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PM Endocrinology > 7.6 Lipid disorders > Flashcards

7.6 Lipid disorders Flashcards

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1
Q

What is the composition of lipoproteins?

A

lipids (cholesteryl esters & triglycerides) + phospholipids + proteins

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2
Q

What are the main classes of lipoprotein?

A 
>Chylomicrons
>VLDL
>IDL
>LDL
>HDL
>Lp(a)
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3
Q

What is the conversion from mg/dl to mmol/L for chol, LDL, and HDL?

A

divide by 39

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4
Q

What is the conversion from mg/dl to mmol/L for TG?

A

divide by 89

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5
Q

What is the conversion from glucose mg/d to mmol/L?

A

divide by 18

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6
Q

What is the name of the equation used to calculate LDL?

A

Friedewald equation

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7
Q

How is LDL calculated?

A

LDL-C = TC- HDL-C – (TG/2.2)

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8
Q

In what situations may LDL be underestimated?

A

Underestimated if TG > 2.5 or LDL-C < 1.8 (in which case directly measure LDL-C)

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9
Q

When should chol profile be measured in relation to AMI?

A

Levels stable up to 24 hours after ACS then decrease and may take 6 weeks to return to normal. Levels may be unstable in any acute illness

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10
Q

List 3 main physical exam findings in hyperlipidaemia?

A

> Tendon xanthomas
Eruptive xanthomas on extensor surfaces
Xanthelasma

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11
Q

What lipid abnormality and level does tendon xanthomas imply?

A

LDL > 7.7

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12
Q

What lipid abnormality and level does eruptive xanthomas on extensor surfaces imply?

A

TG > 11

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13
Q

What are the 5 components of diagnosis for metabolic syndrome?

A
  1. Waist circumference
  2. TG
  3. HDL
  4. BP
  5. FBGL
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14
Q

What is the waist circumference cutoffs for metabolic syndrome?

A

102 cm men, 88 cm women

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15
Q

What is the TG cut off for diagnosis of metabolic syndrome?

A

> 1.7

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16
Q

What is the HDL cut off for diagnosis of metabolic syndrome?

A

< 1.0 (men), <1.28 (women)

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17
Q

What is the BP cut off for diagnosis of metabolic syndrome?

A

> 130/85

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18
Q

What is Lp(a)

A

> LDL particle bound to apo(a) via apoB

>Genetic variants associated with MI

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19
Q

What are two broad categories of lipoprotein disorders?

A

Primary and secondary

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20
Q

What are two main primary lipoprotein disorders?

A

Familial hypercholesterolaemia and familial hypertriglyceridaemia (there are many others)

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21
Q

List 7 secondary lipoprotein disorders?

A

1) DM
2) Hypothyroidism
3) Nephrotic syndrome
4) Liver failure
5) Alcohol
6) Thiazides
7) Protease inhibitors

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22
Q

What is the pattern of lipid abnormality in DM?

A

High TG

Low HDL

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23
Q

What is the pattern of lipid abnormality in hypothyroidism?

A

High LDL

High TG

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24
Q

What is the pattern of lipid abnormality in nephrotic syndrome?

A

High LDL

High TG

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25
What is the pattern of lipid abnormality in liver failure?
low LDL
26
What is the pattern of lipid abnormality in alcoholism?
High TG | High HDL
27
What is the pattern of lipid abnormality from thiazide diuretics?
High LDL | High TG
28
What is the pattern of lipid abnormality from protease inhibitors?
High TG
29
List 7 classes of drugs used to treat dyslipidaemia
``` Statins Ezetimibe PSCK9i Fibrates Omega-3 FAs Resins Niacin ```
30
What % reduction range do statins cause in LDL?
20-60%
31
What % increase in HDL do statins cause?
5-10%
32
What % reduction in TG do statins cause?
10-25%
33
List 4 side-effects of statins
1) Raised ALT 2) Myalgias 3) Rhabdomyolysis 4) Diabetes mellitus
34
What is the rate of ALT elevation with statins?
0.5-3%
35
What is the rate of myalgias with statins?
<10%
36
What is the rate of rhabdomyolysis with statins?
<0.1%
37
Is the risk of diabetes with statins idiosyncratic?
No there is a dose-dependent increase in risk, screen for DM if there are risk factors
38
What is the recommended monitoring of LFTs and CK with statin use?
monitor aminotransferase and CK at baseline, repeat during treatment if indicated clinically
39
What is the recommendation for stopping statin with ALT elevation?
Stop for persistent elevation > 3 x ULN
40
What is the recommendation for stopping statin for CK elevation?
stop if CK > 10 x ULN NB also stop if there is persistent unexplained muscle pain or weakness even if CK is normal
41
What LDL lowering is expected with ezetimibe?
about 25%
42
What LDL lowering is expected with PCSK9i on top of statin?
60%
43
By how much will PCSK9i raise HDL?
5-10%
44
By how much will PSCK9i lower TG?
About 20% | 15-25%
45
By how much do fibrates lower LDL?
About 10% | 5-15%
46
By how much do fibrates raise HDL?
About 10% | 5-15%
47
By how much do fibrates lower TG?
35-50%
48
What are 2 common/important side effects with fibrates?
(1) Myopathy risk increases with statin | (2) Increase creatinine, check renal function 6 monthly
49
What effect does Omega-3 FA have on LDL?
raise 5%
50
What effect does omega-3 have on HDL?
raise 3%
51
What effect does omega-3 have on TG?
lower 25-50%
52
What dose of omega-3 is needed for benefit?
generally 4g /day
53
What are two important forms of omega-3 FAs? just given the TLAs
EPA and DHA
54
What is EPA?
eicosapentaenoic acid
55
What is DHA?
docosahexaenoic acid
56
What effect do resins have on LDL?
decrease by about 20%
57
What qualitative effect does niacin have on lipid profile?
Increase HDL-C and decrease TG and LDL
58
What B vitamin is niacin?
B3
59
When treating with statins, every 1 mmol decrease in LDL-C is associated with what % decrease in major vascular events (CV death, MI, stroke, revasc) in individuals with and without CVD?
22%
60
What trial and in what year/journal was it published showed ezetimibe decreased major vascular events including MI and stroke when added to statin post-ACS?
IMPROVE-IT, NEJM 2015
61
Name 2 approved PCSK9is
Evolocumab | Alirocumab
62
What is the brand name of evolocumab?
Repatha
63
What is the brand name of alirocumab?
Praluent
64
Meta-analysis of pooled data from 4 phase 2 trials of evolocumab in 1359 patients showed what magnitude of LDL-C reduction in what 3 settings?
60% reduction in LDL-C on top of statin, as monoRx and in FH
65
What trial and in what year/journal published showed improved CV outcomes for evolocumab?
FOURIER trial, NEJM 2017
66
What trial and in what year/journal published showed improved outcomes for alirocumab?
ODYSSEY OUTCOMES trial, NEJM 2018
67
What is the impact of treating HDL?
Low levels associated with increased risk of MI, but no clinical benefit shown by raising
68
What is the threshold TG level to treat to reduce the risk of pancreatitis?
>500-1000 mg/dL (>5.6-11.2)
69
What study and journal/year published that evaluated for CV outcomes with fibrates?
ACCORD investigators (simvastatin +/- fenofibrate) NEJM 2010
70
What was the result of the ACCORD investigators (simvastatin +/- fenofibrate) NEJM 2010 study?
negative overall, possible benefit in men and those with high TG/low HDL subgroups
71
What trial and in what/year journal published proved improved CV outcomes with high dose EPA (4g/day) in patients with ASCVD or DM?
REDUCE-IT trial NEJM 2019
72
What target should Lp(a) be lowered to in intermediate to high risk patients if it is being used?
<1.2
73
In the 2018 ACC/AHA cholesterol guidelines, what is the definition of ASCVD?
``` >History of ACS >Stable angina >Arterial revascularisation >Stroke >TIA >PAD ```
74
What are the 5 groups considered in the In the 2018 ACC/AHA cholesterol guidelines?
1. Very high risk ASCVD 2. Clinical ASCVD 3. LDL-C >4.8 4. Diabetes age 40-75 5. Age 40-75 without above for whom 10-year risk should be calculated
75
In the 2018 ACC/AHA cholesterol guidelines how is very high risk ASCVD defined?
>Multiple major ASCVD events (MI, stroke, symptomatic PAD) OR >1 major event + multiple high-risk conditions
76
What 7 multiple high-risk conditions are considered in the 1 major event + multiple high risk conditions to qualify for the category of very high risk ASCVD in the 2018 ACC?AHA guidelines?
(1) Age > 65 years (2) DM (3) HT (4) CKD (5) Smoking (6) FH (7) Prior PCI/CABG
77
What is the website for 10 year risk calculation in Australia?
www.cvdcheck.org.au/calculator
78
What 8 additional risk factors does the 2018 ACC/AHA guidelines recommend considering in making treatment decisions?
1) LDL > 4.1 2) Metabolic syndrome 3) CKD 4) FHx premature CAD 5) hsCRP 6) Lp(a) > 1.2 mmol 7) ABI<0.9 8) high risk ethnic groups
79
What is the recommended treatment for very high risk ASCVD patients in the 2018 AHA/ACC guidelines?
>High intensity statin | >Add EZE then PSCK9 if LDL > 1.8
80
What is the recommended treatment for clinical ASCVD in the 2018 AHA/ACC guidelines?
>High intensity statin (? Mod if >75 years) | >Add Eze if LDL > 1.8
81
What is the recommended treatment for LDL-C > 4.8 in the 2018 AHA/ACC guidelines ?
>High intensity statin | >Add EZE or PSCK9 if LDL > 2.5
82
What is the recommended treatment for diabetes age 40-75 in the 2018 AHA/ACC guidelines?
Diabetes, age 40-75: high intensity statin (? Moderate if no CVRFs)
83
For patients age 40-75 in none of the other specific categories in the 2018 ACC/AHA guidelines, what are the levels 10-year risk for which different recommendations are made?
>20% 7.5-20% 5-7.5% <5%
84
What is the recommendation from the 2018 ACC/AHA for patients age 40-75 with 10 year risk >20 %?
high intensity statin
85
What is the recommendation from the 2018 ACC/AHA for patients age 40-75 with 10 year risk 7.5-20 %?
moderate-intensity statin; if uncertain consider CAC
86
What is the recommendation from the 2018 ACC/AHA guidelines for patients age 40-75% with a 10-year risk of 5-7.5%
moderate-intensity statin reasonable
87
What is the recommendation from the 2018 AHA/ACC guidelines for patients age 40-75 with a 10-year risk of <5%
lifestyle
88
In general a doubling of statin dose with further reduce LDL by what %?
6%
89
High intensity statin will lower LDL by what %?
>50%
90
Moderate intensity statin will lower LDL by what%?
30-50%
91
Low intensity statin will lower LDL by what%?
<30%
92
What are the options for high intensity statin?
>Rosuvastatin 20-40 mg >Atorvastatin 40-80 mg >Simvastatin 80 mg (?)
93
What are the options for moderate intensity statin?
>Rosuvastatin 5-10 mg >Atorvastatin 10-20 mg >Simvastatin 20-40 mg
94
What are the options for low-intensity statin?
>Simvastatin 10 mg >Pravastatin 10-20 mg >Lovastatin 20 mg >Fluvastatin 20-40 mg

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