Gianna Ferretti1, Tiziana Bacchetti2, Amirhossein Sahebkar3. 1. Dipartimento di Scienze cliniche Specialistiche ed Odontostomatologiche (DISCO), Italy. 2. Dipartimento di Scienze della Vita e dell'Ambiente (DISVA), Università Politecnica delle Marche, Italy. 3. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. Electronic address: sahebkara@mums.ac.ir.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.