Lipid Disorders Flashcards
Types of Lipids
Cholesterol
Essential element of all animal cell membranes and the backbone of steroid hormones and bile acids
types of lipids
Triglycerides
Transfers energy from food into cells
types of lipids
lipoproteins
-Transport lipids
-Classified by density
-Apoprotein is dense
-Triglyceride is less dense
types of lipoproteins
Apolipoprotein B (apoB)
-Protein that carries LDL and helps it bind to the cell wall
-Contributes to atherogenesis (plaque forming)
lipoproetins
Lipoprotein (a)
Genetically determined subfraction of LDL (if elevated, increased risk for CAD)
Causal factor in atherosclerosis
One-time measurement recommended in patients with strong family history of ASCVD
Risk enhancing factor favoring early statin treatment
indepedent from rest of lipid panel for risk determination
lipoproteins
Chylomicrons
Least Dense
Found in blood after fat-containing meal
lipoprotein
Low-density lipoprotein (LDL)
carry most of the cholesterol
L for lousy. we want this Low.
lipoprotein
High-density lipoprotein (HDL)
Most dense and smallest
Participate in reverse cholesterol transport
H is for High and Happy, we want this number high.
lipoprotein
Very-Low-Density Lipoprotein (VLDL)
Least dense, large
Consists mostly of triglycerides that is transferred to cells
Which lipid value is most sensitive to fasting?
Trig
Which lipoprotein carries the most cholesterol?
LDL
Which lipoprotein is an independent risk for ASCVD?
Lp(a) is independent risk factor for CAD
how does exercise help cholesterol?
increasing muscles mass increases HDL
How can you reduce LDL?
Eat more fiber. Have to poop it out!
What is always the goal of lipid tx?
reduce LDL
unless TRIG is >500 due to increased risk of pancreatitis
Atherosclerosis
Plaque with large amounts of cholesterols build up in arterial walls
Associated with high LDL and low HDL
Mostly asymptomatic until plaque rupture or vessel occlusion (MI, CVA)
Familial Hypercholesterolemia
defective LDL receptors, genetic mutations of apolipoprotein B, or gain in function of proprotein convertase subtilisin/kexin type 9 (PCSK9)
Typically, patients have elevated total cholesterol and normal triglycerides
Heterozygous (1 in 250 people)
Homozygotes (1 in 1,000,000 people)
probably won’t be tested on this
Familial Chylomicronemia AKA
Lipoprotein Lipase Deficiency (LPLD)
Fredrickson Type 1 Hyperlipoproteinemia
Familial Hypertriglyceridemia
probably wont be tested on this
Familial Chylomicronemia
caused by, characterized by, risk for?
Caused by an abnormality of lipoprotein lipase (LPL) that is responsible for the ability of tissues to take up triglycerides (TG) from chylomicrons
Characterized by marked hypertriglyceridemia
Important for patient to abstain from ETOH, bc at VERY HIGH RISK FOR PANCREATITIS
Dysbetalipoproteinemia
Elevated levels of remnant lipoproteins
Rare familial disease
Associated with premature ASCVD
Familial combined hyperlipidemia
Polygenic combination of lipid abnormalities
Most common genes: LDLR, APOB, PCSK9 (don’t need to memorize these)
When should you suspect genetic disorders?
if you see LDL over 200
Conditions that Affect Lipids (aka. Secondary causes of dyslipidemia)
Metabolic syndrome
Type 2 diabetes
Uncontrolled hyperglycemia
Obesity
Hypothyroidism
Liver disease
Renal disease
Corticosteroid use
Progestin use
Anabolic steroid use
Alcohol use/abuse
You are treating a patient for high cholesterol. Current LDL is non-calculable, triglycerides > 450, HDL 40. TSH is elevated at 10 ( nl range < 4.0), HgA1C 9.8.
Why is her cholesterol not at goal in spite of compliance with cholesterol medications?
Must correct DM and TSH
Specific Clinical Presentation of high cholesterol
Most patients do not have specific signs or symptoms
Primarily detected with laboratory studies
Eruptive Xanthomas/Xanthelasma
Tendinous Xanthomas
common in famial disorders
Lipemia Retinalis
Corneal Arcus (arcus lipoides)
Differs from arcus senilis
Gap between limbus and the lipid deposit distinguishes the two
Corneal Arcus (arcus lipoides)
Screening
fasting requirements
Fasting not required for screening; use Non-HDL-C for guidance
Guidelines vary by organization
Screening Children
Selective screening for children age >2 with family history or lipid disorder or premature ASCVD
Between ages 9-11
Again, between ages 17-21
Lipid screening for Adults
when do you stop screening? (no previous lipid issues)
One time- Adults at age 20 if not previously done as a child
Every 5 years for those at low risk after age
35 in men
45 in women
More often for those at moderate to high risk
Screening not recommended for those over age 75
Risk Levels
Risk-enhancing Factors
primary prevention
Cardiac Calcium Score
Helpful for deciding if they should be put on statins for having calcified vessels.
only catches calcification not lipids in blood which cause events.
Most useful in those with intermediate risk stratification (7.5-< 20%)
The higher the score, the higher risk of heart disease
May repeat every 3 to 7 years based on patient risk
“The single best test for additional risk stratification”
A patient with which of the following characteristics will a cardiac calcium score be most useful in a shared decision-making model?
a. Aged 75
b. Intermediate ten-year risk of heart disease
c. Low-density lipoprotein (LDL) 194
d. Type 2 diabetes
e. Smoker
B-Cac score may be helpful with intermediate ten –year risk
The Pooled Cohort Equation is used to estimate the ten-year risk of heart disease or stroke for an individual. The risk is reported to be 10%. What risk category is the result?
a. Borderline
b. High
c. Intermediate
d. Low
C-intermediate
CVD
Primary Prevention
Refers to therapy in persons with NO known cardiovascular disease
Studies indicate rates of cardiovascular events, heart disease mortality, and all-cause mortality are decreased in the right population
CVD
Secondary Prevention
Refers to therapy in persons with known cardiovascular disease
Studies support that cholesterol lowering leads to decreased mortality and recurrent cardiovascular events
primary prevention for women who anticipate childbearing
Primary prevention with statins are not recommended for women who anticipate childbearing
Primary prevention
Risk factors and LDL goals
who gets statin treatment for primary prevention?
Anyone with LDL-C ≥190 mg/dL –> high intensity statin
Age 40-75 with diabetes –>moderate intensity statin.
Consider high intensity statin if risk enhancing factors or 10-year risk >20%
Age 40-75 without diabetes with LDL 70-189 mg/dL and intermediate or high risk –> moderate intensity statin. & high intensity statin if additional risk enhancers
slide 38
CVD
Secondary Prevention is for
Among patients with established ASCVD, mortality benefits of cholesterol lowering are clear
Regression of atherosclerotic plaque
Slow or reverse carotid artery atherosclerosis
Established ASCVD
Acute coronary syndromes
MI
stable/unstable angina
Coronary/arterial revascularization
Stroke/TIA
Peripheral artery disease of presumed atherosclerotic origin
Persons over the age of 75 should continue statin therapy with decisions based on functional status, life expectancy, comorbidities, and patient preference
Who is at very high risk of CVD?
ACS within the past 12 months
MI other than event listed above
History of ischemic stroke
Symptomatic PAD (ABI <0.85, amputation, previous revascularization)
Hx of plaque related event
Risk factors that are High risk of CVD?
Age ≥65
Heterozygous familial hypercholesterolemia
Diabetes mellitus
Hypertension
CKD (GFR 15-59 mL/min/7.73m2)
Current smoker
LDL-C ≥100mg/dL despite maximally tolerated statin and ezetimibe
History of congestive heart failure
What is the goal LDL for someone with secondary prevention?
less than 70 LDL
Secondary Prevention
memorize this
primary prevention
memorize this
who gets statin for secondary prevention?
Everyone!
High or moderate intensity statin
LDL-C goal < 70 mg/dL
Weight loss affect on Lipids
lowers LDL, increases HDL
For those who are overweight or obese
Tobacco cessation
increases HDL
Modest alcohol use
Will increase? And when is it contraindicated?
increases HDL, contraindicated for very high TG
(red wine)
someone with High TRIG will not benefit
Benefits of Mediterranean Diet
Total fat 35-40% fat but saturated fat replaced with monounsaturated fat
Plant based, lean animal protein (preferably fish)
Lowers LDL without lowering HDL
Reduces endothelial dysfunction, insulin resistance, and vascular inflammatory markers
Specific nutrition guidance for treatment of elevated triglycerides
Low carbohydrate
No simple sugars
No alcohol
A 45-year-old woman with no risk factors for coronary heart disease is found to have a cholesterol level of 165mg/dL. What nutrition advice is most helpful?
a. Abstain from all alcohol
b. Begin a fish oil supplement
c. Cut carbohydrate intake to less than 30% of total calories
d. Decrease saturated fat to less than 15% of total calories
e. Increase soluble fiber to 20 grams daily
E. Increase soluble fiber to 20 grams daily
Which of the following “natural” interventions has not been proven to reduce cholesterol?
a.Almonds
b.Walnuts
c.Increase fiber
dCo-Q-10
e.Plant stanols
f.Red-yeast rice extract
d. Co-Q-10
does not help reduce cholesterol, might help with Side affects from chole meds
Pt is in primary prevention, what is their LDL goal?
what about secondary?
secondary over 75y?
100 if primary
70 if secondary with high intensity statin
70 with POSSIBLE moderate statin
What is first line medication class for lipid management?
Statin
If pt starts on statin, when do we check bloodwork again?
3 months
what if lipid still elevated after check up on statins?
if moderate statin, move them to high intesity statin or consider adding another agent (second line) such as PSK9 inhibitor or Ezetimibe
In what scenario is TRIG reduction more important that LDL reduction?
when TRIG is >500 due to risk of pancreatitis
Fish Oil Medications
icosapent ethyl (Vascepa), omega-3-acid ethyl esters (Lovaza)
Fish oil benefits
for reducing TRIG by up to 30%
Reduces apoB
Reduces hsCRP
Reduces CV death, MI, CVA, unstable angina and coronary revasularization
Niacin (Niaspan) benefits and contraindications
Reduces LDL 15-25%
*Increases HDL 25-35%
Caution with cyclosporine, macrolide antibiotics, various anti-fungal agents, and cytochrome P-450 inhibitors
SE of Niacin (Niaspan)
Flushing
Pruritus
Hyperglycemia
Gout exacerbation
Peptic ulcer disease
Fibrates
gemfibrozil (Lopid), fenofibrate (Tricor, Triglide, Lipofen)
Reduce TRIG 40%
Reduce LDL 10-15%
Increase HDL 15-20%
Reduces CHD and CV events
Statins benefits
Reduces LDL by up to 50% (high intensity statin)
Increases HDL
Decreases TG
Decreases hsCRP
Dosed once daily
Statin MOA
Work by inhibiting the rate-limiting enzyme in the formation of cholesterol in the liver and increases hepatic LDL receptors
Statin Contra
Caution with niacin, fibrates, EES, antifungals, nefazodone, or cyclosporin
Liver failure
Statin SE
Myalgias- bilateral mostly legs and shoulders
CK elevations
Myositis
Rhabdomyolysis
Elevated transaminases
Diabetes development
Statin
Rule of 6 or 7
you get bigest reduction at initial dose, w/ each titration you get 6-7% off as you increase dose
40% at 10mg, then 46% at 20mg
Which of the following statin medications and doses is high-intensity intervention?
a. Atorvastatin 40mg
b. Lovastatin 20mg
c. Pravastatin 40mg
d. Simvastatin 40mg
e. Rosuvastatin 10mg
A. Atorvastatin 40mg
Which of the following statins would you select to reduce LDL by 35-50%
a. atorvastatin (Lipitor) 40 mg
b. atorvastatin (Lipitor) 80 mg
c. rosuvastatin (Crestor) 10 mg
d. rosuvastatin (Crestor) 20 mg
e. simvastatin (Zocor) 10 mg
(moderate intensity)
c. rosuvastatin (Crestor) 10 mg
What is perc goal of LDL lowering for patient with clinical ASCVD taking a high-intensity statin?
a. 10%
b. 20%
c. 25%
d. 30%
e. 50%
e. 50%(high intensity)
Bile Acid Sequestrants
cholestyramine (Questran), colesevelam (Welchol), colestipol (Colestid)
Reduces LDL by 15-25%
Safe in pregnancy
OK with liver disease
Cholesterol Absorption Inhibitors
ezetimibe (Zetia)10mg daily
Reduces LDL 15-20%
Reduces hsCRP
Once daily dosing
Well tolerated
On boards, this is second step for with statins
(has reduced numbers but not shown to reduce events
PCSK9 Inhibitors
alirocumab (Praluent), evolocumab (Repatha)
benefits
Decrease LDL 50-60%
Decrease Lp(a) 20-30%
Reduces CV events and death
shot
Adenosine Triphosphate-Citrate Lyase (ACL) Inhibitors
Bempedoic Acid (Nexletol) Bempedoic Acid + ezetimibide (Nexlizet)
Benefits
Lowers LDL by 17-20%
In combo with ezetimibe (up to 38%)
Decreases hsCRP
Decreases diabetes risk
Once daily dosing
You are treating a patient with CAD and high cholesterol They present in clinic for follow-up with labs: LDL 110, HDL 45, Tg 120. VS: 140/88, HR 12. Current medications include rosuvastatin 20 mg po at hs.
What is target LDL?
< 70
Which of the following is indicated to get patient to goal?
continue rosuvastatin and add atorvastatin 20 mg ?
add ezetimibe 10 mg po daily (cholesterol absorption inhibitor)
start Praulent (PCSK9-I)
start Nexitol (ACL inhibitor)
start gemfibrozil ( bile acid sequestrant)
b- YES
a- NO dont prescribe 2 statins
Primary prevention
age 40-75 with LDL 70-190
Low
Low < 5% - emphasize lifestyle to reduce risk
primary prevention
age 40-75 with LDL 70-190
Borderline
borderline 5-7.5% 10 year risk
If risk enhancers present then DISCUSS moderate intensity STATIN
Primary prevention
age 40-75 with LDL 70-190
Intermediate
7.5-20% risk
moderate intensity STATIN
Primary prevention
age 40-75 with LDL 70-190
High risk
> or = 20%
high intensity STATIN
primary prevention
age 40-75 with DM and LDL 190 or higher
no risk assessment necessary
high intesnity statin
primary prevention
45-75 y with DM
moderate STATIN
risk assessment to decide if High intensity statin
primary
LDL levels
primary
Chlesterol levels
primary prevention
HDL levels
Pooled Cohort Equations
Separate Equations for White and Black patients
Estimates 10-year risk of MI, CVA, CV death
Does over-estimate risk of middle to higher socioeconomic class patients
Disclaimer reads that it is not intended for those with previous MI/CVA, LDL >190, or <40-years-old or >79-years-old
How to interpret cardiac calcium score
SECONDARY prevention
Age < 75 ASCVD NOT at very high risk
Goal and Tx
goal: LDL 70 or less
High intensity statin
if not tolerated moderate statin with ezetimibe
Secondary prevention
pt at very high risk ASCVD
goal and Tx (3 possible steps)
goal: 70 or less
- high intensity statin
- add ezetimibe if LDL not low enough
- if still not low enough add pcsk9
Who is at VERY high risk?
ACS within the past 12 months
MI other than event listed above
History of ischemic stroke
Symptomatic PAD (ABI < 0.85, amputation, previous revascularization)
who is at high risk?
Age ≥65
Heterozygous familial hypercholesterolemia
Diabetes mellitus
Hypertension
CKD (GFR 15-59 mL/min/7.73m2)
Current smoker
LDL-C ≥ 100mg/dL despite maximally tolerated statin and ezetimibe
History of congestive heart failure
Individuals with clinical ASCVD should be on?
what kind of prevention?
STATIN
secondary
Individuals with primary elevation of LDL cholesterol >190 mg/dL
should be on ..
primary prevention
STATIN
Individuals aged 40-75 with diabetes and LDL ≥70mg/dL
primary prevention
statin
Individuals aged 40-75 without clinical ASCVD or diabetes with LDL 70-189 and estimated 10-year CVD risk of 7.5% or higher
primary prevention
statin
