Transcript Lipids 101 - Wayne State University School of Medicine

Lipids 101
Cardiology Board Review
Med-Peds Style!
Americans
requiring
treatment for
Hyperlipidemia
CHD and CHD
Risk Equivalents
10-year risk >20%
Therapeutic
Lifestyle
Changes (TLC)
24.1
Drug
20.7
29
35
2+ Risk Factors
10-year risk 10–20%
10.9
8.3
2+ Risk Factors
10-year risk <10%
14.6
2.8
30.2
0–1 Risk Factor
15.6
Total
7.5
4.7
65.3M
36.5M
Inherited Dyslipidemias
Disease
Phenot y pe Abnormal
Lipid
Def ect
Familial
Hypercholest er olemia
II a
Familial l ipopr ot ein lipase
def iciency
I, V
Familial
Hypertri glycer idemia
Combined Hyper lipidemia
I, V
VLDL
Unknown
I ib
VLDL,LDL
Unknown
Familial
dysb et a lipoprot einemia
III
VLDL
Def ect ive or abs ent
apo- E
Lecit ihin- cholest er ol
acet yltran sf era se
def iciency
Tangier disease
N/A
HDL
Rapid apo- A- 1
catab olism
N/A
HDL
Rapid HDL catab olism
LDL
Def ect in LDL
r ecept or or ap o- B100 may be
heter ozygous o r
homozygous
chylomicr ons Lipoprot ein Lipase
def iciency
Clinical p re se ntat ion
Tendinous xant homas,
Xant helasma, Planar
xant homas
Corneal ar cus
Erupt ive xant homas, Lipemia
r et inalis, Abdominal P ain,
Hepat o-splenomegaly
Oft en as ymptomat ic
Risk
of
CHD
+++
0
+
Oft en as ymptomat ic e xcept
+++
CHD, Yellow- ora nge palmar
cr ease s
Tub er oer upt ive xant homas,
+++
Hyperur icemia, Glucose
int olerance, Cor neal opacit ies
Renal insuff iciency, Hemolyt ic +
anemia
Corneal opacit ies,
polyneur opat hy, ora nge
t onsils
0
Metabolic Syndrome
• Abdominal obesity (>40” in men; >35” in
women
3 Orange
• Atherogenic dyslipidemia
– Elevated triglycerides (>150mg/dl)
– High LDL
– Low HDL (<40 in men; <50 in women)
Criteria =
Diagnosis!
• Raised blood pressure (>130/85)
• Insulin resistance ( glucose intolerance)
– Fasting glucose >110mg/dl
• Prothrombotic state
• Proinflammatory state
Risk Assessment
• Measure fasting LDL in all patients
beginning at age 20yo.
• For patients with multiple (2+) risk
factors
– Recheck LDL every 5 years
• For patients with 0–1 risk factor
– 5 year risk assessment not required
– Most patients have 10-year risk <10%
Major Risk Factors (Exclusive of
LDL) That Modify LDL Goals
• Cigarette smoking
• Hypertension (BP 140/90 mmHg or on
antihypertensive medication)
• Low HDL cholesterol (<40 mg/dL)†
• Family history of premature CHD
– CHD in male first degree relative <55 years
– CHD in female first degree relative <65 years
• Age (men 45 years; women 55 years)
CHD Risk Equivalents
• Other clinical forms of atherosclerotic
disease (peripheral arterial disease,
abdominal aortic aneurysm, and symptomatic
carotid artery disease)
• Diabetes (10-year risk for CHD =20%)
• Multiple risk factors that confer a 10-year risk
for CHD >20%
Lifestyle Risk Factors
• Obesity (BMI  30)
• Physical inactivity
• Atherogenic diet
Causes of Secondary
Dyslipidemia
•
•
•
•
•
Diabetes
Hypothyroidism
Obstructive liver disease
Chronic renal failure
Drugs that raise LDL cholesterol and lower
HDL cholesterol (progestins, anabolic
steroids, and corticosteroids)
Primary Prevention With
LDL-Lowering Therapy
Public Health Approach
• Reduced intakes of saturated fat and
cholesterol
• Increased physical activity
• Weight control
Secondary Prevention With
LDL-Lowering Therapy
• Benefits: reduction in total mortality, coronary
mortality, major coronary events, coronary
procedures, and stroke
• LDL cholesterol goal: <100 mg/dL
• Includes CHD risk equivalents
• Consider initiation of therapy during
hospitalization
(if LDL 100 mg/dL)
LDL Goals and Cutpoints for
Therapeutic Lifestyle Changes (TLC)
and Drug Therapy
Risk Category
CHD or CHD Risk
Equivalents
(10-year risk
20%)
2+ Risk Factors
(10-year risk
20%)
0–1 Risk Factor
LDL Goal
(mg/dL)
<100
<130
LDL to Initiate
Therapeutic
Lifestyle Changes
(TLC) (mg/dL)
LDL
to Consider
Drug Therapy
(mg/dL)
100
130
(100–129: drug
optional)
130
10-year risk 10–
20%: 130
10-year risk
<10%: 160
<160
160
190
(160–189: LDLlowering drug
optional)
July 14, 2004: NCEP updated
stratified cholesterol guidelines
Very high risk individuals: patients with
CAD AND DM, uncontrolled HTN, or
metabolic risk factors including obesity,
high triglycerides, and low HDL. Smokers
with CAD. Goal of therapy--LDL < 70
mg/dl
High-risk individuals: CAD or DM or
multiple risks factors -- Goal of therapy-LDL < 100 mg/dl
July 14, 2004: NCEP updated
stratified cholesterol guidelines
Moderately high risk: Multiple risk factors for
CAD with a 10% to 20% chance of having an
MI or cardiac death within a decade. If the
LDL level is between 100-129 mg/dl then a
statin drug may be started. Goal of
therapy--LDL < 100 mg/dl
Lower or moderate risk: Dietary changes
and exercise unless LDL levels are very
high
LDL-Lowering Therapy…How
low do we go?
Baseline LDL: <100 mg/dL
• Further LDL lowering not required
except in CHD and CHD risk
equivalent then use LDL <70
• Therapeutic Lifestyle Changes (TLC)
• Consider treatment of other lipid risk
factors
– Elevated triglycerides
– Low HDL cholesterol
HMG CoA Reductase
Inhibitors (Statins)
• Reduce LDL-C 18–55% & TG 7–30%
• Raise HDL-C 5–15%
• Major side effects
– Myopathy
– Increased liver enzymes
• Contraindications
– Absolute: liver disease
– Relative: use with certain drugs
Bile Acid Sequestrants
Cholestyramine, Colestipol, Colesevelam
• Major Actions
– Reduce LDL-C 15–30%
– Raise HDL-C 3–5%
– May increase TG
• Side effects
– GI distress/constipation
– Decreased absorption of other drugs
• Contraindications
– Dysbetalipoproteinemia
– Raised TG (especially >400 mg/dL)
Nicotinic Acid
• Major actions
– Lowers LDL-C 5–25%
– Lowers TG 20–50%
– Raises HDL-C 15–35%
• Side effects: flushing, hyperglycemia,
hyperuricemia, upper GI distress,
hepatotoxicity
• Contraindications: liver disease, severe
gout, peptic ulcer
Fibric Acids
Gemfibrozil, Fenofibrate, Clofibrate
• Major actions
– Lower LDL-C 5–20% (with normal TG)
– May raise LDL-C (with high TG)
– Lower TG 20–50%
– Raise HDL-C 10–20%
• Side effects: dyspepsia, gallstones,
myopathy
• Contraindications: Severe renal or
hepatic disease
DRUG TREATMENT
PLAN
Start statin
or bile acid
sequestrant
or nicotinic
acid AFTER
3 MONTHS
OF TLC
6 wks
If LDL goal
not
achieved,
Consider
higher dose
of statin or
add a bile
acid
sequestrant
or nicotinic
acid
6 wks
If LDL goal
not achieved,
intensify
drug therapy
or refer to a
lipid
specialist
If LDL goal
achieved,
treat other
lipid risk
factors
Q 4-6 mo
M
O
N
I
T
O
R
Classification of Serum
Triglycerides
•
•
•
•
Normal
Borderline high
High
Very high
<150 mg/dL
150–199 mg/dL
200–499 mg/dL
500 mg/dL
Management of Very High
Triglycerides (500 mg/dL)
• Goal of therapy: prevent acute
pancreatitis
• Very low fat diets (15% of caloric intake)
• Triglyceride-lowering drug usually required
(fibrate or nicotinic acid)
• Reduce triglycerides before LDL lowering
Causes of Low HDL
Cholesterol (<40 mg/dL)
•
•
•
•
•
•
•
Elevated triglycerides
Overweight and obesity
Physical inactivity
Type 2 diabetes
Cigarette smoking
Very high carbohydrate diet (>60%)
beta-blockers, anabolic steroids,
progestational agents
Management of Low HDL
Cholesterol
• LDL cholesterol is primary target of therapy
• Weight reduction and increased physical
activity (if the metabolic syndrome is present)
• Non-HDL cholesterol is secondary target of
therapy (if triglycerides 200 mg/dL)
• Consider nicotinic acid or fibrates
(for patients with CHD or CHD risk
equivalents)
Previous In-service Topics
Hyperlipidemia due to secondary
causes
Statin associated myositis
Target LDL in DM and HTN
Which statin is least likely to be
metabolized by P450 and least likely to
interact with anti-retrovirals.
Causes of hypertriglyceridemia
Food for Thought…
"The average American may be fine with an LDL of 120,
but when we're born we have an LDL of 25 or 30. If we
put statins in the drinking water, would it help public
health? Yes, but public health endeavors would help
more.
Our obesity epidemic needs to be conquered not with
medicine but with effective change for the whole
population. If you're looking at cost-effectiveness, it’s
time to teach young people to eat right and exercise.
We can do that -- or we can start throwing 10 medicines
at them when they are 40 or 50 years old."
-Lawerence S. Sperling, MD Director of Emory Heart Center Risk Reduction Program