What are the untreatable risk factors for CAD?
male gender age genetics
What is the estimated lifetime risk of DM for persons in the US?
33%
Diabetes and insulin resistance are associated with inflammation, oxidative stress, and dyslipidemia that predispose to _______.
atherosclerosis
_____ are associated with inflammation, oxidative stress, and dyslipidemia that predispose to atherosclerosis.
Diabetes and insulin resistance
In the normal coronary circulation, autoregulation provides protection from _____.
moderate changes in perfusion pressure
What contributes to fibrous plaques and occlusive atherosclerotic plaques?
activated macs (foam cells) smooth muscle proliferation forms fibrous caps progressive lipid accumulation in core of plaque
When is the LV perfused?
diastole only
When oxidized, ____ becomes pro-inflammatory and athrogenic.
LDL cholesterol
Factors that increase myocardial O2 demand?
- HR 2. wall tension 3. inotropic state
An _____ causes a drop in perfusion pressure.
epicardial coronary stenosis
Tachycardia can compromise ______.
coronary flow
The dyslipidemic triad includes ____, ____, and ____.
high HDL low LDL high triglycerides
What are the beneficial effects of HDL?
- inhibits oxidation of LDLs 2. inhibits tissue factor 3. enhances reverse cholesterol transport 4. stimulates NO production 5. inhibits endothelial adhesion molecules *** all oppose atherosclerosis
Oxygen delivery (mol/min) = coronary flow rate (ml/min) x _______
arterial oxygen content (mol O2/ml blood)
What are the acute vascular events associated with plaque rupture/fissure and thrombosis?
unstable angina MI stroke critical leg ischemia
Oxygen delivery (mol/min) = ______ x arterial oxygen content (mol O2/ml blood)
coronary flow rate (ml/min)
What is a reperfusion injury?
early reperfusion that can provoke an additional injury
______ = coronary flow rate (ml/min) x arterial oxygen content (mol O2/ml blood)
Oxygen delivery (mol/min)
How is O2 supply increased in chronic stable angina treated?
prevent HTN, give beta blockers, vasodilators, coronary angioplasty or bypass surgery, treat anemia and hypoxemia
Smoking confers a 50% increase in ___ risk.
CAD
How is O2 demand reduced in chronic stable angina?
antihypertensive drugs, rate slowing drugs (beta-blockers, Ca++ channel blockers, limit preload (diuretics, nitrates), negative inotropes (beta blockers, Ca++ channel blockers)
______ limits coronary flow and cause myocardial ischemia (tissue blood flow insufficient to meet oxygen requirements), particularly when cardiac work and oxygen demand increase.
Obstructive coronary lesions
Oxygen supply may be compromised by ____ or ____.
anemia; hypoxemia
What is the cardinal symptom of an MI?
severe and unremitting chest discomfort at rest (although 30% of MI’s are “silent”)
In coronary heart disease, autoregulation may be exhausted when ______ across an epicardial coronary stenosis.
pressure drops
When is troponin elevated?
in an acute MI
What causes unstable angina?
Near-complete occlusion of vessel with thrombus
What is different about the coronary circulation?
- the myocardium depends on aerobic metabolism for energy supply 2. Under resting conditions, a near-maximal amount of oxygen is extracted from coronary arterial blood; therefore, the only effective means of increasing myocardial O2 supply is to increase blood flow rate 3. the LV is perfused in diastole only
What attributes to a fatty streak?
endothelial injury lipid deposition mac and T cell recruitment
______ (dental, respiratory, immunologic diseases) may also increase the risk of atherosclerotic cardiovascular events.
Extravascular inflammation
Autoregulation occurs at the level of _____.
the small arterioles
How does HTN contribute to CAD risk?
increased shear stress on arterial walls = - endothelial cell injury - initiates pathologic cell signaling program causing oxidant stress, cellular proliferation circulating hormones increased exert adverse affects on arterial wall (angiotensin, aldosterone, NE) LVH
Myocardial ischemia = imbalance between _____ and ______
coronary oxygen delivery; myocardial oxygen demand
How does smoking increase the risk of CAD?
thrombogenic tendencies platelet activation increased fibrinogen aryl hydrocarbons promote atherosclerosis endothelial dysfunction, vasospasms CO decreases myocardial O2 delivery decreased HDL
Smoking confers a _____ in CAD risk.
50% increase
In coronary heart disease, ______ may be exhausted when pressure drops across an epicardial coronary stenosis.
autoregulation
Name the 4 steps of atherosclerosis, starting from normal.
- fatty streak 2. fibrous plaque 3. occlusive atherosclerotic plaque 4. plaque rupture/fissure and thrombosis
What happens w/I 1 hour of acute coronary occlusion?
Myocardial necrosis and infarction
What are the factors that are treatable, but whether the risk is reduced is unclear.
- diabetes/insulin resistance 2. obesity 3. inflammation 4. psychological stress 5. sedentary lifestyle
Diabetes and insulin resistance are associated with _____, _____, and _____ that predispose to atherosclerosis.
inflammation, oxidative stress, and dyslipidemia
What will the biomarkers be for unstable angina?
negative, including troponin
Increased heart rate shortens the cardiac cycle, predominantly by ______.
shortening diastole
_____ = imbalance between coronary oxygen delivery and myocardial oxygen demand
Myocardial ischemia
What are some of the deleterious effects of LDL?
- injures vascular epi and impairs epi function - deposits into arterial wall… taken up by macs, which increases plaque volume - activates inflammatory cells that play a role in progression and instability of lesions - activates platelets = pro-thrombotic
_____ confers a 50% increase in CAD risk.
Smoking
At which stage of atherosclerosis does effort angina and claudication appear?
occlusive atherosclerotic plaque
What causes acute vascular events?
plaque rupture/fissure and thrombosis
_____ can compromise coronary flow.
Tachycardia
Lipid-laden macrophages in an arterial wall plaque are _____.
highly pro-inflammatory
____ occurs at the level of the small arterioles.
Autoregulation
An epicardial coronary stenosis causes _____.
a drop in perfusion pressure
LV perfusion is predominantly diastolic because of ______.
compression of intramural coronary vessels in systole
What happens w.i minutes of an acute coronary occlusion?
- Impaired calcium re-uptake into SR during diastole > diastolic dysfunction (filling impairment) > increased LV filling pressure > pulmonary congestion and edema 2. Depletion of high energy phosphates, intracellular acidosis > systolic dysfunction (contractile failure) 3. ECG signs of myocardial injury 4. Symptoms (chest pain, dyspnea, arrhythmias)
What are 3 treatable factors with CAD that reduce risk?
- smoking 2. HTN 3. dyslipidemia
When oxidized, LDL cholesterol becomes ____ and _____.
pro-inflammatory and athrogenic
_____ in an arterial wall plaque are highly pro-inflammatory.
Lipid-laden macrophages
In coronary heart disease, autoregulation may be exhausted when pressure drops across an _____.
epicardial coronary stenosis
_____ shortens the cardiac cycle, predominantly by shortening diastole.
Increased heart rate
Name one circulating marker of inflammation.
CRP
Inflammation plays a key role in _____ and _____ of atherosclerosis.
initiation and progression
