Distribution of Lipoprotein‑Associated Phospholipase A2 in Czech Population and its interaction with conventional cardiovascular risk

Czech version

Authors: O. Mayer jr. ¹; J. Seidlerová ¹; P. Wohlfart ²; L. Trefil ³; J. Bruthans ⁴; J. Filipovský ¹; R. Cífková ²
Authors‘ workplace: II. interní klinika Lékařské fakulty UK a FN Plzeň, přednosta prof. MU Dr. Jan Filipovský, CSc. ¹; Centrum kardiovaskulární prevence Thomayerovy nemocnice Praha, přednostka prof. MU Dr. Renata Cífková, CSc. ²; Ústav klinické biochemie a hematologie Lékařské fakulty UK a FN Plzeň, přednosta prof. MU Dr. Jaroslav Racek, DrSc. ³; Pracoviště preventivní kardiologie IKEM Praha, přednostka doc. MU Dr. Věra Adámková, CSc. ⁴
Published in: Vnitř Lék 2013; 59(5): 344-351
Category: Original Contributions

Overview

Introduction:
Lipoprotein‑associated phospholipase A2 (Lp‑ PLA₂) represent new cardiovascular risk factor and potential treatment target. We aimed to analyze the epidemiological situation of this factor in Czech population.

Methods and Results:
The study population consisted from 1 962 subjects, a random samples of general population (postMONICA study), and from patients with manifest coronary or cerebrovascular disease (Czech samples of EUROASPIRE III survey). Lp‑ PLA₂ activity was estimated using commercial kits by diaDexus Inc. in frozen samples. Increased activity (by definition, i.e. > 195 nmol/ min/ ml) was observed in 21.1 % of sample, no apparent difference between subject with and without manifest vascular disease was found. Males showed higher Lp‑ PLA₂ activity, than females (179.6 vs 146, resp., p < 0.0001), while no substantial increase with age was observed. Taking Lp‑ PLA₂ activity > 195 as dependent variable, following independent variables entered the multiple logistic regression: male gender [with odds ratio 4.26 (3.26– 5.58)], low HDL‑cholesterol (i.e. < 1.0 mmol/ l in males or < 1.2 mmol/ l in females) [3.49 (2.62– 4.64)], LDL‑cholesterol > 2.5 mmol/ l [6.95 (4.79– 10.07)] and lipid‑ lowering treatment [0.59 (0.44– 0.79)]. In subject without manifest vascular disease, 6.3 % of them showed co‑ incidence of markedly increased Lp‑ PLA₂ activity with high conventional risk (SCORE > 10 %). Expanding this group by intermediate risk subjects (ie. with Lp‑ PLA₂ activity 152– 194 and/ or SCORE 5– 9.9 %) leads to increase of this prevalence to 28.9 % of primary prevention subjects.

Conclusion:
Increased Lp‑ PLA₂ activity is in Czech population highly prevalent and with exception of lipid parameters, generally independent from conventional cardiovascular risk. However, up to 29 % of subject in primary prevention amalgamate increased Lp‑ PLA₂ activity with high conventional cardiovascular risk.

Key words:
lipoprotein – associated phospholipase A2 – primary prevention – secondary prevention – epidemiology

Sources

1. Silva IT, Mello AP, Damasceno NR. Antioxidant and inflammatory aspects of lipoprotein‑associated phospholipase A2 (Lp‑ PLA2): a review. Lipids Health Dis 2011; 10: 170.

2. Cífková R, Skodová Z, Bruthans J et al.. Longitudinal trends in cardiovascular mortality and blood pressure levels, prevalence, awareness, treatment, and control of hypertension in the Czech population from 1985 to 2007/ 2008. J Hypertens 2010; 28: 2196– 2203.

3. Mayer jr. O, Šimon J, Galovcová M et al. The quality of secondary prevention of coronary heart disease in Czech patients in the EUROASPIRE III survey. Cor Vasa 2008; 50: 156– 162.

4. Bruthans J, Mayer jr. O, Šimon J et al. Úroveň sekudární prevence cevních mozkových příhod u českých pacietů ve studii EUROASPIRE III‑ stroke specific module. Cor Vasa 2008; 50: 446– 454.

5. Conroy RM, Pyörälä K, Fitzgerald AP et al. SCORE project group. Estimation of ten‑year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J 2003; 24: 987– 1003.

6. Graham I, Atar D, Borch‑ Johnsen K et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur J Cardiovasc Prev Rehabil 2007; 14: (Suppl. 2): E1– E113.

7. The Lp‑ PLA2 Studies Collaboration. Lipoprotein‑associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet 2010; 375: 1536– 1544.

8. Schaefer EJ, McNamara JR, Asztalos BF et al. Effects of atorvastatin versus other statins on fasting and postprandial C‑ reactive protein and lipoprotein‑associated phospholipase A2 in patients with coronary heart disease versus control subjects. Am J Cardiol 2005; 95: 1025– 1032.

9. Saougos VG, Tambaki AP, Kalogirou M et al. Differential effect of hypolipidemic drugs on lipoprotein‑associated phospholipase A2. Arterioscler Thromb Vasc Biol 2007; 27: 2236– 2243.

10. Lee SH, Kang SM, Park S et al. The effects of statin monotherapy and low‑dose statin/ ezetimibe on lipoprotein‑associated phospholipase A2. Clin Cardiol 2011; 34: 108– 112.

11. Hatoum IJ, Nelson JJ, Cook NR et al. Dietary, lifestyle, and clinical predictors of lipoprotein‑associated phospholipase A2 activity in individuals without coronary artery disease. Am J Clin Nutr 2010; 91: 786– 793.

12. Chen CW, Lin CT, Lin YL et al. Taiwanese female vegetarians have lower lipoprotein‑associated phospholipase A2 compared with omnivores. Yonsei Med J 2011; 52: 13– 19.

13. Filippatos TD, Gazi IF, Liberopoulos EN et al. The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein‑associated phospholipase A2 in obese patients with metabolic syndrome. Atherosclerosis 2007; 193: 428– 437.

14. Carpenter KL, Dennis IF, Challis IR et al. Inhibition of lipoproteinassociated phospholipase A2 diminishes the death‑ inducing effects of oxidized LDL on human monocyte‑ macrophages. FEBS Lett 2001; 505: 357– 363.

15. Mohler ER, Ballantyne CM, Davidson MH et al. Darapladib Investigators. The effect of darapladib on plasma lipoprotein‑associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double‑blind, placebo‑ controlled study. J Am Coll Cardiol 2008; 51: 1632– 1641.

16. Serruys PW, García‑ García HM, Buszman P et al. Integrated Biomarker and Imaging Study‑ 2 Investigators. Effects of the direct lipoprotein‑associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 2008; 118: 1172– 1182.

17. White H, Held C, Stewart R et al. Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease. Am Heart J 2010; 160: 655– 661.

18. O‘Donoghue ML, Braunwald E, White HD et al. Study design and rationale for the Stabilization of pLaques usIng Darapladib‑ Thrombolysis in Myocardial Infarction (SOLID‑ TIMI 52) trial in patients after an acute coronary syndrome. Am Heart J 2011; 162: 613– 619.