1. Arabinda Mohan Bhattarai, MBBS, MD (Biochemistry) Asst Prof, NAIHS
Correlation of Small dense LDL cholesterol and Apolipoprotein B with LDL Cholesterol and its Clinical significance in Overweight, Type 2 Diabetes Mellitus and Coronary Artery Disease
Arabinda Mohan Bhattarai, MBBS, MD (Biochemistry)
Asst Prof, NAIHS

2. Specific objectives Introduction to sdLDL and Apo B
Why is Triglycerides/HDL ratio important
Why particle numbers of LDL are important
Association of sdLDL and Apo B with severity of CAD, DM and obesity
Correlation of sdLDL with LDL cholesterol

4. Introduction Coronary Artery Disease on rise
Disorders of lipid metabolism leading cause
Diabetes and obesity
Central obesity

5. Intro… increased triglyceride and HDL levels
increased triglyceride content of LDL and HDL
glycation of apolipoprotein
increased susceptibility of LDL to oxidation

6. Small dense LDL more atherogenic
they are taken up more easily by arterial wall
readily oxidized and
not easily cleared from plasma

7. Apolipoprotein B Every LDL particle contain an Apo B molecule
Apo B levels within the LDL sub fraction provide a direct measure of LDL particle number in the circulation
more closely associated than non HDL cholesterol with central obesity, insulin resistance and inflammation

8. Standard Lipid Profile
Total Cholesterol
LDLc
HDLc
Triglycerides
Non-HDL

9. Why not to rely on LDL
People with obesity, metabolic syndrome or diabetes have TG
HDLc
normal or near normal LDLc
VLDLc
IDL
Increased risk of atherosclerosis

10. TG/HDL Ratio > 4 , powerful independent indicator of CAD
Ideal (<2)
>6 is much too high
Increased ratio indicates that particles are small
Small particles carries less cholesterol than a large particle

11. Phenotypes Pattern A: TG, Large buoyant LDL, particle size >25.5nm
Pattern B: TG, Small dense LDL, particle size <25 nm

12. AIM
To estimate small dense LDL cholesterol and Apolipoprotein B in serum and to determine their clinical significance in obese, type 2 diabetic and CAD cases.

13. Materials and methods
100 known cases each of CAD, type 2 diabetes, overweight and 100 age and sex matched healthy controls.
BMI>25 kg/m2 were considered overweight.
CAD as >50% stenosis of one or more branches of the coronary arteries

14. Exclusion Criteria
Cases with acute and chronic liver and kidney disease
Cases with clinically overt autoimmune disease like SLE, Rheumatoid
Arthritis
Cases with acute infections
Hypo or hyperthyroidism
Type 1 diabetes
Patients on statin therapy

15. Inclusion criteria for controls
non hypertensive
normal OGTT
normal resting 12 lead ECG
absence of history of angina or myocardial infarction
no risk factors for CAD

17. Severity of CAD
n=25 (62.5%) cases with triple vessel disease (TVD) had sdLDL>50 mg/dL.
n=20 (50%) cases with TVD and n=11 (46%) cases with DVD had Apo B >100 mg/dL.

18. Correlation of sdLDL and Apo B with LDL

19. sdLDL and CAD cases

20. Apo B and CAD cases

21. sdLDL and Diabetics

22. Discussion TG: DM> CAD> Overweight > Controls
HDL: Overweight> Control> DM > CAD
Apo B: Diabetic>CAD>Overweight>Control
sdLDL: Diabetic>CAD>Overweight>Control
TG:HDL: Diabetic (7.07)> CAD (4.29)> Overweight (3.57)> Overweight (3.01)

23. Discussion
M Krauss et al. (40-50%)of CAD patients with small dense LDL phenotype have 2- to 3-fold increase in disease risk.
sdLDL is associated with serum triglyceride level because TG moves from VLDL to LDL and HDL in exchange for cholestryl ester and is ultimately removed from these particles rendering them smaller Witztum et al.

24. Discussion
A larger number of smaller particles is needed to carry a certain amount of cholesterol than if they are larger
LDL particle number, in addition to composition, may be important in cases with CAD Tornvall et al.

25. Conclusion
Present obesity phenotype includes higher percentage of body fat with higher truncal and abdominal fat at a lower lean body mass which has more tendency for atherogenic particles like Apo B and sdLDL.
Prevention and treatment of IHD should be focused on reducing the number of atherogenic particles besides the particle composition Tornvall et al.

26. Take Home Message Importance of triglycerides in lipid profile test
Importance of particle number along with particle
composition
Phenotypes of LDL