Ischemic Heart Disease 1 Flashcards
What is the progressive process of atherosclerosis?
Long asymptomatic phase (deposition of lipid in sub endothelial space, macrophage and T-cell recruitment, activated macrophages and smooth muscle proliferation form fibrous plaque) Symptomatic phase is once the plaque gets big enough to block blood flow. If the plaque ruptures, you end up with acute vascular events (unstable angina, myocardial infarction, stroke, critical leg ischemia)
What are 3 treatable factors (and a recently possible 4th) that are shown to reduce risk for coronary artery disease?
Smoking, hypertension, dyslipidemia (and possibly diabetes)
What are 5 treatable risk factors where it is unclear if risk is reduced by treatment?
Diabetes/Insulin resistance, obesity, inflammation, psychological stress, sedentary lifestyle
What are the 3 non-treatable risk factors for coronary artery disease?
Male, Age, Genetic factors
With other factors held constant, what is the increased risk of CAD with smoking?
~50%
What are the 5 mechanisms of increased CAD risk for smoking?
- Thrombogenic tendency - platelet activation, increased fibrinogen (clot forming) 2. Aryl hydrocarbon compounds promoting atherosclerosis 3. Endothelial dysfunction, vasospasm 4. CO decreases myocardial oxygen delivery 5. Adverse effect on lipoproteins (decreased HDL)
Can cessation of smoking normalize risk for CAD?
YES
There is _______ for CAD depending on blood pressure (severity of hypertension).
Graded risk. This means the worse the hypertension, the greater the risk for CAD.
What are the 4 mechanisms of increased CAD risk for hypertension?
- Increased shear stress on arterial walls may cause endothelial cell injury 2. Increased arterial wall stress initiates pathologic cell signaling causing oxidant stress, cellular proliferation 3. Circulating hormones increased in HTN (angiotensin, aldosterone, norepinephrine) may exert adverse effects on arterial wall 4. A chronic increase in heart work causes LV hypertrophy which may exacerbate myocardial ischemia
Does treatment of hypertension reduce cardiovascular risk?
YES
Hypertension is very common. However, is it well controlled?
No. In the USA, only about 65-70% are estimated to be diagnosed, 50% are being treated, and only 20% are being treated to the target level of 120 systolic pressure.
Which two ethnic groups have higher prevalence of hypertension? (and typically treatment falling short)
African Americans and Asians
What is the increased risk for CAD for people with diabetes and insulin resistance?
1.5 - 2x
What are 3 physiological reasons that diabetes and associated insulin resistance cause greater risk for CAD?
- Inflammation 2. Oxidative stress 3. Dyslipidemia
What is the estimated lifetime risk for diabetes for persons born in the US in year 2000?
33% (depending on race… up to 50% in hispanic females)
How many diabetics are estimated in the world for year 2025?
300 million
Why is diabetes just the “tip of the iceberg”?
Because, even more people have insulin resistance without overt diabetes. These people with insulin resistance have a similar CV risk
What is the dyslipidemic triad? (What are the 3 most important factors of lipid profile that are a risk for CHD?)
- High levels of low-density lipoprotein cholesterol (LDL) 2. Low levels of high-density lipoprotein cholesterol (HDL) 3. High levels of triglycerides
How do we typically control high levels of LDL?
Statin drugs (most often)
Does controlling LDL levels typically help risk for CHD?
YES
Does controlling HDL levels typically help risk for CHD?
No. Low levels of HDL can be a risk for CHD but controlling them to make them high doesn’t seem to decrease risk. This means that low levels of HDL is a good biochemical marker for CHD risk but increasing it doesn’t help.
What is an independent risk factor, usually highly dependent on life style, that increases risk for CHD?
High triglyceride levels
What are the harmful effects of LDL cholesterol?
When oxidized, LDL cholesterol becomes inflammatory and atherogenic! - injury to vascular endothelium impairing endothelial function - deposited in arterial wall and taken up by macrophages, causing progressive increase in plaque volume - activates inflammatory cells that play a role in progression and instability of atherosclerotic lesions - activates platelets pro-thrombotic
What are the theoretical benefits of HDL cholesterol?
Generally, HDL is thought to oppose atherothrombosis. It does this through 5 ways… 1. inhibits oxidation of LDLs 2. Inhibits tissue factor 3. Enhances reverse cholesterol transport 4. Stimulates endothelial NO production 5. Inhibits endothelial adhesion molecules
LDL and HDL are ______ risk factors for CHD.
Independent. The risk for CHD is higher when LDL is low, regardless of HDL level. And the risk for CHD is higher when HDL is low, regardless of LDL level. They don’t influence each other.
Inflammation plays a key role in ____ and _____ of atherosclerosis.
Initiation, progression
Lipid-laden macrophages in arterial wall become _____.
“Foam cells”
Foam cells are highly ______
pro-inflammatory
What percentages of stenosis can be compensated by the autoregulatory system?
Here is the graph… As you can see, the verticle blue lines represent the limits of coronary blood flow and the red shaded area represents how far the autoregulation can compensate (autoregulatory range).
Follow the line for 30%: You can see that with a 30% stenosis, the autoregulation system is still able to achieve maximal coronary blood flow. So, even in heavy exercise situations, 30% stenosis is okay.
For 50% stenosis, same thing.
For 70% stenosis, you can see that with maximum compensation, you only get about half way to maximal coronary blood flow. This means, with exercise, you can get some symptoms or ischemia. Angina can be present as well as ischemia.
What is the time frame for successful perfusion treatment for acute coronary infarction?
If perfused before 30 minutes, 0% of area at risk. If perfused after 4 hours, practically 100% area at risk (98%?).
