7.6 Lipid disorders Flashcards

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
Q

What is the pattern of lipid abnormality in liver failure?

A

low LDL

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26
Q

What is the pattern of lipid abnormality in alcoholism?

A

High TG

High HDL

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27
Q

What is the pattern of lipid abnormality from thiazide diuretics?

A

High LDL

High TG

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28
Q

What is the pattern of lipid abnormality from protease inhibitors?

A

High TG

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29
Q

List 7 classes of drugs used to treat dyslipidaemia

A
Statins
Ezetimibe
PSCK9i
Fibrates
Omega-3 FAs
Resins
Niacin
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30
Q

What % reduction range do statins cause in LDL?

A

20-60%

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31
Q

What % increase in HDL do statins cause?

A

5-10%

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32
Q

What % reduction in TG do statins cause?

A

10-25%

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33
Q

List 4 side-effects of statins

A

1) Raised ALT
2) Myalgias
3) Rhabdomyolysis
4) Diabetes mellitus

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34
Q

What is the rate of ALT elevation with statins?

A

0.5-3%

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35
Q

What is the rate of myalgias with statins?

A

<10%

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36
Q

What is the rate of rhabdomyolysis with statins?

A

<0.1%

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37
Q

Is the risk of diabetes with statins idiosyncratic?

A

No there is a dose-dependent increase in risk, screen for DM if there are risk factors

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38
Q

What is the recommended monitoring of LFTs and CK with statin use?

A

monitor aminotransferase and CK at baseline, repeat during treatment if indicated clinically

39
Q

What is the recommendation for stopping statin with ALT elevation?

A

Stop for persistent elevation > 3 x ULN

40
Q

What is the recommendation for stopping statin for CK elevation?

A

stop if CK > 10 x ULN

NB also stop if there is persistent unexplained muscle pain or weakness even if CK is normal

41
Q

What LDL lowering is expected with ezetimibe?

A

about 25%

42
Q

What LDL lowering is expected with PCSK9i on top of statin?

A

60%

43
Q

By how much will PCSK9i raise HDL?

A

5-10%

44
Q

By how much will PSCK9i lower TG?

A

About 20%

15-25%

45
Q

By how much do fibrates lower LDL?

A

About 10%

5-15%

46
Q

By how much do fibrates raise HDL?

A

About 10%

5-15%

47
Q

By how much do fibrates lower TG?

A

35-50%

48
Q

What are 2 common/important side effects with fibrates?

A

(1) Myopathy risk increases with statin

(2) Increase creatinine, check renal function 6 monthly

49
Q

What effect does Omega-3 FA have on LDL?

A

raise 5%

50
Q

What effect does omega-3 have on HDL?

A

raise 3%

51
Q

What effect does omega-3 have on TG?

A

lower 25-50%

52
Q

What dose of omega-3 is needed for benefit?

A

generally 4g /day

53
Q

What are two important forms of omega-3 FAs? just given the TLAs

A

EPA and DHA

54
Q

What is EPA?

A

eicosapentaenoic acid

55
Q

What is DHA?

A

docosahexaenoic acid

56
Q

What effect do resins have on LDL?

A

decrease by about 20%

57
Q

What qualitative effect does niacin have on lipid profile?

A

Increase HDL-C and decrease TG and LDL

58
Q

What B vitamin is niacin?

A

B3

59
Q

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?

A

22%

60
Q

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?

A

IMPROVE-IT, NEJM 2015

61
Q

Name 2 approved PCSK9is

A

Evolocumab

Alirocumab

62
Q

What is the brand name of evolocumab?

A

Repatha

63
Q

What is the brand name of alirocumab?

A

Praluent

64
Q

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?

A

60% reduction in LDL-C on top of statin, as monoRx and in FH

65
Q

What trial and in what year/journal published showed improved CV outcomes for evolocumab?

A

FOURIER trial, NEJM 2017

66
Q

What trial and in what year/journal published showed improved outcomes for alirocumab?

A

ODYSSEY OUTCOMES trial, NEJM 2018

67
Q

What is the impact of treating HDL?

A

Low levels associated with increased risk of MI, but no clinical benefit shown by raising

68
Q

What is the threshold TG level to treat to reduce the risk of pancreatitis?

A

> 500-1000 mg/dL (>5.6-11.2)

69
Q

What study and journal/year published that evaluated for CV outcomes with fibrates?

A

ACCORD investigators (simvastatin +/- fenofibrate) NEJM 2010

70
Q

What was the result of the ACCORD investigators (simvastatin +/- fenofibrate) NEJM 2010 study?

A

negative overall, possible benefit in men and those with high TG/low HDL subgroups

71
Q

What trial and in what/year journal published proved improved CV outcomes with high dose EPA (4g/day) in patients with ASCVD or DM?

A

REDUCE-IT trial NEJM 2019

72
Q

What target should Lp(a) be lowered to in intermediate to high risk patients if it is being used?

A

<1.2

73
Q

In the 2018 ACC/AHA cholesterol guidelines, what is the definition of ASCVD?

A
>History of ACS
>Stable angina
>Arterial revascularisation
>Stroke
>TIA
>PAD
74
Q

What are the 5 groups considered in the In the 2018 ACC/AHA cholesterol guidelines?

A
  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
Q

In the 2018 ACC/AHA cholesterol guidelines how is very high risk ASCVD defined?

A

> Multiple major ASCVD events (MI, stroke, symptomatic PAD) OR
1 major event + multiple high-risk conditions

76
Q

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?

A

(1) Age > 65 years
(2) DM
(3) HT
(4) CKD
(5) Smoking
(6) FH
(7) Prior PCI/CABG

77
Q

What is the website for 10 year risk calculation in Australia?

A

www.cvdcheck.org.au/calculator

78
Q

What 8 additional risk factors does the 2018 ACC/AHA guidelines recommend considering in making treatment decisions?

A

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
Q

What is the recommended treatment for very high risk ASCVD patients in the 2018 AHA/ACC guidelines?

A

> High intensity statin

>Add EZE then PSCK9 if LDL > 1.8

80
Q

What is the recommended treatment for clinical ASCVD in the 2018 AHA/ACC guidelines?

A

> High intensity statin (? Mod if >75 years)

>Add Eze if LDL > 1.8

81
Q

What is the recommended treatment for LDL-C > 4.8 in the 2018 AHA/ACC guidelines ?

A

> High intensity statin

>Add EZE or PSCK9 if LDL > 2.5

82
Q

What is the recommended treatment for diabetes age 40-75 in the 2018 AHA/ACC guidelines?

A

Diabetes, age 40-75: high intensity statin (? Moderate if no CVRFs)

83
Q

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?

A

> 20%
7.5-20%
5-7.5%
<5%

84
Q

What is the recommendation from the 2018 ACC/AHA for patients age 40-75 with 10 year risk >20 %?

A

high intensity statin

85
Q

What is the recommendation from the 2018 ACC/AHA for patients age 40-75 with 10 year risk 7.5-20 %?

A

moderate-intensity statin; if uncertain consider CAC

86
Q

What is the recommendation from the 2018 ACC/AHA guidelines for patients age 40-75% with a 10-year risk of 5-7.5%

A

moderate-intensity statin reasonable

87
Q

What is the recommendation from the 2018 AHA/ACC guidelines for patients age 40-75 with a 10-year risk of <5%

A

lifestyle

88
Q

In general a doubling of statin dose with further reduce LDL by what %?

A

6%

89
Q

High intensity statin will lower LDL by what %?

A

> 50%

90
Q

Moderate intensity statin will lower LDL by what%?

A

30-50%

91
Q

Low intensity statin will lower LDL by what%?

A

<30%

92
Q

What are the options for high intensity statin?

A

> Rosuvastatin 20-40 mg
Atorvastatin 40-80 mg
Simvastatin 80 mg (?)

93
Q

What are the options for moderate intensity statin?

A

> Rosuvastatin 5-10 mg
Atorvastatin 10-20 mg
Simvastatin 20-40 mg

94
Q

What are the options for low-intensity statin?

A

> Simvastatin 10 mg
Pravastatin 10-20 mg
Lovastatin 20 mg
Fluvastatin 20-40 mg