Lipoprotein-Associated Phospholipase A2 Bound on High-Density Lipoprotein Is Associated With Lower Risk for Cardiac Death in Stable Coronary Artery Disease Patients A 3-Year Follow-Up

ObjectivesThe aim of this study was to examine the prognostic value of lipoprotein-associated phospholipase A2 (Lp-PLA2) associated with high-density lipoprotein (HDL) (HDL-Lp-PLA2) in patients with stable coronary artery disease (CAD).BackgroundLp-PLA2 is a novel risk factor for cardiovascular disease. It has been postulated that the role of Lp-PLA2 in atherosclerosis may depend on the type of lipoprotein with which it is associated.MethodsTotal plasma Lp-PLA2 and HDL-Lp-PLA2 mass and activity, lipids, and C-reactive protein were measured in 524 consecutive patients with stable CAD who were followed for a median of 34 months. The primary endpoint was cardiac death, and the secondary endpoint was hospitalization for acute coronary syndromes, myocardial revascularization, arrhythmic event, or stroke.ResultsFollow-up data were obtained from 477 patients. One hundred twenty-three patients (25.8%) presented with cardiovascular events (24 cardiac deaths, 47 acute coronary syndromes, 28 revascularizations, 22 arrhythmic events, and 2 strokes). Total plasma Lp-PLA2 mass and activity were predictors of cardiac death (hazard ratio [HR]: 1.013; 95% confidence interval [CI]: 1.005 to 1.021; p = 0.002; and HR: 1.040; 95% CI: 1.005 to 1.076; p = 0.025, respectively) after adjustment for traditional risk factors for CAD. In contrast, HDL-Lp-PLA2 mass and activity were associated with lower risk for cardiac death (HR: 0.972; 95% CI: 0.952 to 0.993; p = 0.010; and HR: 0.689; 95% CI: 0.496 to 0.957; p = 0.026, respectively) after adjustment for traditional risk factors for CAD.ConclusionsTotal plasma Lp-PLA2 is a predictor of cardiac death, while HDL-Lp-PLA2 is associated with lower risk for cardiac death in patients with stable CAD, independently of other traditional cardiovascular risk factors

Urine 8-Hydroxyguanine (8-OHG) in Patients Undergoing Surgery for Colorectal Cancer

Purpose Cellular RNA is less compact than DNA, more easily accessible to ROS and therefore could be more susceptible to oxidative damage. This study was conceived in order to analyze the RNA oxidative damage in the urine of patients undergoing operation for colorectal cancer (CRC), to compare with healthy controls, and correlate with the stage. Materials and methods The study population was constituted by a group of 147 patients and a group of 128 healthy controls. Urine and blood samples were collected before the colonoscopy in all participants and 24 hours post-operatively for those who underwent surgery. Urine 8-hydroxyguanine (8-OHG) was determined as marker of RNA oxidation, and serum uric acid (UA) as antioxidant marker. Results Preoperatively, 8-OHG (ng/ml) values of CRC patients were found to be significantly higher than those of controls (p = 0.001). More specifically, stages II/III had significantly higher 8-OHG values (p < 0.001 and p = 0.007) than stages 0/I. Post-operatively, 8-OHG values were similar to controls (p = 0.053). Preoperatively, UA values (mg/dl) were significantly lower (p = 0.001), while postoperatively were similar to controls (p = 0.069). Conclusion Oxidative RNA damage occurs in CRC patients. Stages II/III are associated with higher values of 8-OHG than stages 0/I. 8-OHG could act as a marker for the identification of patients with advanced disease

Plasma Lp-PLA2 mass and apoB-lipoproteins that carry Lp-PLA2 decrease after sodium

Eur J Clin Invest 2012; 42 (11): 12351243 Abstract Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel cardiovascular risk marker, which is predominantly complexed to apolipoprotein (apo) B-containing lipoproteins in human plasma. As increasing dietary sodium intake may decrease plasma apoB-containing lipoproteins, we tested whether a sodium challenge lowers plasma Lp-PLA2 mass, as well as the levels of apoB-containing lipoprotein particles carrying Lp-PLA2 (apoB-Lp-PLA2), employing a newly developed enzyme-linked immunosorbent assay. Materials and methods In 45 women and 31 men (mean age 44 +/- 14 years), plasma Lp-PLA2 mass (turbidimetric immunoassay), the level of apoB-Lp-PLA2, expressed in apoB concentration and lipoproteins were measured in response to a 3-day challenge with 9 g sodium chloride tablets daily. Results Urinary sodium excretion increased from 165 +/- 60 to 321 +/- 70 mmol/24 h (P <0.001) after salt loading. Plasma Lp-PLA2 mass decreased from 618 (493719) to 588 (465698) mu g/L (P <0.001), and apoB-Lp-PLA2 decreased from 0.276 (0.2000.351) to 0.256 (0.1890.328) g LDL protein/L (P = 0.004) in response to the sodium challenge together with decreases in plasma total cholesterol, nonhigh-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B and the total cholesterol/HDL cholesterol ratio (P <0.01 for all). Changes in plasma Lp-PLA2 mass were correlated positively with changes in total cholesterol, LDL cholesterol and non-HDL cholesterol (r = 0.2600.276, P <0.05 to P <0.02), whereas changes in apoB-Lp-PLA2 were correlated positively with changes in non-HDL cholesterol and in the total cholesterol/HDL cholesterol ratio (r = 0.2320.385, P <0.050.01). Conclusion Both plasma Lp-PLA2 mass levels and apoB-Lp-PLA2 decrease in response to a short-term oral sodium challenge

Plasma levels of lipoprotein-associated phospholipase A2 are increased in patients with β-thalassemia

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent cardiovascular risk factor. We investigated the plasma levels of Lp-PLA2 activity and mass as a function of plasma lipid levels, LDL subclass profile, and oxidative stress in patients with β-thalassemia. Thirty-five patients with β-thalassemia major (β-TM) and 25 patients with β-thalassemia intermedia (β-TI) participated in the study. Lp-PLA2 activity and mass were measured in total plasma, in apolipoprotein (apo)B-depleted plasma (HDL-Lp-PLA2), and in LDL subclasses. Lp-PLA2 activity produced and secreted from peripheral blood monocytes in culture was also determined. Patients with β-thalassemia are characterized by a predominance of small-dense LDL particles, increased oxidative stress, and very high plasma levels of Lp-PLA2 mass and activity, despite low LDL-cholesterol levels. A significant positive correlation between plasma Lp-PLA2 activity or mass and 8-isoprostane (8-epiPGF2a) and ferritin levels as well as intima-media thickness (IMT) values was observed. An increase in secreted and cell-associated Lp-PLA2 activity from monocytes in culture was observed in both patient groups. The HDL-Lp-PLA2 activity and mass as well as the ratio of HDL-Lp-PLA2/plasma Lp-PLA2 were significantly higher in both patient groups compared with the control group. In conclusion, patients with β-thalassemia exhibit high plasma Lp-PLA2 levels, attributed to increased enzyme secretion from monocytes/macrophages and to the predominance of sdLDL particles in plasma. Plasma Lp-PLA2 is correlated with carotid IMT, suggesting that this enzyme may be implicated in premature carotid atherosclerosis observed in β-thalassemia