CVPR Week 4: Introduction to lipids Flashcards
Objectives
Epidemiology
Leading cause of death worldwide
Approaches to CVD prevention
4 listed
Lipoprotein management
CVD Risk
- Abnormal lipid metabolism
- ↑ LDL
- ↑ ApoB
- ↓ HDL
- ↑ Triglycerides
- Age, gender, race, FHx
- Inflammation, hypercoagualation
- HTN
- Smoking, physical inactivity
- Unhealthy eating
- Insulin resitance
- Obesity/overweight
Heart deaths during the last century
- in 1900 CVD very low
- decrease in mid-80s because the first statin was released in 1984 and HTN drugs
*
Features of a ruptured atherosclerotic plaque
eccentric
lipid-rich
prior luminal obstruction
visible rupture and thrombus
Identify
What are these?
What is this?
What do statins inhibit?
HMG-CoA Reductase
What do biphosphonates inhibit?
Farnesyl-PP synthase
Synthesis of cholesterol biochemistry
Ubiquinone AKA
Co-enzyme Q10
Muscle aches and pains from statin therapy
(Co-Q10) Ubiquinone supplement to decrease myalgias on statins (Co-Q10)
The process of fat digestion
8 steps listed
APO-lipoprotein B48
on chylomicron
Apoprotein C-II
increases efficiency of lipoprotein lipase on the intestinal wall
Lipoprotein lipase
breaks down triglycerides into Free-fatty acids
feeds muscle tissue and adipocytes and cells that can use FFAs
Identify
Lipoprotein subclasses
Lpa is. . .
thrombogenic
Apo B can cause
CVD
ApoAI is
good cholesterol kind of
Lipoprotein metabolism
Fats into intestine LPL lipoprotein lipase breaks down into FAs and make chylomicron remnant to the liver and forms VLDL
CII improves LPL, CIII is antagonistic to CII
VLDL with LPL forms IDL
IDL with Hepatic lipase forms LDL
LDL donates cholesterol to the liver but sometimes it gets into the interluminalmedial space and gets oxidized
oxidized LDL gets phagocytosed by macrophages
ABCA1 (ATP binding Cassette A1) on macrophage allows free cholesterol to get into a Free nascent HDL particle that has APO-AI and some has APO-AII
HDL has a scavenger receptor B1 to donate cholesterol to the liver or other tissues and take excess cholesterol back to the liver and the liver can make bile and can be excreted or recycled
Size of Lipoproteins
Types of hypercholesterolemia
6 listed
Fill in the table
Type I
Fill in the table
Type IIA
Fill in the table
Type IIB
Features of Type I Hypercholesterolemia
Features of Type IIA Hypercholesterolemia
Features of Type IIB Hypercholesterolemia
Features of Type III Hypercholesterolemia
Features of Type IV Hypercholesterolemia
Features of Type V Hypercholesterolemia
Cause of Type I Hypercholesterolemia
Cause of Type IIA Hypercholesterolemia
Cause of Type IIB Hypercholesterolemia
Cause of Type III Hypercholesterolemia
Cause of Type IV Hypercholesterolemia
Cause of Type V Hypercholesterolemia
Other features of Type I Hypercholesterolemia
Other features of Type IIA Hypercholesterolemia
Other features of Type IIB Hypercholesterolemia
Other features of Type III Hypercholesterolemia
Other features of Type IV Hypercholesterolemia
Other features of Type V Hypercholesterolemia
Type I Hypercholesterolemia AKA
Familial hyperchylomicronemia
Familial hyperchylomicronemia AKA
Type I Hypercholesterolemia
Type IIA Hypercholesterolemia AKA
Familial hypercholesterolemia
Familial hypercholesterolemia AKA
Type IIA Hypercholesterolemia
Type IIB Hypercholesterolemia AKA
Familial combined (mixed) hyperlipidemia
Familial combined (mixed) hyperlipidemia AKA
Type IIB Hypercholesterolemia
Type III Hypercholesterolemia AKA
Familial dysbetalipoproteinemia
Familial dysbetalipoproteinemia AKA
Type III Hypercholesterolemia
Type IV Hypercholesterolemia AKA
Familial hypertriglyceridemia
Familial hypertriglyceridemia AKA
Type IV Hypercholesterolemia
Type V Hypercholesterolemia AKA
Familial mixed hypertriglyceridemia
Familial mixed hypertriglyceridemia AKA
Type V hypercholesterolemia
Type I hypercholesterolemia drug treatment
no effective drug treatment
Type IIA hypercholesterolemia drug treatment
limits usefulness of some drugs, especially statins
The initial steps in atherosclerosis
fatty streak is the first sign of atherosclerotic disease
The fatty streak
Question 1
C. Less than 50% stenosis
Most myocardial infarctions are caused by what grade of stenosis
Low-grade stenosis because the thought is that a low-grade stenosis the fibrous cap is weaker when there is a small stenosis and haven’t had time to form a stable stronger fibrous cap
Lab Cholesterol levels
< 200 is normal
Lab LDL Cholesterol levels
Lab HDL Cholesterol levels
Lab Triglyceride levels
High triglyceride and low HDL ratio clinical pearl greater than?
greater than 3.8
higher than normal risk for insulin resistance and heart disease
Guiding principles for treating hyperlipidemia
Mediterranean diet
Diet recommendations for hyperlipidemia
If you can eat more than 30g of fiber per day
you can decrease the chance of CVD by 30%
Recommendations for hyperlipidemia
4 listed
HMG Co-A Reductase inhibitors AKA
Statins
Statins Effect on LDL
↓↓↓ LDL
Statins effect on HDL
↑ HDL
Statins effect on TG
↓
Statins MOA
Inhibits the rate-limiting step of cholesterol precursor formation HMG Co-A Reductase
Statins Side effects
- Hepatotoxicity
- Rhabdomyolysis (especially in combo with fibrates & niacin)
Statins contraindicated in?
Active liver disease and pregnancy
Statins caveats
Statins pathway & effects
- lower intracellular concentrations of cholesterol
- when this happens it increases the number of receptors on the cell surface for cholesterol and thereby increases clearance
Pleiotropic effects of statins
6 listed
Statin effect on thrombus formation
Reduce thrombus formation by
↓ PAI-1
↓ tF
Statin effect on platelet aggregability
Reduce platelet aggregability
Statin effect on plaque inflammation
reduced inflammation within plaque by
↓ CRP
↓ monocyte adhesion
Statin effect on endothelial function & vasomotion
improve endothelial function & vasomotion by
↑ NO bioavailability
↑ circ. endothelial progenitor cells
Statin effect on matrix degradation
Decrease matrix degradation by
↓ macrophage metalloproteinase
↑ collagen content
Statin effect on plaque remodeling
Promote plaque remodeling by
↑ HDL - Cholesterol
↓ LDL - Cholesterol
↓ TGL
Comparison of statin dose response
if you double a dose of a statin
6% lowering of LDL
double again another 6% dose
RULE OF 6
6% reduction for doubling the dose
Risk-enhancing factors that favor the initiation of statin therapy
9 listed
Summary of drugs to treat hyperlipidemia
KNOW THIS!
the only drug in this group that lowers LP a
Niacin
Omega 3 FAs effects
CCT of hyperlipidemia
22% reduction by 1mmol/L
HMG CoA reductase primary prevention
HMG CoA reductase secondary prevention
Proprotein convertase Substilisin / Kexin-9
PCSK-9 is made by the liver, it binds to LDL receptor and everything gets metabolized
when you dont have this you get degradation of LDL
so we now have antibodies to PCSK-9
which can decrease LDL by 60% on top of statins
want to get below 20 mg/dl of LDL and decrease events
if you get LDL below 50 and 40 can regress already built up plaque
lower the LDL the healthier the patient
PCSK-9 AKA
Proprotein convertase Substilisin / Kexin-9
Summary of cholesterol metabolism and synthesis and drug therapy
Fibric acid derivatives AKA
Fibrates
Homozygous hyperlipidemia drugs
1 in 1,000,000
have first coronary event between 10 and 20 years old
mipomersen APOb levels go down
Lomitapide inhibits microsomal transfer protein (MTP) Decreasing TG loading into VLDL
New risk calculator
Secondary prevention
means they’ve already had an event
under 75 need a minimum of 50% reduction and get under 70 mg/dl
Primary prevention
if unsure if they need treatment
CAC (coronary artery Ca2+) score will help make a decision
LDL conc. vs particle number
Apo and lipid measures relationship
LDL and LDL
CHD
