1
Q
Hyperlipidemia
A
dyslipidemia
dyslipoproteinemia
elevation of both cholesterol and triglycerides
2
Q
Hypercholesterolemia
A
elevation of cholesterol
3
Q
Hypertriglyceridemia
A
elevation of triglycerides
4
Q
Primary Dyslipidemia
A
genetic abnormality of cholesterol metabolism
5
Q
Secondary Dyslipidemia
A
diabetes mellitus excessive alcohol use hypothyroidism cholestatic liver disease renal disease smoking obesity medications (OCPs, thiazide diuretics, beta blockers, some atypical antipsychotics, protease inhibitors)
6
Q
Cholesterol
A
lipid that helps to form steroid hormones and bile acids
7
Q
Triglycerides
A
lipid that helps transfer energy from food to cells
TG=fat
transported into skeletal muscle and adipose tissue to use as energy
8
Q
Lipoproteins
A
how lipids are transported
contain proteins (apoproteins)
classified by density
9
Q
Low Density Lipoprotein
A
more triglycerides
“bad”
10
Q
High Density Lipoprotein
A
more apoproteins
low triglycerides
smaller size
“good”
11
Q
Total Cholesterol
A
HDL+LDL+VLDL
12
Q
Lipid Fractions: measured
A
most clinical labs measure
- total cholesterol
- triglycerides
- HDL
LDL and VLDL are calculated
13
Q
Lipid Fractions: calculated
A
most triglycerides are found in VLDL particles
VLDL cholesterol = TG/5
14
Q
Friedewald Equation
A
[LDL-chol]=[total chol]-[HDL-chol]-([TG]/5)
- must be fasting
- TG>200 –> est LDL will be significantly incorrect
15
Q
Cardiovascular Disease
A
cvd=ascvd
- coronary heart disease
- cerebrovascular disease
- peripheral artery disease
- aortic atherosclerosis and thoracic or abdominal aortic aneurysm
16
Q
CVD primary prevention
A
no evidence of ascvd
17
Q
CVD secondary prevention
A
known ascvd
goal: prevention of a second event
18
Q
ASCVD
A
fatty material collects in arterial walls, hardening over time
19
Q
ASCVD: process started by…
A
excess cholesterol (VLDL, LDL)
result of abnormal cholesterol metabolism
- genetic
- insulin resistance
- organ dysfunction
20
Q
ASCVD: process enhanced by…
A
lifestyle factors
- saturated/trans fats
- obesity
- smoking
- BP level
21
Q
Plaque Formation
A
small dense LDL enters and sticks to artery wall
- oxidation of LDL (pro-inflammatory, thrombotic)
- attracts macrophages (foam cells)
- endothelial dysfunction
- vasoconstriction
22
Q
Plaque Ruptures
A
MI in coronaries
TIA or CVA in brain
23
Q
Cardiovascular Risk Factors: non-modifiable
A
age
- M > 45
- F > 55
sex
M>F
family hx of premature heart disease in first degree relative
- M<55
- F<65
24
Q
Cardiovascular Risk Factors: modifiable
A
HTN DM dyslipidemia kidney disease obesity smoking HDL
25
CVD Risk Calculators
hard coronary framingham risk score
(designed to asses risk of heart disease only)
ACC/AHA risk estimator
(designed to assess risk of heart disease and stroke) (factors in race (AA) and diabetes)
26
Lipids and CVD Risk
inc LDL --> inc ASCVD risk
inc HDL --> dec ASCVD risk
27
Hyperlipidemia: physical exam
mostly asymptomatic
- xanthomatous tendons
- corneal arcus
- lipemia retinalis
- xanthelasma
- eruptive xanthomas
28
ATP III Guidelines: 1. obtain fasting lipid profile
<100 LDL = optimal
< 70 LDL for those with CAD
<40 HDL = low
(<50 HDL for F)
>60HDL = negative RF
29
ATP III Guidelines: 2. identify presence of clinical atherosclerotic disease (CHD risk equivalent)
coronary artery disease
peripheral arterial disease
abdominal aortic aneurysm
diabetes mellitus
30
ATP III Guidelines: 3. determine presence of major risk factors
smoking
hypertension
HDL<40
family history of premature coronary disease
M>45, F>55
31
ATP III Guidelines: 4. if 2+ RF without CHD or CHD risk equivalent, assess 10 year CHD risk
>20%: CHD risk equivalent
10-20%: need to find risk score
<10%: none or 1 RF
32
ATP III Guidelines: 5. determine risk category
CHD, CHD risk equivalents(>20%): <70 LDL goal
2+ RF (<20%): <100 LDL goal
0-1 RF: <160 LDL goal
33
ATP III Guidelines: 6. initiate therapeutic lifestyle changes
AHA low fat diet
dietary cholesterol intake
increase viscous fiber
add plant stanols/sterols
aggressive weight management
increased physical activity
34
ATP III Guidelines: 7. consider adding drug therapy
simultaneously with TLC for CHD and CHD equivalents
if LDL levels high after 3 months TLC
35
ATP III Guidelines: 8. identify metabolic syndrome
MS = 3+ RF
-abdominal obesity
(M>40", F>35")
-TG > 150
-low HDL
(M<40, F<50)
- increased BP (>130/85)
- impaired fasting glucose (>100)
36
ATP III Guidelines: 9. treat elevated TG and low HDL
```
TG:
<150 = normal
150-199 = borderline
200-499 = high
>500 = very high
```
HDL
- exercise
- inc monosaturated fats
- smoking cessation
- moderate EtOH use
TG
- maximize statin therapy
- consider Rx with non statins
37
ACC/AHA Guidelines: major ascvd events
acute coronary syndrome (within past 12 months)
history of MI
history of ischemic stroke
symptomatic PAD
- claudication with ABI <0.85
- previous revascularization surgery
- amputation
38
ACC/AHA Guidelines: high intensity statins
>50% LDL
atorvastatin 80mg
rosuvastatin 20mg
39
ACC/AHA Guidelines: moderate intensity statins
30-49% LDL
atorvastatin 10mg
rosuvastatin 10mg
simvastatin 20-40mg
pravastatin 40mg
lovastatin 40mg
fluvastatin 40mg
pitavastatin 1-4mg
40
ACC/AHA Guidelines: low intensity statins
<30% LDL
simvastatin 10mg
pravastatin 10-20mg
lovastatin 20mg
fluvastatin 20-40mg
41
ACC/AHA Guidelines
screening: 20+yo
no specified targeted goal for TC and LDL
clinical judgement and shared decision making are emphasized
42
ACC/AHA Guidelines: statin benefit groups
- secondary prevention in patients w/ clinical ascvd
- severe hypercholesterolemia (LDL>190)
- DM
- primary prevention based on risk
43
ACC/AHA Guidelines: secondary prevention in patients with clinical ascvd
goal: reduce LDL with HIGH INTENSITY statin
50% reduction
very high risk: consider adding non statin
44
ACC/AHA Guidelines: severe hypercholesterolemia
maximally tolerated statin therapy recommended
45
ACC/AHA Guidelines: DM
40-75yo: MODERATE INTENSITY statin
10yr risk:
- multiple ascvd RF (HIGH INTENSITY statin)
- >20% (add EZITIMIBE to maximally tolerated statin)
20-39yo: with DM risk enhancers (consider initiating statin therapy)
46
DM specific risk enhancers
long duration
- type 2: 10 years
- type 1: 20 years
albuminuria >30
eGFR<60
retinopathy
neuropathy
ABI<0.9
47
ACC/AHA Guidelines: primary prevention based on risk
<5%: lifestyle changes
<5-7.5%: risk enhancers present --> discuss moderate intensity statin
>7.5-20%: estimate+enhancers --> initiate moderate intensity statin
>20%: initiate statin
48
ACC/AHA Guidelines: ascvd risk enhancers
family history of premature ascvd
persistent elevated LDL
CKD
metabolic syndrome
F: preeclampsia, premature menopause, etc.
inlammatory disease (rheumatoid arthritis, psoriasis, HIV)
ethnicity
49
Treatment: TLC
typical success: 5-10%
```
diet
-inc soluble fiber
-plant stanols, sterols
-garlic, soy protein, vitamin C, pecans
antioxidants
```
50
Statins
HMG CoA reductase inhibitors
MOA: inhibit rate limiting enzyme formation of cholesterol
reduces mortality
best dosed at night
LDL dec 20-55%
51
Statin: contraindications
- pregnancy/breastfeeding
- active liver disease
- unexplained elevated LFTs
52
Statins: side effects
```
myalgias
myositis,myopathy
rhabdomyolysis
hepatotoxicity
increased diabetes risk
```
53
Cholesterol Absorption Inhibitor
ex: ezetimibe
MOA:
- decreases absorption of cholesterol in small intestine
- upregulates LDL receptors on peripheral cells
dec LDL 15-20%
add to statin when LDL>70 in very high risk ascvd
contraindications: hepatic impairment, fibrates
54
PCSK9 Inhibitor
ex: alirocumab, evolocumab
MOA: monoclonal antibodies blocks PCSK9 effect of degrading LDL receptors
dec LDL 50-60%
$$$$
consider:
- familial hypercholesterolemia
- very high risk ascvd on max tolerated LDL tx and LDL>70
- statin intolerance
55
Fibric Acid Derivatives
gemfibrozil, fenofibrate
MOA: reduced synthesis and increased breakdown of VLDL particles
drug of choice for TG>500 on initial presentation (dec TG 40%)
NOT recommended with statin use
side effects:
- cholelithiasis
- hepatitis
- myositis
56
Bile Acid Binding Resins
ex: choletyramine, colesevelam, colestipol
MOA: bind bile acids in the intestines
only lipid lower medication considered safe in pregnancy
side effect: GI symptoms
contraindications:
- current/history of GI obstruction
- hypertriglyceridemia
- pancreatitis
57
Niacin
reduces the production of VLDL particles
inc HDL 25-35%
side effect: flushing
contraindications
- pregnancy/breastfeeding
- active liver disease
- active peptic ulcer
caution:
- gout/hyperuricemia
- DM
58
Omega 3 Fatty Acids
improve TG
lower CV risk
anti inflammatory
59
Familial Hypercholesterolemia
LDL receptors absent or dysfunctional
homozygote v. heterozygote
60
Familial Hyperchylomicronemia
lipoprotein lipase abnormality
severe hypertriglyceridemia
61
Mild Hypertriglyceridemia
200-499
possible other cause: high fat meal before testing
62
Moderate Hypertriglyceridemia
>500
start to worry about pancreatitis risk
63
Severe Hypertriglyceridemia
>1000
milky white serum
acute pancreatitis
