Review Q's Week 5 Flashcards
1. genetics of CVS medicine (1-20) 2. pharmacogeneric and nutrigenetics (21-32) 3. physio coronary blood flow and reserve (33-62) 4. clinical med cardiovascular diseases (63-77)
Which of the following is more rare?
a. polygenetic diseases
b. multifactorial diseases
c. mendelian diseases
c. mendelian diseases
(aka monogenic diseases. they’re very rare and tend to run in families)
What is a genetic risk score?
its a way of accumulating genetic risks to evaluate the risk of a patient acquiring a disease
How do biobanks evaluate genetic variants?
detailed algorithms
Which if the following is a better predictor of coronary artery disease?
a. diabetes
b. metaGRS (genetics)
c. conventional risk factors
d. B and C are equal
c. conventional risk factors (ex/ smoking, diabetes, age, etc.)
** if you combine B+C, you’re able to get a better prediction
T/F: having high risk SNPs significantly raises the risk of getting coronary artery disease in both men and women
false, high risk SNPs does increase the risk that males get CAD four times, but for women, the high risk SNPs don’t cause a big change in cumulative risk of CAD
T/F: genetic information does not replace conventional risk factors
true, it acts to complement them
Who is more likely to benefit from intensive preventive interventions?
Men with high GRS (genetic risk factor) are more likely to benefit from intensive preventive interventions
How are Mendelian diseases inherited?
autosomal dominant
Individuals with the same Mendelian genotype can show different degrees of the phenotype referred to as
a. Penetrance
b. Expressivity
c. Pleiotropy
b. Expressivity
A family is known to have very high lipid levels, but the condiiton skipped one generation. What describes this?
a. Penetrance
b. Expressivity
c. Pleiotropy
a. Penetrance
The proportion of individuals with the genotype that exhibit the phenotype/disease is referred to as
a. Penetrance
b. Expressivity
c. Pleiotropy
a. Penetrance
A family who’s known to have Marfan’s syndrome has two kids. One of them has more extreme conditions (ex/ ocular symptoms) while the other has almost no symptoms. What most likely defines this senario?
a. Penetrance
b. Expressivity
c. Pleiotropy
b. Expressivity
A mutation in one gene can lead to more than one disease is referred to as
a. Penetrance
b. Expressivity
c. Pleiotropy
c. Pleiotropy
What kind inheritance does familial hypertrophic cardiomyopathy have? What two mutations are known to cause it?
autosomal dominant cardiac β-myosin heavy chain (MYH7) + cardiac myosin binding protein C (MYBPC3)
If a patient is suspected of having familial hypertrophic cardiomyopathy, what is the first genetic test looking for?
cardiac β-myosin heavy chain (MYH7) (check for this mutation first because it the most common)
How does a mutation in MYH7 cause hypertrophic cardiomyopathy? explain.
MYH7 is expressed predominantly in normal human ventricle and expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein correlate with the contractile velocity of cardiac muscle
Which mutation causes more severe symptoms of familial hypertrophic cardiomyopathy?
a. cardiac β-myosin heavy chain (MYH7)
b. cardiac myosin binding protein C (MYBPC3)
a. cardiac β-myosin heavy chain (MYH7)
Which of most likely affected in patient with familial hypertrophic cardiomyopathy?
a. sarcomere
b. Z-disc
c. intracellular calcium modulators
a. sarcomere
What kind of mutation most commonly causes familial hypertrophic cardiomyopathy?
missense (amino acid change)
What’s the most common symptom of familial hypertrophic cardiomyopathy?
most patients are asymptomatic
Most common side effect of warfarin?
bleeding
Mechanism of action of warfarin.
Warfarin is a specific inhibitor of vitamin K expoide reductase (VKOR), which is involved in Vitamin K-dependent clotting factors
Which gene is responsible for making the enzyme that inactivates warfarin?
CYP2C9
CYP2C9 and VKORC1 enzyme activity increased. How do adjust the dosage of warfarin?
more dosage of warfarin is needed
What does VKORC1 enzyme do? Which genotype of this enzyme is more active?
blood clotting (Vitamin K-dependent clotting factors) GG genotype is most active
How much of variability is CYP2C9 and VKORC1 responsible for in warfarin response? a. 20% b. 30% c. 40% d. 50%
c. 40% (age and weight= 15%)
What percent of patient taking Clopidogrel/Plavix show no response?
30%
Which isoenzyme has the most important role in Clopidogrel/Plavix?
CYP2C19
Whcih of the following CYP2C19 SNPs have a higher risk of major adverse cardiac events when using clopidogrel medication?
a. CYP2C19*2
b. CYP2C19*3
c. CYP2C19*17
a. CYP2C19*2 (Carriers of the CYP2C19*2 receiving clopidogrel are found to be associated with 42% of higher risk of major adverse cardiac events)
Which genotype is responsible for metabolizing caffeine? a. CYP1A
b. CYP1B
c. CYP1C
d. CYP1D
a. CYP1A
Which of the following CYP1A genotypes is a fast caffeine metabolizer?
a. AA
b. AC
c. CC
a. AA
Which of the following CYP1A genotypes has the lowest risk of MI after consuming four cups of coffee a day?
a. AA
b. AC
c. CC
a. AA (AC and CC have a higher risk when consuming the same amount)
How do you calculate ventricular wall stress?
intraventricular pressure X ventricular cavity radius /(divided by)/ 2 X ventricular wall thickness
How does ventricular wall stress affect O2 demand?
more wall stress more O2 demand
T/F: Increasing ventricular wall thickness can only decrease ventricular wall stress
false, as ventricular wall thickness increases, O2 demand can increase because there are more sarcomeres (more O2 required) and higher contractility (also increases O2 demand)
How will heart failure affect ventricular wall stress?
it will increase it by causing ventricular dilation (increase radius of the ventricular cavity)
How will aortic stenosis affect ventricular wall stress?
it will increase it by increasing intraventricular pressure
How does tachycardia increase O2 demand?
more contractions= more ATP and O2 needed
How does tachycardia decrease O2 demand?
the heart gets its blood supply in diastole. When tachycardia occurs, the time for diastole gets reduced to fit more contractions per minute. So instead of diastole lasing 0.55secs it becomes 0.15escs. Less diastole= less perfusion time= less blood required
How does contractility increase O2 demand?
by increasing the number of active cross-bridges (more demand) and the rate at which they turnover
What are positive inotropic drugs used to treat? Long term effect of their use?
treat acute heart failure associated with excess mortality
How do you calculate the amount of O2 tissues consume?
Oxygen consumption = coronary blood flow x (CaO2 -CvO2) CaO2 – arterial oxygen content CvO2 – venous oxygen content
What is the driving force for the coronary flow?
The pressure difference (dP) between the ascending aorta and the right atrium. (remember BF=dP/R)
How does aortic insufficiency affect the coronary blood flow? explain.
Why does the heart get no blood supply during systole? What causes the rush of blood when diastole occurs?
branches of the coronary arteries penetrate into the myocardium and thus are squeezed during contraction, so no blood is allowed through.
reactive hyperemia happens at the diastole due to the accumulation of the vasodilator metabolites after a period of no flow in the systole (the radius increases, so resistance decreses)
Which of the following are more affected by intramyocardial compressive forces?
a. subendocardium
b. subepicardium
a. subendocardium
greater in subendocardium (120 mmHg) than in subepicardium (20 mmHg)
Which of the following has a better perfusion by intramural arteries?
a. subendocardium
b. subepicardium
b. subepicardium
Which of the following has is perfused by class B intramural arteries?
a. subendocardium
b. subepicardium
c. both
b. subepicardium
T/F: the O2 supply in the body cannot be increased by increasing O2 extraction from the blood, it has to be increased by increasing blood flow
false, this statement is only true for the heart (because the extraction rate in it is always high) but for the rest of the body, we can increase the O2 by increasing extraction
The myocardial O2 supply depends on these 3 things:
1- coronary blood flow
2- blood O2 carrying capacity
3- myocardial O2 extraction
Which one of these will the body manipulate to increase O2 supply? How?
number 1 is the only one the body can change (number 2 can’t be changed and number 3 is already at the max)
coronary blood flow is increased when the myocardial releases vasodilator metabolites due to the increase work or demand. This will cause relaxation of VSMC and thus less resistance (cuz bigger radius) and more flow.
How does the endothelium control coronary blood flow?
Healthy endothelium = vasodilatory functions in response to a variety of stimuli.
In endothelial dysfunction = coronary vascular tone is increased + inappropriate vasoconstriction due to acetylcholine
Which (1 or more) of the following cause coronary artery dilation?
a. alpha 1 adrenoceptor response
b. beta 1 adrenoceptor response
c. M1 muscarinic response
d. M2 muscarinic response
e. M3 muscarinic response
b. beta 1 adrenoceptor response
+
e. M3 muscarinic response
Which (1 or more) of the following cause coronary artery constriction?
a. alpha 1 adrenoceptor response
b. beta 1 adrenoceptor response
c. M1 muscarinic response
d. M2 muscarinic response
e. M3 muscarinic response
a. alpha 1 adrenoceptor response
+
d. M2 muscarinic response
Explain how the sympathetic system causes coronary artery constriction/dilation.
causes constriction via alpha 1 adrenergic receptors, but then the heart’s activity increases causing metabolites to accumulate and dilate the arteries via beta 1 adrenergic receptors.
Explain how the parasympathetic system causes coronary artery constriction/dilation.
causes dilation via M3 muscarinic receptors, but then the heart’s activity decreases causing a decrease in metabolites. This causes constriction via M2 muscarinic receptors (compensatory)
T/F: resting flow of coronary arteries does not change with narrowing of coronaries
true
How much can the coronary flow reserve increase during vasodilation (whats the maximum flow)? How much constriction does it take for the maximal flow to decrease?
increase 4 to 5 times (maximal)
Reduction of the maximal CBF begins when coronary diameter is narrowed by more than 50%
What are two methods used to measure coronary flow reserve?
transient coronary occlusion (inflate balloon to get reactive hyperemia)
vasodilatory drugs
What condition causes decreased coronary flow reserve?
atherosclerosis
How do you measure coronary flow reserve?
coronary flow reserve= maximum coronary blood flow / rest coronary blood flow
What is Fractional flow reserve?
Fractional flow reserve (FFR) is a technique used in coronary catheterization to measure pressure differences across a coronary artery stenosis (narrowing, usually due to atherosclerosis) to determine the likelihood that the stenosis impedes oxygen delivery to the heart muscle (myocardial ischemia).
How do you calculate the fractional flow reserve? What does it mean when fractional flow reserve is =1?
if it’s equal to one, then the flow or pressure before and after the plaque is the same and this is the normal value.
Differentiate between primary and secondary risk prevention
primary risk prevention is preventing high risk patients from getting the first cardiovascular attack.
secondary risk prevention is for patients who already had a cardiovascular attack- we want to prevent further attacks from occurring
What is considered a low 10 year ASCVD risk? What’s a high risk?
low risk =5% or less
high risk= 20% or more
T/F: lifestyle modification of people with high MI risk includes banning salt completely from the diet
false, salt is still a necessary nutrient
T/F: exercise reduces the risk of cardiovascular disease due to its effect on weight
false, exercise reduces the risk of cardiovascular disease independently on its affect on weight
Drugs are mostly used in what type of prevention?
a. primary
b. secondary
b. secondary
Which medications do you give all already established atherosclerotic cardiovascular disease patients?
aspirin
+
statin
Patient has established CAD, an ejection fraction of 34%, and no signs of heart failure.
What should we give him?
beta blocker
ACEI
aldosterone antagonist
(Give these when CAD established + less that 40% EF)
When should you give aspirin for primary prevention of CAD? How about statins?
aspirin can’t be used for primary prevention (due to bleeding risk)
statins are used when the patient has an intermediate or high risk (ex/ high LDL + diabetes)
What are the qualifications needed for a patient to be given an implantable cardiovascular defibrillator (ICD) for primary prevention?
1- left ventricle ejection fraction 35% or less
2- is on optimal medical therapy (OMT) to increase the ejection fraction
3- NYHA Class II or III
4- nonischemic dilated cardiomyopathy
A patient had an MI 20 days ago, his ejection fraction is 27%. You want to prevent further attacks by implanting an ICD (implantable cardiovascular defibrillator). Is this valid?
no, you have to wait for at least 40 days after the MI because the ejection fraction may improve with time. If you measure the ejection fraction again after 40 days and it’s still below 35%, an ICD is an appropriate secondary prevention.
What is the prevention method for atrial fibrillation?
anticoagulant
(atria not contracting, so blood may pool and coagulate in them- then leaving the heart and embolizing in the body)
Which is more dangerous, embolic stroke or ischemic stroke?
embolic stroke
What is Valvular Atrial Fibrillation?
Atrial Fibrillation with mitral stenosis
Which two kinds of patients should always be on anticoagulation?
- patients who have artificial heart valves
- patients who have Valvular Atrial Fibrillation (atrial fibrillation and mitral stenosis)
What is the CHA2DS2-VASc Score used for?
the most commonly utilized method to predict thromboembolic risk in atrial fibrillation
(stroke risk)
