Dyslipidemia Part 1 Flashcards
Thiazide diuretics
Increase TC
Increase LDL
Increase/same HDL
Increase TG
B-blockers
Decrease HDL
Increase TG
Corticosteroids
Increase ALL lipid (including HDL)
Estrogens
Decrease TC and LDL
Increase HDL and TG
Benzodiazepine
Increase TG
Decrease HDL
Retinoic acid
Increase TC, LDL, TG, decrease HDL
Antiretroviral
Increase TG
Diabetes
Increase TC, LDL, TG
Decrease HDL
Hypothyroidism
Increase TC, LDL, TG
Renal failure
Increase TC, TG, decrease HDL
Obesity
Decrease HDL and TG Increases
Cirrhosis
Increase TC, TG and decrease HDL
High cholesterol diet
Increase TC, LDL, HDL remains the same
High SFA diet
Increase in TC, LDL, HDL
High Trans fat diet
Increase TC, LDL while decreasing HDL
High sugar diet
Increase TG while decreasing HDL
High alcohol diet
Increase HDL and TG
Smoking
TC and LDL increase or remain the same while HDL decreases
Lack of PA
HDL decreases while TG increases
Explain the effects of obesity on lipoprotein metabolism
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
What is the consequence of increased production of VLDL and increased lipolysis in obesity?
Normal VLDL and LDL, but increased fat deposits (adipose tissue). HDL will NOT decrease if this balance is achieved
How is hyperTG caused in obesity?
May have a defect in the lipolytic effect (HSL) and will cause an accumulation of VLDL (not deposited), causing hyperTG and likely decreased HDL
How is hypercholesterolemia caused in obesity?
Defective LDL receptor, high SFA diet
(T/F) All individuals who are obese have high LDL levels
FALSE, need a defective receptor, or high SFA intake
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
What is higher BMI associated with?
Lower HDL
(T/F) Higher BMI is associated with higher LDL
False, associate with lower HDL
What are the two key factors associated with low HDL?
High BMI
Abdominal obesity
(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
Abdominal fat and lower HDL is has a more stronger association in ___
Men and post-menopausal women
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
Which form of HDL is likely to undergo RCT? Which form is transported to liver?
HDL3
HDL2
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
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
What is sceened?
- History and physical examination
- Standard lipid panel
- Glucose
- eGFR
What is included in a standard lipid panel?
TC
LDL-C
HDL-C
TG
Lipid testing can be done ___
non-fasting
What is optional in-screening?
- Apo-B instead of LDL cholesterol
- Urine albumin:creatinine ratio (renal function)
(T/f) Fasted lipid and lipoprotein testing is recommended
F, non-fasting (more accessible)
When should individuals have fasted lipid and lipoprotein testing?
If TG levels >4.5 mmol/L
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
What is promoted to calculate non-HDL C?
TC - HDL-C = non-HDL C
CV risk assessment to be completed every ___ for men and women aged ___
3-5 years
40-75
What are the two risk assessment models?
10-year (Framingham Model) Cardiovascular Age (CV Life Expectancy Model)
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
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
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
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
High risk FRS?
> /= 20%
Low risk FRS?
<10%
Intermediate risk FRS?
10-19%
Statin indicated conditions? (CAC-D)
- Clinical atherosclerosis
- Abdominal aortic aneurysm
- Chronic Kidney disease
- Diabetes (most)
- LDL-C >/= 5 mmol/L
When is diabetes a statin indicated condition?
- Age >40 y/o
- Age > 30y y/o and 15 yr duration (T1DM)
- Microvascular disease
Statin indicated LDL-C level?
> /= 5 mmol/L
Primary prevention conditions?
- Intermediate Risk
- FRS >/= 20%
- Men over 50 and women over 60 with one additional risk factor
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
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
(T/F) Patient with High risk FRS (>/= 20%) is a statin-indicated condition
F, is a primary prevention condition
(T/F) Patient with FRS of 15% and LDL-C of 4 mmol/L is a primary prevention condition
True
What indicates Low risk and no Pharmacotherapy
FRS <10%
What does non-HDL cholesterol include?
All Apo-B particles, LDL, VLDL, IDL, Lp(a), CM, CM remnants
Apo-B containing lipoproteins are known as ____ and are ____
Non-HDL cholesterol, atherogenic
What is recommended as an alternative target to LDL-C when evaluating risk in adults?
Non-HDL-C and Apo-B
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
(T/F) Stating therapy is recommended for patients with FRS <10%
False
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
Primary target goal in intermediate risk patients?
<2 mmol/L or >50% decease in LDL-C (Same as high risk)
Primary target goal in low risk patient?
> 50% decrease in LDL-C
Alternative target goal in high risk patients?
-Apo-B <0.8 g/L or non-HDL <2.6 mmol/L
Alternative target goal in intermediate risk patients?
Same as high risk
Alternative target goal in low risk patients?
None
Define atherosclerosis
Thickening of the blood vessel wall caused by the presence of an atherosclerotic plaque
When is the ath plaque dangerous?
If it completely blocks off or ruptures (ischemia)
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
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
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.
Damage to endothelial wall?
- HTN
- Smoking
- Ang II
- Decreased NO (Smoking, Ang II)
- Glycated proteins
- Oxidized LDL
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
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
Macrophages secrete cytokines, what else does it activates? What does that secrete?
T-cell
-TNF-alpha
-IFN-gamma
Further aggravates the inflammatory state
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.
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.
Examples of ath risk factors
- Family history
- Age/Sex (65 y/o W and 55 y/o M)
- Obesity (abdominal)
- Dyslipidemia
- HTN
- DM
(T/F) Hyperlipidemia is always a risk factor for atherosclerosis
FALSE - hyperlipidemia also includes high HDL, which would be a good thing
Irreversible RF CVD?
- Age
- Male
- Genetics
Age CVD increases men?
Men over 55
Age CVD increased women?
Women over 65
Reversible RF CVD?
- DM
- HTN
- Abdominal obesity
- Hyperlipidemia
- Low HDL C
Low HDL C men?
<1.0 mmol/L
Low HDL C women?
<1.3 mmol/L
Apo-B 100 is of _____ origin
Hepatocyte
Apo-B 48 is of ____ origin
Enterocyte
Explain the endogenous pathway of cholesterol metabolism
Learn it
Explain the exogenous pathway of cholesterol metabolism
Learn it
CM and VLDL
contain more TG
LDL contains more
CE
HDL contains more
Apo-P and phospholipids
Normal TC
<5.2 mmol/L
Normal HDL
1.-1.5 mmol/L (Higher the better)
Normal LDL
<2.6 mmol (High risk should aim for lower)
Normal TG
<1.7 mmol/L
Function of apoproteins?
- Stability
- Activation of enzymes (Apo-CII)
- Interact with receptors (Apo-B100)
Apoproteins are major determinants if what?
The metabolic fate of lipoproteins:
- changes is composition
- indicative of # in plasma
- indicative of presence/severity of diseases
CM apoproteins?
A-I, A-IV
B-48
C-II, C-III
E
VLDL apoproteins
B-100
C-II
E
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
Most common Apo-E mutation? Most detrimental?
Apo E3/E3
Apo E2/E2 (least common)
What happens in the Apo E2/E2 mutation?
Generates an apolipoprotein that will NOT be recognized by the LDL receptor
Primary cause of dyslipidemias?
Genetics - a single or polygenetic abnormality
Secondary cause of dyslipidemias?
Environments/predisposition, disease state
What are the 3 hypolipoproteinemias? (Rare)
1) Abetalipoproteinemia
2) Familial hypobetalipoproteinemia
3) Familial alpha-lipoprotein deficiency (Tangiers disease)
Abetalipoproteinemia
Absence in Apo-B synthesis results in no CM/VLDL/LDL and TAG accumulation in liver and intestine
Familial hypobetalipoproteinemia
Decrease in apo-B synthesis results in LDL levels 10-50% of normal range while CM remains the same
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.
Hypercholesterolemia?
Increased LDL, causes vascular diseases and xanthomas. Serum remains normal. + CVD risk
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
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
Dysbetalipoproteinemia?
E2/E2 not recognized, accumulation of VLDL/IDL. Serum more white and IDL accumulates on-top.
Hypertriglyceredemia?
Accumulation of TG and VLDL, while HDL decreases.. Exacerbated by alcohol and diabetes. Serum white due to TG accumulation.
Mixed hyperlipidemia ?
Visual band of CM floating within blood, high TG and VLDL. Serum white with CM band.
Which serums appears normal?
Hypercholesterolemia, as only LDL increases
Which serum appears white-ish?
All but hypercholesterolemia
Which serum has band of CM?
- Hyperchylomicronemia
- Mixed Hyperlipidemia
Which serum has IDL band?
-Dysbetalipoproteinemia
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.
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)
