Lipoprotein-associated Phospholipase A2 Activity In Patients Research Articles

Impact of Plasma Lp-PLA2 Activity on the Progression of Aortic Stenosis: The PROGRESSA Study

ObjectivesThe purpose of this prospective study was to examine the relationship between plasma lipoprotein–associated phospholipase A2 (Lp-PLA2) activity and the progression rate of aortic stenosis (AS). BackgroundWe recently reported that Lp-PLA2 is highly expressed in stenotic aortic valves where it may contribute to the mineralization of valvular interstitial cells. MethodsPatients with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. AS progression rate was assessed by annualized increase in peak aortic jet velocity (Vpeak), mean gradient (MG), and aortic valve area index (AVAi). Circulating Lp-PLA2 activity was measured and dichotomized based on the median value. ResultsOf 183 patients included in this subanalysis of the PROGRESSA study, 70% were men and the mean age was 66 ± 13 years. Over the 2.5 ± 1.4 years of follow up, the AS progression rate tended to be higher in patients with high versus low Lp-PLA2 activity (annualized Vpeak = 0.17 ± 0.23 m/s vs. 0.12 ± 0.18 m/s; p = 0.14). There was a significant interaction (p < 0.05) between baseline AS severity and Lp-PLA2 activity with respect to impact on AS progression rate. In patients with mild AS (i.e., Vpeak <3 m/s; n = 123), increased Lp-PLA2 activity was associated with a significantly faster AS progression rate (Vpeak 0.16 ± 0.18 m/s vs. 0.09 ± 0.14 m/s; p = 0.01) but not in patients with moderate or severe AS (p = 0.99). After adjustment for other risk factors, increased Lp-PLA2 activity remained independently associated with faster AS progression rate (p = 0.005) in the former subset. ConclusionsThere was no significant association between plasma Lp-PLA2 activity or mass and stenosis progression in the whole cohort. However, increased Lp-PLA2 activity was associated with a faster stenosis progression rate in the subset of patients with mild AS. These findings provide an impetus for the elaboration of a randomized trial targeting Lp-PLA2 activity in patients with early stages of calcific aortic valve disease.

Lipoprotein-associated phospholipase A2 and arterial stiffness evaluation in patients with inflammatory bowel diseases

Background and aimsThe association between inflammatory bowel diseases (IBD) and cardiovascular disease (CVD) remains equivocal. Arterial stiffness, as assessed by pulse wave velocity (PWV), and lipoprotein-associated phospholipase A2 (Lp-PLA2) are surrogates of CVD risk. AimThe aim of this study was to assess carotid–femoral PWV and Lp-PLA2 in patients with IBD without history of CVD. MethodsEstablished CVD risk factors, IBD characteristics, PWV and Lp-PLA2 activity were assessed in 44 patients with IBD, 29 with Crohn's disease (CD) and 15 with ulcerative colitis (UC), and 44 matched controls. ResultsIBD patients had lower total and low density lipoprotein cholesterol (LDL-C) levels. There was no difference in PWV between patients and controls (6.8 vs 6.4m/s), but patients with CD had higher PWV compared to those with UC (7 vs 6.3m/s; p=0.044), and to controls. Smoking rates were significantly higher among CD patients. Factors associated with PWV were age, mean arterial pressure and smoking. Lp-PLA2 activity was significantly lower in patients with IBD (46.8 vs 53.9nmol/mL/min; p=0.011). There was no difference in Lp-PLA2 between CD and UC patients. LDL-C was the only significant predictor of Lp-PLA2. ConclusionsOur study showed lower Lp-PLA2 activity in patients with IBD compared with controls, reflecting lower LDL-C in the former. There was no difference in PWV between the two groups. Arterial stiffness was higher in patients with CD, which is likely related to higher smoking rates. These findings challenge a possible association between IBD and CVD, but further studies are required.

Sleep apnea and gender: Lessons from studying women

This study examined the effects of darapladib, a selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, on biomarkers of cardiovascular (CV) risk.Elevated Lp-PLA2 levels are associated with an increased risk of CV events.Coronary heart disease (CHD) and CHD-risk equivalent patients (n = 959) receiving atorvastatin (20 or 80 mg) were randomized to oral darapladib 40 mg, 80 mg, 160 mg, or placebo once daily for 12 weeks. Blood samples were analyzed for Lp-PLA2 activity and other biomarkers.Baseline low-density lipoprotein cholesterol (LDL-C) was 67 ± 22 mg/dl. Plasma Lp-PLA2 was higher in older patients (≥75 years), in men, in those taking atorvastatin 20 mg, at LDL-C ≥70 mg/dl or high-density lipoprotein cholesterol (HDL-C) <40 mg/dl, or in those with documented vascular disease (multivariate regression; p < 0.01). Darapladib 40, 80, and 160 mg inhibited Lp-PLA2 activity by approximately 43%, 55%, and 66% compared with placebo (p < 0.001 weeks 4 and 12). Sustained dose-dependent inhibition was noted overall in both atorvastatin groups and at different baseline LDL-C (≥70 vs. <70 mg/dl) and HDL-C (<40 vs. ≥40 mg/dl). At 12 weeks, darapladib 160 mg decreased interleukin (IL)-6 by 12.3% (95% confidence interval [CI] −22% to −1%; p = 0.028) and high-sensitivity C-reactive protein (hs-CRP) by 13.0% (95% CI −28% to +5%; p = 0.15) compared with placebo. The Lp-PLA2 inhibition produced no detrimental effects on platelet biomarkers (P-selectin, CD40 ligand, urinary 11-dehydrothromboxane B2). No major safety concerns were noted.Darapladib produced sustained inhibition of plasma Lp-PLA2 activity in patients receiving intensive atorvastatin therapy. Changes in IL-6 and hs-CRP after 12 weeks of darapladib 160 mg suggest a possible reduction in inflammatory burden. Further studies will determine whether Lp-PLA2 inhibition is associated with favorable effects on CV events. (SB-480848 in Subjects With Coronary Heart Disease; NCT00269048)