DYSLIPIDEMIA CARRY HIGHER RISK FOR CARDIOVASCULAR DSE

2. Dyslipidemia
From Guidelines To Practice
ALAA WAFA. MD
Associate Professor of Internal Medicine
PGDIP DM CARDIFF University UK
Diabetes and Endocrine unit
Mansoura university
2014

4. HTN treatment vs. lipid lowering
• HTN TREATMENT LIPID LOWERING
Multiple mechanisms
Many drug classes
More frequent ADE
Disputes about
measurement
Benefits reduced by wt
gain and high salt
Patients tend to need
more drugs with ageing
Fewer mechanisms
Fewer drugs
Less frequent ADE
Simple standard
measurement
Benefits less affected by
life style
The effective dose
remains effective

5. 0
20
40
60
80
100
Atorvastatin
(n=78)
Simvastatin
(n=76)
Lovastatin
(n=78)
Fluvastatin
(n=76)
Overall
(n=308)
Initial dose
First dose adjustment
%Patientsnotreachinggoal
Many Pts Do Not Reach Goal even after
First Dose Adjustment
Adapted from Brown AS J Am Coll Cardiol 1998;32:665–672.
68
47
78
61
90
69
99
90
83
66

6. Long-term adherence with CV regimens
Basal prescription & discontinuation (gray bar) at 1 yr
Kulkarni sp et al. Am Heart J 2006;151: 185-91

7. Dr.Sarma@works
7
Atherosclerosis – Time line

8. The Continuum
Risk factors
Hypertension
Dyslipidemia
Diabetes
Death Death Death
Adapted from: Dzau V, et al. Am Heart J 1991;121:1244--1263.
CAD
Myocardial
infarction
HF
End--stage
heart disease
Arteriosclerosis

9. Nizzar Qabbani .... Died with MI in 1998

10. Mohamed A. Wahab
EL AHLY Club player
Died in a match
No One is immune

11. 12
CVD=cardiovascular disease; MRFIT=Multiple Risk Factor Intervention Trial.
1. Stamler J et al. Diabetes Care. 1993;16:434–444.
CVDMortalityper
10,000Person-Years
Diabetes
No diabetes
Serum Cholesterol at Baseline, mg/dL
0
20
40
60
80
100
120
140
<180 180–199 200–219 220–239 240–259 260–279 ≥280
160
Higher CVD Mortality Risk in Patients With Diabetes
and Low Cholesterol Than in Patients Without Diabetes and High
Cholesterol1
• Cohort study in 347,978 men aged 35 to 57 years, screened in 20 centers for MRFIT
• Vital status ascertained over an average of 12 years
• Outcome measure was CVD mortality
n = 1105
n = 972
n = 1038 n = 823
n = 529
n = 343
n = 353
n = 62,448 n = 64,363 n = 75,112
n = 60,386 n = 40,090
n = 22,802
n = 17,604

12. Mechanisms Contributing to
Arterial Disease in Type 2 Diabetes
Adapted from Libby et al. Circulation. 2002;106:2760-2763.

13. 361,662 men (age 35-57) screened during the MRFIT STUDY
JAMA 1986, 258-282

14. Lipid research council study
NEJM 1990; 322:1700

15. Relationship Between Changes in LDL-
C and HDL-C Levels and CHD Risk
Third Report of the NCEP Expert Panel. NIH Publication No. 01-3670 2001.
1% decrease
in LDL-C reduces
CHD risk by
1%
1% increase
in HDL-C reduces
CHD risk by
3%

16.  39-50 % of pts with high LDL-C achieve goal on
current therapy
Non-compliance
Fear of high dose titration
 More effective cholesterol-lowering is needed to
attain LDL-C goals1,2
1
Kotseva, K, Wood D, de Backer, G et al. 2001
2
Pearson T et al. 2000
Why Do We Need a powerful Statin?

17. Rosuva
Atorva
Simva
Prava
10 20 40 80
Fluva
Statin Dose Required to Achieve
45–50% LDL-C Reduction
mg
Not achieved with max.
authorised dose
Not achieved with max.
authorised dose
Adapted from Jones P.H. et al. Am J Cardiol 2003;92:152–160

18. Rosuvastatin is the most effective statin to
lower LDL-C
Expert Opin. Pharmacother. (2008), 9(12) :2145-2160

19. *P<0.002 RSV 20 mg vs ATV 20, 40 & 80 mg; RSV 40 mg vs ATV 40 & 80 mg
Jones P.H. et al. Am J Cardiol 2003;92:152–160
0
2
4
6
8
10
12
MeanchangeinHDL-C
frombaseline(%)
7.7%
9.6%*
Rosuvastatin*
10 20 40 80
Dose, mg (log scale)
3.2%
5.6%
Pravastatin
6.8%
Simvastatin
5.3%
2.1%
Atorvastatin
5.7%
Rosuvastatin achieves significantly greater increase
in HDL-C than other statins (STELLAR)

20. JUPITER
Primary Trial Endpoint : MI, Stroke, UA/Revascularization, CV Death
Placebo 251 / 8901
Rosuvastatin 142 / 8901
HR 0.56, 95% CI 0.46-0.69
P < 0.00001
Number Needed to Treat (NNT5) = 25
- 44 %
0 1 2 3 4
0.000.020.040.060.08
CumulativeIncidence
Number at Risk Follow-up (years)
Rosuvastatin
Placebo
8,901 8,631 8,412 6,540 3,893 1,958 1,353 983 544 157
8,901 8,621 8,353 6,508 3,872 1,963 1,333 955 534 174
Ridker et al NEJM 2008

21. Cost-effectiveness issues

22. More effectLess effect
More cost
Less cost

23. Update on guideline content:
History of ATP dyslipidemia
guideline development
ATP IV
Nov 12
2013

24. It is advised that intensity of therapy be sufficient to achieve at least a
45% to 50% reduction in LDL-C levels.
High Risk/
Very High Risk
CHD or CHD risk
equivalents
(10-yr risk
>20%)
LDL-Clevel
100
-
160
-
130
-
190
-
Lower
Risk
< 2 risk
factors
Moderately
High Risk
≥ 2 risk
factors
(10-yr risk
10-20%)
goal
160
mg/dl
goal
130
mg/dl
70 -
goal
100
mg/dl
or
optional
70
mg/dl
Moderate
Risk
≥ 2 risk
factors
(10-yr risk
<10%)
goal
130
mg/dl
or
optional
100
mg/dl
Grundy SM et al. Circulation 2004;110:227-23
2002 LDL-C goals
revised 2004 LDL-C goals
NCEP ATP III

29. 30

34. Who receives a statin without
Risk calculation?
1. LDL above 190
2. Type 1 or 2 DM over 40y
3. Existing ASCVD

35. New risk calculator
Age
Gender
Ethnicity
Total cholesterol
HDL cholesterol
Systolic BP
HYPERTENSION MEDS
DIABETES
SMOKING
36

37. Important risk factors
not in the score
• CKD
• COLLAGEN DISEASE
• CANCER
• MORBID OBESITY
• DRUGS
• NSAID
• CANCER CHEMO/RADIO
• IMMUNOSUPPRESSIVE
38

38. IBRAHIM
 Age
 Diabetes
 Smoking
 Cholesterol
 LDL
 HDL
 Systolic Hypertension
 57 Y
 Non Diabetic
 Smoker
 250 mg/dl
 180 mg/dl
 35 mg/dl
 140
 ibrahim.xls

40. Samira
 Age
 Diabetes
 Smoking
 Cholesterol
 LDL
 HDL
 Systolic Hypertension
 51 Y
 Non Diabetic
 non Smoker
 300 mg/dl
 200 mg/dl
 45 mg/dl
 180

41. Adel
 Age
 Diabetes
 Smoking
 Cholesterol
 LDL
 HDL
 Systolic Hypertension
 47 Y
 Diabetic
 Non Smoker
 280 mg/dl
 160 mg/dl
 30 mg/dl
 140
 adel .xls

43. Living Under the
Umbrella of Good
Cardiovascular
Health
FBG
<100
LDL-C
<100
SBP
<140

44. 45