Atherosclerosis/MI/Peripheral Artery Diseases Flashcards
Fatty Streak
occurs early on in the disease process before it becomes obstructive. asymptomatic Endothelial dysfunction Lipoprotein Entry and Modification Leukocyte Recruitment Foam Cell formation
what is endothelial dysfunction?
Stressors, mostly at arterial branch points impair atheroprotective function. More broadly, stressors, cause an imbalance between vasodilation and vasoconstriction.
Also associated with increased coagulability, increased adhesion synthesis, chemokine release and reactive oxygen species.
What happens with lipoprotein entry?
LDLs migrade through the endothelium and accumulate in the subendothelail space where they are modified by oxidation and glycosylation.
What cells are recruited to the fatty streak?
macrophages and T-cells
What T cells contribute to Atherosclerosis?
TH1 and Th17
TH1 produces what cytokines
IFNy
TH-17 produces what cytokines
IL17a, IL21, IL22
what cytokines are triggered with oLDL
TNFalpha, IL1, IL6, IFN
what T cells inhibit atherosclerosis?
Tregs which produce TGF beta and IL10
What helps in leukocyte recruitment?
increased expression of VCAM1 on endothelial surface and Increase in Monocyte Chemotactic Protein 1 (MCP1).
These interact with CD11c and VLA-4 on the macrophages.
Reversible Risk Factors for Atherosclerosis
Smoking, hypertension, hyperlipidemia
Questionable whether effective treatment to decrease risk of atherosclerosis
DM, obesity, obesity, increased inflammation, psychiatric disorders, sedentary lifestyle.
non alterable changes for atherosclerosis risk
Male, Males >45, Females >55, genetics
what are non traditional markers of atheroscelrosis?
ApoB, lipoprotein A, CRP, homocystein
Plaque Progression
the fibrous and occlusive plaque that leads to stable angina and claudication.
Activated macrophages
Smooth muscle cell migration and proliferation
Secretion of ECM/degradation
start of the weakening of fibrous cap to cause instability and necrosis.
what weakens the fibrous cap?
increased expression of IFNy, MMPs and TF
MMPs activate collaginase and gelatinases
What causes plaque to rupture?
increased accumulation of Foam and T cells, so much so that there is increased ECM exposure
Neovascularization
what makes a stable vs. an unstable plaque
stable is calcified with decreased amounts of lipid, inflammation, and apoptosis.
Unstable is uncalcified, with increased amounts of lipid, inflammation, apoptosis, and it is neovascularized
plaque rupture or thrombosis causes
unstable angina (still reversible effects) MI, stroke or CLI
Complications of atherosclerosis
infarction, hemorrhage, emobolization, aneurysm, microvessel growth/intraplaque hemorrhage
how is smoking a risk factor for atherosclerosis?
Increased Platelet activation, increased fibrinogen
hydrocarbons, increased endothelial dysfunction and decreased HDL
Why is hypertension a risk factor of atherosclerosis?
Increase shear stress to cause endothelial injury, pathological signaling and circulating hormones.
why is DM a risk factor for atherosclerosis?
Inflammation, oxidative stress, dyslipidemia
NO synthesis is triggered by..
ACh, Bradykinin, thrombin, serotonin, shear stress
Cofactors of NO synthesis
Calmodulin, NAPDH, BH4
what is NO synthesized from
Arginine
Cholesterol normal function
synthesis and repair of membranes.
Precursor to steroid hormones
Triglyceride normal function
Fuel for muscles, forms adipose tissue
Lipoprotein structure
Hydrophobic core of TG and CE
Hydrophilic surface of phospholipids, cholesterol, and apoprotein.
Chylomicron
Packaged dietary lipids
Mostly made up for TGs
VLDL
Liver Lipid Structure
55% TG, 20% cholesterol, 15% PL, 10% Protein
LDL
Created from LDL
50% cholesterol
HDL
Extracts Cholesterol from cells to take to liver
Increases NO, inhibits adhesion, LDLoxidation and TF
40% protein, 30% Cholesterol, 30% PL. NO Triglycersides.
what lipid structure is mostly triglycerides
Chylomicron > VLDL
what structure is mostly cholesterol
LDL
what structure is mostly protein
HDL
what is the difference between Chylomicron and VLDL?
synthesis - cylomicron is dietary, VLDL is liver.
Cylomicron is virtually all Triglycerides.
VLDL: is 55% TG, 20% cholesterol, and then small amount of PL and proteins
what makes up total cholesterol?
LDL + HDL + VLDL
VLDL =
TG/5 if TG
LDL =
Total Cholesterol - HDL - (TG/5)
what is recommended for LDL if 1 or less risk factors?
160 below
what is recommended for LDL if 2 or more risk factors?
130 blow (100)
what is recommended for LDL if CAD, ASCVD, DM?
100 below (70)
Path for exogenous lipids
Dietary fat –> Chylomicron –> LPL removes TG to form Remnant (decreased size) –> binds to remnant on receptor on liver.
Endogenous LIpids
Liver produces VLDL –> LPL removes TG to form IDL –> LPL removes TG to from LDL –> LDL binds to LDL receptor on cells.
HDL path
Nascent HDL has no lipids and only protein, but trough LCAT turns into mature HDL with cholesterol and takes it to liver.
when are statins recommended?
Known ASCVD
LDL >190
if you have DM >40y/o and LDL >70
If you are >40 YO without ASCVD or DM with 10 year risk >7.5%
High does statins
Atorvastatin and Rosuvastatin
Low dose statin
Sminvastatin, Pravastatin, Lovastatin, fluvastatin, Pitavastatin
how much fat should be in a heart healthy diet?
5-6% saturated fats, no trans fat
Hypertriglyceridemia
If moderate: risk factor of atherosclerosis
If severe - risk of acute pancreatitis
Primordial Prevention
Steps before development of risk factors
Primary Prevention
Steps before development of disease
Secondary Prevention
Steps after disease to halt progression (confirmed CAD, MI, Angina, stroke, PAD)
Prevent plaque rupture
Tertiary Prevention
Steps to reduce disability and minimize suffering
Pharmacologic Secondary Prevention
Thromboxane Synthesis Inhibitiors P2Y12 Antagonists GP IIb/IIIa antagonists Beta Blockers RAAs (ACEI, ARBs, AA) Statins Vasodilators, diuretics, CCBs
Class 1 post ACS or PCI
P2Y12 inhibitor + aspirin for 1 year
Class 1 Post Bypass
Aspirin 1 year
Class 1 Post Stroke
Aspiring +/- Clopidogrel chronically
Class 1 PAD symptomatic
Aspirin or Clopidogrel
Class 1 beta blockers
with LVEF less than 40% with heart failure symptoms or MI or ACS in last three years
Class 2a Beta Blockers
-LVEF Less than 40% wihthout HF symtpoms OR no change in LVEF but with history of MI or ACS
Class 1 for ACEI
LVEF Less than 40% with DM, HTN, Chronic Kidney Disease
Class 1 for ARBs
LVEF Less than 40% with prior MI or HF symptoms or ACE I intolerant
Class I for AA
Post MI with LVEF Less than 40% with BB + ACEI/ARB + HF or DM
Recommendations for BP
Under 60 less than 140/90; over 60 less than 150/90
are non statin cholesterol lowering effective?
not really because they don’t have vasodilation effects
Class I DM management to lower CV risk
Lifestyle changes with PCP
Class IIa and IIb DM management to lower CV risk
IIA: metforming
IIB: HbA1C
Depression and Class IIa
assessment of depression
Class IIb depression
Treat depression, but does not lower CV risk.
Lifestyle modifications CLass I
BMI 18.5-24.9 Men less than 40 inches; women less than 35 inches
Primary Prevention
for 20-79 yo asses Risk Factors every 4-6 years. for thoes 40-99 calcuate 10 year risk factor.
If 10 year risk factor is greater than 7.5%
Cholesterol lower, obesity, lifestyle changes
If 10 year risk factor is less than 7.5%
Assess 30 Year or lifetime risk
Primary Prevention for Adults 50-59; >10% 10 year risk
LD aspirin
Primary Prevention for Adults 60-69; >10% 10 year risk
Individual decision about apirin
Primary Prevention for adults 70
No recommendation
Depression and CV disease
depression predicts mortality after CV, adverse outcomes among HF, decline in heath status.
Dose response relationship
increased cost of care for those Post MI and CHF
How is depression related to CV disease
depression triggers defective serotonin –> dysfunctional amygdala–> leads to both autonomic dysfunction and hypercorticolemia –> increased cholecatamines, inflammation, endothelial dysfunction, platelet activation.
Depression treatment and CV disease
Treatment lowers Platelet activation markers, HR variability, inflammation, normalizes brain serotonin.
Treatment improves depression, quality of life, physiology
No known effect on adherence, cost, CV events.
Percentage of CV patients with undiagnosed depression
75.5%
What contributes to Oxygen supply
Oxygen content (hemoglobin and systemic O2) and coronary blood flow
What determines perfusion pressure
is approximately aortic diastolic pressure
what determines coronary blood flow
perfusion pressure, perfusion time, vascular resistance
Myocyte Oxygen Delivery =
CBF * O2 content (intrinsic control)
Autoregulation
protection of small changes in perfusion pressure at small arterioles. Dilation of vessels downstream of stenosis to decrease resistance to accomodate for drop in pressure. This makes sure that flow is maintained.
If diastolic perfusion pressure is low, what can you do?
prevent hypotension
If diastolic time is low, what can you do?
rate slowing drugs
is coronary resistance is high, what can you do?
vasodilators or angioplasty
if oxygen content is low, what can you do?
tx anemia and hypoxemia
what contributes to O2 demand
HR, wall tension, inotropic state
when does troponin I rise?
3-4 hours, peaks at 18-36 hours
when does CK-MB rise?
3-8 hours, peaks 24 hours
Functional Flow measurement in CV
upstream and downstream catheter to measure pressure difference.
At rest, pressure might be similar.
Administer vasodilator to mimic exercise and increase flow. Is distal coronary/aortic
what populations is BNP naturally higher?
Women, elderly, renal insufficiency
A type B type C type BNP
A is from atrium, B is from ventricles, C is endothelium
Stroke is due to…
Atheroembolism (Cartoid bifrication ) goes to ophthalmic artery
Thromboembolism from Left Atrial appendage
MI is due to..
Rupture plaque, in situ thromobsis
Stable obstructive plaque
Claudication is due to..
obstructive stable plaque
Acute Limb Ischemia is due to..
Atheroembolization or thromboembolization (rarely in situ thrombosis)
Venous vs Arterial Thrombosis
Thrombosis: rich in fibrin and RBC due to stasis, there is usually a genetic and environmental predisposition.
Arterial: Platelet rich due to plaque rupture that occurs in areas of high flow, due to atherosclerosis, trama.
Arterial vs venous thrombosis treatment
Arterial: antiplatelet
Venous: anticoagulation
stress testing with left main a. or 3 vessel CAD
75-95% sensitive
Sensitivity of stress testing with 1 Vessel CAD
only 25-70%, LAD>RCA>circumflex
expected results of a stress tests
HR above 85% increase in BP systolic >20 mmHg Duration of exercise ECG symptoms
pharmacologic vasodilators for stress tests
dipyradimole, adenosine, regadenoson, dobuatmine (HR dependent)
Imaging of stress test
due to abnormal baseline ECG, to do with increased sensitivity, localization of damage, pre-op cardiac risk assessment, myocardial variability.
Done with radionucleotide perfusion
Thallium 201
Older contract method of Stress imaging - K analog that must be imaged rapidly
Tecnetium 99m
new contrast, monovalent liophilic cation that does not need to be imaged rapidly
what happens with exercise to the wall thickness and motion
increase in rate and thickens with exercise and chamber size decreases.
Tx of stable angina - basic regimen
Antianginal - nitrates, beta blocker
antihypertensives
lipid lowering
anti-platelet
Tx of unstable angina - basic regimen
Hosptialization IV nitroglycerin Beta blockers Antiplatelet anticoagulation Catheterization
Tx of Acute MI - basic regimen
ASAP repurfusion with angioplastly or thrombolytic of no cath lab.
Problems with baloon angioplasty
recurrent symptoms within 6 months (keloid not atheroscelrosis scar)
solution: stents
PAD
flow limiting lesion that limits blood flow to the limbs due to atherosclerosis.
Epidemiology of pAD
10-12% of adults have it
20% are over 70 yo or younger with smoking and diabetes
risk factors of PAD
DM (4x), Smoking (2-3X), Lipids (2x), HBP (2X)
How many factors does PAD increase CV death
6X
what arteries are affected with PAD?
aortoiliac, superficial femoral, tibial a.
Intermittent claudication vs. critical Leg ischemia
IC: cramp, calf fatigue with exercise that is resolved with rest.
CLI: decreaesd blood flow at rest that leads to ischemic ulcers, gangrene, skin necrosis
Symptoms of CLI
critical leg ischemia
Ulcers, gangrene, skin necrosis
Pain in distal foot/heel, ulcers on toes and heels
worsened by elevation
Signs of PAD
decreased of absent pulses
Bruits in abdominal, femoral due to turbulance.
muscle atrophy
pallor with elevation
ABI
ankle brachial index: ratio of systolic ankle BP with doppler to systolic Arm BP. if BP
Tx of PAD
surgery or angioplasty
Exercise training to increase muscle metabolism
Drugs - platelet inhibitors, cilostzole (vasodilators and platelet inhibitors)
Risk modification
what does PAD cause pallor when elevated
stenosis cant work against gravity.
why is foot red when hung over the bed in PAD?
gravity increases circulation and remains at max dilation as you dangle your foot.
arterial aneurysm
extansion of all three layers of the vessel.
Normal aortic side
Root is 3 cm
Distal thoracic 2.5 cm
Infrarenal aoritc 2 cm
Definition of AAA
> 3cm or increase in 50%
Fusiform vs. Saccular Aneurysm
Fusiform in all around, saccular is only one side.
Pseudoaneurysism
accumulation of blood due to a rupture vessel wall with blood leading through a hole in the intima and media.
Epidemiology of AAA
16,000 deaths/year
13 cause f death
Rupture most common with >5 cm
Pathophysiology of AAA
weakened aortic wall due to decreased elastin and decreased collagen due to inflammation, proteolysis, and biochemical stress.
Inflammation in AAA
B and T lymphocytes
Macrophages
Cytokines
autoantigens
Proteolysis in AAA
increase in MMP 2 and 9
increase in tPA
decreases in TIMPs (regulation
Biochemical Stress in AAA
Elastin distrubance, Turbulance, mural thrombus
clinical Presentation of AAA
70% asymptomatic with sudden death
30% abdominal discomfort and back pain with death.
Not often found on exam, found with imaging for another problem
Diagnosis of AAA
X-ray, US, CT, MRI, renal function and contrast. Arteriography - misses them becuase they are viewing lumen and not wall.
Tx of AAA
surgical repair
Endovascular aortic repair (EVAR) - device to bypass aneurysm.
Aortic Dissection
blood passes through tar in intima through medial layer and spreads out.
Could also be due to vaso vasorum with hemorrhage into media.
Aortic dissection epidemiology
30 cases per million/year
3-5% sudden eath
1% risk of death if untreated in 24 hours, 75% in 2 weeks. 90% if untreated at 3 months.
Risk factors of aortic dissection
hypertension, cocaine, CT disorders (marfans, Ehlers Hanios), bicuspid AV
A type Aortic dissection
involves the asscending aorta
B type aortic dissection
does NOT involve ascending aorta
Symptoms of Aortic Dissecion
Severe tearing pain, stroke (carotid), syncope (vertebral), MI (coronary), intestinal ischemia, renal failure
Symptom differences in Aortic dissection vs Aortic aneurysm
AA: often asymptomatic, if symptomatic has abdominal discomfort
AD: severe tearing pain
Diagnosis of Aortic Dissection
CT, trans esophageal ECHO, angiography
Tx of Aortic Dissection
Decreased BP meds, Nitrates, ACEI, CCB, Pain relief
Surg: repair, stent, synthetic graft
Venous Thromboembolic Disease
prone to development of thrombus in superficial and deep veins.
2/3 are asymptomatic of undiagnosed.
how many hospital deaths are due to VTE?
5-10%; 58% were not treated prophylactically
Risk factors of no anticoagulant prophylaxis
24% MI get VTE, 60% paralytic stroke get VTE, 75% of hip survey patients get VTE
Post Phebotic Syndrome
in 40-80% of untreated VTE Disease
Valvular damage due to persistent occlusion by DVT to cause chronic leg swelling, stasis pigmentation, ulceration
Virchows Triad
1) stasis (decreased laminar flow)
2) hypercoagulability
3) vascular damage
Thrombophilia
hypercoagulability state due to increased thrombin, increase platelet activation and aggregate and mediates endothelail damage and fibrinolytic inhibition.
Severe thrombophilia
is due to inherited Protein C/S deficiency
Mild Thrombophilia is
inherited due to factor V leiden
Acquired Thrombophilia is due to..
infection, inflammaion, drugs (estrogen)
what contributes to increase stroke volume in exercise
Vasodilation and increased venous return due to venoconstriction, muscle pumps, and respiratory pump to preserve ventricular filling.
what is the respiratory pump in exercise
negative thoracic pressure in exercise increases venous return
what preserves ventricular filling in exercise
increased Venous Return, increase distensibility, pericardial constraint.
how much does strove volume increase in exceris
40-60%
stroke volume in upright vs supine exercise
Increased basal stroke volume supine, but only 20-40% increase in exercise.
why is there a continual increase in SV with athletes and not sedentary during exercise
continual rise due to increased EDV and increased contractility at lower ESV.
standard rule for increasing CO during exercise
6L/min required for every 1 L/min in O2 uptake increase.
Increasing HR and SV
> 50% VO2 max is determined by
only increased HR
CO athletes vs. sedendary
same at rest
Rest CO for men vs women
Men: 5 L women 4.5 L
Men CO during exercise Athlete vs. Sedenary
Sed: 22 L Ath: 34
Women CO during exercise Athlete vs. Sedendary
Sed: 18 L Ath 24
Athlete vs Sedenary increase in CO in exercise
Sedentary is 4-5x; Athletes in 6-7X
Coronary Vein O2 saturation in rest vs. exercise
Rst; 25%
Exercise: lower than 10%
what happens to blood pressure in excercise
Increase Mean Arterial Pressure, Increase in systolic BP, same Diastolic BP.
Mean arterial pressure:
average BP of the cardiac cycle
Redistribution during exercise.
Vasoconstriction of non-exercising tissues via ergoreceptors and cardiovascular control center in medulla.
Vasodilations of arterioles and small a. via autoregulation
Increase capillary recruitment
Autoregulation of vasodilation in exercise
increase PCO2, NO, K, Acidosis, Adenosine
Decrease PO2
Capillary recruitment
increased recruitment in exercise 5-10% at rest, but 100% in exercise
Skeletal muscle blood flow in exercise
15-20% –> 80-85%
Brain blood flow in exercise
Increased flow from 5 L/min –> 25 L/min
but decrease in total CO% from 15-3-4%
O2 extraction in exercise
increased extraction, but most due to increase CO.
Rest: change in O2 is 5, but 15 in exercise
O2 extraction VO2 =
CO * a-v(O2) in exercise CO (increased by 5) a-v(O2) (increased by 3)
OR {Hgb} 1.34O2 saturation
Rate Pressure Product
is myocardial workload = HR * SBP = mVO2
RPP is more dependnet on
HR^2SVSVR
