarred appearence. In kidney lose renal parenchyma and is called benign nephrosclerosis. Hyaline changes also in elderly and diabetic microangopathy
2nd is hyperplastic arteriosclerosis- in malignant HTN, onion skin leasion, with concentric laminated thickening of walls and lumen narrowing. Laminations= smooth muscle cells with reduplicated thick basement membranes. Sometimes accompanied with fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis) esp in kidney
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3. Know the gross and microscopic appearance of benign and malignant nephrosclerosis, and their associations with hypertension
Benign nephrosclerosis- HTN leads to vascular changes, hyaline arteriosclerosis, medial and intimal thickening- leads to ISCHEMIC damage- glomerulosclerosis and chronic tubulointerstitial injury leads to cortical scarring and shrinking of kidney grossly, kideny with surface granulations (grain leather) with subscapular microscopic scars with sclerosed glomeruli and tubular drop outs
Malignant nephrosclerosis- malignant or accelorated HTN leads to VASCULAR DAMAGE (fibrinoid necrosis of arterioles and small arteries, hyperplastic arterioscelerosis)- ischemic kidneys with rupture of arterioles/capillaries- small pinpoint petechiae hemorrhages on kidney= flea bitten appearance on kidney
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4. Know the effects of HTN on the CNS and be able to recognize and describe gross and microscopic findings (Lacunar infarcts, Slit hemorrhages, intracerebral hemorrhage, hypertensive encephalopathy)
Lacunar infarcts- lake like spaces less than 15mm. Cerebral vessels develop arteriolar sclerosis and may become occluded leading to small cavity infarcts known as lacunae. Microscopically: see tissue loss, lipid laden macrophage (swallow debris from necrosis), surrounding gliosis (glial cells react and proliferate)
Slit hemmorhages- d/t rupture of small-caliber penetrating vessels and the development of small slit hemorrhages, with time they resorb and leave behind a slit cavity surrounded by brownish discoloration. Mic: focal tissue destruction, pigment laden macrophages, gliosis
brain parechymal hemorrhage- HTN is the most common underlying cause of primary brain parenchymal hemorrhage, arteriolar walls are weakened and vulnerable to rupture. HTN can lead to minute aneursyms (Charcot--Bouchard microaneursyms) which may rupture
Hypertensive encephalopathy- acute syndrome arising in pt with malignant HTN, characterized by: diffuse cerebral dysfunction -headaches, confusion, vomitting, convulsions, coma. Need to reduce the increased intracranial pressue. Autopsy show edematous brain with or without herniation. Petehiae and fibrinoid necrosis of arterioles in gray and white matter
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5. Know the effects of hypertension on the retina and be able to recognize and describe the findings.
Hypertensive retinopathy from HTN. Commonly associated with arteriosclerosis affects retinal microvasculature, light reflected from thickened walls has silver (total occlusion) or copper (some bloodflow) wire appearance. See cotton wool spots d/t axonal ischemic damage. Hemorrhages are common in retina and exudates frequently form a star around the macula (macular star). See AV nicking where arterioles cross veins. Optic head is edematous= blurry
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6. Define aortic dissection and know the pathogenesis with underlying risk factors
Aortic dissection- separation of aortic media by blood entering aortic media through an intimal tear
HTN is the major risk factor for aortic dissection. HTN leads to degen changes of aortic wall- weakened media- dissection.
Also occurs in CT disorders= Marfan, EDS, etc
Most frequent preexisting histo lesion is cystic medial degeneration. Inflammation is characteristically absent
Once a tear has occurred, blood flow under systemic pressure dissects through the media leading to progression of hematoma
56
Compare and contrast retina outcomes in malignant vs chronic HTN.
Severe malignant HTN with acute onset- burst small retinal vessels-
hemorrhages!, exudation of plasma lipids, areas of local infarction.
Papillidema!- swelling of optic disc with blurring of its margins, from high intracranial pressure when BP reaches malignant levels and regulation fails
Chronic HTN: VASOCONSTRICTION- results in arterial narrowing and medial hypertrophy thickens the vessel wall- AV nicks
With more severe chronic HTN arterial sclerosis is evident as an increased reflection of light through scope- copper or silver wire
NO PAPILLEDEMA
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1. Lipoprotein classes and their atherogenic properties
Pro-atherogenic= Chylomicrons, VLDL, Remnant lipoproteins (over 30nm) and LDL (20-22nm). ApoB is pro atherogenic- 90% of ApoB is LDL. ApoB is more indicative of risk than just measuring cholesterol.
Anti-atherogenic- ApoA=HDL (9-15nm)
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2. Primary and secondary causes of dyslipidemia
Primary= genetic
Two ones he wants us to know:
Type II familia hypercholsterolemia (defect in LDL receptor apoB100 or PCSK9), majority of genetic lipid defects are with LDL-R, consider if LDL greater than 190. Heterozygotes will have LDL above 190 and half have CV events before 50. Homozygotes have LDL 500-600 and very rare. CV events in twenties
Type IV familial hypertriglyceridemia- If triglycerides over 900 it is a genetic defect, can lead to pacreatitis which can be fatal
PE: xanthomas (cholesterol) or arcus senilus ( lipids) are deposits
Secondary= diet, lifestyle, medical conditions. is more common by far
Important one: drugs (corticosteroids, protease inhibitors for HIV, immunosuppresants)
Others: diet, inactivity, obesity, DM, metabolic syndrome, hypothyroidism, cholestatic liver disease, nephrotic syndrome
59
How does the body regulate cholesterol stores?
The liver makes cholesterol (VLDL) to bloodstream or gets rid or excess as bile to intestine to poop out. Intenstines can reabsorb bile in form of chylomicrons back to liver
60
4. Describe the classes of lipid-lowering therapies, their mechanisms of action, and their impact on lipid profile
1st line to lower cholesterol= statins
Statins- block HMG CoA reductase, a key enzyme in liver production of cholesterol, this makes liver produce more receptors to suck more LDL out of blood to increase its LDL levels and decrease blood levels, reduce LDL-C about 30-50%, less apoB=less CHD disease, NNT=25, provide benefit in pts with elevates CRP levels
Bile acid sequestrants- body can't resorb bile, decreases LDL-C, increase BA excretion and increase LDL receptors increase VLDL and LDL removal
Ezetimibe- blocks receptor that reputes BA back into circulation, decrease LDL by 10%
Nicotinic acid- niacin- reduces the amount of free FA out of adipose tissue and VLDL your liver is making, decreased FFA release with niacin, more HDL, less LDL, much less TG
Fibrates- lower triglycerides, same MOA as niacin, turn on PPAR, increase HDL, decrease TG and LDL
PCSK9 inhibitors- new, effective in lowering LDL, THEY WERE EMPHASIZED-
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5. Toxicities/side-effects of common lipid-lowering therapies
Statins- small number get elevated transaminase but not causing liver failure and reversible. increased myositis. REAL problem is with rhabdomyolysis- breakdown of muscle, low incidence but can be fatal
Drug interactions: broken down by CYP450-3A4 so grapefruit can increase simvastatin and lovastatin. Protease inhibitors can increase rosuvastatin (use atorvastatin), use pravastatin or rosuvastatin in all transplant patients, Interactions with fibrates
BA sequestrants- GI upset, decreased absorption fat soluble vitamins or rx
Ezetimibe- diarrhea
Niacin- flushing (better with NSAIDs or ASA), hyperglycemia, hyperuricemia (avoid in gout)
Fibrates- myopathy (increased with statin use), cholesterol gallstones, rhabdo with statins
PCSK9 inhibitors- PCSK9 is a cofactor for LDL receptor , when binds to LDLR it marks it for degradation, if inhibit with MAB that bind up all PCSK9, get more LDLR and less circulating LDL, reduces LDL by 60% on top of statin reduction, injections twice a month, very expensive now
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6. Understand the core principles of ATP-IV guidelines for primary and secondary prevention
Secondary- "highest dose of statin that they can tolerate" if previous MI= highest risk
primary- no previous event, if risk of CV event greater than 7.5% over 10 years should be on statin
63
What dietary adjustments can reduce LDL?
increasing dietary soluble fiber, soy protein, stanol esters
Mediterrean diet is as or adding these to diet reduce LDL and CRP equal to statins
64
What dietary adjustments can reduce LDL?
increasing dietary soluble fiber, soy protein, stanol esters
Mediterrean diet is as or adding these to diet reduce LDL and CRP equal to statins, reduces CV events by 70%
65
What should be avoided and what should be eaten in Mediterrean diet?
Eat: grains, rice, pasta, fruit/vegs, beans, legumes, nut, olive oil, cheese, yogurt
then fish poultry eggs
Avoid: sweet, red meats
66
What are some clinical presentations of atherosclerosis?
Range from -asymptomatic,
-stable or unstable angina (angina pectoris, supply demand mismatch to myocardium leading to ischemia)
Stable= exercise induced, dyspnea, nausea/vomiting Unstable= prolonged, at rest
-Acute MI- acute lost of blood flow to myocardium leading to cell injury, arrhythmias, or death
-stroke- loss of blood flow to the brain leading to injury and cell death
- Claudication- insufficient blood flow to muscles outside the myocardium leading to pain, typically in LE with walking
67
What impact does CVD have in terms of reduction of life expectancy and % deaths caused by it?
If eliminated CVD then life expectancy would increase by 7 years
Prob of birth leading to CVD death is 47% (the highest)
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What is the strongest risk factor for CVD?
Age, increases with age
69
How does atherosclerosis present in varying age groups histologically or at cell level?
Infants and children= foam cells
Young children= fatty streaks
Adolescents= fatty streaks, fibrous plaques
Adults= fatty streaks, fibrous plaques, thrombosis
70
What is the difference in arterosclerosis and atherosclerosis?
Arteriosclerosis- diffuse, age related intimal thickening, loss of elasticity, increase in Ca contact of arteries, results in hardening of arteries
Atherosclerosis- focal arterial disease, mainly involves aorta, coronary, cerebral, renal, iliac, femoral arteries, result of plaque formation
71
What theory Atherosclerosis seems to have most support
Monoclonal/proliferative hypothesis has had DNA studies show that as plaques mature they becomes definitively monoclonal, proliferative smooth muscle cells
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What are the risk factors for atherosclerosis
Env: smoking, high fat diet, inactivity
Genetics: Fhx, LDL, low HDL, HTN, DMII, homocystinuria, progeria syndromes
Other: age, gender (M>F?), inflammation
73
What role does inflammation play in atherosclerosis? How is it used to predict risk?
Serum hsCRP (inf marker) are associated with risk of CAD, can predict MI 6 years into future
Many inflammatory markers ass. with CAD are part of acute phase response (systemic, triggered by infection, causes inflammation and repair)
74
What inflammatory markers carry highest risk for MI?
CRP+TC:HDL> CRP> IL6> ICAM1> fibrinogen
75
What are key features of each layer of blood vessels?
Intima- single layer of endothelial cells
Media- Smooth muscle cells bound by elastic lamina on both sides
Adventitia- ECM: collagen, elastin, smooth muscle, fibrolblasts, and VASO VASOVARUM- small vessels that feed arteries, and nerves
76
What roles does endothelial cells play in regulation of arteries? Are endothelial cells in arteries permeable?
Endothelial cells in arteries regulate:
vessel tone, thrombosis, inflammation via NO
In most arteries tight junctions make endothelial layer impermeable, in kidney and spleen have fenestrations
77
What are the most potent vasodilators and contrictors? and what are the others?
Vasodilators: most potent- NO
PGI2
Vasoconstrictor: most potent- Endothelin 1 (ET)
PAF (platelet activating factor)
78
What does a dysfunctional endothelium indicate? How does it function and why?
It indicates repetitive transient or chronic decrease in NO levels that lead to progression of atherosclerosis
It indicates an inappropriate vasodilatory response to shear stress or Ach. vasoconstricts when it should dilate bc low levels of NO released from dysfunctional endothelium (high inflammatory state)
Caused by CV risk factors, fatty meals, is precursor to atherosclerosis
79
What is response seen in post Ach and post NTG in dysfunctional endothelium?
In dysfunctional endothelium Ach will vasoconstrict when it should dilate the endothelium
NTG works at the smooth muscle cells so will still dilate
80
What does dysfunctional endothelium predispose someone to?
Severe endothelium dysfunction increases risk of CV events in patients with mild CAD, without dysfunction there was little risk in these patients
81
What is a secondary effect of statins on endothelium that improves their function?
Statins improve eNOS function which gets NO into endothelial cells, improves statins effectiveness
NO Helps as a vasodilator, anti thrombotic, anti inflammator
82
What are some of NO properties and functions in the body?
It is a free radical, short half life, diffuses across cell membranes, reacts with superoxides metal and thiols, arginine + O2----NOSandNADPH---citruline+ NO
In endothelium smooth muscle and platelets it is a vasodilator/vasoprotector, can be a NT or cytotoxin elsewhere
83
What are the good and bad things about NO? Where is it produced?
Produced by endothelial cells mainly, also macrophages and neurons
Good: vasodilates, anti thrombotic, anti inflammator
Anti atherosclerotic: decreases proliferation of SMC, LDL oxidations, platlet/moncyte adhesion, SMC contraction
Bad: Too much causes shock, too little predisposes to athersclerosis. Mice with eNOS knockout= much more plaque buildup
84
How does NO increase relaxation and dilation? How is this action reversed?
NO works to activate guanylate cyclase, increasing cGMP, activating kinases that cause vasodilation or relaxing smooth muscle
Phosphodiesterase's break down cGMP to decrease smooth muscle relaxation/vasodilation
85
Describe the natural history of plaque formation in atherogenesis
1) Initial injury to endothelium
2) progressive lesion formation/ inflammation- when endothelium is injured LDL which is normally in the blood comes across the endothelial cells into injured intima, LDL gets oxidized, leukocytes bind to adhesion molecules and transverse the endothelial layer, absorb and oxidize LDL particles leading to intimal thickening
LDL cholesterol trapped in vessel wall
3) Foam cells formation- monocytes react to injury and come across endothelial cells via diapedesis and gobbles up oxidized LDL via scavenger receptors to becomes foam cells in intima
4) fibrous plaque development-Activated macrophages (from oxidized LDL) and endothelial release compounds that activate smooth muscle cells to proliferate and migrate to leave media to go to intima. There SMC form a fibrous cap over the fatty streak (endothelial layer facing lumen, cap just below endothelial cells, collagen with core of foam cells, cholesterol, necrotic debris core
5) advanced lesions and thrombosis- death of foam cells leaves mass of extracellular lipids and cell debris, SMC migrate (induced by interaction of macrophages and T cells forming cytokines and growth factors, stim by homocysteine and angiotensin II, intimal SMC secrete ECM creating fibrous cap)
Crack at plaque shoulder then flowing blood leads to clots- angina
86
Describe process of Monocytes entering vessel wall in atherosclerosis progression
1) rolling
2) activation- tissue damage releases chemokines like MCP1, MCP1 attract and activate monocytes, is an early marker to atherosclerosis. Cytokines call for new receptors on endothelium to be expressed like ICAM and integrins
3) Adhesion- endothelial cells and monocyte interactions increase, monocytes adhere tightly to endothelial cells via interns
4) diapedesis- monocytes migrate to endothelial cell junction, separate the junction, cross the endothelial cell barrier into vessel wall, now called macrophages
5) macrophages migrate to site of vessel wall inflammation, oxidized LDL activates macrophages and they ingest oxidized LDL, become foam cells- form fatty streaks
also macrophages release toxic compounds- cytokines and chemokines (more inflammation), GF, Radicals
87
What are foam cells?
Leukocytes and macrophages that continue to scavenge oxidized LDL and become distorted into foam cells in intima
88
Explain the characterization of plaque in the detail he wanted us to know. What is the vulnerable levels of plaque?
Stary classification characterizes atherosclerotic plaque morphology via I-VIII classes.
Stary I-II= edema in intima and fatty streaks starting (intima proliferation). See leukocytes with intracellular lipid inclusions, might be a 3 yo M with fatty streaks forming. No symptoms from fatty streaks
Stary III- Mature fatty streak in a 6yo M, progreesion of fatty streak and edema
Regression to normal is possible up to this point
Stary IV- VI= vulnerable plaque, form lipid core and thin fibrous plaque, regression from here leads to VII or VIII
IV- confluent extracellular lipid core formed, intima media thicken
V- fibromuscular tissue layers produced, classic vulnerable plaque, statin can make plaque more stable
VI- surface defect, hematoma, thrombosis, this and fibrosis can add to type V defect and lead to loss of lumen, can form complicated atheroma- recurrent plaque rupture and thrombosis with organzation of new overlying atheroma forming laminated atheroma
Stary VII- calcified atheroma- cholesterol clefts without lipid core, lumen occlusion but not going to rupture, see crystals in plaque
VIII- includes old intimal myofibroblastic reaction, won't rupture just a block
89
What characteristics of plaque makes them vulnerable to rupture? What factors trigger rupture?
Vulnerable plaques= soft core, thin cap, inflammation, endothelial erosion
Physiological triggers to rupture= shear stress (HTN, exercise), SNS,
inflammation-activated macrophages destabilize the plaque- secrete cytokes, activate SMC, release matrix metalloproetinases 2/9 that break down wall of vessel from inside leading to rupture
-activated SMC destabilize the plaque by secreting cytokines and metalloproteinases
90
How does plaque pathology lead to symptoms and diseases in heart? Which ones are caused by it?
Fatty streaks- asymptomatic
Fibrous plaque- stable angina from 75 % occlusion of lumen, lack of vasodilation (impaired NO), heart need more blood to meet demand and can't get it= myocardial ischemia
Plaque rupture with thrombus- unstable angina or MI
91
What determines coronary artery dominance?
The origin of the PDA, 85% of people are right dominate- PDA off of RCA, PDA supplies posterior and inferior heart
92
Where does septal blood supply come from
2/3 LAD, 1/3 RCA
93
Where does the SA node get its blood? What about Right bundle? AV node?
SA node 55-60% from RCA, left bundle multi vessel, right bundle from LAD. AV node artery from PDA right off RCA
94
What factors can influence Coronary blood flow?
Heart rate- diastolic filling time
Coronary perfusion pressure- aortic diastolic pressure/LVEDP- pressure in ventricle in diastole- in heart failure volume and pressure goes up and perfusion pressure goes down
Coronary vascular tone- dilated vs constrict
Intraluminal obstruction- atherosclerosis
Variation in right and left circulation- right side is not compressed as much during systole, less auto regulation, higher O2 extraction reserve
95
What happens to coronary perfusion pressure as HR increases?
the systolic component of blood flow increases, less filling of coronary overall because systole impedes flow through vessels that dive to the myocardium from the epicardium
96
Where is the coronary arteries located? What layer of heart muscle is most susceptible to ischemia? Why?
Coronaries are in the epicardium, subendocardium is the most susceptible to ischemia. As contractility and LVEDP increases subendocardium is less perfused
97
What are the determinants of myocardial oxygen supply mainly affecting the coronaries?
Coronary vasodilation- hypoxia and acidosis stimulated vasodilation, flow dependent dilation in response to shear stress, catecholamines, serotonin
Increased DBP, but usually SBP is higher too which would increase work for heart so balance out if that is case
Luminal obstruction/spasm- more plaque, less supply
smaller effect: oxygen carrying from Hb and O2 sats
98
What are the determinants of myocardial oxygen demand mainly affecting the coronary arteries?
Tachycardia- need more O2
High LVEDP- in Heart failure more volume and pressure in LV so coronary perfusion pressure decreases
Increased contractility
LVH or increased wall tension- proportional to intracavity pressure and wall radius, inversely proportional to wall thickness
99
How does atherosclerosis development lead to coronary artery symptoms?
Atherosclerosis is a progressive disease beginning with fatty streaks. Mainly asymptomatic but there are periods of progression may occur, symptoms occur from supply and demand mismatch in blood flow, it is triggered by inflammation in arterial wall
100
How does the size of a plaque in atherosclerosis affect the blood flow?
per bernouli flow equation flow=flow, pressure drop is inversely related to the stenosis cross sectional area squared
As the lesion gets bigger (from 30% still good flow) to 90% (symptoms from not enough blood) the flow exponentially decreases
stable agina= 75% blocked
Unstable agina=100% blocked
MI= 100% blocked with cell death
101
How do you define acute MI and what is the criteria to define it?
Acute MI- evidence of myocardial necrosis in setting of acute myocardial ischemia
Critieria: rise and or fall of cardiac biomarkers with at least 1 value greater than the 99th percentile with at least one of the following:
1) symptoms of ischemia
2) new ST segment or T wave changes or new LBBB
3) development of pathological Q waves
4) imaging of myocardial loss or WMA
5) id an intracoronary thrombus
102
What is the basic sequence of MI
1) reduce blood flow to subendocardium- less ATP, LV delayed relaxation= diastolic dysfunction, this leads to pulmonary edema
2) dyspnea
3) systolic dysfunction from sarcomeric dyskinesis with impaired ventricular ejection
4) ST segment deviation- depressions, TW flattening or inversion
5) usually substernal chest pain
103
Compare the solid state vs liquid state stimulus in plaque rupture in MI
Solid state- whats happening in the endothelium
-Disrupted plaque incites thrombus and coagulation, contact with collagen in plaque's ECM activates and aggregates platelets, TF from macrophages and SMC activates coagulation cascade, convert fibrinogen to fibrin and release vWF forms cross linking platelets and white arterial thrombus
Liquid state stimulus- what's happening in the lumen
Disrupted plaque elaborates TF to enhance thrombogeneticity, distal embolization causes no reflow, PAI extingushes body natural lytic mechanism- inhibits urikinase-like and tPA so acts inhibiting lysis of thrombus
PAI-1 levels increase with CV risk factors like DM and HTN
104
What is Acute Coronary Syndrome and what diseases fall under it?
ACS= the rupturing of a plaque with a blood clot forming to block an artery
Includes unstable angina, NSTEMI, STEMI
105
How does unstable angina occur and what is the difference btn stable angina?
UA= chest pain caused by a disruption or erosion of atherosclerotic plaque (rupture) in coronary artery and the pathology from decreased coronary blood flow. Chest pain at rest, squeezing substernal chest can radiate to L shoulder/jaw, no elevation in cardiac biomarkers, ECG may or may not change
Different from stable angina- fixed coronary stenosis with compromised flow from slow progressive plaque growth, happens everytime on exertion
106
What is the similarities and differences in UA vs NSTEMI
NSTEM Same pathophysiology and EKG manifestations as UA (occluded artery from disrupted plaque) but cardiac markers are positive due to prolonged decreased coronary flow resulting in myocyte necrosis/death. NSTEMI is more severe and higher risk
107
What are some clinical presentations of NSTEMI
chest pain at rest (usually greater than 6 hours) is main sx
associated with nausea, vomitting, SOB, diaphoresis (sweating)
Women and DM- burning chest pain , SOB only
108
Describe the pathology leading to STEMI, EKG findings, lab findings, and treatment plan for STEMI
This is more emergent than other ACS because there is 100% coronary occlusion causing myocyte necrosis/death. STE on EKG, cardiac biomarkers are positive but can't wait to make dx, need to tx immediately to restore blood flow and prevent significant loss of myocardium arrythmia or sudden cardiac death
Tx: tPA
109
What is the pathophysiology of variant/prinzmetal angina? What are the symptoms and EKG finding? Tx?
It occurs secondary to vasospasm of endothelium with or without coronary stenosis. Can be caused by increased thromboxane A2 from thrombus overlying a plaque or increased endothelin
Sx: episodic chest pain that occurs at rest, may see STE on EKG due to transmural ischemia
Tx: may respond to vasodilators like nitroglycerin or CCB
110
When do you see ST elevations vs depressions on ECG?
In STEMI see complete occlusion of artery after a plaque rupture- transmural infarct and ST elevations
In UA and NSTEMI get plaque rupture with incomplete occlusion- subendocardial ischemia- ST depression or T wave changes (flattened or psuedonormalized)
111
What is the guidelines for determining STEMI
ST elevation in 2 contagious leads or new LBBB
| ST elevation= 1mm in limb leads or 2mm in precordial leads
112
Describe the 6 steps of evolution of transmural MI on EKG
1) hyperacute T
2) ST rises to meet T
3) pathologic Q begins (signal of irreversible myocardial damage) and T wave inverts
4) ST starts coming down and Q deepens further
5) ST normalizes
6) T normalizes, Q still deep
113
What leads can Q be found in? What is signs of pathologic Q wave?
Q waves in all leads except V1-3 and aVR
Normal Q is 0.03s, pathologic: Q > 0.04s in 2 contiguous leads and greater than 1mm in depth
114
How can we localize an artery responsible for STEMI?
true plaque rupture STEMI the vector of ST segments points towards the area of infarction, Q waves vector point away from the infarct
115
What leads would be STE in an anteroseptal infarct? what artery is responsible?
Anteroseptal= V1-V3
| LAD
116
What leads would be STE in anteroapical infaract? what artery is responsible?
V2-V4
LAD
117
What leads correspond with lateral territory? What arteries are responsible?
Lateral= I aVL, V5 V6
Left circumflex
LAD diagonal
118
What leads correspond to the inferior territory? What arteries are responsible?
Inferior= II III aVF
RCA in right dominant heart
LCx in left dominant heart
Mid LAD with V3 V4 changes
119
What leads would be elevated in proximal LAD infarct? what territory
STE in aVL, V1-V3,
anteroseptal with slightly lateral
120
What leads would be elevated in RCA infarct with RV involvement?
Inferior infarct= II III aVF in right dominant heart
| V1 also up indicates it is RCA not LCx or LAD!!!
121
Describe the timeline for cell death in MI?
Injury is reversible up to 20 minutes from occlusion
Irreversible damage to subendocardium past 20 minutes to 60 minutes, 1 hour to 3 hours necrosis extends to myocardium/subepicardium
Past 3 hours there is transmural infarction
122
What are the approximate timelines for gross morphology s/p MI
From 4-24 hours= day = dark mottling
1-3 days dark mottling with yellow pallor
3-7 days hyperremic red border with central tan softening. becomes worse and soft 7-10 days (mushy looking)
10 days+= red gray with red rim, looking like coag necrosis, mostly red and squooshy looking
2 weeks= white fibrous scar
123
When would heart rupture occur s/p MI
heart ruptures occur early within 1 week s/p MI
124
What is the most common complications s/p MI
Arrythymias can occur in 90% of people people in first week, CHF and shock can happen early too
Late complications= CHF in 70% of people, thromboemboli
very late in years= CHF and left heart weakness
125
What is the most common ASA side effect?
GI upset, in upper GI ulcers can develop, increase with dose so keep at 81mg unless indicated
Less likely: bleeding outside GI tract, salacity sensitivity, tinnitus
126
When is ASA contradicted?
Avoid ASA usage in hepatic failure.
127
What is the mainstay of therapy for ACS (NSTEMI/ UA)?
i. MOST UA/NSTEMI pts should receive dual therapy of ASA + a P2Y12 receptor blocker (usually Clopidogrel). Don't give clopidogrel if undergoing or suspected to undergo surgery bc risk for operative bleeding
ii. In pts w/ UA/NSTEMI: everyone gets an anti-coagulant (usually Heparin) in addition to ASA
- Once an anticoagulant is chosen, it should NOT BE SWITCHED
- Take special caution in dosing the elderly Check their GFR!!! (many need to be on smaller dose)
128
What is the major contradiction of thienopyridines? ( ADP P2Y12 antagonists)
i. Clopidogrel (plavix) has delayed onset of action, large variability in platelet response, & is irreversible (blocks platelet receptor for life 7-10days)– all of these factors led to development of newer Thienopyridines
ii. The newer drugs have higher levels of platelet inhibition, and thus, higher risk of bleeding, Bleeding is major side effect, don’t give in patients with active bleeding
iii. Prasugrel still IRREVERSIBLE (like Clopidogrel), but has rapid onset & higher level of platelet inhibiton- not for active bleeding, hx of stroke or TIA. More effective at reducing CV events though
iv. Ticagrelor & Cangrelor REVERSIBLY bind
129
What is a consideration when treating with clopidogrel?
It is a prodrug requiring CYP2C19 to be metabolized to active form. Poor metabolizers have higher CV events but studies show genotyping is not worth it
130
What drugs is added third in patients with high risk?
• GP IIb/IIIa inhibitors (Eptifibatide, Abciximab)
i. MOA: occupy Gp IIb/IIIa receptor, preventing fibrinogen from binding, & thereby preventing platelet aggregation
ii. Use for high-risk UA/NSTEMI pts (those w positive biomarkers for troponin or undergoing PCI) who still have symptoms already on dual therapy ASA & P2Y12 receptor blocker; use IV for pts going into cardiac cath lab; only high-risk pts have consistent benefits
131
What are contradictions to GIIbIIIa inhibitors?
Major side effects in bleeding esp in smaller patients, sometimes need transfusion, not for recent stroke, severe HTN, recent surgery
1. Eptifibatide: immediate onset, must avoid in pts with renal disease; reversible – platelet fx restored in 4-8 hrs
2. Abciximab: safe in pts with renal disease; irreversible - platelet fx remains abnormal up to 7 days but safe for renal insufficiency
132
When is heparin/ LMWH used in ACS?
• Heparin (UFH & LMWH)
i. MOA:
1. UFH – potentiates actions of AT3, binding and inactivating thrombin & Factor Xa; prevents conversion of fibrinogen fibrin
i. less chance of bleeding than LMWH or any other anticoagulant
2. LMWH – strongly binds & inhibits Factor Xa; easy to use, reduced platelet activation, less monitoring (more predictive dose response curve), less risk of HIT, longer ½ life
a. Still needs to be monitored in pregnancy, obesity, renal insufficiency (metabolized renally). Can be used in pregnancy unlike UFH, difficult to use in renal insufficiency
ii. UFH = mainstay for pts coming in w a suspected clot
iii. In pts with UA/NSTEMI – everyone gets an anticoagulant (Heparin) in addition to Aspirin
133
When are direct thrombin inhibitors used in ACS?
• Direct Thrombin Inhibitors- bilvarudin
i. MOA: binds to both circulating AND bound thrombin – prevents thrombin mediated conversion of fibrinogen to fibrin and activation of V VIII XIII; An anti-coagulant that is SPECIFIC, REVERSIBLE, immediate onset, & labs will return to normal an hour after stopping the drug
ii. Increases PT and PTT
iii. Only approved for management of UA/NSTEMI in pts undergoing invasive approach
134
When are factor Xa inhibitors used in ACS?
• Factor Xa inhibitors (Fondapurinux),
i. MOA: AT3 mediated selective binding & inhibition of Factor Xa (like LMWH); interrupts transition of prothrombin thrombin, inhibiting thrombus development
ii. Can be used as an anticoagulant in treatment of UA/NSTEMI
135
Pros and cons of UFH?
Pro: less bleeding risk, used for long time, easy to assess PTT, cheap
Con: variable response, HIT
136
Pros cons of LMWH (enoxaparin)
Pro: less platelet activation, can be used in pregnancy, longer half life, no HIT
Con: difficult in renal insufficiency, long half life (pro or con?)
137
Pro and cons of Direct thrombin inhibitors? (bivalirudin)
Pro: no HIT, short half life
Con: only approved for UA NSTEMI in patients undergoing invasive approach
138
Pros and cons of Factor Xa inhibitors? (fondaparinux)
Pro: less bleeding risk, can use with renal impairment
Cons: expensive? not important
139
What are the similarities and differences in treating NSTEMI UA vs STEMI
many of the medical therapies are the same but STEMI is an emergency
STEMI: emergent reperfusion is needed via lyrics or PCI (gold standard)
140
How is timing important for tx of STEMI? what are the target times?
Worse results and more mortality with longer time until reprofusion.
i. Indicated for STEMI (pts w 100% occlusion) when you won’t be able to get to Cardiac Cath lab for primary PCI within ~90 minutes (also used for stroke or PE, but NOT for UA/NSTEMI)
1. If you wait too long to give tPA, there’s not much benefit (door-to-needle time < 30 minutes) just go for PCI (door to balloon time less than 90 minutes)
141
What situations causes lytics to fail?
Resistance to fibrinolyis, more platelets- the less the lyrics work
142
What are the MOA and contradictions to lytics
• Tissue plasminogen activator (a Thrombolytic/clot buster)
i. MOA: stimulates activation of plasminogen to plasmin; plasmin will go bust up the fibrin clot
ii. Indicated for STEMI (pts w 100% occlusion) when you won’t be able to get to Cardiac Cath lab for primary PCI within ~90 minutes (also used for stroke or PE, but NOT for UA/NSTEMI)
1. If you wait too long to give tPA, there’s not much benefit (door-to-needle time < 30 minutes) just go for PCI (door to balloon time less than 90 minutes)
iii. Contraindications: LOTS – not indicated for hx of significant bleeds, HTN, stroke, recent CNS trauma/surgery
143
What are the advantages to PCI vs Lytics in STEMI tx?
PCI is gold standard- more effective reperfusion, fewer bleeding adverse events
Lytics- widely available and easy to administer, inexpensive
144
What are the goals of anti-ischemic therapies? When are they used?
ANTI-ISCHEMIC THERAPIES: “This is the feel better, secondary prevention stuff.” BB, Renin-Angiotensin-Aldosterone blockers, statins, O2, NTG, Morphine
“Everybody who has a heart attack will go home with a statin, BB, & an ACEi.”
Goals of treatment: to decrease myocardial O2 demand, increase coronary blood flow & O2 supply, & limit myocardial injury in pts with UA/NSTEMI and STEMI
145
When is O2 used in ACS?
a secondary anti ischemic therapy
• 100% inspired oxygen
i. Only indicated in pts whose O2 Sat drops below 90%, bc hyperoxia can cause ROS formation & oxidative damage
146
When is nitroglycerin indicated in ACS? MOA?
Contradictions?
• Nitroglycerin:
i. MOA: main MOA is dilation of venous side (decrease SVR), dilates coronary arteries to improve flow, reducing myocardial O2 demand while increasing O2 supply to myocardium.
ii. Recommended IV for 48 hrs following UA/NSTEMI for tx of persistent ischemia, HF, or HTN Helps with chest pain
Contradictions- Severe aortic stenosis (CAN KILL THEM AND GET SUED BY DECREASING SVR and return to heart)
RV infarct, concurrent used of PDE, hypotension
147
When is morphine indicated and contradicted in ACS?
• Morphine
i. Recent study showed potential harm in UA/NSTEMI pts treated w morphine; NO LONGER A CLASS 1 recommendation
ii. Administer ONLY after NTG & other anti-ischemic therapies have failed to resolve pt symptoms.
Contradictions: hypotension, respiratory distress (vasodilates pulmonary)
148
When are Beta blockers indicated and contradicted in ACS?
• Metoprolol (Beta Blocker)
i. MOA: a selective B-1 antagonist that works to decrease HR & contractility (negative chronotrope & inotrope)
ii. Indicated in post-discharge setting; studies showed that giving BBs in acute hospital setting led to cardiogenic shock from slowing down heart conduction too much too soon, better in post discharge setting.
iii. Contraindications: any sign of HF, heart block, asthma, evidence of low EF, hypotension, bradycardia. if contradicted give CCB in absence of LV dysfunction
149
When are renin-aldosterone agents indicated and contradicted in ACS?
• Renin-angiotensin-aldosterone agents:
i. WARNING: do not start any of these in the acute setting if pt’s SBP < 100mmHg
ii. ACEi’s- can lead to remodeling after MI
1. IV ACEi SHOULD NOT be given to pts within the first 24 hrs of UA/NSTEMI because of increased risk of hypotension (give via oral route)
iii. ARBs – Aldosterone Receptor Blockers (Eplerenone)
1. Give ARBs to UA/NSTEMI pts who are ACEi intolerant & have signs of HF or low LV EF (< 40%), given when increased bradykinin from ACEi cause cough
a. Monitor them for HYPERKALEMIA!
150
When are statins indicated in ACS?
Studies show that patients given highest dose statin tolerated after ACS have less risk of CV events. Higher dose was better
Secondary treatment- ANTI-ISCHEMIC THERAPIES: “This is the feel better, secondary prevention stuff.” BB, Renin-Angiotensin-Aldosterone blockers, statins, O2, NTG, Morphine
“Everybody who has a heart attack will go home with a statin, BB, & an ACEi.”
151
How many people have HTN in the world? How many are controlled?
20% of world's population- 1.2 B people, only 15% controlled, 1 B uncontrolled
152
How many people in US have HTN? How many controlled?
About 30% of HTN-70 mil
83% aware, 75% on meds, 56% controlled- high controlled rate compared to rest of world
153
how many years does HTN cut off a life?
about 15 years
