1

(Therapeutics)How to approach a case of Dyslipidemia

(30-31) Year II
By Dr Attia Jabr
A)
1. Check the random level of total cholesterol (TC) as initial screening.
2. If it is increased, do a fasting level of TC, TG, and HDL.
During weight loss and MI What about Lipid profile?

As regards the level of TC

a.
b.
c.
d.

The normal total cholesterol is < 200 mg/dl

If it is between 200-239..Moderate
If it is > 240.. Severe.
The ratio between TC/HDL: is more senstive

As regards TG
a.
b.
c.
d.

If it is < 150 it is normal

If it is 150-199Mild increase
If it is 200-499.Moderate increase
If it is > 500..Severe increase.

B) Ask for a second fasting lipid profile (12h fasting)

The NCEP guidelines are:
1. LDL>160 + or other risk factors
2. LDL 130-159 +2 risk factors
3. LDL >100 + atherosclerotic disease
4. HDL< 40
How can you calculate the LDL.C?
C) Assess for the number of risk factors
NB; DM is considered now CHD equivalent

present in the patient:

The Major risk factors are:

1. Current Cigarette smoking
2. Hypertension (BP > or = 140/90 or on Anti-hypertensive therapy. > stroke
3. Low HDL.C < 40 mg/dl
4. Family history of CHD (definite MI) or sudden death due to CHD in father or other first
degree relatives < 55Y or before 65 y in mother or other female first degree relatives.
5. Age (men 45 y; women 55y
6. Risk equivalent: DM, PVD
Minor risk factors:
A. Sedentary life style: 50%
B. Obesity (BMI >30) & Waist > 102 cm M & 88cm F: 50%
C. Dietary: Alcohol HT, CVS risk
D. Triglycerides, VLDL, IDL
Contributing factors:
A. CRF
B. Radiation therapy
C. SLE.

2
Putative factors:
A. Homocyteine
B. Lpa
C. Small LDL
D. C-reactive protein,
E. Chronic infection
NB. Some criteria that raise the suspicion of familial dyslipidemia are:
1. CHD or dyslipidemia in first degree female < 65y
2. CHD or dyslipidemia in first degree males < 55Y
3. Xanthelasma OR corneal arcus under age of 50
4. Tendon xanthomata
5. High TC at any age

Types of familial dyslipidemias (60% of cases of dyslipedimia):

Type

TG

TC

LDL.C

I
IIa 1/500
IIb 1/200
III
1/5000

+++
N
++
+++

+
++
++
+

IV

++

V
+++
1/1000000
Polygenic +
HC

N
++
++
N

Raised
lipoproteins
Chylomicrons
LDL
LDL/VLDL
VLDL/chylo

Atheroma
risk
N
+++
+++
++

N/+

VLDL

++

VLDL/Chylo

++

++

LDL

++

Associated
Signs
Xanthomas,CA
Common
Obesity,
DM,HT
xanthomas
Obesity, DM,
Hyperuricemia,
alcoholic
Obesity, DM
Family H 25%
No physical

D) Assess for presence of secondary causes of hyperlipidemia (because they can

be treated) 40%. The most important secondary causes are:
1. DM type I, type II(High TG, Low HDL, High LDL) ( CHD 4times)
2. Hypothyroidism (Combined or High TG)
3. Pregnancy
4. Inappropriate diet
5. Alcohol abuse (TG)
6. Chronic renal failure (TG)
7. Renal & cardiac transplantation
8. Nephrotic syndrome (LDL-C) + corticosteroids.
9. Hepatocellular disease
10. Cholestasis
11. Myeloma
12. Obesity (High TG& Low HDL-C)
13. Drugs; the most important drugs are

3
a. Antihypertensives (Diuretics (thiazides (LDL-c, VLDL-c, TG& Loop, B. blockers
TG, HDL). What are the alternatives?
b. Oral contraceptives (Ht, DM)
c. Androgens
d. Corticosteroids (TC, LDL, TG, VLDL)
e. Ciclosporines (LDL, Ht, DM) + corticosteroids.
f. Progestogens (LDL, HDL)
g. Vit. A derivatives
h. Protease inhibitors, Tamoxifen
i. Hepatic microsomal enzyme inducers (like phenytoin, rifampicin, carbamazepine,
grisofulvin etc). Increase all (HDL, LDL, VLDL) But good ratio TC: HDL

E) Define your goal of treatment concentrating on level of LDL as

follows:
Risk category
No CHD with 0 or
1 risk factors
No CHD wit 2 risk
factors
DM
CHD
CHD + Multiple
risk factors or DM

LDL goal
Mg/dl
<160

Diet/life style
indicated
160-190

Drug therapy
indicated
>190

<130

130-160

>160

<100
<100
<70

100-130
100-130
70-100

>130
>130
>100

F) The design of treatment is as follows:

1. Treat risk factors (life style changes)
1. Stop smoking
2. Encourage regular excersize. Value?
3. Treat secondary causes of hyperlipidemia, DM, HT.
4. Obese should lose weight. (Relation?)
5. Stop alcohol
2. Diet (step II) (3-6%)
30% total fat (10% polyunsaturated, 15% monosaturated, < 7% saturated fat), Cholesterol 200
mg/day. Increase fiber at least 30 gm/day.
Nutrient
Total fat
Saturated fat
Polyunsaturated
Monosaturated
CHO
Protein
Cholesterol

Step I
30%
10%>
Up to 10%
Up to 15%
55%<
15%
mg/day 300

Step II
30%
7% >
Up to 10%
Up to 20%
55%<
15%
mg/day 200

Dietary management of hyperlipoproteinemia

Always initiated firstly in the management.

Except patients with familial hypercholestrolemia and combined hyperlipidemia in which
both drugs and diet should begin together.
Total fat restrictionhypertriglyceridemia
Cholesterol & Saturated fatHypercholestrolemia (LDL)
Decrease CHO (Sucrose & simple sugars) VLDL.
Increase dietary fibers (oat or rice bran)LDL
Increase vegetables, fresh fruit, cereals, whole grain.
Stanol esters and plant sterols ( reduce Cholesterol absorption)
No alcoholHypertriglyceridemia
Decrease caloric intake and stabilization of weight.
Total fat calories should be 20-25% with saturated fat < 8%, Allow monousaturated
(olive oil, and polyunsaturated like sun & corn flower oil (not excess. Why?) &
Cholesterol < 200 mg/day( not more than 4 eggs /w)
Take care of hydrogenated fat & prolonged heating
Increase complex CHO and fiber Monosaturated fat should predominate fat allowance.
Omega 3 fatty acids found in fish oils (Cod liver oil) salmon fish can induce profound
lowering of triglycemia with endogenous or mixed type. However, Omega 6 in plant oils
raises these levels.
The diet should contain anti-oxidants 500 mg ascorbic acid + Mixed natural tocopherols
(200-400 IU) + other natural antioxidants present in fruits and vegetables.
Reduce the total amount of proteins to reduce homocysteine
Daily supplementation with 1 mg folic acid + vit. B complex
Salt: reduce the amount from 9 gm to 6 gm

3. Continue on diet and life style changes for 3-6M if ineffective or unacceptable or if
there is evidence of IHD, hypertension, DM, positive family history, or there is
hypertriglyceridemia, lipid lowering drugs should be used.

Indications of drug therapy:

1.
2.
3.
4.

In whom the above dietary measures are not successful

Who find the dietary restrictions risky
Who are at great risk of IHD, pancreatitis >1000 mg TG
For secondary prevention after IHD
A) Primary prevention:
The aims of treatment of 1ry hyperlipoprotinemia are (When there is risk of CHD of 15% or
more in 10Y)
A) To reduce the risk of atheroma in familial hypercholesterolemia, familial
hypertriglyceridemia , remnant hyperlipoprotenimia)
B) To reduce the risk of acute pancreatitis in chylomicronemia and familial
hypertriglyceridemia).
C) The treatment can reduce xanthomatous eruption in the skin and tendons.
D) Important factors to consider in risk management in primary prevetion:
1. Dietary advice
2. Smoking
3. Physical activity
4. Body weight
5. Hypertension

5
6. Control of diabetes
7. Low dose aspirin: in high risk especially with HT
8. Lowering of cholesterol by statins according to the risk factors (<200 TC, <130
LDL)
(According to Sheffield table (Age, gender, smoking, DM, BP, TC/HDL.c
1. If the CHD risk < 15% life style modification and reassess after 5 years
2. If the CHD risk > 15% but TC < 200 mg/dl Life style modification + Yearly lipid
profile + Treat risk factors
3. If the CHD risk > 15% and Tc> 200 mg/dlLife style modification + Drug therapy
e.g. statin.

B) Secondary prevention:
9. Statins except when the major abnormality is low HDL
10. Treat other risk factors
11. Low dose aspirin
12. ACE inhibitors for left ventricular dysfunction
13. B. blockers for MI
14. Warfarin or aspirin for those over 60 y who have atrial fibrillation
15. Omega 3 fatty acids

Treatment of hypertriglyceridemia:
1. Begin with non-pharmacological measures
2. Control of diet, weight diabetes, alcohol
3. If insufficient, use drugs as follows:
a. Modest TG + TCuse statins
b. Extremely high TGuse fibrates or niacin
c. High risk individuals combine statins + fibrates
The use of drugs in lowering plasma lipid concentration:
a.
b.
c.
d.
e.
f.
g.
h.
i.
j.
k.
l.

Statins & Resins for cholesterol

Fibrates & Nicotinic A for TG.
All have side effects, see the table.
Two drugs with mg (statins & Fibrates)
Two drugs with Gms (Resins & Niacin).
Begin with small doses then increase gradually till full therapeutic doses.
Follow up the effect of drugs every 4-6 w until you reach your goal then every 6
months, then annually.
Nicotinic acid increases uric acid & fenofibrates decreases it.
Lipid profile is done /6 W until adjustment, then annually.
Liver function test & kidney function & creatine kinase E should be done during
treatment for follow up the side effects of drugs.
Before therapy you may look for the secondary causes by some investigations like
TSH, liver function, kidney functions, blood glucose, drugs
It should be known that drug therapy should be continued life long. Why?

Drug combinations:
4. If one drug is not effective, you can add one or more drug, the following drug
combinations are possible:
a. Fibrates + Resins ( familial combined hyperlipidemia)

b.
c.
d.
e.

Statins + Resins ( Familial hypercholesterolemia)

Niacin + Resins ( Familial hypercholesterolemia)
Niacin + Statins (Familial hypercholesterolemia)
Ternary combinations of (Resins + Niacin + Statins)
Never use Statins + fibrates except. Why?
Examples
Doses
Effect
Mechanism

Statins
Simva, fluva,
Atorva-statin
(10-80 mg)

Resins
Colistipol
Choestyramine
(15-30 gm)

Fibrates
Nicotinic acid
Bezafibrate
1.5-6gm/day
400-600 mg/day
Gemfibrozil
600mg/12h
Lower TG, VLDL/2ry C,LDL
Lipoprotein lipase E
Adipose tissue lipolysis

TC
TG
VLDL
LDL
HDL

Predominantly lower Cholesterol

HMG-COA reductase E
Bile acid
absorption
Familial hypercholestolemia(type IIa, familial
combined hyperlipidemia type IIb
Pruritus
Diarrhea
Digitalis toxicity
45%
30%
30%
20%
10%
60%
20%
15%
5%

Side effects
Hepatitis

Hepatic injury

Hepatic injury

Myositis

Muscle injury

Loss of bile salts

Muscle injury

GIT

GIT

GIT(constipatio
n)

Gall stones & GIT

Uses
Other uses

Others
Pregnancy and
lactation
Drug-drug
interactions

Hypersensitivity
NO
C.P450 inducers and
inhibitors (grapefruit)
Nicotinic, cyclosporine

Yes
Binding
drugs( digoxin,
diuretics,thyroxi
ne, statins, Vit K

Hypertriglyceridemia (type IV, V) combined

hyperlipidemia (type IIb,III)
Never combine with
May be used in combination to
statins for sever
HC
myositis
20%
20%
50%
60%
60%
10%
25%
30%
20%
25%

Large doses
SR
Glucose
Uric acid
GIT(PU)

NO
Statins& Oral
anticoagulants & oral
antidiabetics& Resins&
Ciclosporin

Cutaneous flush & pruritus

NO
Drugs of DM & Gout

Questions for revision:

Q1. What are the pathways of lipoprotein metabolism?
Q2. Enumerate the important types of lipoproteins? Their content?
Q3. Why do we say Dyslipidemia not hyperlipidemia?
Q4. What are the common familial disorders of dyslipidemia? Which is raised?
Q5. Can dyslipidemia cause MI in adolescents < 20Y? Which type?
Q6. Which of the familial disorders is not associated with atherosclerosis?
Q7. What are the common disorders known to affect adversely the lipid profile?
Q8. What is the effect of B.blockers on lipid profile?
Q9. Which B. Blockers do not affect the lipid profile? Why?
Q10. What are the other antihypertensive drugs which do not affect lipids?
Q11. What are the life style changes you advise a patient to do before treatment?
Q12. What is the BMI? Formula? Scales?
Q13. What is your advice as regards diet for patients with dyslipidemia?
Q14. What is your opinion in antioxidants in CHD?

7
Q15. For how long will you advise for diet and life style changes? 1ry& 2ry
Q16. What are the general lines for primary prevention for cases of dyslipidemia?
Q17. What are the general lines for secondary prevention for cases of dyslipidemia?
Q18. What is the mechanism of action of statins?
Q19. Why statins are useful in CHD?
Q20. What are the most important side effects of statins?
Q21. What is the effect of grapefruit on statins effect and toxicity?
Q22. What is the mechanism of action of fibrates?
Q23. What are the main side effects of fibrates?
Q24. What are the drug-drug interactions of statins?
Q25. What are the drug-drug interactions of fibrates?
Q26. What is the mechanism of action of Resins?
Q27. Which drug raises the TG?
Q28. What are the precautions taken while taking resins?
Q29. What are the major adverse effects of Resins?
Q30. What is the mechanism of action of nicotinic cid?
Q31. What are the major side effects of NA?
Q32. What is your opinion about fish oil in treating hyperlipidemia?
Q33. Why statins are preferred to be taken at evening?
Q34. When do you expect the results of statins?
Q35. How can you overcome the hot flushes of nicotinic acid?
Q36. Are the accompanying statements false or true? Why?
a. An individual with high HDL there is a lowering in the risk of CHD if the HDL is reduced.
b. An important contributor to the development of hypercholesrolemia is a genetic defect.
c. Anion exchange resins act by enhancing the absorption of bile acids from the gut.
d. Decreased cholesterol synthesis results in increased number of HDL receptors
e. Simvastatin lowers LDL by 5%
f. Co-administration of bile acid resins and statins has no greater effect than giving each drug
separately.

When do you think to use drug combinations in treating dyslipidemia?

Indicated in:
1. Very high VLDL during ttt of HC
2. Combined high LDL and VLDL
3. LDL and VLDL not responsive to single agent
4. Elevated level of Lpa or HDL + other dyslipidemia
The combinations are:
1. Statins + Resins or EzetimibeFHC # VLDL. (+ 20-30%)
2. Statins (25% dose) + Niacin FHC & FCH. (Myopathy)
3. Statins (25% dose) + fibratesFCH. (fenofibrate + rosuvastatin)
4. Statin + Niacin +Resins FHC & FCH ,VLDL + LDL. 70%
5. Fibric acid + ResinsFCH. #Niacin or statin
6. Statins + Ezetimibe FHC (even Homozygous)
7. Resins + niacin + statins+ Ezetimibe LDL(doses)

Case discussion

Case 1: A 42-year-old woman, has a plasma total triglyceride of 1042 mg/dl and total cholesterol
of 368 mg/dl. Plasma HDL is 72 mg/dl. Electrophoresis of the plasma lipoproteins an intense pre-Bband; all others are normal or absent. Blood glucose is normal. She is not taking any medications.
Q1. What hyperprlipoproteinemia does this patient most likely have?
Q2. What is the greatest health risk to this patient based upon the provided information?
Q3. Which individual drug or combination can safely be used to produce maximum lowering
of her plasma lipids?
Q4. IF the patient is given fenofirate to treat his condition, what enzyme or receptor activity
will most increase?

Case 2; Awatif a 45 years is an asymptomatic female. She is screened with a lipoprotein profile
during an annual physical evaluation. She has non-insulin dependent DM treated with 60 U NPH.
She is overweight. Her fasting lipoprotein profiles: total cholesterol 234 mg/dl, triglycerides 2300
mg/dl, HDL-24 mg/dl, LDL 160 mg/dl, fasting BG 290 mg/dl. What is your assessment of CHD
risk and what treatment if any should be given?
Control DM-Fibrates-Lipid profile<400 mg/dl then LDL if >100 give statin.

Case 3;

Mr D.F is a 43-year-old man who has been relatively fit and well for the past 20 y
during which he has rarely visited his GP. Two weeks ago he was admitted to hospital suffered MI.
On questioning it was revealed that his brother had died in a road traffic accident at the age of 19
and his father had died from CHD aged 54Y. Examination of Mr D.F. revealed tendon xanthomas.
Blood drawn within 2 h of the onset of MI revealed TC 350, HDL 40 and triglycerides 200 mg/dl
Questions
Q1. Calculate the concentration of LDL and comment on the finding?
Q2. What is the likely diagnosis and treatment of DF on discharge?
Q3. D F wants to know why he was not identified as being at high risk of CHD before he
suffered his MI?
Case 4; Mr P.T. is a 50-year-old man with a blood pressure of 140/85 mm Hg and type 2 DM,
but no history of CHD. He smokes 10 cigarettes a day. On a routine clinic visit he is found to have a
TC of 240 mg/dl, HDL 30 , and TG 150 mg/ dl.
Questions:
Q1. Is PT at high risk of CHD?
Q2. What advice/ treatment would be appropriate?

Case 5: Mrs Soad is a 49-year-old woman who visits her doctor complaining of menopausal
symptoms including hot flushes, night sweats and irritability. She is concerned about her risk of
CHD because her husband and mother have angina. Her mother developed angina at the age of 68
and 5 years later was diagnosed with breast cancer. In general Mrs Soad does not like taking
medicines and would not much prefer exercise to hormone replacement therapy (HRT)?
Q1. Is Mrs Soad at risk of CHD?
Q2. What advice would you give her about the relative benefits of exercise and HRT?

Case 6. A 58-year-old man has recovered from anterior MI. His fasting plasma cholesterol is 210
mg/dl. You want to reduce his risk of a further MI by lowering his cholesterol.
a. What advice would you give him?

9
b. What drug would you recommend and why?
c. What reduction of plasma cholesterol would you expect, and when would you expect an
adequate response?
d. How do statins work?
e. What target total cholesterol would you aim for?
f. What unwanted effects would you warn him about?
g. If the target cholesterol is not attained, how could you reduce cholesterol further?
h. How the additional drugs you have recommended work?

Case 7:
A 45-year- man has a plasma total triglyceride of 105 mg/dl and total cholesterol of 431 mg/dl.
Plasma HDL is 53 mg/dl. Electrophoresis of his plasma lipoproteins show an intense B-band; all
others are normal. He is taking itraconazole for persistent fungal infections. He had two older
brothers who both died of MI at 53 and 51 years of age.
Q1. What hyperlipoproteinemia does this patient most likely have?
Q2. What is the most likely biochemical basis of this patient's hyperlipidemia?
Q3. What drugs would be contraindicated in this patient if his use of itraconazole was not
discontinued?
Q4. If the patient was treated with cervistatin, what adverse effects would be of greatest
potential concern?

Case 8;

Essam, a 53-year-old man, has a mean LDL.c of 200 mg/dl determined on two
appointments after following a step II diet, low-saturated fat diet for 6 months. His high BP is under
marginal control with enalapril 10 mg/day ( BP,134/88). His glucose level is 80 mg/dl. He reports
no family history of premature CHD events. He does not smoke. His HDL.c is 45 mg/dl. There are
no secondary or familial causes of his hypercholesterolemia, and no evidence of atherosclerosis
was found during his initial medical evaluation. He jogs 2 miles 3 times a week. Is Essam a
candidate of cholesterol lowering drug therapy, and if so,
Q 1; What drug (s) should be considered for lowering his LDL.c level?
Q2. According to the answer in previous question either a bile acid resin, niacin, or HMG-CoA
reductase inhibitor would be acceptable? What about fibrates?
Q3. Which one of these 3 major drugs would be used first to manage L.W lipid disorder? Your
goal? Which drug from this group? Why? If failed, what will you do? Combinations?
Q4. How can you monitor each of these drugs?
A. BAR (Lipid profile /4-8 w)
B. Statins (Lipid profile, LFTs (0-3m-A), CPK((0-symptoms)
C. Niacin therapy (Lipid profile, LFTS (0-6-8w for 1year, symptoms) Glucose, uric
acid, BP (hypertensive & elderly patients)
Q5. What are the doses of theses drugs? Time of administration?
Q6. What is the difference between colesevelam and cholestyramine?
Q7. What do you know about Ezetimibe?
Q8. What role can supplemental fibers play in the treatment of the patient? 5%
Q9. Can fish oils be used to treat elevated LDL-C in patient's treatment?TG 30-60%

Case 9. Asmaa is a 55-year-old recently postmenopausal woman. She has a mean LDL of 200
mg/dl after a 6-month trial of a step II diet. She has a strong family history of CHD. Her mother is

10
78 years complaining of fracture as a result of osteoporosis. No DM, No HT. She smokes 10
cigrettes/day. HDL 58 mg/dl. Tg 78 mg/dl. No evidence of secondary or familial dyslipidemia and
no evidence of atherosclerosis. No hysterectomy. Physically active and with normal weight. She
complains of hot flashes and night sweats.
Q1. Does this patient need cholesterol lipid lowering? If so. Which drug?
Q2. What is your opinion for using estrogen therapy in treating this lady?
Q3. What are the adverse effects of estrogen in this lady?
Q4. How can you decrease the side effects of estrogen therapy in this lady?
Q5. What are the contraindications of estrogen?
Q6. Do you think that statins are good for the patient?
Q7. What is your opinion in using BAR or niacin?

Case 10: If the Ali's BP persists after lifestyle changes are made, how should he be managed?
Q1. Which drugs Beta blockers (ISA?), alpha blockers, mixed, thiazides?, CCBs, ACEI
Q2. Which diuretics do not affect blood lipids?
Q3. Are B. Blockers essential in Ali's condition?
What is your opinion in anti-oxidant in management of hyperlipidemic patients especially
who have developed CHD?
References:
1. The pharmacological basis of therapeutics By Goodman & Gillman's,
2006
2. Medical pharmacology and therapeutics By Derek Waller,2006
3. Basic and clinical pharmacology By Katzung, 2006
4. Modern pharmacology with clinical applications by Craig & Stitzel, 2004
5. Clinical pharmacy and therapeutics By Roger Walker,2003
6. Clinical pharmacology By George Carruthers, 2001
7. Clinical pharmacology By Bennet & Brown, 2003
8. Illustrated pharmacology By Bastawi and AbdelBary, 2003
9. Pharmacolgy and Pharmacotherapeutics By Satoskar, 2000.