Dyslipidemia Part 1 Flashcards
(126 cards)
1
Q
Thiazide diuretics
A
Increase TC
Increase LDL
Increase/same HDL
Increase TG
2
Q
B-blockers
A
Decrease HDL
Increase TG
3
Q
Corticosteroids
A
Increase ALL lipid (including HDL)
4
Q
Estrogens
A
Decrease TC and LDL
Increase HDL and TG
5
Q
Benzodiazepine
A
Increase TG
Decrease HDL
6
Q
Retinoic acid
A
Increase TC, LDL, TG, decrease HDL
7
Q
Antiretroviral
A
Increase TG
8
Q
Diabetes
A
Increase TC, LDL, TG
Decrease HDL
9
Q
Hypothyroidism
A
Increase TC, LDL, TG
10
Q
Renal failure
A
Increase TC, TG, decrease HDL
11
Q
Obesity
A
Decrease HDL and TG Increases
12
Q
Cirrhosis
A
Increase TC, TG and decrease HDL
13
Q
High cholesterol diet
A
Increase TC, LDL, HDL remains the same
14
Q
High SFA diet
A
Increase in TC, LDL, HDL
15
Q
High Trans fat diet
A
Increase TC, LDL while decreasing HDL
16
Q
High sugar diet
A
Increase TG while decreasing HDL
17
Q
High alcohol diet
A
Increase HDL and TG
18
Q
Smoking
A
TC and LDL increase or remain the same while HDL decreases
19
Q
Lack of PA
A
HDL decreases while TG increases
20
Q
Explain the effects of obesity on lipoprotein metabolism
A
Excessive dietary consumption (CHOs) and alcohol will suppress oxidation of Acyl-CoA –> Packaged into VLDL, increasing lipogenesis while lipolysis increases and TGs uptake into the peripheral tissues
21
Q
What is the consequence of increased production of VLDL and increased lipolysis in obesity?
A
Normal VLDL and LDL, but increased fat deposits (adipose tissue). HDL will NOT decrease if this balance is achieved
22
Q
How is hyperTG caused in obesity?
A
May have a defect in the lipolytic effect (HSL) and will cause an accumulation of VLDL (not deposited), causing hyperTG and likely decreased HDL
23
Q
How is hypercholesterolemia caused in obesity?
A
Defective LDL receptor, high SFA diet
24
Q
(T/F) All individuals who are obese have high LDL levels
A
FALSE, need a defective receptor, or high SFA intake
25
There is likely an increase in VLDL in obesity (due to high dietary intakes) what explain the HDL lowering relationship?
As VLDL increases, CETP activity will increase as more TG (from VLDL) is exchanged for a CE (from HDL). HDL that is saturate with TG will be destined for catabolism in adipose tissue and in liver
26
What is higher BMI associated with?
Lower HDL
27
(T/F) Higher BMI is associated with higher LDL
False, associate with lower HDL
28
What are the two key factors associated with low HDL?
High BMI
| Abdominal obesity
29
(T/F) There is a stronger association with total body fat than abdominal fat in lower HDL
False, stronger correlation with higher abdominal fat and lower HDL levels
30
Abdominal fat and lower HDL is has a more stronger association in ___
Men and post-menopausal women
31
Besides uptake and catabolism in LIVERR of HDL once saturated with TG, what are other possible mechanism?
Increased HDL uptake by adipocytes
| Increased clearance of Apo-A1
32
Which form of HDL is likely to undergo RCT? Which form is transported to liver?
HDL3
| HDL2
33
According to the CCS 2016 guidelines, which ages should be screened for CVD risk? Ethnic groups?
Men AND Women > 40 y/o
| High risk ethnic groups: south asian, indigenous
34
Which conditions require screening for CVD risk despite age? (A-CAD-OF)
- Arterial HTN
- Clinical evidence of atherosclerosis
- Abdominal aortic aneurysm
- DM
- Obesity
- Family history
35
What is sceened?
- History and physical examination
- Standard lipid panel
- Glucose
- eGFR
36
What is included in a standard lipid panel?
TC
LDL-C
HDL-C
TG
37
Lipid testing can be done ___
non-fasting
38
What is optional in-screening?
- Apo-B instead of LDL cholesterol
| - Urine albumin:creatinine ratio (renal function)
39
(T/f) Fasted lipid and lipoprotein testing is recommended
F, non-fasting (more accessible)
40
When should individuals have fasted lipid and lipoprotein testing?
If TG levels >4.5 mmol/L
41
In non-fasting lipid and lipoprotein levels, how will lipid panel be affected?
- Minimal change in non-HDL-C
- Slight decrease in LDL-C
- Small increase in TG
42
What is promoted to calculate non-HDL C?
TC - HDL-C = non-HDL C
43
CV risk assessment to be completed every ___ for men and women aged ___
3-5 years
| 40-75
44
What are the two risk assessment models?
```
10-year (Framingham Model)
Cardiovascular Age (CV Life Expectancy Model)
```
45
Whats important about the risk assessment tool?
Info should be shared with patients to support shared decision making and improve the likelihood that they will reach lipid-targets
46
How was the 10-year FRS developed?
Assessed a baseline of a population, then followed them for as long as possible and were able to track risk factors that contributed or did not contribute to their development of CVD/mortality
47
Describe the steps used in the FRS scoring model
1) Gender, age group, lipid-profile, BP, smoking and diabetes risk points are added.
2) Using risk points from step 1, patients 10 -year CVD risk % can be identified.
3) Using risk points calculated in Step-1, we can also determine cardiovascular age.
4) Based on the 10-year CVD risk %, we can determine if patient is low, moderate or high-risk
48
What is important concerning family history and FS score? (Modified FRS score)
That is 10-year risk % DOUBLES for individuals between the ages of 30 and 59 without diabetes and in presence of a positive family history of premature CVD
49
High risk FRS?
>/= 20%
50
Low risk FRS?
<10%
51
Intermediate risk FRS?
10-19%
52
Statin indicated conditions? (CAC-D)
- Clinical atherosclerosis
- Abdominal aortic aneurysm
- Chronic Kidney disease
- Diabetes (most)
- LDL-C >/= 5 mmol/L
53
When is diabetes a statin indicated condition?
- Age >40 y/o
- Age > 30y y/o and 15 yr duration (T1DM)
- Microvascular disease
54
Statin indicated LDL-C level?
>/= 5 mmol/L
55
Primary prevention conditions?
- Intermediate Risk
- FRS >/= 20%
- Men over 50 and women over 60 with one additional risk factor
56
What are intermediate risks that qualify for primary prevention conditions? (Hint FRS between 10-19% and [3])
```
FRS 10-19% AND:
-LDL >3.5 mmol/L
OR
-Non-HDL-C > 4.3 mmol/L
OR
-Apo-B > 1.2 g/L
```
57
What additional risk factors for men over 50 and women over 60 pose an intermediate risk that qualify for primary prevention conditions?
- Low HDL-C
- Impaired fasting glucose
- High waist circumference
- Smoker
- HTN
58
(T/F) Patient with High risk FRS (>/= 20%) is a statin-indicated condition
F, is a primary prevention condition
59
(T/F) Patient with FRS of 15% and LDL-C of 4 mmol/L is a primary prevention condition
True
60
What indicates Low risk and no Pharmacotherapy
FRS <10%
61
What does non-HDL cholesterol include?
All Apo-B particles, LDL, VLDL, IDL, Lp(a), CM, CM remnants
62
Apo-B containing lipoproteins are known as ____ and are ____
Non-HDL cholesterol, atherogenic
63
What is recommended as an alternative target to LDL-C when evaluating risk in adults?
Non-HDL-C and Apo-B
64
What must be considered when using HDL-C and Apo-B?
Value and preferences, as most clinicians are most familiar with LDL-C and we recommend its use as the primary target, but recognize the advantages of non-HDL-C and Apo-B
65
(T/F) Stating therapy is recommended for patients with FRS <10%
False
66
Primary target goal in high risk patients? Coronary disease?
- <2 mmol/L or >50% decrease in LDL-C
| - <1.8 mmol/L if coronary disease
67
Primary target goal in intermediate risk patients?
<2 mmol/L or >50% decease in LDL-C (Same as high risk)
68
Primary target goal in low risk patient?
>50% decrease in LDL-C
69
Alternative target goal in high risk patients?
-Apo-B <0.8 g/L or non-HDL <2.6 mmol/L
70
Alternative target goal in intermediate risk patients?
Same as high risk
71
Alternative target goal in low risk patients?
None
72
Define atherosclerosis
Thickening of the blood vessel wall caused by the presence of an atherosclerotic plaque
73
When is the ath plaque dangerous?
If it completely blocks off or ruptures (ischemia)
74
What are the two hypothesis of the development of ath? Where do they link?
Endothelial injury and lipid-filtration, where oxidized LDL, macrophages and fatty streak will contribute to the endothelial injury
75
Describe the endothelial injury hypothesis
Damage to endothelial wall, which causes the adherence of platelets which will release platelet-derived growth factors. This will encourage cell proliferation and migration, eventually resulting in the formation of a lesion
76
Describe the lipid-infiltration process
High amounts of circulated LDL will enter sub-endothelial space, will become oxidized, engulfed by macrophages to become foam cells and result in the formation of a fatty streak.
77
Damage to endothelial wall?
- HTN
- Smoking
- Ang II
- Decreased NO (Smoking, Ang II)
- Glycated proteins
- Oxidized LDL
78
Explain the progression of ath to foam cells.
LDL exceeds endocytic capacity, and infiltrates into sub-endothelial space. Subject to oxidation, monocytes transmigrate the endothelium and become macrophages and engulf the oxidized LDL, becoming foam cell.s
79
What cytokines do macrophages secrete? Which one interacts with CRP (from liver) to activate other inflammatory molecules?
- TNF-alpha
- IL-G --> Interacts with CRP
- IL-1
- NF-xB
80
Macrophages secrete cytokines, what else does it activates? What does that secrete?
T-cell
-TNF-alpha
-IFN-gamma
Further aggravates the inflammatory state
81
Explain the formation of the fibrous cab
Endothelial cells will secrete growth factor FGF and FDGF which will promote smooth muscle cell migration and proliferation. Smooth muscle cells secrete collage --> Formation of the fibrous cap. Accumulation of these cells contributes to the narrowing of the vessel.
82
What is a smooth muscle derived foam cell? How is it sustained?
When the fibrous cap attracts lipids, will be sustained by the growth of a blood vessel.
83
Examples of ath risk factors
- Family history
- Age/Sex (65 y/o W and 55 y/o M)
- Obesity (abdominal)
- Dyslipidemia
- HTN
- DM
84
(T/F) Hyperlipidemia is always a risk factor for atherosclerosis
FALSE - hyperlipidemia also includes high HDL, which would be a good thing
85
Irreversible RF CVD?
- Age
- Male
- Genetics
86
Age CVD increases men?
Men over 55
87
Age CVD increased women?
Women over 65
88
Reversible RF CVD?
- DM
- HTN
- Abdominal obesity
- Hyperlipidemia
- Low HDL C
89
Low HDL C men?
<1.0 mmol/L
90
Low HDL C women?
<1.3 mmol/L
91
Apo-B 100 is of _____ origin
Hepatocyte
92
Apo-B 48 is of ____ origin
Enterocyte
93
Explain the endogenous pathway of cholesterol metabolism
Learn it
94
Explain the exogenous pathway of cholesterol metabolism
Learn it
95
CM and VLDL
contain more TG
96
LDL contains more
CE
97
HDL contains more
Apo-P and phospholipids
98
Normal TC
<5.2 mmol/L
99
Normal HDL
1.-1.5 mmol/L (Higher the better)
100
Normal LDL
<2.6 mmol (High risk should aim for lower)
101
Normal TG
<1.7 mmol/L
102
Function of apoproteins?
- Stability
- Activation of enzymes (Apo-CII)
- Interact with receptors (Apo-B100)
103
Apoproteins are major determinants if what?
The metabolic fate of lipoproteins:
- changes is composition
- indicative of # in plasma
- indicative of presence/severity of diseases
104
CM apoproteins?
A-I, A-IV
B-48
C-II, C-III
E
105
VLDL apoproteins
B-100
C-II
E
106
What is the issue is Apo-E mutations?
Exchangeable, and can be found on any lipoprotein where an mutation can have great effects on lipoprotein metabolism
107
Most common Apo-E mutation? Most detrimental?
Apo E3/E3
| Apo E2/E2 (least common)
108
What happens in the Apo E2/E2 mutation?
Generates an apolipoprotein that will NOT be recognized by the LDL receptor
109
Primary cause of dyslipidemias?
Genetics - a single or polygenetic abnormality
110
Secondary cause of dyslipidemias?
Environments/predisposition, disease state
111
What are the 3 hypolipoproteinemias? (Rare)
1) Abetalipoproteinemia
2) Familial hypobetalipoproteinemia
3) Familial alpha-lipoprotein deficiency (Tangiers disease)
112
Abetalipoproteinemia
Absence in Apo-B synthesis results in no CM/VLDL/LDL and TAG accumulation in liver and intestine
113
Familial hypobetalipoproteinemia
Decrease in apo-B synthesis results in LDL levels 10-50% of normal range while CM remains the same
114
Familial alpha-lipoprotein deficiency (Tangiers disease)
Absence of HDL, causing CE to accumulate in tissues. Results in normal CM, VLDL, LDL but hyperTG due to lack of RCT.
115
Hypercholesterolemia?
Increased LDL, causes vascular diseases and xanthomas. Serum remains normal. + CVD risk
116
Combined hyperlipoproteinemia?
Mutation of LDL-receptor or apo-B. Causes increased lipid panel while HDL decreases. Symptoms include vascular diseases and serum appears lighter due to high TG. +++ CVD risk
117
Hypochylomicronemia?
Absence or deficiency in LPL/Apo-CII - Increasing CM even during fasting and TGs while HDL decreases. . Serum is very white with band of CM on top. 0 CVD risk
118
Dysbetalipoproteinemia?
E2/E2 not recognized, accumulation of VLDL/IDL. Serum more white and IDL accumulates on-top.
119
Hypertriglyceredemia?
Accumulation of TG and VLDL, while HDL decreases.. Exacerbated by alcohol and diabetes. Serum white due to TG accumulation.
120
Mixed hyperlipidemia ?
Visual band of CM floating within blood, high TG and VLDL. Serum white with CM band.
121
Which serums appears normal?
Hypercholesterolemia, as only LDL increases
122
Which serum appears white-ish?
All but hypercholesterolemia
123
Which serum has band of CM?
- Hyperchylomicronemia
| - Mixed Hyperlipidemia
124
Which serum has IDL band?
-Dysbetalipoproteinemia
125
Explain why obesity is not a major risk factor for dyslipidemia's?
Obesity primarily only lowers HDL as TG is elevated. Co-morbidities associated with obesity are more likely to pose risk factors.
126
What is the effect of obesity on dyslipidemia?
Constant flux of FFA during fed and fasted state. In fasted state, HSL activity is increased (likely due to insulin resistance)
