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

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

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

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

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

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

Standard Lipid Profile Total Cholesterol LDLc HDLc Triglycerides Non-HDL

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

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

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

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.

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

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

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

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.

Correlation of sdLDL and Apo B with LDL

sdLDL and CAD cases

Apo B and CAD cases

sdLDL and Diabetics

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)

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.

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.

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.

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