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首页> 外文期刊>Clinical drug investigation >Effect on the atherogenic marker plasminogen activator inhibitor type-1 of addition of the ACE inhibitor imidapril to angiotensin II type 1 receptor antagonist therapy in hypertensive patients with abnormal glucose metabolism: a prospective cohort study in primary care.
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Effect on the atherogenic marker plasminogen activator inhibitor type-1 of addition of the ACE inhibitor imidapril to angiotensin II type 1 receptor antagonist therapy in hypertensive patients with abnormal glucose metabolism: a prospective cohort study in primary care.

机译：在糖代谢异常的高血压患者中，在血管紧张素II 1型受体拮抗剂治疗中加入ACE抑制剂咪达普利对动脉粥样硬化标记物纤溶酶原激活物抑制剂1型的影响：前瞻性队列研究。

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BACKGROUND AND OBJECTIVE: Renin-angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), are recommended by the American Diabetes Association for blood pressure control and prevention or management of cardiovascular disease in patients with diabetes mellitus. However, some investigators have suggested that ARBs may increase the risk of myocardial infarction in hypertensive patients. Activation of the RAS is associated with an increased risk of ischaemic events. Angiotensin II stimulates the production of plasminogen activator inhibitor type-1 (PAI-1), a powerful predictor of cardiovascular disease. ACE inhibitors are reported to reduce PAI-1 levels and activity, while ARBs do not reduce or may even elevate levels of this atherogenic marker. The objective of this study was to determine whether the ACE inhibitor imidapril reduces PAI-1 levels in hypertensive patients already being treated with an ARB. METHODS: This was a prospective cohort study carried out in primary care with a follow-up period of 6 months. Estimating the alpha error (p-value) at 0.05, the power of the test as 80%, and the difference in PAI-1 levels as 10 + or - 15 ng/mL, the required sample size was calculated to be 40. Participants were hypertensive patients taking ARBs for more than 8 weeks, and having dyslipidaemia, obesity or abnormal glucose metabolism. Imidapril 5-10 mg/day was prescribed for 6 months to reduce blood pressure to <130/80 mmHg. The main outcome measure, PAI-1 level, was measured before and 6 months after the addition of imidapril to ARBs in 21 subjects (13 men, eight women), all with abnormal glucose metabolism, nine with dyslipidaemia, and six who were obese. Bodyweight, body mass index, blood pressure, homeostasis model assessment of insulin resistance, glycosylated haemoglobin, creatinine, potassium, high sensitivity C-reactive protein (hs-CRP), and high molecular weight adiponectin levels were measured as secondary outcomes. RESULTS: PAI-1 level was not significantly changed overall. Hs-CRP level was also not significantly changed; however, the high molecular weight adiponectin level was significantly increased (p = 0.044), especially in men (p = 0.026). There were no significant changes in the other outcomes measured. CONCLUSION: The current study showed that imidapril added to ARBs did not decrease PAI-1 levels in hypertensive patients with abnormal glucose metabolism; however, this combination therapy significantly increased high molecular weight adiponectin levels in men.
机译：背景与目的：美国糖尿病协会推荐使用肾素-血管紧张素系统（RAS）抑制剂，例如血管紧张素转换酶（ACE）抑制剂和血管紧张素II 1型受体拮抗剂（血管紧张素受体阻滞剂[ARBs]）。和预防或管理糖尿病患者的心血管疾病。但是，一些研究人员建议ARB可能会增加高血压患者的心肌梗塞风险。 RAS的激活与缺血事件的风险增加有关。血管紧张素II刺激1型纤溶酶原激活物抑制剂（PAI-1）的产生，它是心血管疾病的有力预测因子。据报道，ACE抑制剂可降低PAI-1水平和活性，而ARBs则不会降低甚至可能不会升高该动脉粥样硬化标志物的水平。这项研究的目的是确定ACE抑制剂咪达普利是否可以降低已经接受ARB治疗的高血压患者的PAI-1水平。方法：这是一项在初级保健中进行的前瞻性队列研究，随访期为6个月。估计alpha误差（p值）为0.05，测试的功效为80％，并且PAI-1水平的差异为10 +或-15 ng / mL，计算出的所需样本量为40。高血压患者服用ARB超过8周，并且患有血脂异常，肥胖或葡萄糖代谢异常。服用5-10毫克/天的咪达普利6个月，以将血压降至<130/80毫米汞柱。主要结果指标PAI-1水平是在21名受试者（13名男性，8名女性）中将吡with普利加到ARB之前和之后6个月进行测量的，这些受试者均具有糖代谢异常，血脂异常9例和肥胖6例。体重，体重指数，血压，胰岛素抵抗的稳态模型评估，糖基化血红蛋白，肌酐，钾，高敏感性C反应蛋白（hs-CRP）和高分子量脂联素水平被作为次要结果。结果：PAI-1水平总体上没有显着改变。 Hs-CRP水平也没有明显改变;然而，高分子量脂联素水平显着增加（p = 0.044），尤其是男性（p = 0.026）。测得的其他结局无明显变化。结论：目前的研究表明，在糖代谢异常的高血压患者中，将咪达普利加入ARBs中并不能降低PAI-1水平。然而，这种联合疗法显着提高了男性的高分子量脂联素水平。

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