Dipartimento di Scienze cliniche Specialistiche ed Odontostomatologiche (DISCO), Italy.
Dipartimento di Scienze della Vita e dell'Ambiente (DISVA), Università Politecnica delle Marche, Italy.
Prog Lipid Res. 2015 Oct;60:50-73. doi: 10.1016/j.plipres.2015.08.003. Epub 2015 Sep 28.
Decreased activity of the enzyme paraoxonase-1 (PON1) has been demonstrated in cardiovascular diseases. Statins, the forefront of pharmacotherapy for dyslipidemia, have been shown to enhance PON1 activity but clinical findings have not been conclusive.
To systematically review the clinical findings on the impact of statin therapy on PON1 status (protein concentrations and activities of paraoxonase and arylesterase) and calculate an effect size for the mentioned effects through meta-analysis of available data.
Scopus and Medline databases were searched to identify clinical trials. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential confounders on the estimated effect sizes.
Meta-analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities, but not PON1 protein concentration. The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose, treatment duration and changes in plasma low-density lipoprotein cholesterol concentration.
The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes.
已证实，酶对氧磷酶-1（PON1）的活性降低与心血管疾病有关。他汀类药物是治疗血脂异常的前沿药物，已被证明能增强 PON1 的活性，但临床研究结果尚无定论。
系统回顾他汀类药物治疗对 PON1 状态（蛋白浓度和对氧磷酶及芳基酯酶活性）的临床影响，并通过对现有数据进行荟萃分析计算出上述影响的效应大小。
在 Scopus 和 Medline 数据库中检索临床试验。采用随机效应模型和通用倒数方差法进行定量数据合成。采用逐个剔除研究的敏感性分析来评估潜在混杂因素对估计效应大小的影响。
荟萃分析表明，他汀类药物治疗与 PON1 对氧磷酶和芳基酯酶活性的显著升高有关，但与 PON1 蛋白浓度无关。他汀类药物的 PON1 增强作用在敏感性分析中是稳健的，且独立于他汀类药物剂量、治疗持续时间和血浆低密度脂蛋白胆固醇浓度的变化。
他汀类药物增加对氧磷酶和芳基酯酶活性是一种多效性的、与脂质无关的临床获益，这可能部分解释了他汀类药物在预防心血管结局方面的潜在作用。
