CVPR Week 4: Introduction to lipids Flashcards
1
Q
Objectives
A
2
Q
Epidemiology
A
3
Q
Leading cause of death worldwide
A
4
Q
Approaches to CVD prevention
4 listed
A
5
Q
Lipoprotein management
A
6
Q
CVD Risk
A
- Abnormal lipid metabolism
- ↑ LDL
- ↑ ApoB
- ↓ HDL
- ↑ Triglycerides
- Age, gender, race, FHx
- Inflammation, hypercoagualation
- HTN
- Smoking, physical inactivity
- Unhealthy eating
- Insulin resitance
- Obesity/overweight
7
Q
Heart deaths during the last century
A
- in 1900 CVD very low
- decrease in mid-80s because the first statin was released in 1984 and HTN drugs
*
8
Q
Features of a ruptured atherosclerotic plaque
A
eccentric
lipid-rich
prior luminal obstruction
visible rupture and thrombus
9
Q
Identify
A
10
Q
What are these?
A
11
Q
What is this?
A
12
Q
What do statins inhibit?
A
HMG-CoA Reductase
13
Q
What do biphosphonates inhibit?
A
Farnesyl-PP synthase
14
Q
Synthesis of cholesterol biochemistry
A
15
Q
Ubiquinone AKA
A
Co-enzyme Q10
16
Q
Muscle aches and pains from statin therapy
A
(Co-Q10) Ubiquinone supplement to decrease myalgias on statins (Co-Q10)
17
Q
The process of fat digestion
8 steps listed
A
18
Q
APO-lipoprotein B48
A
on chylomicron
19
Q
Apoprotein C-II
A
increases efficiency of lipoprotein lipase on the intestinal wall
20
Q
Lipoprotein lipase
A
breaks down triglycerides into Free-fatty acids
feeds muscle tissue and adipocytes and cells that can use FFAs
21
Q
Identify
A
22
Q
Lipoprotein subclasses
A
23
Q
Lpa is. . .
A
thrombogenic
24
Q
Apo B can cause
A
CVD
25
ApoAI is
good cholesterol kind of
26
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
27
Size of Lipoproteins
28
Types of hypercholesterolemia
6 listed
29
# Fill in the table
Type I
30
# Fill in the table
Type IIA
31
# Fill in the table
Type IIB
32
Features of Type I Hypercholesterolemia
33
Features of Type IIA Hypercholesterolemia
34
Features of Type IIB Hypercholesterolemia
35
Features of Type III Hypercholesterolemia
36
Features of Type IV Hypercholesterolemia
37
Features of Type V Hypercholesterolemia
38
Cause of Type I Hypercholesterolemia
39
Cause of Type IIA Hypercholesterolemia
40
Cause of Type IIB Hypercholesterolemia
41
Cause of Type III Hypercholesterolemia
42
Cause of Type IV Hypercholesterolemia
43
Cause of Type V Hypercholesterolemia
44
Other features of Type I Hypercholesterolemia
45
Other features of Type IIA Hypercholesterolemia
46
Other features of Type IIB Hypercholesterolemia
47
Other features of Type III Hypercholesterolemia
48
Other features of Type IV Hypercholesterolemia
49
Other features of Type V Hypercholesterolemia
50
Type I Hypercholesterolemia AKA
Familial hyperchylomicronemia
51
Familial hyperchylomicronemia AKA
Type I Hypercholesterolemia
52
Type IIA Hypercholesterolemia AKA
Familial hypercholesterolemia
53
Familial hypercholesterolemia AKA
Type IIA Hypercholesterolemia
54
Type IIB Hypercholesterolemia AKA
Familial combined (mixed) hyperlipidemia
55
Familial combined (mixed) hyperlipidemia AKA
Type IIB Hypercholesterolemia
56
Type III Hypercholesterolemia AKA
Familial dysbetalipoproteinemia
57
Familial dysbetalipoproteinemia AKA
Type III Hypercholesterolemia
58
Type IV Hypercholesterolemia AKA
Familial hypertriglyceridemia
59
Familial hypertriglyceridemia AKA
Type IV Hypercholesterolemia
60
Type V Hypercholesterolemia AKA
Familial mixed hypertriglyceridemia
61
Familial mixed hypertriglyceridemia AKA
Type V hypercholesterolemia
62
Type I hypercholesterolemia drug treatment
no effective drug treatment
63
Type IIA hypercholesterolemia drug treatment
limits usefulness of some drugs, especially statins
64
The initial steps in atherosclerosis
fatty streak is the first sign of atherosclerotic disease
65
The fatty streak
66
Question 1
C. Less than 50% stenosis
67
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
68
Lab Cholesterol levels
\< 200 is normal
69
Lab LDL Cholesterol levels
70
Lab HDL Cholesterol levels
71
Lab Triglyceride levels
72
High triglyceride and low HDL ratio clinical pearl greater than?
greater than 3.8
higher than normal risk for insulin resistance and heart disease
73
Guiding principles for treating hyperlipidemia
74
Mediterranean diet
75
Diet recommendations for hyperlipidemia
76
If you can eat more than 30g of fiber per day
you can decrease the chance of CVD by 30%
77
Recommendations for hyperlipidemia
4 listed
78
HMG Co-A Reductase inhibitors AKA
Statins
79
Statins Effect on LDL
↓↓↓ LDL
80
Statins effect on HDL
↑ HDL
81
Statins effect on TG
↓
82
Statins MOA
Inhibits the rate-limiting step of cholesterol precursor formation HMG Co-A Reductase
83
Statins Side effects
* Hepatotoxicity
* Rhabdomyolysis (especially in combo with fibrates & niacin)
84
Statins contraindicated in?
Active liver disease and pregnancy
85
Statins caveats
86
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
87
Pleiotropic effects of statins
6 listed
88
89
Statin effect on thrombus formation
Reduce thrombus formation by
↓ PAI-1
↓ tF
90
Statin effect on platelet aggregability
Reduce platelet aggregability
91
Statin effect on plaque inflammation
reduced inflammation within plaque by
↓ CRP
↓ monocyte adhesion
92
Statin effect on endothelial function & vasomotion
improve endothelial function & vasomotion by
↑ NO bioavailability
↑ circ. endothelial progenitor cells
93
94
Statin effect on matrix degradation
Decrease matrix degradation by
↓ macrophage metalloproteinase
↑ collagen content
95
Statin effect on plaque remodeling
Promote plaque remodeling by
↑ HDL - Cholesterol
↓ LDL - Cholesterol
↓ TGL
96
Comparison of statin dose response
97
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
98
Risk-enhancing factors that favor the initiation of statin therapy
9 listed
99
Summary of drugs to treat hyperlipidemia
KNOW THIS!
100
the only drug in this group that lowers LP a
Niacin
101
Omega 3 FAs effects
102
CCT of hyperlipidemia
22% reduction by 1mmol/L
103
HMG CoA reductase primary prevention
104
HMG CoA reductase secondary prevention
105
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
106
PCSK-9 AKA
Proprotein convertase Substilisin / Kexin-9
107
Summary of cholesterol metabolism and synthesis and drug therapy
108
Fibric acid derivatives AKA
Fibrates
109
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
110
New risk calculator
111
Secondary prevention
means they've already had an event
under 75 need a minimum of 50% reduction and get under 70 mg/dl
112
Primary prevention
113
if unsure if they need treatment
CAC (coronary artery Ca2+) score will help make a decision
114
LDL conc. vs particle number
115
Apo and lipid measures relationship
116
LDL and LDL
117
CHD
