Atherosclerosis and lipoprotein metabolism Flashcards
Atherosclerosis=
Atherosclerosis= the build up of a
waxy plaque on the inside of
blood vessels
Atherogensis=
Atherogensis= formation of
abnormal fatty or lipid masses in
arterial walls
main risk factor of atherosclerosis and atherogenesis
high blood cholesterol
High Blood Cholesterol
* Estimated _____ million adults ≥ 20YO have TC ≥ _____
* New Cholesterol guidelines in 2018:
* Focused on?
* primary treatment to reduce cholesterol?
* Very high risk patients may need?
High Blood Cholesterol
* Estimated 28.5 million adults ≥ 20YO have TC ≥ 240mg/dL (High)
* New Cholesterol guidelines in 2018
* Focused on identifying high risk and very high risk patients
* Statins are the primary treatment to reduce cholesterol
* Very high risk patients may need combination therapy to reach LDL ≤ 70mg/dL
lipoproteins of interest
chylomicrons, LDL, HDL, VLDL
- Chylomicrons
% TG % pro
- Highest proportion of triglycerides
- VLDL
%TG %chol %pro
- Very Low Density Lipoprotein
- LDL
%TG %chol %pro
- Low Density Lipoprotein
- “Bad Cholesterol”
- HDL
%TG %chol %pro
- High Density Lipoprotein
- “Good Cholesterol”
lipoprotein density scale
Optimal Cholesterol Levels:
* Total Cholesterol
* HDL
* LDL
* Triglycerides
- Total Cholesterol: ≤ 200mg/dL
- HDL: ≥ 60mg/dL
- LDL: ≤ 100mg/dL
- Triglycerides: ≤ 150mg/dL
Friedewald Formula
less predictive with TG>400
Risk Factors for ASCVD
- Smoking
- Hypertension
- Hyperlipidemia: increased LDL and TC/ decreased HDL
- Diabetes mellitus
- Age (men ≥45 yo, women ≥55yo)
- Obesity
- Physical Inactivity
multiple risk factor effects
additive
ASCVD Risk Assessment
risk factors included? estimates? used to guide?
ASCVD Risk Score can be calculated with online tool
* Risk Factors used include: age, gender, total and HDL cholesterol, smoking status, blood pressure, diabetes,
and race
* Estimates 10-year risk of MI or stroke
* Used to guide lipid therapy
No need to calculate ASCVD score if patient has?
No need to calculate ASCVD score if patient has Clinical ASCVD
Clinical ASCVD:
* Established Coronary Artery Disease (CAD)
* History of stroke or TIA
* Peripheral Artery Disease (P
atherogenesis steps
HDL involvment?
- Endothelial dysfunction
- Endothelial injury
- LDL deposits into vessel wall
- Formation of foam cells (Macrophages filled with LDL)
- Fatty Streak
- Inflammation (Smooth muscle growth)
- Fibrous cap over lipid core
at steps 3-5 HDL may remove cholesterol from vessel walls (The process of HDL mobilizing cholesterol and transporting back to the liver is called ‘reverse cholesterol transport)
normal Aa with athersclerosis
status of plaque and pt symptoms
Lipoprotein metabolism
* Exogenous pathway
- Cholesterol and TG absorbed from diet transported as chylomicrons to muscle and adipose tissue
- Chylomicrons metabolized by lipoprotein lipase to release TG
- Chylomicron remnants (mostly cholesteryl esters) return to the liver
- Cholesterol in liver may be:
1) stored
2) turned into bile, or
3) enter endogenous pathway
Lipoprotein metabolism
* Endogenous pathway
- Cholesterol and TG made in liver leave as VLDL
- VLDL metabolized by lipoprotein lipase to release TG- VLDL becomes LDL
- LDL provides cholesterol source for cells to make cell membranes- also atherogenesis
- Cell use an LDL-receptor to take up LDL
- Liver releases HDL to collect cholesterol and return to liver (reverse cholesterol transport)
- Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesterol to HDL
HMG-CoA reductase inhibitors (Statins)
Mechanism of Action
- Inhibit HMG-CoA reductase
- Rate-limiting step in endogenous cholesterol production
- Also induce an increase in hepatic LDL receptors
HMG CoA inhibitor names
all end in -statin
HMG-CoA reductase inhibitors (Statins)
Effects on Lipid parameters
HMG-CoA reductase inhibitors (Statins)
Relative potency
high intensity statins
Atorvastatin 40-80mg
Rosuvastatin 20-40mg
HMG-CoA reductase inhibitors (Statins) Clinical benefits for primary prevention
* Target age? LDL?
* Use what to guide therapy?
* >7.5% to ≤ 20% risk?
* > 20% risk?
* helpful test?
* Diabetes?
- Target age 40-75 YO with LDL 70- 189mg/dL
- Use ASCVD risk score to guide therapy
- > 7.5% to ≤ 20% risk= moderate intensity statin
- > 20%- high intensity statin
- Coronary Calcium Score helpful
- Diabetes: All patients get at least moderate intensity statin
HMG-CoA reductase inhibitors (Statins) Clinical benefits secondary prevention
* All patients that are?
* intensity statin?
* Very-high risk consider?
- All patients under 75 YO with established ASCVD
- High intensity statin
- Very-high risk consider combo therapy if LDL > 70mg/dL
HMG-CoA reductase inhibitors (Statins) Pleiotropic effects Positive:
* Plaque?
* inflamm?
* endothelial function?
* platelets?
* neovascularization?
- Plaque stabilization
- Reduced inflammation
- Improved endothelial function
- Reduced platelet aggregability
- Increased neovascularization of ischemic tissue
HMG-CoA reductase inhibitors (Statins)
Pleiotropic effects* Negative/Neutral:
pregnancy?
immune?
- Inhibition of germ cell migration during development (Pregnancy contraindication)
- Immune suppression