Sai Giridhar Sairam1, Srikanth Sola2, Asha Barooah2, Sai Kiran Javvaji2, Jiten Jaipuria3, Vijayalakshmi Venkateshan4, Janardhana Chelli1, Carani Balaraman Sanjeevi5. 1. Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, India. 2. Department of Cardiology, Sri Sathya Sai Institute of Higher Medical Sciences, Bangalore, India. 3. Department of Urology, Sri Sathya Sai Institute of Higher Medical Sciences, Prasanthi Gram, India. 4. Department of Stem Cell Biology, National Institute of Nutrition, Hyderabad, India. 5. Department of Medicine, Karolinska Institutet, Solna, Sweden.
Abstract
BACKGROUND: Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Lipoprotein associated phospholipase A2 (Lp-PLA2) is an emerging biomarker for inflammation that has shown association with CAD. Its significance in the Asian Indian population is not clearly known. We sought to compare the possible association of various biomarkers of atherosclerosis along with Lp-PLA2, in symptomatic individuals with CAD vs. healthy controls in Asian South-Indians. METHODS: We conducted a cross-sectional case control study at three centers in a South Indian population. A total of 100 CAD patients with acute coronary syndrome (ACS), 100 age and gender matched healthy controls participated, of which, 166 subjects or 83 case-control pairs with complete data for both participants were identified for the statistical analysis. Lp-PLA2 concentration and activity were measured using PLAC test and PLAC activity assay respectively (diaDexus Inc., San Francisco, CA, USA), while all other parameters were measured using standard commercially available kits. RESULTS: We enrolled a total of 200 subjects (mean age 50.7±9.6 years, 87.5% males). A total of 83 subjects completed the study in the CAD group (mean age 51 ±8.9 years, 85% males) and 83 subjects in the control group (mean age 50±8.9 years, 86.5% males). In the CAD group, Lp-PLA2 concentration positively correlated with TC (ρ=0.19, P=0.02), non-HDL-C (ρ=0.20, P=0.02), Lp-PLA2 activity (ρ=0.27, P=0.001) and Lp(a) (r=0.25, P=0.02). Lp-PLA2 activity correlated positively with TC (ρ=0.28, P=0.001), LDL-C (ρ=0.30, P<0.001), non-HDL-C (ρ=0.35, P<0.001), ApoB (ρ=0.35, P<0.001) and negatively correlated to HDL-C (ρ=-0.24, P=0.004). Cox proportionality hazards model revealed Lp-PLA2 concentration (β=0.006, SE =0.002, P=0.009) to have positive association with the event of CAD, while negative association was observed for ApoA1 (β=-0.06, SE =0.02, P=0.001). ROC analysis revealed that the highest quartile of Lp-PLA2 concentration to have area under curve (AUC) of 0.80 (95% CI, 0.65-0.9; P<0.001) with cut off value of >427 ng/mL and ApoA1 with AUC of 0.78 (95% CI, 0.70-0.85; P<0.001) with cut off value of ≤129.6 mg/dL with the optimum balance of sensitivity and specificity. CONCLUSIONS: In this study population, circulating plasma Lp-PLA2 was found to be elevated in CAD group. ApoA1 showed negative association and Lp-PLA2 concentration showed positive association with risk for CAD. In the highest quartile, Lp-PLA2 concentration had the best diagnostic utility. Our results support the hypothesis that Lp-PLA2 may be a potential risk marker for CAD in Asian Indians.
BACKGROUND: Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Lipoprotein associated phospholipase A2 (Lp-PLA2) is an emerging biomarker for inflammation that has shown association with CAD. Its significance in the Asian Indian population is not clearly known. We sought to compare the possible association of various biomarkers of atherosclerosis along with Lp-PLA2, in symptomatic individuals with CAD vs. healthy controls in Asian South-Indians. METHODS: We conducted a cross-sectional case control study at three centers in a South Indian population. A total of 100 CAD patients with acute coronary syndrome (ACS), 100 age and gender matched healthy controls participated, of which, 166 subjects or 83 case-control pairs with complete data for both participants were identified for the statistical analysis. Lp-PLA2 concentration and activity were measured using PLAC test and PLAC activity assay respectively (diaDexus Inc., San Francisco, CA, USA), while all other parameters were measured using standard commercially available kits. RESULTS: We enrolled a total of 200 subjects (mean age 50.7±9.6 years, 87.5% males). A total of 83 subjects completed the study in the CAD group (mean age 51 ±8.9 years, 85% males) and 83 subjects in the control group (mean age 50±8.9 years, 86.5% males). In the CAD group, Lp-PLA2 concentration positively correlated with TC (ρ=0.19, P=0.02), non-HDL-C (ρ=0.20, P=0.02), Lp-PLA2 activity (ρ=0.27, P=0.001) and Lp(a) (r=0.25, P=0.02). Lp-PLA2 activity correlated positively with TC (ρ=0.28, P=0.001), LDL-C (ρ=0.30, P<0.001), non-HDL-C (ρ=0.35, P<0.001), ApoB (ρ=0.35, P<0.001) and negatively correlated to HDL-C (ρ=-0.24, P=0.004). Cox proportionality hazards model revealed Lp-PLA2 concentration (β=0.006, SE =0.002, P=0.009) to have positive association with the event of CAD, while negative association was observed for ApoA1 (β=-0.06, SE =0.02, P=0.001). ROC analysis revealed that the highest quartile of Lp-PLA2 concentration to have area under curve (AUC) of 0.80 (95% CI, 0.65-0.9; P<0.001) with cut off value of >427 ng/mL and ApoA1 with AUC of 0.78 (95% CI, 0.70-0.85; P<0.001) with cut off value of ≤129.6 mg/dL with the optimum balance of sensitivity and specificity. CONCLUSIONS: In this study population, circulating plasma Lp-PLA2 was found to be elevated in CAD group. ApoA1 showed negative association and Lp-PLA2 concentration showed positive association with risk for CAD. In the highest quartile, Lp-PLA2 concentration had the best diagnostic utility. Our results support the hypothesis that Lp-PLA2 may be a potential risk marker for CAD in Asian Indians.
Authors: John D Brunzell; Michael Davidson; Curt D Furberg; Ronald B Goldberg; Barbara V Howard; James H Stein; Joseph L Witztum Journal: Diabetes Care Date: 2008-04 Impact factor: 19.112
Authors: K Sarat Chandra; Manish Bansal; Tiny Nair; S S Iyengar; Rajeev Gupta; Subhash C Manchanda; P P Mohanan; V Dayasagar Rao; C N Manjunath; J P S Sawhney; Nakul Sinha; A K Pancholia; Sundeep Mishra; Ravi R Kasliwal; Saumitra Kumar; Unni Krishnan; Sanjay Kalra; Anoop Misra; Usha Shrivastava; Seema Gulati Journal: Indian Heart J Date: 2014-12-24
Authors: Christie M Ballantyne; Ron C Hoogeveen; Heejung Bang; Josef Coresh; Aaron R Folsom; Gerardo Heiss; A Richey Sharrett Journal: Circulation Date: 2004-02-02 Impact factor: 29.690
Authors: Guo-Hua Wang; Jun Jin; Ya-Qiong Liu; Fu-Yan Yang; Dan Shi; Yi Zhang; Yi-Mei Zhao; Yang Wang Journal: Medicine (Baltimore) Date: 2021-07-30 Impact factor: 1.817