急性心肌梗死患者中断大剂量他汀治疗后炎症因子的变化

目的探讨在入院时及出院后持续使用大剂量他汀调脂治疗的急性心肌梗死（AMI，包括非ST段抬高者在内）患者，因各种原因中断大剂量治疗后血清炎症标识物水平的变化。方法接受标准治疗的急性心肌梗死患者（均接受了冠脉介入治疗），在入院24h内即开始使用大剂量的阿托伐他汀（40mg／d）治疗，并在住院期间及出院后继续使用阿托伐他汀（40mg／d），出院后均接受长期随访，分别在入院时及出院后1、3、6个月检测所有患者的高敏C反应蛋白（hs-CRP）、白介素-6（IL-6）等炎症标记物水平。根据随访结果分为持续大剂量（40mg／d）用药组（A组，50例）和大剂量中断组（B组，0-20mg／d，62例），比较两组患者在各时期炎症标识物水平的变化。结果（1）两组患者出院后除他汀药物外的其他治疗情况无明显不同；两组患者均接受了至少1个月的大剂量调脂治疗。（2）两组患者的hs-CRP、IL-6等水平随服用时间的延长逐渐降低，但B组患者在中断大剂量治疗后hs-CRP、IL-6的降低程度不如A组；第6个月时B组患者的hs-CRP及IL6水平均显著高于同期的A组患者（hs-CRP：2.62（1．41～16．12）mg／L vs 1．53（0．36～7．92）mg／L，P〈0．01；IL-6：9．61（3．26～17．86）ng／L vs 5．26（0．20～10．51）ng／L，P〈0．05]。结论急性心肌梗死患者长期坚持大剂量他汀调脂治疗后hs-CRP等炎症标识物水平持续下降，中断大剂量治疗后炎症标识物水平将逐渐升高。     

Deciphering the reasons for milky-white blood donor plasma

Donors who eat a fatty meal before donating blood are known to have an increased level of plasma triglyceride concentrations for several hours. This may contribute to “milky-white” appearance of their plasma samples. We herein report the case of a blood donor who gave a history of the intake of a fatty meal, on the night prior to donation. This was affirmed by his serum lipid concentration done on the following day and on repeating the same subsequently after two weeks of donation respectively.     

Hemostatic Factors in Hypertriglyceridemic Men: Effects of a Fatty Meal before and after Triglyceride-Lowering Treatment with Etofibrate

The aims of this double-blind study were to examine whether in hypertriglyceridemic men the ingestion of a standardized fatty meal alters hemostasis negatively and whether triglyceride-lowering treatment with etofibrate for 6 weeks alters fasting and postprandial hemostasis positively, thus reversing the potential negative effects of a fatty meal on postprandial hemostasis. To answer these questions, we measured markers of hemostasis immediately before a standardized fatty meal, and 4, 6, 8, and 10 hours after the meal in 21 hypertriglyceridemic men both before and after treatment with etofibrate. We found that the concentration of plasmin alpha2antiplasmin complex markedly increased for at least 10 hours after the fatty meal, but that the activation of factor XII and the concentration of prothrombin activation fragment1+2 decreased after the fatty meal. These results on factor XII contradict reported in vitro data. Triglyceride-lowering treatment with etofibrate in 10 of these men for 6 weeks increased fasting and postprandial protein C and plasminogen and also slightly decreased the activation of fXII; however, it did not reverse the postprandial increase of PAP or change the decrease of prothrombin activation fragment1+2. Our findings indicate that postprandial lipoproteins alter markers of hemostasis positively in an antithrombotic and profibrinolytic direction. In addition, triglyceride-lowering treatment with etofibrate only slightly improves markers of fasting and postprandial hemostasis in an antithrombotic and profibrinolytic direction.     

Postprandial response to a fat tolerance test in young adults with a paternal history of premature coronary heart disease - the EARS II study (European Atherosclerosis Research Study)

BACKGROUND: The European Atherosclerosis Research Study (EARS) I had shown that fasting plasma concentrations of apolipoprotein B (apo B) and triglycerides were the most discriminant variables between offspring with a paternal history of coronary heart disease (CHD) and controls. The EARS II study was undertaken to investigate whether a paternal history of CHD was associated with differences in postprandial lipemia. DESIGN: Male subjects with a paternal history of CHD (cases, n = 407) and age-matched male controls (n = 415) were recruited from 14 European universities. All subjects had an oral fat tolerance test. RESULTS: In the sample as a whole, the postprandial triglyceride responses did not significantly differ between the two groups. However, in the upper tertile of fasting triglycerides, cases displayed a higher area under the curve (5.71 vs. 4.49 mmol.h L-1, P < 0.001), a higher peak (1.76 vs. 1.43 mmol L-1, P < 0.001) and a more delayed time to peak (3.15 vs. 2.91 h, P < 0.05) than controls. In the upper tertile, fasting apo B levels (P < 0.05) and triglyceride area under the curve (P = 0.002) significantly discriminated cases from controls in a multivariate analysis. Cases had also higher Lp C-III:B levels at 4 h than controls (11.2 vs. 9.9 mg dL-1, P < 0.01) and this difference remained significant after adjustment for apo B and triglyceride levels. CONCLUSIONS: These results indicate that in subjects with a moderate elevation of fasting triglycerides, an impaired postprandial response to a fat load constitutes an early biological expression of a paternal history of premature CHD.     

Elevated levels of platelet microparticles in carotid atherosclerosis and during the postprandial state

Background

Platelet microparticles (PMPs) possess proatherogenic and procoagulant properties which may play a role in atherogenesis and subsequent thromboembolic complications. The present study was conducted to investigate the possible relationship between carotid atherosclerosis and plasma concentrations of PMPs, and elucidate if plasma levels of PMPs were affected by postprandial hypertriglyceridemia.

Methods and results

Subjects with ultrasound-assessed carotid atherosclerotic plaques (echogenic; n = 20 and echolucent; n = 20), assessed by ultrasonography, and subjects without carotid plaques (n = 20) were recruited from a population-based study and underwent a standard fat tolerance test. Subjects with carotid plaques had significantly higher levels of large PMPs than subjects without carotid atherosclerotic plaques (96.7 ± 50.4 µg/l versus 56.1 ± 34.9 µg/l), after adjustments for traditional cardiovascular risk factors and use cardiovascular drugs (p = 0.021). Plasma PMPs were not associated with plaque echogenicity. Postprandial hypertriglyceridemia induced a similar increase in plasma PMPs within all groups. Significant correlations were found between an increase in plasma triglycerides and percent elevation in total PMPs (r = 0.29, p < 0.05) and large PMPs (r = 0.34, p < 0.01) in the postprandial phase.

Conclusions

Individuals with echogenic and echolucent carotid atherosclerotic plaques have statistically significant elevation of large plasma PMPs compared to age/sex-matched normal controls. Postprandial hypertriglyceridemia induces a significant, similar increase in plasma PMPs in individuals with and without carotid atherosclerotic plaques which could be of pathophysiological importance in atherogenesis.     

Effect of prior exercise on postprandial lipemia and markers of inflammation and endothelial activation in normal weight and overweight adolescent boys

Postprandial lipemia (PPL) is associated with impaired endothelial function and inflammation. Acute exercise reduces PPL in adults. This investigation examined the effect of an acute bout of exercise on postprandial changes in triglycerides (TG), glucose, insulin, inflammation [white blood cell count (WBC), interleukin-6 (IL-6) tumor necrosis factor-alpha, C-reactive protein (CRP)] and endothelial activation [soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1)] following a high-fat meal in adolescents. Ten normal weight (NW) (BMI, 20.9 ± 1.7 kg m⁻²; 15.6 ± 0.7 years) and eight overweight (OW) (BMI, 28.3 ± 3.6 kg m⁻²; 15.9 ± 0.4 years) adolescent boys underwent two 6-h oral fat tolerance tests (OFTT) separated by 7–10 days. On the evening prior to each OFTT, subjects either rested or completed a treadmill exercise bout (65% 600 kcal expended). Exercise reduced (P < 0.01) the postprandial TG area under the curve by ~20% in the NW and OW groups. The postprandial glucose and insulin response did not differ between the control and exercise trials or between the NW and OW groups. Circulating leukocytes and plasma IL-6 levels increased (P < 0.01) in the NW and OW groups 6 h following the OFTT in both experimental conditions. There were no changes in CRP, sVCAM-1 or sICAM-1 following the OFTT and there were no differences between experimental condition or NW and OW groups. In conclusion, a moderate exercise bout prior to a high-fat meal effectively reduces postprandial TG concentrations to a similar degree in both NW and OW adolescents, but does not reduce the concomitant postprandial increase in WBC or IL-6.     

The endothelial microparticle response to a high fat meal is not attenuated by prior exercise

Triglyceride-rich postprandial lipoproteins are known to activate endothelial cells in vitro, contributing to atherosclerosis. Endothelial microparticles (EMP) are membranous vesicles released into the circulation from vascular endothelial cells that permit cell activation to be monitored in vivo. The objective of the study was to examine changes in EMP following a high fat meal, consumed with and without prior exercise. Eight recreationally active young men underwent two oral fat tolerance tests following either 100 min exercise at 70% VO₂peak (EX trial) or no exercise (CON trial) on the previous evening. Postprandial triglycerides were reduced (1.97 ± 0.31 vs. 1.17 ± 0.13 mmol L⁻¹, p < 0.05) and HDL-cholesterol (HDL-C) increased (1.20 ± 0.07 vs. 1.30 ± 0.08 mmol L⁻¹, p < 0.05) in the EX compared to CON trial. EMP (CD31+/42b−) increased postprandially (p < 0.05). However, counts were not different between trials (postprandial CON and EX trial counts × 10³ μL⁻¹, 3.10 ± 0.14 vs. 3.26 ± 0.37). There were no changes in sICAM-1 or sVCAM-1 postprandially and no differences between trials. Interleukin-6 (IL-6) and leukocytes increased postprandially (p < 0.05). IL-6 values were not different between trials. Leukocytes were higher at 0 h in the EX trial with CON and EX trial values similar at 6 h. EMP, but not sICAM-1 or sVCAM-1, increase in response to a high fat meal. However, EMP are not attenuated by acute exercise, despite a considerable reduction in postprandial lipemia and an increase in HDL-C. M. Harrison and R. P. Murphy contributed equally to this work.