title: Interpretation of lipoprotein-associated phospholipase A2 levels is influenced by cardiac disease, comorbidities, extension of atherosclerosis and treatments.
abstract: OBJECTIVE
  Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker secreted in the atherosclerotic plaque. Blood levels of Lp-PLA2 predict future cardiovascular events in patients with ischemic disease and heart failure. This association seems to be independent of traditional cardiovascular risk factors. The aims of our study were (1) to assess relationships between Lp-PLA2 levels, cardiac disease and treatments; (2) to evaluate the association of Lp-PLA2 level with the severity of angiographic coronary artery disease (CAD) and the extracoronary atherosclerosis.
  
  
  METHODS
  Between December 2009 and June 2010, 494 subjects were recruited from a population scheduled for diagnostic coronary angiography. Routine clinical (age, gender, BMI and treatment), cardiac (echocardiography, coronarography, carotid ultrasonography) and biochemical parameters were recorded for all patients. Lp-PLA2 mass concentration was assessed in serum with a Plac®-test turbidimetric immunoassay. Control Lp-PLA2 values were specifically obtained in 61 healthy subjects aged 44.5 ± 17.6 years (range: 25 to 59 years) without known cardiovascular risk factors (diabetes, smoking, hypertension, dyslipidemia) or cardiac treatment.
  
  
  RESULTS
  In healthy controls, mean Lp-PLA2 level was 163 ± 43 μg/L (166 ± 45 μg/L in men and 159 ± 39 μg/L in women, non significant difference). In our cohort of 494 patients (69.8% men) aged 64.2 ± 16.7 years, the main etiologies of cardiomyopathies were ischemic (40%), valvular (22%), cardiac failure with left ventricular (LV) dysfunction (14%), infection (5%) and aortic aneurysm (7%). Mean Lp-PLA2 levels were 216 ± 17 μg/L. Lp-PLA2 correlated with age, BMI, current smoking, history of hypertension but not with diabetes and gender. The bivariate analysis showed a significant correlation between Lp-PLA2, and BMI (p=0.001) but no correlation with serum creatinine or NYHA status. A multivariate correlation showed that Lp-PLA2 was associated with total cholesterol, LDL-cholesterol and apoB (r=0.95, p<0.0001) but not with Lp(a). We observed that Lp-PLA2 was significantly associated with treatments such as statins and ACEi/ARA2 but not with β-blockers, antiaggregant drugs or diuretics. Lp-PLA2 levels were significantly higher in patients with CAD than in patients without CAD (223 ± 54 vs. 208 ± 52 μg/L, respectively; p<0.007). Moreover, Lp-PLA2 levels were significantly higher in patients with the most extensive angiographic CAD [single (n=24)=215.2 ± 52 μg/L; two (n=55)=222 ± 53 μg/L and three vessels (n=140)=251.9 ± 53.7 μg/L, respectively; p<0.0001]. Patients with heart failure, sepsis or aortic aneurysm had increased Lp-PLA2 levels: 256.2 ± 46.8; 226.7 ± 47.3; 218.1 ± 38.9 μg/L, respectively, as compared to controls (p<0.0001). In patients with carotid artery disease, Lp-PLA2 significantly increased with the severity of atherosclerosis. Mean Lp-PLA2 levels were 218.8 ± 51 μg/L in the group without any stenosis (n=108), 224 ± 51 μg/L in the group with mild stenosis (n=101), and 231 ± 46 μg/L in the group with severe stenosis (n=22); p=0.004.
  
  
  CONCLUSIONS
  This study clearly shows that interpretation of Lp-PLA2 levels needs a good assessment of cardiac parameters and treatments, especially statins and ACEi/ARA2. Lp-PLA2 levels are significantly associated with coronary heart disease and with the extension of extra coronary disease after adjustment for age and gender.
authors.affiliation: AP-HP, Avicenne Hospital, Department of cardiology, Université Paris 13, UFR SMBH Bobigny, France. jean-christophe.charniot@avc.aphp.fr
authors.forename: J C
authors.initials: JC
authors.lastname: Charniot
authors.forename: R
authors.initials: R
authors.lastname: Khani-Bittar
authors.forename: J P
authors.initials: JP
authors.lastname: Albertini
authors.forename: P
authors.initials: P
authors.lastname: Giral
authors.forename: C
authors.initials: C
authors.lastname: Cherfils
authors.forename: C
authors.initials: C
authors.lastname: Cosson
authors.forename: E
authors.initials: E
authors.lastname: Guillerm
authors.forename: P
authors.initials: P
authors.lastname: Leprince
authors.forename: I
authors.initials: I
authors.lastname: Gandjbakhch
authors.forename: D
authors.initials: D
authors.lastname: Bonnefont-Rousselot
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000328:Adult; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006331:Heart Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase
keywords: Comorbidities; Lp-PLA2; Treatments