Lipoprotein abnormality
Plasma appearance
Change in lipids
I
High Chylomicrons
(Juvenile onset)
creamy layer
High chol, Trig
IIA
LDL increased
VLDL normal
Clear
High chol
Normal Trig
IIB
LDL increased
VLDL increased
sl Turbid
High chol
High Trig
III
IDL increased
Turbid
Normal chol
High Trig
IV
VLDL increased
Turbid
Normal chol
High Trig
V
VLDL increased
Chilomicrons
High Trig.
Creamy layeron top
Turbid
High chol



The classifications are based on the lipid profile which includes the LDL-C,
VLDL's, and Chylomicrons. In most labs the triglycerides are reported. If not, the triglyceride level can be calculated as the VLDL x 5. Example; A VLDL of 40=
triglycerides of 200mg/dl


Still confused with all of the different classifications? First. Types I and III are rare.

Even though there are 5 Frederickson types only 3 are usually seen in clinical practice. We recently analyzed 578 patients seen at the MUSC Cholesterol Center and
found the following types:

CLASS
N
%
I
0
0
IIA
280
48.4
IIB
189
32.7
III
2
0.03
IV
92
15.9
V
9
1.6


Note that the majority of patients are type II and IV ( 97%). Type II is subdivided into IIA and IIB. IIA has a primary elevated LDL-C with normal triglycerides while
type IIB has both elevated LDL-C and triglycerides. Most of your patients with primary triglyceride elevations will be type IV.



You should be able to determine a patient's Lipoprotein classification in most cases in a few seconds. Let's look at a some examples:

Case 1.
HDL-C
40

LDL-C
190

Trig
85


What's high? The LDL-C. Triglycerides are normal. Class = IIA

Case 2.
HDL-C
40

LDL-C
190

Trig
320


What's high? LDL-C and triglycerides. Class II B

Case 3.
HDL-C
28

LDL-C
-

Trig
1,245



What's high? Triglycerides. Very high at 1,245 mg/dl. Note that the LDL-C is not reported. Why? The LDL-C is a calculated value in most labs and the formula
(Friedewald) does not work when the triglycerides are over 400 mg/dl.

Since the triglyceride level is so high we know that this patient most likely has a type 4 or 5 classification. The method to determine which is to order a lipoprotein
electrophoresis. This will give you the % Chylomicrons, % beta's( LDL-C), % pre-beta's (VLDL's) and % alpha(HDL-C). Chylomicrons >1 % after an overnight fast
means that the patient has a type V classification.

Lipoprotein Electrophoresis

Lipid profile: T. Chol 641mg/dl, HDL-C 18mg/dl, Trig 4,952mg/dl




Another problem with classification is to determine if your patient with a very high LDL-C has Familial Hypercholesterolemia. Clinically you can suspect that your
patient may have the familial type if the LDL-C is 250mg/dl or greater and has a strong family of CHD. It is important to know this since these patients often will be
difficult to treat and may have early CHD. Most of the patients with Familial Hypercholesterolemia have decreased receptors for LDL-C or defective receptors. This
occurs in one in 500 persons.

Severe Polygenic Hypercholesterolemia has very high elevations of LDL-C and triglycerides in different members of the same family. Occurs in about 1% of the
population and is associated with premature CHD.

END OF SECTION I - RETURN TO CHAT ROOM FOR DISCUSSION



II. Work-up of the patient with elevated cholesterol.

1.Medical history - In addition to your usual history be sure to:

A. Identify secondary causes such as hypothyroidism, renal disease, medications( diuretics, beta blockers estrogen), menopausal.

B. Identify CHD risk factors: Diabetes, HBP, smoking, family medical history, previous history MI, by-pass, angioplasty, TIA, stroke, PVD

C. Obtain detailed diet history: Ask the patient what they usually eat for breakfast, lunch, and dinner plus snacks Ask what they usually drink with meals and between
meals.

D. Ask about exercise and if they have an exercise program.

2. Physical Exam - In addition to your usual physical be sure to check:

Blood vessels -checking pulses, listening for bruits. Check liver for hepatomegaly( possible fatty infiltration). Check skin for xanthomas, xanthelasmas.

One object with the physical is to determine if the patient is a primary or secondary prevention problem. For example, if you find evidence of PVD this moves the patient
from primary to secondary prevention, changing your LDL-C goal from 130mg/dl to 100mg/dl.

3. Laboratory

Lipid profile on all patients. Do not start a treatment program with only the total cholesterol.

T4/TSH on patients suspect hypothyroid.

Baseline liver function tests, CPK. I do not always order but would if I have a patient whose job involves lot's of physical activity. For example, I have a patient who
operates a floor sander every day. Baseline CPK is 350.

Lipoprotein electrophoresis in patient's with very high triglycerides.
Lp(a) or Homocysteine. Consider ordering if a strong family history of CHD, or patient has had an early MI, stroke, or PVD.

END OF SECTION II - RETURN TO CHAT ROOM


III. Rationale for differences in dietary therapy.



Diet for primary LDL-C problems:.

All patients are started on the AHA step I or step II diet based on the
amount of LDL-C lowering needed. The focus is on decreasing fats and saturated fats with less
than 30% and 7-10% respectively of total calories. We try to keep dietary concepts simple and
manageable. For example, we teach our patients to read food labels, focusing on the saturated fat
content and instruct them to buy foods with < 3 grams of saturated fat per serving. In general, by
being on a low saturated fat diet, patients are also on a low cholesterol diet.

However, there are a few foods that even though they are low in saturated fat, their cholesterol content is very high. Namely, organ
meats (liver), egg yolks, and shrimp. A serving of any one of these can bring you over your recommended daily cholesterol total intake
of 250mg.

It is important to note that diet reductions in LDL-C are only 6-10% on average. This is relevant clinically in terms of the patient with a high baseline LDL-C. For
example a baseline LDL-C of 190mg/dl; the dietary reduction will only be 19mg/dl, resulting in a LDL-C of 171mg/dl. If goal LDL-C is 130mg/dl, it is obvious that you
will not be able to achieve this with dietary therapy alone.We usually begin
dietary therapy for 6-8 weeks before deciding to begin medications.


Diet for Primary Triglyceride Problem:

The key to dietary treatment of high triglycerides is a low sucrose diet along with a low saturated fat diet. Most patients can lower moderate levels of triglycerides by
stopping the intake of excess sugar and decreasing fats. Below I have outlined a patients cholesterol profile with high triglycerides seen in our practice and placed on low
sucrose diet:



45 yo
male
BMI
27.9

7/21/95
7/28/95
T. Chol
163
156
Trig.
724
286
HDL-C
18
20


Note that after one week of the no added sucrose diet the triglycerides decreased by 60%. No other medications were used.

Some examples of sources of simple sugars:

Soft drinks- 8-10 teasp/can
Sugar added to tea, coffee (Sweet Tea)
Low fat/fat free ice cream
Candy, snacks, desserts, cake, doughnuts
Juices-check label for sugar content.

The general rule is if your patient has a primary high triglyceride problem, less than 800mg/dl, and has a high sucrose intake on diet history, it is worth a 2-4 weeks trial
on a no added sugar diet prior to starting lipid lowering medications.

SUMMARY

HIGH LDL-C - LOW FAT/SATURATED FAT DIET

HIGH TRIG. - LOW SUCROSE/LOW FAT DIET



END OF SECTION III - RETURN TO CHAT ROOM


IV. Differences of pharmacological interventions for patients with LDL-C, triglyceride & combined cholesterol problems.

How to decide which cholesterol lowering medicine to use when diet alone will not reach
cholesterol goals?

First decide if you are dealing with a primary LDL-C, trigylceride, or
combined problem:




Primary LDL-C, IIA class

Medications of choice
Binders
Niacin
Estrogen's
Statins

Primary triglyceride problem, IV or V class.

Medication of choice
Gemfibrizol
Fenofibrate
Niacin

Combined Problem, both LDL-C and Trig, IIB

Let's look at the medications which can be used for primary LDL-C in more detail:

Niacin
Over the counter, fairly inexpensive
Not first choice in patients with diabetes, may increase glucose
Major side effect is flushing, GI
To reduce side effects start at small doses(100mg) taken with meals and
gradually increase over a few weeks. Usual dose 1,000-2,000mg QD.
Will increase HDL-C and lower Lp(a)
Has to be given at least BID. A new extended release niacin, Niaspan can be given QHS.

Binders- Colestipol, Cholestyramine, Psyllium

Good for mild to moderate elevations of LDL-C
Not effective for triglycerides
Major side effect is GI, constipation, gas, bloating
Remember these are 'binders' and will bind with other
medications, and must be spaced around other meds.
Recommended take other meds 1 hour before or 4 hours after.
Should be taken prior to meals.
Often can reduce side effects by combining with psyllium.

Estrogen's

Good for menopausal females, class IIA.
Often get an excellent LDL-C lowering and increase in HDL-C.
If patient has uterus, must use progesterone which blunts LDL-C
lowering.
Worth a try before starting other medications
In some patients may increase triglycerides.

Statins - HMG CoA Reductase Inhibitors

Generic Name
Brand Name
Dose
Atorvastatin
Lipitor
Tab:10,20,40mg
Cerivastatin
Baycol
Tab: 0.3mg
Fluvastatin
Lescol
Caps:20,40mg
Lovastatin
Mevacor
10,20,40mg
Pravastatin
Pravachol
Tabs:10,20,40mg
Simvastatin
Zocor
Tab:5,10,20,40mg



Lowers LDL-C 24-60% , triglycerides 10-33%, and increases HDL-C an average of 8%, dependent on medication and dose.
Once a day dosing
Infrequent side effects. Most common muscle cramps, elevation LFT's.
Most taken QHS, with exception of atorvastatin and cerivastatin which can be taken at any time.
Possible drug interactions; Cyclosporin, erythromycin, ketoconazole, warfarin, cimetidine. Fluvastatin only; rantidine, omeprazole.

Medications for Primary Triglyceride Problems:

Gemfibrozil (Lopid)
Lowers triglycerides 20-50%.
Must be given as BID dose
Rare side effects, abdominal pains, gas, mild indigestion
Can be used in patients with diabetes

Fenofibrate - Tricor
Very effective in lowering triglycerides
Once a day dosage.
Rare side effects

Fish Oils- Omega-3 fatty acids
Reduce VLDL's in liver and decrease triglycerides.
May cause increase in LDL-C and HDL-C.
Useful in patient's resistant to single drug therapy.
Eicosapentanoic acid(EPA) and Docosahexanoic acid(DHA)
found in health food stores.
Starting dose 1-2 capsules (300-600mg EPA and DHA) TID
with meals.
Side effects nausea and GI complaints, may increase bleeding time.

Medications for Combination Problems

Combination drug therapy can be used when single drug therapy with diet and exercise has achieved suboptimal results. Combining drugs at lower doses may be better
tolerated, more efficacious, increase compliance and be more cost effective than monotherapy. Some of the drug combinations which have been used effectively include
niacin with a binder, statins with a binder, and statins plus gemfibrozil (very important to monitor hepatic/renal function and CPK).

END OF SECTION IV - RETURN TO CHAT ROOM



CASE STUDIES

Case 1. Hypothyroidism and the history and physical exam.

MAL, a 50 yo female, known elevated cholesterol for 12 yrs. On vegetarian diet, walks 5 miles/day. On no medications.

Hx - C/O fatigue, SOB, weight gain, abnormal periods.
FMH - Mother - goiter, MI age 65.
Px - wgt. 158.5 lbs, pulse 60/min., BP 110/86, otherwise normal physical.


Lab
2/2/95
T.Chol
336 mg/dl
HDL-C
67 mg/dl
LDL-C
225 mg/dl
Trig.
70 mg/dl
T4
1.99
TSH
58.0


Pt. was Dx with hypothyroidism and started on Synthroid. F/U visit in 2 months. Pt lost 9 lbs. Feels better, more energy. Repeat labs>


T.Chol
176 mg/dl
HDL-C
35 mg/dl
LDL-C
118 mg/dl
Trig.
115 mg/dl
T4
8.7
TSH
3.85


Hypothyroidism causes an elevation in total cholesterol and LDL-C. Look for clues during your patient history and physical exam. Treating the hypothyroidism will
usually normalize the lipid profile.


Case 2. Primary Prevention

MG, a 36 yo male engineer, was diagnosed as having a high cholesterol of 290mg/dl during a routine check-up. He was totally asymptomatic, does not drink, smokes a
pack/day, and, being a bachelor, eats most meals out. At home, he keeps high fat snacks such as cheese and crackers. He has a positive family history for CAD. His
father died at age 46 of an MI and several of his sibs had MI's in their 50's. There is no diabetes in the family. His physical exam is WNL, BP 130/80.

Initial lipid profile:


T.Chol
277 mg/dl
HDL-C
38 mg/dl
LDL-C
205 mg/dl
Trig.
171 mg/dl


Lipoprotein type; IIA

Risk factors for CHD; smoking, positive FMH

The patient was started on a step I AHA diet and advised to exercise 3-4 times/week for 30-45 minutes. He was asked to stop smoking. After 3 months the patient
returned with the following cholesterol profile:


T.Chol
222 mg/dl
HDL-C
36 mg/dl
LDL-C
169 mg/dl
Trig.
85 mg/dl


The use of lipid lowering drugs should be considered for primary prevention if diet and exercise cannot lower the LDL-C to acceptable levels. In patients with 2 or more
risk factors for CHD, drug therapy should begin if the LDL-C is 160mg/dl or >. The goal is an LDL-C of < 130mg/dl. If the patient has less than 2 risk factors for CHD
therapy should be started if the LDL-C is 190mg/dl or greater with the goal LDL-C being < 160mg/dl (NCEP guidelines 1993).

The patient was started on pravastatin 20mg QD with the following results:

T.Chol
185 mg/dl
HDL-C
40 mg/dl
LDL-C
125 mg/dl
Trig.
92 mg/dl



Case 3 Secondary Prevention

GJ is a 60 yo college professor who had an MI at age 56 and had a subsequent PTCA for a 100% RCA and 75% distal RCA. Post PTCA =30% stenosis. Only other
PMH was nephrolithiasis. FMH negative for CHD. No smoking. Drinks glass red wine daily, swims 1/2 mile 3-4 times/week. Physical was WNL.

He had known hypercholesterolemia for 6-7 years prior to his MI but never placed on diet or medications. Cholesterol profile prior to MI :


T.Chol
246 mg/dl
HDL-C
40 mg/dl
LDL-C
168 mg/dl
Trig.
190 mg/dl

CLASS IIA/B

After his MI he was placed on a Step I AHA diet with the following cholesterol results:


T.Chol
196 mg/dl
HDL-C
32 mg/dl
LDL-C
121 mg/dl
Trig.
213 mg/dl


Since he has had PTCA and known CAD, his LDL-C goal is less than 100mg/dl. His HDL-C is also very low and is a risk factor in itself since it is less than 35mg/dl.
He was advanced to a step II AHA diet and simvastatin 5mg/day was started.
Repeat cholesterol profile after 2 months:


T.Chol
137 mg/dl
HDL-C
33 mg/dl
LDL-C
83 mg/dl
Trig.
106 mg/dl


He has been maintained at a LDL-C of less than 100mg/dl for the last 6 years. Yearly stress thalliums have shown no changes and he has had no further cardiac
events. With exercise and statins his HDL-C is in the low 40's.

SECONDARY PREVENTION LDL-C GOAL = < 100mg/dl


Case 4. Hypertriglyceridemia

RH is a 42yo male who has had a known elevated cholesterol for 2 years. He was placed on Lovastatin and a low fat diet by his referring physician. He had a
questionable 'stroke' one year ago. He has a positive FMH for early MI's. He smokes 1 pack QD, no ETOH. Physical exam WNL. He was referred with the following
cholesterol profile:

T.Chol 430mg/dl
Trig 1,853mg/dl

Risk factors for CHD - Smoking, +FMH CAD

We know that this patient has a primary triglyceride problem and that lovastatin would not be our first drug choice. The following recommendations were made:

1. D/C lovastatin and start gemfibrozil 600mg BID.
2. Low fat/ no sucrose diet.
3. Begin an exercise program. Stop smoking.
4. Order a lipoprotein electrophoresis. This patient could be a type IV, V, or IIB.

On return in 6 weeks he had the cholesterol profile below:


T.Chol
365 mg/dl
HDL-C
58 mg/dl
LDL-C
230 mg/dl
Trig.
342 mg/dl


He had lost 9 pounds and had stopped smoking. Since we now have his trig. below 400mg/dl his LDL-C can be calculated and is elevated. He most likely has a IIB
lipoproteinemia with elevation of LDL-C and Trig. We must now control his LDL-C.
Lescol (fluvastatin) 20mg was added QHS. On return his next profile was:


T.Chol
220 mg/dl
HDL-C
62 mg/dl
LDL-C
102 mg/dl
Trig.
279 mg/dl


Discussion
The patient presented with a primary triglyceride problem. His initial medication should have been either gemfibrozil, fenofibrate, or niacin.
When the triglyceride levels are > than 1000mg/dl, diet and medication should be started simultaneously to quickly lower the level since there is an increased risk of
pancreatitis.
After the triglycerides were controlled, it was noted that the LDL-C was also elevated at 230mg/dl and a statin was started. With this combined regimen there is a slight
risk of elevated LFT's and CPK and one should monitor these values more closely.



Case 5. Familial Hypercholesterolemia

MB is a 36 yo male who was first diagnosed with a cholesterol of 424mg/dl at age 30.
Stress ECG at that time was positive for an inferior scar. Cardiac cath the next year showed LAD 70% stenosis, Lf Circ, obtuse marginal totally occluded. Distal RCA
40%.
FMH was positive for grandfather died age 50 of MI, mother has very high cholesterol.
His initial cholesterol profile:


T.Chol
424 mg/dl
HDL-C
13 mg/dl
LDL-C
365 mg/dl
Trig.
235 mg/dl


He was initially started on a low fat/saturated diet, lovastatin, and later Questran. There was only slight improvement in his cholesterol level;


T.Chol
380 mg/dl
HDL-C
14 mg/dl
LDL-C
377 mg/dl
Trig.
143 mg/dl


He was later switched to simvastatin 40mg QD, Niacin 1.5g QD, and Colestipol 15g QD.
The best control over the last few years is the following profile:


T.Chol
279 mg/dl
HDL-C
30 mg/dl
LDL-C
225 mg/dl
Trig.
121 mg/dl


A recent repeat cardiac cath has shown progression of his disease. Cholesterol testing of his children showed;



Michelle
Shantese
Michael

3 yo female
5 yo male
6 yo male
T. Chol
249
331
119
HDL-C
18
50
39
LDL-C
211
272
70
Trig.
101
46
62


MB has familial hypercholesterolemia, type IIA. This is an autosomal dominant disease which affects 1 in every 500 persons. It is caused by a mutation in the gene
for the LDL-C receptor. Heterzygotes have a 2-3 fold elevation in the total cholesterol which is mostly LDL-C. Symptoms usually begin to develop in the 3rd or 4th
decade as premature and accelerated atherosclerosis. By age 60, 85% have had an MI.

How to diagnose;
1. Very high LDL-C usually 250mg/dl or >
2. T. cholesterol 350-400mg/dl or >.
3. Family history of elevated cholesterol, early MI
4. Tendon xanthomas

Treatment:
1. Multiple drug Rx
2. Diet
3. Plasmapheresis
4. Liver transplants

END OF TUTORIAL - RETURN TO CHAT ROOM