Dr. Syed Waleem Pasha Assistant Professor Yenepoya Medical College COMPARISON OF SERUM PARAOXONASE LEVELS IN PATIENTS WITH ACUTE CORONARY SYNDROME AND NORMAL SUBJECTS: CASE CONTROL STUDY Dr. Syed Waleem Pasha Assistant Professor Yenepoya Medical College

Background Materials and methods Results Conclusion

Background Atherosclerosis Role of HDL Risk factors

Risk factors conventional newer hs-CRP Markers of inflammation Smoking Hypertension Elevated LDL Low HDL Insulin resistance and diabetes Obesity Mental stress and depression hs-CRP Markers of inflammation Homocysteine Fibrinogen and D-dimer Lipoprotein (a) Paraoxonase 1

Paraoxonase 1 (PON 1) Synthesized in liver Transported along HDL Antioxidant function – prevents LDL oxidation Activity exclusively associated with HDL

Materials and Methods 60 patients with Acute Coronary Syndrome (ACS) 30 matched controls Serum paraoxonase (PON) levels, blood sugar, lipid profile History of smoking and alcohol intake History of diabetes and hypertension

Paraoxonase assay: Lipid profile: UV spectrophotometer Enzymatic activity Reference range: 53 – 186 kU/L Lipid profile: Fasting Total cholesterol, High density lipoprotein and trigycerides – enzymatic method Low density lipoprotein – friedwald’s formula

Inclusion criteria: Exclusion criteria: Age > 18 yrs Cases: patients diagnosed as acute coronary syndrome Controls: patients with ACS (history and investigations) Exclusion criteria: Renal failure Hepatic parenchymal disease Prior IHD, stroke, peripheral vascular disease in last three months Anti-lipid treatment for more than three months

Analysis: SPSS (statistical package for the social sciences) version 18 Department of statistics, Manipal university

Results

Age distribution

Age distribution AGE (YRS) CASES CONTROLS N PON 1 31-40 6 54.67 7 93.86 41-50 9 49.67 5 71.6 51-60 23 59.26 10 78.3 61-70 12 54.75 8 71.25 >70 50 TOTAL 60 30 P Value 0.307 0.098

Gender distribution GENDER CASES CONTROLS N PON 1 MALE 50 54.1 24 74.88 FEMALE 10 59 6 95.17 TOTAL 60 30 P Value 0.203 0.129

Smoking SMOKER CASES CONTROLS N PON 1 YES 36 53.06 14 82.21 NO 24 57.71 16 76.06 TOTAL 60 30 P value 0.266 0.865

Alcohol ALCOHOLIC CASES CONTROLS 23 N PON 1 YES 16 50.06 7 83.71 NO 44 56.68 77.48 TOTAL 60 30 P value 0.99 0.252

Diabetes DIABETIC CASES CONTROLS N PON 1 YES 36 52.89 9 78.78 NO 24 57.96 21 79 TOTAL 60 30 P value 0.81 0.435

Hypertension HYPERTENSIVE CASES CONTROLS N PON 1 YES 31 54.58 14 77.21 NO 29 55.28 16 80.44 TOTAL 60 30 P value 0.244 0.578

Total cholesterol TC (mg/dl) CASES CONTROLS N PON 1 <100 2 65 87.5 101-150 11 55.27 4 66.5 150-200 19 57.16 10 84.8 201-250 21 58.1 85.8 >250 7 35.86 55.25 TOTAL 60 30 P value 0.642 0.055

Triglycerides TG (mg/dl) CASES CONTROLS N PON 1 <80 11 60.73 7 90 81-160 30 57.1 12 83.8 161-240 16 48.12 10 66.55 >240 3 48 1 59 TOTAL 60 P value 0.247 0.702

HDL HDL (mg/dl) CASES CONTROLS N PON 1 <30 23 41.87 9 60.89 31-45 25 61.56 18 84.11 46-60 64.56 3 102 >60 71.33 TOTAL 60 30 P value 0.166 0.086

LDL LDL (mg/dl) CASES CONTROLS N PON 1 <100 11 56.82 5 78.4 101-125 20 58.15 8 74.38 126-150 12 61.5 7 92.14 151-175 9 50.44 83.4 >175 39.38 63.8 TOTAL 60 30 P value 0.238 0.074

Master CASES (N=60) CONTROLS (N=30) P value TC 193.4 197.23 0.663 TG 140.13 135.13 0.865 LDL 124.06 129.69 0.791 HDL 35.77 34.43 0.213 RBS 150.02 142.27 0.541 PON 1 54.92 78.93 0.034

Comparative study SINGH et al PRESENT STUDY CONTROLS (191) CASES (120) PON 1 64.92 57.19 <0.05 54.92 78.93 0.034 TC 155.38 160.81 197.23 193.4 0.663 TG 150.4 131.45 135.13 140.13 0.791 LDL 84.77 97.59 <0.01 129.69 124.06 HDL 41.82 36.92 <0.001 34.43 35.77 0.213

Conclusion Cases had significantly lower serom PON 1 levels when compared to controls Low PON 1 levels can be an independent risk factor for IHD

Future Target for prophylaxis Marker of morbidity/ mortality Risk stratification Other organ dysfunction (atherosclerosis)

Limitations: Small sample size Obesity not considered Stable angina not considered Wide reference range

References Mackness MI, Bouiller A, Hennuyer M, Mackness B, Hall M, Tailleux A, et-al. Paraoxonase activity is reduced by a pro-atherosclerotic diet in rabbits. Biochem Biophys Res Commun. 2000; 269: 232-236. Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipoproteins in LDL. FEBS Lett. 1991; 286:152-154. Watson AD, Berliner JA, Hama SY, La Du BN, Fault KF, Fogelman AM. Protective effect of HCL associated paraoxonase: inhibition of the biological activity of minimally oxidised LDL. J Clin Invest. 1995; 96:2882-2891

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