Oldgren Jonas, James Stefan K, Siegbahn Agneta, Wallentin Lars
Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden.
Eur Heart J. 2007 Mar;28(6):699-704. doi: 10.1093/eurheartj/ehl565. Epub 2007 Feb 21.
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been suggested as an independent predictor of cardiovascular events in epidemiological studies. We sought to evaluate Lp-PLA(2) as a risk factor for future cardiovascular events in patients with acute coronary syndromes (ACS) and to elucidate the relationship between Lp-PLA(2) and other known risk markers in ACS patients and healthy control subjects.
Blood samples were obtained at randomization in a random subset of ACS patients in the FRISC II (n = 1362) and GUSTO IV (n = 904) studies and in 435 apparently healthy controls of similar age and gender. Median Lp-PLA(2) (mass) levels were 305 ng/mL (FRISC II), 373 ng/mL (GUSTO IV), and 254 ng/mL (healthy controls). Time delay from symptom onset did not influence Lp-PLA(2) levels. In the FRISC II patients and healthy controls, Lp-PLA(2) was significantly correlated with cholesterol (r = 0.3), low-density lipoprotein (r = 0.4 and r = 0.3, respectively), and C-reactive protein (r = 0.08 and r = 0.1, respectively), all P < 0.01. Lp-PLA(2) was not correlated with age, interleukin-6, troponin T, or NT-proBNP in any of the three cohorts. There was no difference in the composite of death and myocardial infarction at 30 days (GUSTO IV) or 180 days (FRISC II) in relation to low, middle, and top tertiles of Lp-PLA(2) at randomization. In FRISC II, the 1 year mortality was 4.2, 4.2, and 4.8% in the low, middle, and top Lp-PLA(2) tertiles, respectively, P = 0.8. In GUSTO IV, 1 year mortality was 7.0, 8.3, and 9.6% in the low, middle, and top Lp-PLA(2) tertiles, respectively, P = 0.5.
ACS patients had higher Lp-PLA(2) levels than healthy controls. Lp-PLA(2) was significantly correlated to lipid levels but only weakly correlated or unrelated to other well-established risk markers in ACS. The risk of future cardiovascular events or mortality was not related to Lp-PLA(2) levels in ACS patients. The biological role of Lp-PLA(2) and its role as a risk marker in ACS patients still remain unclear.
在流行病学研究中,脂蛋白相关磷脂酶A2(Lp-PLA2)已被认为是心血管事件的独立预测因子。我们试图评估Lp-PLA2作为急性冠状动脉综合征(ACS)患者未来心血管事件的危险因素,并阐明ACS患者和健康对照者中Lp-PLA2与其他已知风险标志物之间的关系。
在FRISC II(n = 1362)和GUSTO IV(n = 904)研究的ACS患者随机子集中以及435名年龄和性别相似的明显健康对照者中,在随机分组时采集血样。Lp-PLA2(质量)水平中位数在FRISC II中为305 ng/mL,在GUSTO IV中为373 ng/mL,在健康对照者中为254 ng/mL。症状发作后的时间延迟不影响Lp-PLA2水平。在FRISC II患者和健康对照者中,Lp-PLA2与胆固醇(r = 0.3)、低密度脂蛋白(分别为r = 0.4和r = 0.3)以及C反应蛋白(分别为r = 0.08和r = 0.1)显著相关,所有P < 0.01。在三个队列中的任何一个中,Lp-PLA2与年龄、白细胞介素-6、肌钙蛋白T或NT-proBNP均无相关性。在随机分组时,Lp-PLA2处于低、中、高三分位数的患者在30天(GUSTO IV)或180天(FRISC II)时死亡和心肌梗死的复合终点无差异。在FRISC II中,Lp-PLA2低、中、高三分位数组的1年死亡率分别为4.2%、4.2%和4.8%,P = 0.8。在GUSTO IV中,Lp-PLA2低、中、高三分位数组的1年死亡率分别为7.0%、8.3%和9.6%,P = 0.5。
ACS患者的Lp-PLA2水平高于健康对照者。Lp-PLA2与血脂水平显著相关,但与ACS中其他已确立的风险标志物仅呈弱相关或无相关性。ACS患者未来心血管事件或死亡风险与Lp-PLA2水平无关。Lp-PLA2在ACS患者中的生物学作用及其作为风险标志物的作用仍不清楚。