1. MANAGEMENT OVERVIEW
DYSLIPIDEMIA
DR / KHALID AL –HARBY
FAMILY MEDICINE CONSULTANT
MBBS, ABFM, SBFM
DR/KHALID AL-HARBY 1

2. Prevalence in Saudi Arabia
al –Nuaim AR 1997
 The prevalence of HC, 5.2-6.2 mmol/l was 9% and
11% for all male and female (above 15 y.)respect.
 The prevalence of HC, > 6.2 mmol/l was 7% and
8% for male and female (>15y.) respectively
 The prevalence of HC, 5.2-6.2 for subjects aged
40-59 y. was 14% and 10% for male and female
respectively
 The prevalence of HC > 5.2 increase with BMI
DR/KHALID AL-HARBY 2

3. Al – Awali PHC 1422
A pilot study on male adult diabetic patients
High Cholesterol level Pie Chart
yes
34.8 %
65.2 %
no
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4. Al – Awali PHC 1422
A pilot study on male adult diabetic patient
High TG level Pie Chart
yes
30.4 %
69.6 %
no
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5. Screening
 National Cholesterol Education Program (NCEP):
• Random TC and HDL for all adult > or = 20 years
• Every 5 years
 U.S.Preventive Task Force:
• Men 36-65 y. and women 45-65y. Every 5 years
• TC
DR/KHALID AL-HARBY 5

6. Recommended algorithm for adults
Measure total chol. And HDL chol.
High: > or = 240 mg/dl Desirable: < 200 mg/dl
Borderline high: 200-239 mg/dl
HDL < 35 mg /dl or > HDL > or = 35 mg /dl HDL < 35 HDL > or =
or = 2 risk factors And < 2 risk factors mg/dl 35 mg /dl
Offer advice
offer advice
on risk
on risk
Measure fasting cholesterol and calculate LDL
DR/KHALID AL-HARBY 6

7. Recommended algorithm for adults
No evidence of CHD Evidence of CHD
High LDL >optimal LDL Optimal LDL
Desirable Borderline > 100 mg/dl < or = 100mg/dl
LDL > or=160
LDL
130-159
Clinical
evaluation
Offer instru-
< 2 R.F > or 2 R.F Clinical evaluat. ctions on diet
Diet
and activity
therapy
retest Diet
Offer advice retest
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8. Recommended algorithm for adults
LDL > or = 190 LDL > or = 160 mg/dl LDL > 100
mg/dl and < 2 R.F and > or = 2 R.F Mg/dl
Consider drug therapy
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9. NCEP for cholesterol levels
Risk category (mg/dl)
LIPID
Desirable Borderline High
Total cholesterol < 200 200-239 >or=240
HDL cholesterol > 60 --- < 35
LDL cholesterol < 130 130-159 > or= 160
Triglycerides < 200 200-400 400-1000
DR/KHALID AL-HARBY 9

10. Friedewald Formula
 LDL cholesterol = total cholesterol – HDL
cholesterol + 0.16 TG
 It is valid for estimating LDL cholesterol if the TG
level is < 400 mg /dl and if the individual does not
have familial dysbetalipoproteinemia
DR/KHALID AL-HARBY 10

11. General Treatment Guidelines
Status Initiation level (mg/dl) Goal level (mg/dl)
No CHD and < 2 risk factors
Diet > or = 160 < 160
Drugs > or = 190 < 160
No CHD and > or = risk factors
Diet > or = 130 < 130
Drugs > or = 160 < 130
CHD
Diet > 100 < or = 100
Drugs > or = 130 < or = 100
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12. The efficacy of primary prevention
 AFCAPS/TexCAPS< RCT> (1998):
6605 men and women with average total
cholesterol levels (mean 228mg/dl) and low HDL
cholesterol (mean 40 mg/dl for women and 36
mg/dl for men), Lovastatin 20 or 40 mg /d reduced
cardiovascular event by 37%
DR/KHALID AL-HARBY 12

13. The efficacy of secondary prevention
A. Scandinavian Simvastatin Survival Study (1994):
• Decrease in cardiac mortality of 42%, and decrease in
all-cause mortality of 30%
• In 4444 pt.s with CHD over 5.4 years
B. Cholesterol and Recurrent Event (CARE) (1996):
• Decrease in coronary events of 24% with 5y. On
Pravastatin 40mg/d, decrease in need for PTCA of 23%
,and decrease in need for CABG of 26%
• In 4000 post MI with mean TC of 209 and LDL of 139
DR/KHALID AL-HARBY 13

14. 4444 with mild high chol.
Simvastatin, placebo
5.4 years
Reduce T.Chol, LDL
, risk of major CAD
Increase 6 y. survival
DR/KHALID AL-HARBY 14

15. 4000 post MI
Pravastatin, placebo
5 y.
Reduce C events, need
For PTCA, CABG
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16. post CHD with high chol.
LIPID
Pravastatin, placebo
1y.
5.2 / 1000 live saved
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17. The efficacy of secondary prevention
C. The AVERT trial (1999):
• 341 patient with stable CAD, LDL > or = 115 mg/dl and
TG < or = 500mg/dl
• Randomized to either aggressive lowering of LDL with
atrovastatin (80mg/d), or PTCA and usual care
• The atrovastatin group had a reduced but not statistically
significant rate of ischemic events(13.4% vs. 10.1%)
• This reassures that drugs are safe and as good as PTCA
for pt.s with stable CAD
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18. 341 for PTCA
177 PTCA, 164 LIPITOR
18 MONTHS
LIPITOR reduces
ischemia
& need for PTCA
DR/KHALID AL-HARBY 18

19. The role of dietary intervention
A. Oslo Study Group (1981):
established the recommendation of dietary intervention
and smoking cessation to improve lipid profiles
B. Physician Health Study:
• Men who ate fish (including shellfish) at least once a
week had a 52% reduction of sudden cardiac death
compared with those who consumed fish < once/month
• Data did not find an inverse association between fish
consumption and the rate of MI
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20. Comparison of step I and II diets
Recommended intake
Nutrient Step I Step II
Total fat < 30 % of total calories
Saturated fat 8% - 10% of total calories < 7% of total calories
Polyunsaturated fat up to 10 % of total calories
Monounsaturated fat up to 15 % of total calories
Cholesterol < 300 mg/dl < 200 mg/dl
Carbohydrates 50% - 60% of total calories
Protein 10 % - 20 % of total calories
Calories to achieve and maintain desired weight
DR/KHALID AL-HARBY 20

21. Sources of dietary Fatty Acids
 Cholesterol :
egg yolk, organ meats
(liver, sweetbreads, brain), animal meats
(beef, pork, lamb), butter
 Saturated Fatty Acids:
animal fat (beef, pork), whole dairy products
(milk, cream, ice cream, cheese), palm oil, coconut
oil
DR/KHALID AL-HARBY 21

22. Sources of dietary Fatty Acids
 Polyunsaturated Fatty Acids:
safflower oil, sunflower oil, soybean oil, corn oil
 Monounsaturated Fatty Acids:
olive oil, canola oil
DR/KHALID AL-HARBY 22

23. Diet therapy guidelines
Step I Diet Patient with CHD
Monitor at 4-6 W,
3 Months
Goal not achieved Step II Diet
Goal achieved
Monitor 4 times in 1st year, then 2 / year Goal achieved
Monitor at 4-6 W,
3 Months
Drug therapy
Goal not achieved
DR/KHALID AL-HARBY 23

24. Lipid-modifying drugs
Drug class initial dosage maximum dosage monthly cost(S.R) LDL HDL VLDL S.Es
HMG COA reductase inhibitors elevated LFT
Atrovastatin 10 mg / d 80 mg / d 210- 783 GI upset
Cerivastatin 0.3 mg / d 0.3 mg / d 150 myalgia/myosi.
Fluvastatin 20 mg / d 40 mg bid 142- 281
Lovastatin 20 mg / d 40 mg bid 262- 941
Pravastatin 20 mg / d 40 mg / d 243- 398
Simvastatin 10 mg /d 40 mg /d 221- 735
Bile acid sequestrants drug interactions
Cholestyramine 4 gm bid 20 gm (divided) 93- 686 GI upset
Colestipol 5 gm / d 30 gm (divided) 108- 1233 dec. absorption of vit A,E,K
DR/KHALID AL-HARBY 24

25. Lipid-modifying drugs
Drug class initial dosage maximum dosage monthly cost(S.R) LDL HDL VLDL S.Es
Niacin flushing/pruritus
50 – 100 mg bid 3 gm (divide) 6 – 187 rash/ GI upset
gout exacerbation
hyperglycemia
elevated LFT
Fibric acid derivatives pruritus/rash
Gemfibrozil 300 mg bid 600 mg bid 40 – 303 GI upset
Fenofibrate 67 mg / d 201 mg / d 75 – 228 myositis
( micronized) cholelithiasis
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26. Probucol
 Mechanism of action: not fully understood
 It lowers LDL by 10-20% but also lowers HDL (neutral
effect on total/HDL cholesterol ratio)
 Dose: 500 mg BID
 S.E: GI upset
 C.I: prolonged QT interval or H/O ventricular
dysrhythmia
 Limited benefit on lipid profile but can be used as an anti-
oxidant
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27. ERT
INCREASES: DECREASES:
1) HDL 1) LDL
2) TG 2) LIPOPROTEIN (a)
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28. ERT
 Recommended by NCEP II expert panel to all
postmenopausal women with lipid disorder (but this is
controversial: no support by clinical trials)
 Meta-analysis of observational studies: 44% RR in
primary prevention of CHD risk by ERT
 The postmenopausal Estrogen/Progestin international
(PEPI) trial (1995): combined HRT had a less desirable
effect on HDL cholesterol than ERT alone
DR/KHALID AL-HARBY 28

29. ERT
 The Heart and Estrogen/Progestin replacement (HERS)
1998 <RCT> for secondary prevention : 2763
postmenopausal women with CHD, combined HRT or
placebo, 4 years, no significance difference in the rate of
non-fatal MI & CHD mortality between the groups
despite significant improvement in LDL, HDL, TG, in the
treatment group
 For primary prevention: will be evaluated by the ongoing
Women’s Health Initiative clinical trial (27500 women
over 9 years) will be reported in 2005
DR/KHALID AL-HARBY 29

30. 2763 postmenop. + CHD
Combined HRT & placebo
4 years
HRT improved lipid
but not CHD
Increase S.E
DR/KHALID AL-HARBY 30

31. Other drugs
1) Raloxifen : non steroidal benzothiopene that
inhibits the growth of Estrogen receptor-
dependent mammary tumors
o It also lowers serum T.chol and LDL chol.
o RCT of 601 postmenopausal women over 2
years: dose-dependent reduction of T. chol
(9.7%) & LDL chol. (14.1%) in treatment group
(Raloxifen 150 mg/ day)
DR/KHALID AL-HARBY 31

32. Other drugs
2) D –thyroxin: lower LDL chol. 10 –15 % by enhancing
its clearance from circulation , BUT :
mild hyperthyroidism, cardiac S.Es
3) Neomycin : lower LDL by 10-15% by decreasing its
intestinal absorption BUT:
alter normal flora, ototoxicity, renal insufficiency
4) Olestra : non absorbable sucrose polyester fat substitute
that interfere with chol. absorption, FDA approved as
food not as a drug
DR/KHALID AL-HARBY 32

33. Other drugs
5) Sitostanol-ester margarine:
o A pine tree extract Stanol
o RAISIO group (1995) in Finland <RCT> studied
153 non-obese subjects with mild dyslipidemia
(TC > 216, TG > 265) : after 1 year –
10.2% reduction in TC, 14.1% reduction in LDL
in treatment group
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34. Combination therapy
 To achieve a synergistic effect
 Usually used in severe cases but can be used in less severe
cases by using low doses of 2 agents rather than a high
dose of single agent ( less toxicity, cost advantage)
 The ideal regimen is bile acid sequestant + statin
( 50% reduction in LDL, good tolerability (bile acid seq.
should be taken 1 h. prior to statin)
 Statin and fibric acid derivative should not be combined
(increase risk of myositis)
DR/KHALID AL-HARBY 34

35. Patient Education
 One study demonstrated that only approximately
50% of patients who were prescribed a lipid
lowering drug were taking it 1 year later
 Another study: 20-30 % of women given HRT
never started on them, and only 40 % of those who
started on HRT were still compliant with the
regimen 1 year later
DR/KHALID AL-HARBY 35

36. 875 healthy postmenop.
Placebo, ERT, 3 HRT regimens
3 years
ERT should be used
if no uterus, CEE with
Cyclic MP if uterus +
DR/KHALID AL-HARBY 36

37. Controversies and future considerations
(hypertriglyceridemia)
 Large studies initially linked high TG levels with
CHD, but it was associated with low HDL!!
( it might be due to the low HDL )
 Until intervention data are available, TG– lowering
agents should be reserved for patients with TG
levels > or = 400 mg/dl and other cardiac disease
DR/KHALID AL-HARBY 37

38. Controversies and future considerations
small, Dense LDL and the Atherogenic Dyslipidemic syndrome
LDL subclass
Pattern B
Pattern A (Small, dense)
LDL-I LDL-III
LDL-II LDL-IV
ADS:-
Dominant dyslipidemia
In patient with CHD and familial combined type
(H) TG ? Risk factor for development of type II DM
(L) HDL (similar lipid profile)
(B) TC Standard screening with total chol. And HDL
Chol. Is not adequate for those with ADS
“normal lipid profile”
Treatment : combination
Type II DM, HTN, central
obesity, procoagulant state Syndrome X
metabolic syndrome
DR/KHALID AL-HARBY 38

39. Controversies and future considerations
hyperpobetalipoproteinemia (Hyperapo B)
 Apolipoprotein B is the component of LDL that serves as
the ligand for its receptor
 Hyperapo B : increased apo B levels in the absence of
hyperlipidemia
 It is found in hypertriglyceridemia
 Analysis of some clinical trials has recognized that apo B
is a strong predictor of CHD risk
 Prospective studies are needed to determine if apo B is a
better predictor of CHD risk than the current lipid
measurements
DR/KHALID AL-HARBY 39

40. Controversies and future considerations
Lipoprotein (a)
 Contains LDL + apoprotein (a)
 Is considered an independent RF for premature CHD, but
its importance appears to lessen with advancing age
 Levels of Lp (a) are genetically determined (common in
African-American), but external factors may account for
up to 10% of the variation in concentration
 No trials to support the view that lowering Lp (a) levels
reduces CHD risk
DR/KHALID AL-HARBY 40

41. Controversies and future considerations
Diabetes Mellitus
 CHD is the principal cause of death in DM pt.
 Subgroup analysis of secondary prevention trials of
statin therapy: decreased LDL in DM is beneficial
 Unanswered Qs:
1) Should LDL goal of < 100 mg/dl in DM with CHD be
further lowered?
2) How aggressively to treat pt.s with DM and no CHD?
 At present NCEP II recommends : 1) a target LDL of
130mg/dl for primary prevention and < 100 for
secondary 2) 200 and 150 for TG
DR/KHALID AL-HARBY 41

42. Controversies and future considerations
Cerebrovascular disease
 Similar RF as CHD except for dyslipidemia
 No large trials look to CVA as an endpoint
 Secondary analysis of data from the CARE and the 4S
trials : significant reduction in stroke among pt.s treated
with statins
 A systemic review of 16 trials using statin therapy: 25%
reduction in all forms of stroke when total –chol. And
LDL chol. were reduced 22% and 30% respectively
DR/KHALID AL-HARBY 42

43. Controversies and future considerations
Alcohol
 It increases HDL and TG
 Studies have shown that alcohol in moderation (2-6
drinks/wk) leads to 34-53% reduction in CHD
 When heavy drinkers (> 2 drinks /d) were compared with
the light drinkers, they had 51% increase in all-cause
mortality
 Helsinki Heart study: the beneficial effect of moderate
alcohol consumption may be restricted to tobacco smokers
only
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44. Controversies and future considerations
Nutritional supplement
A. Fruits and vegetables: epidemiological data
showed lower prevalence of CHD in populations
with a higher intake of fruits and vegetables
B. Antioxidant vitamins (vit. C&E):
o Widespread belief: decrease risk of CHD (based on
the belief that LDL oxidation reduce CHD risk)
o GISSI-Prevenzione trial(1999): a RCT on secondary
prevention, randomized 1324 pt. with recent MI to
one of 3 groups (Omega-3-PUFAs, vit E, or both)
DR/KHALID AL-HARBY 44

45. Controversies and future considerations
Nutritional supplement
after 42 months : (1) significant reduction of non-fatal MI +
all-cause deaths + stroke in Omega-3 PUFAs group (2)
neutral effect of Vit.E supplement
o HOPE study 2000: no effect of vit. E on cardiovascular
events in subjects with CAD or DM over 4.5 years
C. Folic acid & vit.B6:
o Widespread belief: dec. CHD risk by dec. high
homocystein levels (another Atherogenic factors)
o Have yet to be proven by large clinical trials
DR/KHALID AL-HARBY 45

46. 1324 post MI on MDT diet
Ở- PUVA, Vit E, both
1y.
5.7 / 1000 live saved
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47. 1062 infant
540 dietary counseling, 522 control
5 y.
Reduce T.Chol,
Reduce LDL
In boys only !!!
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48. 1232 healthy men.
With high chol.
Dietary intervention
& smoking cessation
5 y.
Improve lipid, reduce
CHD morb&mortality
Even after 3 y.
DR/KHALID AL-HARBY 48

49. 9297 at risk for CAD
Ramipril , placebo
5 y.
Reduce rate of death,
MI, stroke
DR/KHALID AL-HARBY 49

50. 4081 asymptomatic
Dyslipidemeic men
2051 gemfibrozil, 2030 placebo
Same death rate
Increase HDL, reduce
LDL, TChol, TG
DR/KHALID AL-HARBY 50

51. 16608 healthy postmenop with
Intact uterus
Combined HRT, placebo
Planed 8.5 y.
(stopped at 5 y.)
Risks exceed benefits
DR/KHALID AL-HARBY 51

52. DM vs. control
20 years
Increases 2-3 x
Risk of clinical
Atherosclerotic diseases
Same in both sexes
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53. 6605 with average chol.
Lovastatin vs. diet + placebo
5.2 y.
Reduce incidence
1st major
CAD
DR/KHALID AL-HARBY 53