Association of Lipoprotein-Associated Phospholipase A(2) with Coronary Artery Disease in African-Americans and Caucasians

Department of Medicine, University of California, Davis, California 95817, USA.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.31). 03/2010; 95(5):2376-83. DOI: 10.1210/jc.2009-2498
Source: PubMed

ABSTRACT Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is bound predominately to low-density lipoprotein and has been implicated as a risk factor for coronary artery disease (CAD).
We investigated the association between Lp-PLA(2) and CAD in a biethnic African-American and Caucasian population.
Lp-PLA(2) mass, activity, and index, an integrated measure of mass and activity, and other cardiovascular risk factors were determined in 224 African-Americans and 336 Caucasians undergoing coronary angiography.
We assessed the distribution of Lp-PLA(2) levels and determined the predictive role of Lp-PLA(2) as a risk factor for CAD.
Levels of Lp-PLA(2) mass and activity were higher among Caucasians compared with African-Americans (293 +/- 75 vs. 232 +/- 76 ng/ml, P < 0.001 for mass and 173 +/- 41 vs. 141 +/- 39 nmol/min/ml, P < 0.001 for activity, respectively). However, Lp-PLA(2) index was similar in the two groups (0.61 +/- 0.17 vs. 0.64 +/- 0.19, P = NS). In both ethnic groups, Lp-PLA(2) activity and index was significantly higher among subjects with CAD. African-American subjects with CAD had significantly higher Lp-PLA(2) index than corresponding Caucasian subjects (0.69 +/- 0.20 vs. 0.63 +/- 0.18, P = 0.028). In multivariate regression analyses, after adjusting for other risk factors, Lp-PLA(2) index was independently (odds ratio 6.7, P = 0.047) associated with CAD in African-Americans but not Caucasians.
Lp-PLA(2) activity and index was associated with presence of CAD among African-Americans and Caucasians undergoing coronary angiography. The findings suggest an independent impact of vascular inflammation among African-Americans as contributory to CAD risk and underscore the importance of Lp-PLA(2) as a cardiovascular risk factor.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Rosuvastatin reduces low-density lipoprotein cholesterol (LDL-C) and plasma lipoprotein-associated phospholipase A₂ (Lp-PLA₂) Some sartans partially activate peroxisome proliferator-activated receptor-γ (PPARγ), possibly having a favorable effect on metabolic parameters. Telmisartan is the most potent partial PPARγ activator, followed by irbesartan, whereas olmesartan does not hold such capacity. In an open-label randomized study, we assessed the effects of combining sartans of different PPARγ- activating capacity with rosuvastatin on LDL subfractions and plasma Lp-PLA₂ in patients with mixed dyslipidemia, hypertension, and prediabetes. Following dietary intervention, patients were allocated randomly to rosuvastatin (10 mg/day) plus telmisartan 80 mg/day (RT group, n = 52) or irbesartan 300 mg/day (RI group, n = 48) or olmesartan 20 mg/day (RO group, n = 51). After 6 months of treatment, changes in LDL subfraction cholesterol and plasma Lp-PLA(2) activity and mass were evaluated blindly. A total of 151 patients (73 male; mean age 60 years) were included. Large LDL-C decreased in the RT (-36%), RI (-39%), and RO (-41%) groups (P < 0.001 for all vs. baseline). Small dense LDL-C decreased in the RT (-67%), RI (-58%), and RO (-61%) groups (P < 0.001 for all vs. baseline). All regimens increased LDL particle size versus baseline (RT + 1.4%, P = 0.002; RI + 1.0%, P = 0.04; and RO + 1.4%, P = 0.001). No difference for the change of LDL subfractions and LDL size was noticed among groups. Plasma Lp-PLA₂ activity decreased equally in all groups (RT -38%, RI -38%, RO -43%) (P < 0.001 for all vs. baseline). Plasma Lp-PLA₂ mass decreased similarly in all groups versus baseline (RT -28%, P = 0.001; RI -32%, P = 0.01; and RO -27%, P = 0.001). No difference for the change of Lp-PLA₂ mass or activity was noticed among groups. The combination of rosuvastatin with sartans of different PPARγ-activating capacity did not differentiate alterations of LDL subfraction cholesterol and plasma Lp-PLA(2) activity and mass.
    Metabolic syndrome and related disorders 02/2011; 9(3):217-23. DOI:10.1089/met.2010.0120
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Levels of acute phase reactants are affected by age. The extent to which cardiovascular risk associated with aging is due to an increase in the inflammatory burden is not known. We assessed the relationship with age of inflammatory markers, representing (1) systemic (C-reactive protein, fibrinogen, and serum amyloid-A) and (2) vascular (lipoprotein-associated phospholipase A(2) and pentraxin-3) inflammation. We determined lipoprotein-associated phospholipase A(2) mass and activity, C-reactive protein, fibrinogen, serum amyloid-A, and pentraxin-3 levels and other cardiovascular disease risk factors in 336 whites and 224 African Americans. Levels of systemic inflammatory markers increased significantly with age in both ethnic groups (P<0.05 for all), whereas trend patterns of vascular inflammatory markers did not change significantly with age for either group. In multivariate regression models adjusting for confounding variables, age remained independently associated with a composite Z score for systemic but not vascular inflammation (β=0.250, P<0.001, and β=0.276, P<0.001, for whites and African Americans, respectively). We report an increase in the systemic but not vascular inflammatory burden with age. Levels of both categories of inflammatory markers with age were similar across ethnicity after adjustment for confounders. Our results underscore the importance of age in evaluating inflammatory markers to assess cardiovascular risk.
    Arteriosclerosis Thrombosis and Vascular Biology 06/2011; 31(9):2151-6. DOI:10.1161/ATVBAHA.111.232348
  • [Show abstract] [Hide abstract]
    ABSTRACT: The clinical relevance of serum lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) in populations prone to cardiometabolic risk needs exploration. We determined major covariates of Lp-PLA(2) mass, and its associations with cardiometabolic disorders. In 736 Turkish adults, serum total Lp-PLA(2) mass was determined by immunoassay. Its association with cardiometabolic risk was assessed in three categories. In a second sample of 98 subjects, enzyme protein in high-density lipoprotein (HDL) was also assayed after precipitation. Significant inverse correlation existed with high triglyceride/low HDL cholesterol dyslipidemia, waist girth, apolipoprotein C-III, homeostatic model assessment, and linear inverse associations in women with lipoprotein (a) and fibrinogen, suggesting that Lp-PLA(2) mass reflected insulin sensitivity and that HDL bound enzyme mass dominated the associations. Among men, positive linear association with total cholesterol suggested additional association with low-density lipoprotein (LDL)-bound enzyme. High (>450 ng/mL) opposed to low (<210 ng/mL) circulating Lp-PLA(2) mass was associated with prevalent and incident coronary heart disease (CHD) in men. One SD increment in Lp-PLA(2) was associated with a 1.64-fold (95% CI 1.00; 2.70) likelihood of CHD, after adjustment for potential confounders. Furthermore, Lp-PLA(2) categories were significantly, independently and inversely associated in men with diabetes only (OR 0.61) and in women with metabolic syndrome only (OR 0.68), for a 1-SD increment. Serum total Lp-PLA(2) mass may indicate either elevated or diminished cardiometabolic risk, specific for gender, depending on its partitioning in lipoprotein groups.
    Clinical Chemistry and Laboratory Medicine 08/2011; 49(8):1349-57. DOI:10.1515/CCLM.2011.110