2. Should we move from Lipids to Lipoproteins, from Dyslipidemia to Dyslipoproteinemia in future guidelines for CVD?

5. Discordance: Quebec Cardiovascular Study (n=2,103)
Correlation
Concordance
Percent
Concordance 49%
Discordance 51%
LDL-C
ApoB
Percent
Concordance 63%
Discordance 37%
Non HDL-C
ApoB
Correlation refers to the overall linear relationship of two laboratory measures in a population.
Concordance examines the variability of one laboratory measure at a defined value of the other.
Adapted from Sniderman AD, et al. Am J Cardiol 2003;91:

6. Major Lipids apolipoproteins and the risk of vascular disease
Major Lipids apolipoproteins and the risk of vascular disease. The Emerging Risk Factors Collaboration Group JAMA: 302;
302,430 subjects from 68 long term prospective studies
2.79 million years patient follow up
8857 nonfatal MI
3928 CHD deaths

7. Non-HDL C and apoB equal HR TC/HDL C and apoB/apoA-I equal HR
ERFC Major Findings
Non-HDL C and apoB equal HR
TC/HDL C and apoB/apoA-I equal HR

8. Issues in ERFC Non-HDL C and LDL C also had equal HR.
The most important pro-apoB studies are not included eg INTERHEART, ISIS, Casale Monferrato, Taiwan Heart Study

9. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Sarwar N, Danesh J et al Circulation. 2007;115(4):450-8.
After adjustment for baseline values of several established risk factors, the strength of the association was substantially attenuated, and the adjusted odds ratio for coronary heart disease was 1.76 (95% CI, 1.39 to 2.21) in the Reykjavik study and 1.57 (95% CI, 1.10 to 2.24) in the EPIC-Norfolk study in a comparison of individuals in the top third with those in the bottom third of usual log-triglyceride values. Similar overall findings (adjusted odds ratio, 1.72; 95% CI, 1.56 to 1.90) were observed in an updated meta-analysis involving a total of 10,158 incident coronary heart disease cases from 262,525 participants in 29 studies.

13. Risk of C in Non-HDL versus risk of C in LDL in FOS
Men HR
LDL C
1.11 (11%/35 mg C)
Non-HDL C
1.22 (22%/42 mg C)

14. Risk of C in Non-HDL versus risk of C in LDL in FOS
Men HR
R/mg C
LDL C
1.11 (11%/35 mg C)
0.30%
Non-HDL C
1.22 (22%/42 mg C)
0.47%
Non-HDL C/LDL C
157%

16. In a man in whom VLDL C accounts for 25% of non-HDL C
If risk increases 57% more per mg VLDL C than per mg LDL C
Then the atherogenic risk of 1 mg VLDL C is 228% > than the risk of 1 mg LDL C
However in a man in whom VLDL C accounts for only 10% of non-HDL C, the atherogenic risk per mg VLDL C must be 567% greater than per mg LDL C.

17. These differences in risk per mg of cholesterol are not biologically credible.
That risk increases as the proportion of VLDL C decreases is not biologically credible.
It follows that the additional cholesterol in VLDL C is not a credible explanation for why non-HDL C is a more potent marker of risk than LDL C.

19. Non-HDL is more closely related to LDL P/apoB than to LDL C.
Non-HDL C vs LDL P/apoB
LDL C vs LDL P/apoB
Pischon et al
0.93
0.83
Ridker et al
0.87
0.81
Shai et al
0.75
0.74
Mora et al
0.62
Cromwell et all
0.79
S-Muthu
0.69
0.72
Non-HDL C is a backwards way
of measuring LDL P/apoB

20. The clinical test of two tests is determined by how often they would lead to different clinical decisions.

23. INTERHEART: Discordance Analysis-Non-HDL C/apoB
U OR
A OR
Low Non-HDL C
Low apoB
High apoB
1.57 ( )
1.62 ( )
High Non-HDL C
1.44 ( )
1.52 ( )

24. INTERHEART: Discordance Analysis- ApoB/Non-HDL C
U OR
A OR
Low apoB
Low Non-HDL C
Low apoB High Non-HDL C
0.92 ( )
0.92 ( )
High apoB
High Non-HDL C
0.84 ( )
0.87 ( )

26. Baseline Lipid Values in JUPITER
Parameter
Baseline Value
Triglycerides
118 mg/dl
Total Cholesterol
186 mg/dl
LDL Cholesterol
108 mg/dl
HDL Cholesterol
49 mg/dl

27. Population Percentiles in JUPITER
FPP Males
FPP
Females
LDL C
108 mg/dl
23rd
30th
Non-HDL C
137 mg/dl
25th
40th

28. Population Percentiles in JUPITER
FPP Males
FPP
Females
LDL C
108 mg/dl
23rd
30th
Non-HDL C
137 mg/dl
25th
40th
apoB
109 mg/dl
60th
70th

31. apoB=0.72 non-HDL C g/ml

35. TNT-IDEAL: apoB vs non-HDL CHR
Low S Rx %ile FOS
High S Rx %ile FOS
Non-HDL C
1.19 30 5
apoB 60

36. Equivalent Target Levels
LDL C
mg/dl
Non-HDL C mg/dl
apoB mg/dl
LDL P
nmol/l
High Risk
100
130 80
1000
Very High Risk 70
100 mg/dl 60
800

37. Should we move from Lipids to Lipoproteins, from Dyslipidemia to Dyslipoproteinemia in future guidelines for CVD?
YES!