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serum-lipid-abnormalities(1)
1. Serum Lipid
Abnormalities
M Chadi Alraies, MD
Chief Medical Resident
Case Western Reserve University / St. Vincent Hospital
Cleveland, Ohio
Saturday, December 20, 2007
2. A quick look at the
differential diagnosis of
Heart Murmurs
6. General consideration
The two main lipids in blood are cholesterol and
triglyceride.
Why lipids are deposited into the walls of large
and medium-sized arteries is not known.
medium-
7. Lipoproteins
Particles that have a hydrophobic core
(TG/Cholesterol),
Surrounded by a hydrophilic phospholipid outer
layers which allows transport through the blood.
LDL, VLDL, IDL, CHYLOMICRONS, HDL
9. LIPOPROTEINS ATHEROGENESIS
The higher the LDL, the greater the risk of CHD.
The higher the HDL, the lower the risk of (CHD).
The mechanism of formation of atherosclerotic
plaques is not known.
10. Lipid Fractions
In fasting serum«
Most triglyceride is found in VLDL particles,
which contain five times as much triglyceride by
weight as cholesterol.
11. Lipid Fractions
the LDL should always be estimated as the
mean of at least two determinations«
Valid only if TG 400 mg/dl
13. Chylomicrons (I)
Large globules.
Apo (B48, CII, E)
CII activates LPL (lipoprotein lipase).
LPL removes TG from chylomicrons.
Familial LPL deficiency
Familial CII deficiency.
14. VLDL (IV)
Apo (B100, CII, E)
Smaller than chylomicrons
Contain more cholesterol than chylomicrons.
Metabolized by LPL by means of CII.
Familial LPL deficiency
Familial CII deficiency.
FCHL
15. IDL (III)
Apo B100, E
VLDL remnant.
½ taken by liver. Strong affinity to B100 E
½ stays in plasma and convert to LDL.
Familial betadyslipoproteinemia.
16. LDL (IIA)
Apo B100«ONLY!
Formed from IDL
2/3 binds to receptors 1/3 scavenged.
Liver receptors have a weak affinity to B100.
Familial hypercholesterolemia.
FCHL
17. LDL receptors
DownDown-regulated or decreased:
High dietary cholesterol or saturated fat.
Age
Familial hypercholesterolemia.
UpUp-regulated or increased:
Low dietary cholesterol
Estrogen
Thyroxine
Acute illness
Meds: statins and bile acid resins.
18. HDL
Apo (A1, A2, C)
Protein and phospholipids.
Very little cholesterol and TG
Scavenges the unesterified cholesterol.
Low HDL
low apo C (including CII)
increased VLDL and Chylomicrons.
19. Familial hyperlipidemia syndromes
Type
What is elevated?
Defect
Name
I
TG
(chylomicrons)
LPL deficiency
CII deficiency
Familial LPL deficiency
Familial CII deficiency
IIA
Cholesterol
(LDL)
Decreased LDL receptors
Apo B + VLDL overproduction
Familial
hypercholesterolemia
FCHL
IIB
TG + Cholesterol
(LDL VLDL)
Apo B + VLDL overproduction
FCHL
III
TG + Cholesterol
(IDL)
Abnormal apo E (E2/E2)
Familial
dysbetalipoproteinemia
IV
TG
(VLDL)
LPL deficiency
CII deficiency
Apo B + VLDL overproduction
Familial hyper TG
FCHL
Familial CII deficiency
V
TG
Chylomicrons
VLDL
LPL deficiency
CII deficiency
Apo B + VLDL overproduction
Familial LPL deficiency
FCHL
Familial CII deficiency
20. I + IV = V have isolated hypertriglyceridemia
IIa = cholesterol alone
IIb and III = both cholesterol and TG.
29. CLINICAL PRESENTATIONS
No specific symptoms or signs.
Triglyceride level (1000 mg/dL)
High LDL concentrations
eruptive xanthomas
Tendinous xanthomas on tendons of (Achilles,
patella, back of the hand).
Triglyceride levels (above 2000 mg/dL):
Lipemia retinalis.
31. Cause
Associated Lipid Abnormality
Obesity
Increased triglycerides, decreased HDL cholesterol
Sedentary lifestyle
Decreased HDL cholesterol
Diabetes mellitus
Increased triglycerides, increased total cholesterol
Alcohol use
Increased triglycerides, increased HDL cholesterol
Hypothyroidism
Increased total cholesterol
Hyperthyroidism
Decreased total cholesterol
Nephrotic syndrome
Increased total cholesterol
Chronic renal insufficiency
Increased total cholesterol, increased triglycerides
Hepatic disease (cirrhosis)
Decreased total cholesterol
Obstructive liver disease
Increased total cholesterol
Malignancy
Decreased total cholesterol
Cushing's disease (or corticosteroid use)
Increased total cholesterol
Oral contraceptives
Increased triglycerides, increased total cholesterol
Diuretics
Increased total cholesterol, increased triglycerides
Beta Blockers
Increased total cholesterol, decreased HDL
32. Therapeutic Effects of Lowering Cholesterol
Primary prevention is statistically significant and
showed clinically important reductions in:
Rates of myocardial infarctions,
New cases of angina,
Need for coronary artery bypass procedures.
In general, decrease in morbidity.
morbidity.
34. Secondary prevention
1.
2.
3.
Regression of atherosclerotic plaques.
Reduces the progression of atherosclerosis in
saphenous vein grafts.
Slow or reverse carotid artery atherosclerosis.
35. SECONDARY CONDITIONS THAT
AFFECT LIPID METABOLISM
These are important for two reasons:
Abnormal lipid levels may be the presenting sign of
some of these conditions.
correction of the underlying condition may obviate
the need to treat an apparent lipid disorder.
37. Who should be screened for high lipids?
CHD
CHD risk equivalents:
1.
2.
3.
4.
5.
Peripheral artery disease.
AAA
Symptomatic carotid artery disease
Diabetes mellitus
Multiple risk factors that confer a greater than 20%
10-year risk for developing CHD!
10-
38. National Cholesterol Education Program (NCEP):
Screen all adults aged 20 years or older.
USPSTF:
Screen every 35 years in men and age 45 years in
women unless there are other risk factors for CHD.
39. Risk factors of coronary artery disease
Age and gender
Men aged 45 years or older.
Women aged 55 years or older
A family history of premature CHD:
1.
MI or sudden cardiac death
1.
2.
2.
3.
4.
55 years in a 1st degree male relative.
65 years in a 1st degree female relative.
Hypertension (whether treated or not.)
Current cigarette smoking (10 or more cigarettes per day).
HDL cholesterol ( 40 mg/dL).
40. 10-year risk of developing CHD using
10Framingham projections of 10-year risk
10
Because risk factors alone are an imprecise
measure of CHD risk, estimating the 10-year
10risk using Framingham data is likely to be
helpful even in patients with one or no risk
factors.
41.
42.
43. Screening in Women
Low HDL is more important risk factor than a
high LDL cholesterol in women.
Using estimates of 10-year CHD risk may be
10particularly helpful in women.
Women are less likely to benefit from therapy
unless their LDL cholesterol is extremely high
(greater than 190 mg/dL).
44. Screening in Older Patients
Patients age 75 years or older:
+ CHD: LDL-lowering therapy can be continued.
LDL No CHD: recommend screening and treatment.
Decisions to discontinue therapy:
Overall functional status.
Life expectancy.
Comorbidities.
Patient preference.
47. Risk Category
LDL Goal (mg/dL)
LDL Level at
Which to Initiate
Lifestyle Changes
(mg/dL)
LDL Level at
Which to Consider
Drug Therapy
(mg/dL)
High risk: CHD or
CHD risk
equivalents (10-year
risk 20%)
100
100
100
Moderately high risk:
2+ risk factors
(10-year risk 10% to
20%)
130
130
130
Moderate risk:
2+ risk factors
(10-year risk 10%)
130
130
160
Low risk: 0±1 risk
factors
160
160
190
48. Treatment of High LDL Cholesterol
General measures:
Quitting smoking: increase HDL lower LDL.
Exercise (and weight loss) reduce the LDL increase
the HDL.
Modest alcohol use (1²2 ounces a day): raises HDL
(1²
50. Diet Therapy
5²10% decrease in LDL cholesterol.
Should be assessed 4 weeks after initiation.
Reduce«
Total daily fat to 25²30%
25²
Saturated fat to less than 7% of daily calories.
Dietary cholesterol less than 200 mg/d.
Polyunsaturated fats decrease LDL and HDL
Monounsaturated fats:
Decrease LDL
Increase HDL« GOOD!
51. Diet Therapy
Mediterranean diet´, monounsaturated fat such
as that found in canola oil and in olives, peanuts,
avocados, and their oils.
Soluble fiber, reduce LDL cholesterol by 5²
5²
10%.
Garlic, soy protein, vitamin C, pecans, and plant
sterols.
Antioxidants, found primarily in fruits and
vegetables.
53. General measures
Aspirin prophylaxis at a dose of 81 mg/d.
The therapeutic goal is:
Approached slowly
Watching for side effects.
Encouraging adherence to nonpharmacologic Rx.
Achieve a 30²40% reduction in LDL.
30²
Combinations of drugs may be necessary.
Monitor periodically (every 6²8 weeks) after
6²
starting therapy.
54. NIACIN (NICOTINIC ACID)
Decrease the production of VLDL.
FullFull-dose niacin therapy, 3²4.5 g/d
3²
15²25% reduction in LDL cholesterol.
15²
25²35% increase in HDL cholesterol.
25²
Reduce triglycerides by half.
Side effects:
Flushing and pruritus. Less with aspirin 325 mg.
Increase blood sugar.
Exacerbate gout and peptic ulcer disease.
55. BILE ACID-BINDING RESINS
ACID
Cholestyramine and Colestipol.
Decrease plasma LDL levels 15²25%.
15²
Increase Triglyceride level.
Don·t affects HDL.
Side effects:
constipation and gas
Nausea and vomiting.
Absorption of fat-soluble vitamins.
fat
56. (HMG(HMG-COA) REDUCTASE INHIBITORS
(STATINS)
atorvastatin, fluvastatin, lovastatin, pravastatin,
rosuvastatin, and simvastatin.
Reduce MI and total mortality in secondary prevention.
Significant reduction in risk of stroke.
Decrease LDL level by up to 35%.
Increases HDL levels
Decreases triglyceride levels.
Myositis and hepatitis.
Monitor LFT·s Q 2-3 months then 2x/year if stable.
2-
57. Fibric Acid Derivatives
Gemfibrozil, Fenofibrate and Clofibrate.
Increase the activity of LPL on VLDL.
Reduce triglyceride levels by about 40%
Reduce LDL levels by about 10²15%.
10²
Raise HDL levels by about 15²20%.
15²
Side effects (mainly Clofibrate):
cholelithiasis, hepatitis and hepatic cancer and
myositis.
58. EZETIMIBE
Inhibits the intestinal absorption of dietary and
biliary cholesterol.
Reduces LDL 15% - 20% when used as
monotherapy.
The usual dose of ezetimibe is 10 mg/d orally.
64. High Blood Triglycerides
The primary therapy is dietary:
Avoiding alcohol
Avoiding simple sugars
Avoiding refined starches
Avoiding saturated trans fatty acids.
Restricting total calories.
Medications: niacin, a fibric acid derivative, or an
HMGHMG-CoA reductase inhibitor.
Elevated TG increase CHD risk in men by 14% and in
women by 37%.
65. Metabolic syndrome
25% of Americans
3 or more of the following:
1.
2.
3.
4.
5.
Waist circumference 102 cm in men or 88 cm
in women
Serum triglyceride level of at least 150 mg/dL
HDL level of 40 mg/dL in men or 50 mg/dL
in women.
Blood pressure of at least 130/85 mm Hg
Serum glucose level of at least 110 mg/dL.
66. NCEP ATP III
1.
2.
TG (150²199 mg/dL): calorie restriction and
(150²
exercise.
TG ( 200 mg/dL): Diet and medications to
make non-HDL cholesterol 30 mg/dL higher
nonthan the LDL goal.
Should be used for high risk patients.
67. References
CMDT 2007.
Harrison·s principles of internal medicine.
MedStudy 2007/2008.
Executive Summary of the Third Report of The National
Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment of High Blood
Cholesterol In Adults (Adult Treatment Panel III).
JAMA. 2001 May 16;285(19):2486²97.
16;285(19):2486²
http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm
