Dyslipidemia and CVD Part 1 Flashcards
1
Q
What is the role of the cardiovascular system?
A
- regulates blood flow to tissues (delivers 02 blood and nutrients, retrieves waste products)
- thermogulation
- hormone transport
- maintenance of fluid volume
- regulation of ph
- gas exchange
2
Q
What are the major forms of CVD?
A
- HTN
- Atherosclerosis
- CHD
- Peripheral Vascular Disease (Cerebrovascular Disease, Deep Vein Thrombosis)
- CHF (congestive heart failure)
3
Q
How is the atherosclerosis plaque form?
A
- monocytes respond to injury on the artery wall, slip under blood vessel cells
- engulf LDL cholesterol becoming foam cells
- the thin layer of foam cells develop on artery walls form fatty streaks
- a fatty streak thickens and forms plaque
- plaque accumulates additional lipids, smooth muscle cells, connective tissue, and cellular debris
- artery expands to accommodate the plaque making it more prone to rupture and thrombosis
4
Q
What is atherosclerosis?
A
thickening of the blood vessel walls caused by presence of atherosclerotic plaque
5
Q
Atherosclerosis results in _____
A
restriction of blood flow
6
Q
Atherosclerosis is associated with _____
A
- myocardial infarction (MI)
- cerebrovascular accident (CVA, stroke)
- peripheral vascular disease (PVD) –> impede with the venous return of the blood to heart
- CHD
- CHF when severe CHD or MI occurs
7
Q
What is the pathophysiology of atherosclerosis?
A
- complex and not well understood
- involves endothelial cells, smooth muscle cells, platelets, and leukocytes
- begins as a response to endothelial lining injury that results in an inflammatory process
- results in restriction of arterial blood flow
- asymptomatic until it progresses to ischemic heart disease
8
Q
How does the damage to the arterial wall happens?
A
- high blood pressure
- chemicals from tobacco
- oxidized LDL
- glycated proteins
- decreased NO
- Angiotensin II
9
Q
What is the normal range for total cholesterol levels
A
<5.2 mmol/L
10
Q
What is the normal range for HDL
A
1.0 - 1.5 mmol/L
11
Q
What is the normal range for LDL
A
<2.6 mmol/L
12
Q
What is the normal range for TG
A
< 1.7 mmol/L
13
Q
What are the risk factors for atherosclerosis?
A
- risk factors have an additive effect
- family history
- age and sex (more common over age of 65 and in men)
- obesity
- dyslipidemia
- physical inactivity
- DM
- impaired fasting glucose/metabolic syndrome
- cigarette smoke
- obstructive sleep apnea
14
Q
What are the irreversible risk factors for atherosclerosis?
A
- age
- gender
- genetics
- familial history of CVD (1st relative, men<55y, 2nd relative women <65y)
15
Q
What are the reversible risk factors for atherosclerosis?
A
- diabetes
- HTN
- obesity
- hyperlipidemia
- atherogenic diet
- smoking
- lack of physical activity
- low HDL (<1.0 mmol/L; <1.3 mmol/L women)
16
Q
What are the functions of apoproteins?
A
- synthesis and secretion of specific lipoproteins
- stabilize surface coat of lipoproteins
- activate enzymes (e.g. Apo C-II activates LPL)
- interact with cell surface receptors
17
Q
What is the major role of apoproteins on lipoproteins?
A
primary determinants of the metabolic fate of lipoproteins
18
Q
What do apoproteins reflect in terms of lipoproteins?
A
reflect changes in lipoprotein composition
19
Q
What do apoproteins indicate on plasma?
A
indicative of the number of lipoproteins in plasma (concentration)
- apoproteins may be better predictors of heart disease than lipid levels and may correlate with the severity of the disease
20
Q
What are the major apoproteins found on chylomicrons?
A
B-48, E, A-1, A-IV, C-II, C-III
21
Q
What are the major apoproteins found on VLDL?
A
B-48, C, E
22
Q
What are the major apoproteins found on LDL?
A
B-100
23
Q
What are the major apoproteins found on HDL?
A
A-1, A-2, C, E
24
Q
What is the most frequent genotype that is seen of Apo-E?
A
E3/E3 (60%)
25
What is the problem with E2 genotype of ApoE?
does not react with ApoE receptor of LDL
26
How dyslipidemia classified?
primary and secondary
27
What is primary dyslipidemia?
single or poly-genetic abnormalities affecting lipoprotein function resulting in hyper or hypo lipidemia
28
How is primary dyslipidemia diagnosed?
- history (age, onset, family members)
- physical signs (e.g. xanthomas)
- lab analysis: lipid profile, apoproteins, LPL activity
- appearance of serum
- genetic sequencing for rare cases
29
What is secondary dyslipidemia?
environmental causes +/- predisposition
- due to other causes than genetic
- more prevalent
- may exacerbate primary dyslipidemia
30
What are the classes of primary hypolipoproteinemias?
- Abetalipoproteinemia
- Familial hypobetalipoproteinemia
- Familial alpha-lipoprotein deficiency (Tangier disease)
31
What is abetalipoproteinemia?
- hypolipoproteinemia
- defect in apoporotein B synthesis
- no chylo, VLDL, LDL formed and TAG accumulate in liver and intestine
32
What is Familial hypobetalipoproteinemia?
- hypolipoproteinemia
| - LDL concentration is 10-50% of normal but chylomicron formation occurs
33
What is Familial alpha-lipoprotein deficiency (Tangier disease)?
- hypolipoproteinemia
- virtual absence of HDL (Apo-A), CE accumulate in tissues
- Chylo, VLDL, LDL are all normal
- moderate hyper TG
34
What are the 5 phenotypes of hyperlipoproteinemia?
Type I --> hyperchylomicronemia
Type IIa --> hypercholesterolemia
Type IIa, IIb, IV, or III --> combined hyperlipidemia
Type III --> endogenous hypertriglyceridemia
Type IV --> hypertriglyceridemia
Type V --> mixed hyperlipidemia
35
Which type of hyperlipoproteinemia is the most common?
Type II
36
What is the lipid abnormality of type I hyperlipoproteinemia (hyperchylomicronemia)?
- increased TG
| - decreased HDL
37
What is the lipoprotein abnormality of type I hyperlipoproteinemia (hyperchylomicronemia)?
chylomicron
| increased chylo fasting
38
What are some clinical features of type I hyperlipoproteinemia (hyperchylomicronemia)?
- early
- xanthomas
- abdominal pain
- pancreatitis
- lipemia
- retinalis
39
What is the lipid abnormality of type IIa hyperlipoproteinemia (hypercholesterolemia)?
- increased LDL-C
| - TG: N or H
40
What is the lipoprotein abormality of type IIa hyperlipoproteinemia (hypercholesterolemia)?
high LDL
41
What are some clinical features of type IIa hyperlipoproteinemia (hyperchylomicronemia)?
vascular disease
42
What is the lipid abnormality of combined hyperlipidemia?
- increased cholesterol AND/OR
- increased TG
- decreased HDL-C
43
What is the lipoprotein abnormality of combined hyperlipidemia?
IIb --> increased LDL +/- VLDL, apoB
| III --> b-VLDL
44
What are some clinical features of combined hyperlipidemia?
- xanthomas
- vascular disease
- variable
45
What are lipid abnormalities of type IV hyperlipoproteinemia (endogenous hyperTGemia)?
- cholesterol N or H
| - increased TG
46
What is the lipoprotein abnormality of type IV hyperlipoproteinemia (endogenous hyperTGemia)?
high VLDL
47
What are some clinical features of type IV hyperlipoproteinemia (endogenous hyperTGemia)?
- Xanthomas
- diabetes
- obesity
- alcohol
48
What are the lipid abnormalitiess of type V hyperlipoproteinemia (mixed hyperlipidemia)?
- Cholesterol N or H
- Increased TG
- decreased HDL-C
49
What is the lipoprotein abnormality of type V hyperlipoproteinemia (mixed hyperlipidemia)?
- high VLDL, chylomicrons present
50
What are some clinical features of type V hyperlipoproteinemia (mixed hyperlipidemia)?
idem to I and IV
51
What are the effects of obesity on lipoprotein metabolism?
- increased substrate flux to liver
- POSTPRANDIAL = due to excess calories (lipids and CHO)
- POSTABSORPTIVE = due to high adipose tissue and hormones sensitive lipase (HSL) activity (bc of insulin resistance) resulting in increased FFA flux to liver
52
How is obesity is related to HDL-C reduction?
BMI and Abdominal visceral fat
53
How is BMI related to HDL-C reduction?
- inverse relationship between BMI and HDL
| - stronger association of BMI with HDL than LDL
54
How is abdominal/visceral fat related to HDL-C reduction?
- stronger association with HDL than total body fat
| - stronger association in men and post-menopausal women
55
How are TOT-CHOL, LDL-C, HDL-C affected by a diet high in cholesterol?
TOT CHOL = increases
LDL-C = increases
HDL-C = no change
56
How are TOT-CHOL, LDL-C, HDL-C affected by a diet high in sat fats?
TOT CHOL = increases
LDL-C = increases
HDL-C = increases
57
How are TOT-CHOL, LDL-C, HDL-C affected by a diet high in trans fats?
TOT CHOL = increases
LDL-C = increases
HDL-C = decreases
58
How are HDL-C and TG affected by a diet high in sugars?
```
HDL-C = decreases
TG = increases
```
59
How are HDL-C and TG affected by alcohol?
```
HDL-C = increases
TG = increases
```
60
How are TOT-CHOL, LDL-C, HDL-C affected by smoking?
TOT CHOL = increases/no change
LDL-C = increases/no change
HDL-C = decreases
61
How are HDL-C and TG affected by lack of physical activity
```
HDL-C = decreases
TG = increases
```
62
How are TOT-CHOL, LDL-C, HDL-C, TG affected by thiazide diuretics
TOT CHOL = increases
LDL-C = increases
HDL-C = increases/no change
TG = increases
63
How are HDL-C and TG affected by beta blockers?
```
HDL-C = decreases
TG = increases
```
64
How are HDL-C and TG affected by obesity?
```
HDL-C = decreases
TG = increases
```
65
How does hypercholesterolemia occur in obesity?
total calories/increased saturated fa., cholesterol --> overproduction of VLDL particles --> VLDL-TG ---> VLDL remnants --> Conversion to LDL --> reduced activity of LDL receptors --> accumulation in blood
66
Why does HDL decrease in obesity?
increased catabolism of HDL by excess of adipose tissue
- increased uptake of HDL 2 by adipocytes
- increase clearance of apoA1 --> HDL catabolism
67
What is the importance of apoproteins?
* Primarydeterminantsofthemetabolicfateoflipoproteins
* Reflectchangesinlipoproteincomposition
* Indicative of # of lipoproteins in plasma (concentration)
* Apoproteinlevelsmaybebetterpredictorsofheartdisease than lipid levels and may correlate with the severity of the disease
* Aid in diagnostic of lipoprotein disorders and risk for developing CHD or CVD
68
What is the main lipoprotein affected in type I hyperlipoproteinemia?
chylomicrons
69
What is the specific marker of type I hyperlipoproteinemia?
absence or deficiency of LPL or apo C-II
70
What is the main lipoprotein affected in type IIa hyperlipoproteinemia?
LDL
71
What is the specific marker of type IIa hyperlipoproteinemia?
none (polygenic)
72
What is the main lipoprotein affected in type IIb hyperlipoproteinemia?
LDL + VLDL
73
What is the specific marker of type IIb hyperlipoproteinemia?
Mutation of LDL receptor or apo B
74
What is the main lipoprotein affected in type III hyperlipoproteinemia?
Beta VLDL
75
What is the specific marker of type III hyperlipoproteinemia?
Apo E2/E2
76
What is the main lipoprotein affected in type IV hyperlipoproteinemia?
VLDL
77
What is the specific marker of type IV hyperlipoproteinemia?
none
78
What is the main lipoprotein affected in type V hyperlipoproteinemia?
chylo + VLDL
79
What is the specific marker of type V hyperlipoproteinemia?
serum aspect: chylo band over VLDL
80
What is Postprandial effect of obesity on lipoprotein metabolism?
due to excess calories (lipids and CHO)
81
What is Postabsorptive effect of obesity on lipoprotein metabolism?
due to high adipose tissue and hormones sensitive lipase (HSL) activity (bc of insulin resistance) resulting in increased FFA flux to liver
