Fenofibrate Improves Vascular Endothelial Function by Reducing Oxidative Stress While Increasing Endothelial Nitric Oxide Synthase in Healthy Normolipidemic Older Adults

Walker, Ashley E.; Kaplon, Rachelle E.; Lucking, Sara Marian S.; Russell-Nowlan, Molly J.; Eckel, Robert H.; Seals, Douglas R.

doi:10.1161/hypertensionaha.112.203661

Cited by 67 publications

(52 citation statements)

References 39 publications

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“…Included studies were published during the period of 2001-2012, and they were conducted in Italy were performed on healthy subjects [24,41]. Demographic and baseline biochemical parameters of the included studies are shown in Table 1.…”

Section: A Included Studiesmentioning

confidence: 99%

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Sahebkar

Giua

Pedone

et al. 2016

Pharmacological Research

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Flow-mediated dilation (FMD) of the brachial artery reflects endothelium-dependent vasodilator function; since it correlates with coronary endothelial function, its reduction could predict cardiovascular events. Several studies have investigated the potential impact of fibrates therapy on endothelial function, but clinical findings have not been fully consistent. We aimed to conduct a meta-analysis of randomized placebo-controlled trials in order to clarify whether fibrate therapy could improve endothelial function. A systematic search in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases was performed to identify randomized placebo-controlled trials investigating the effect of fibrates on endothelial function as estimated by FMD. A randomeffects model and generic inverse variance method were used for meta-analysis. Sensitivity analysis, risk of bias evaluation, and publication bias assessment were carried out using standard methods. Random-effects meta-regression was used to evaluate the impact of treatment duration on the estimated effect size. Fifteen trials with a total of 556 subjects met the eligibility criteria. Fibrate 3 therapy significantly improves FMD (weighted mean difference [WMD]: 1.64%, 95% CI: 1.15, 2.13, p < 0.001) and the result was confirmed in both subgroups with treatment durations ≤8 weeks (WMD: 1.35%, 95% CI: 0.85, 1.86, p < 0.001) and >8 weeks (WMD: 2.55%, 95% CI: 1.21, 3.89, p < 0.001). When the analysis was stratified according to the fibrate type, a significant effect was observed with fenofibrate but not with gemfibrozil, though difference between the two subgroups was not significant. Meta-analysis of data from trials where nitrate mediated dilation (NMD) was available did not suggest a significant change in NMD following treatment with fibrates. The results of this meta-analysis suggest that fibrates may exert beneficial effects on endothelial function, even over a short-term treatment course.

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Section: A Included Studiesmentioning

confidence: 99%

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Sahebkar

Giua

Pedone

et al. 2016

Pharmacological Research

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“…Fenofibrate, a lipid-lowering agent with pleiotropic actions, improved endothelial function, measured by brachial flow-mediated dilation, in middle-aged and older normolipidemic adults by reducing oxidative stress and by increasing endothelial NOS expression and activity (227).…”

mentioning

confidence: 99%

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

237

177

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Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redoxsensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182]

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“…I have 3 statistical concerns on the study of Walker et al 1 First, distributions of triglyceride, insulin-related indicators, and C-reactive protein are normal in general after logarithmic transformation. Among several insulin-related biomarkers, they used indices of insulin resistance, named the homeostasis model assessment-insulin resistance.…”

Section: To the Editormentioning

confidence: 99%

Effect of Fenofibrate on Vascular Endothelial Function: Statistical Appraisal and its Validity

Kawada

2013

Hypertension

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Fenofibrate Improves Vascular Endothelial Function by Reducing Oxidative Stress While Increasing Endothelial Nitric Oxide Synthase in Healthy Normolipidemic Older Adults

Cited by 67 publications

References 39 publications

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Effect of Fenofibrate on Vascular Endothelial Function: Statistical Appraisal and its Validity

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