Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque dest...Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.展开更多
Background Lipoprotein-associated phospholipase A2 （Lp-PLA2） has recently been shown to be positively related to coronary events in patients with coronary artery disease （CAD）. However, direct evidence about the r...Background Lipoprotein-associated phospholipase A2 （Lp-PLA2） has recently been shown to be positively related to coronary events in patients with coronary artery disease （CAD）. However, direct evidence about the relationship between circulation Lp-PLA2 activity and vulnerable plaque in patients with CAD remains lacking. Methods Plasma Lp-PLA2 activity was determined in 146 consecutive patients with CAD who underwent clinically-indicated coronary angiography and preinterventional intravascular ultrasound （IVUS）. Results Eighty-three patients were included in the final analysis after the initial screening. Sixty （72.3%） were acute coronary syndrome （ACS） patients and 23 （27.7%） were stable angina pectoris （SAP） patients. Plaque rupture occurred in 39 （47.0%） patients, and 34 （87.2%） were from ACS patients and 5 （12.8%） from SAP patients. There were no significant differences in clinical and angiographic characteristics between patients with plaque rupture and those without plaque rupture, except for smoking, high-sensitive C-reactive protein （hs-CRP） level and Lp-PLA2 activity （all P 〈0.05）. IVUS measurement uncovered that patients with plaque rupture had more frequent positive remodeling （74.4% vs. 43.2%, P=0.004）, soft plaques （64.1% vs. 36.4%, P=-0.012） and higher remodeling index （1.13~0.16 vs. 0.99＋_0.11, P=0.041） as compared with those without plaque rupture. Multivariate Logistic regression analysis showed that plasma Lp-PLA2 activity was independently associated with plaque rupture after adjusting for smoking, positive remodeling and soft plaque （Model 1： odds ratio （OR） 1.13, 95% confidence interval （CO ： 1.06-1.20） or adjusting for smoking, hs-CRP level, positive remodeling and soft plaque （Model 2： OR 1.11,95%C1： 1.04-1.19）. Conclusions Plasma Lp-PLA2 activity is associated with plaque rupture in patients with CAD, independently of traditional CAD risk factors, hs-CRP level and IVUS parameters. Lp-PLA2 may be a risk mar展开更多
基金Supported by FORICA(the FOundation for Advanced Research in Hypertension and Cardiovascular diseases,www.forica.it)
文摘Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30570712 to CHEN Hong, No. 30840040 to REN Jing-yi） and the Beijing Natural Science Foundation （No. 7092109 to CHEN Hong）.
文摘Background Lipoprotein-associated phospholipase A2 （Lp-PLA2） has recently been shown to be positively related to coronary events in patients with coronary artery disease （CAD）. However, direct evidence about the relationship between circulation Lp-PLA2 activity and vulnerable plaque in patients with CAD remains lacking. Methods Plasma Lp-PLA2 activity was determined in 146 consecutive patients with CAD who underwent clinically-indicated coronary angiography and preinterventional intravascular ultrasound （IVUS）. Results Eighty-three patients were included in the final analysis after the initial screening. Sixty （72.3%） were acute coronary syndrome （ACS） patients and 23 （27.7%） were stable angina pectoris （SAP） patients. Plaque rupture occurred in 39 （47.0%） patients, and 34 （87.2%） were from ACS patients and 5 （12.8%） from SAP patients. There were no significant differences in clinical and angiographic characteristics between patients with plaque rupture and those without plaque rupture, except for smoking, high-sensitive C-reactive protein （hs-CRP） level and Lp-PLA2 activity （all P 〈0.05）. IVUS measurement uncovered that patients with plaque rupture had more frequent positive remodeling （74.4% vs. 43.2%, P=0.004）, soft plaques （64.1% vs. 36.4%, P=-0.012） and higher remodeling index （1.13~0.16 vs. 0.99＋_0.11, P=0.041） as compared with those without plaque rupture. Multivariate Logistic regression analysis showed that plasma Lp-PLA2 activity was independently associated with plaque rupture after adjusting for smoking, positive remodeling and soft plaque （Model 1： odds ratio （OR） 1.13, 95% confidence interval （CO ： 1.06-1.20） or adjusting for smoking, hs-CRP level, positive remodeling and soft plaque （Model 2： OR 1.11,95%C1： 1.04-1.19）. Conclusions Plasma Lp-PLA2 activity is associated with plaque rupture in patients with CAD, independently of traditional CAD risk factors, hs-CRP level and IVUS parameters. Lp-PLA2 may be a risk mar
