Does statin therapy reduce plasma VEGF levels in humans? A systematic review and meta-analysis of randomized controlled trials

Sahebkar, Amirhossein; Ponziani, Maria Chantal; Goitre, Ilaria; Bo, Simona

doi:10.1016/j.metabol.2015.08.002

Cited by 40 publications

(28 citation statements)

References 67 publications

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“…However, notably, we adjusted our multivariable models for standard cardiovascular risk factors, rendering confounding by metabolic risk factors an unlikely explanation for our findings. Similarly, VEGF levels have been associated with statin intake 16. However, exploratory additional adjustment for statin intake had no relevant effect on our findings (data not shown).…”

Section: Discussionmentioning

confidence: 55%

Circulating vascular endothelial growth factor and the risk of cardiovascular events

Kaess

Preis

Beiser

et al. 2016

Heart

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Section: Discussionmentioning

confidence: 55%

Circulating vascular endothelial growth factor and the risk of cardiovascular events

Kaess

Preis

Beiser

et al. 2016

Heart

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“…However, it is unclear whether the association is due to confounding or reverse causation because VEGF may be a symptom of acute myocardial infarction . VEGF is pharmacologically modifiable, so assessment of its potential as a target of intervention for CVD prevention is important, and clarifying its etiological role may improve understanding of CVD. Trials have shown that statins lower VEGF, raising the possibility that one of the additional benefits of statins may be due to effects on VEGF.…”

Section: Introductionmentioning

confidence: 99%

“…VEGF is pharmacologically modifiable, so assessment of its potential as a target of intervention for CVD prevention is important, and clarifying its etiological role may improve understanding of CVD. Trials have shown that statins lower VEGF, raising the possibility that one of the additional benefits of statins may be due to effects on VEGF. Little evidence from randomized controlled trials concerning the effects of VEGF on CVD in the general population is available.…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study

Yeung

Lam

Schooling

2017

JAHA

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BackgroundVascular endothelial growth factor (VEGF) has angiogenic and possibly proatherosclerotic properties. Observationally it is positively associated with cardiovascular disease, although these observations could be confounded or due to reverse causation. We assessed ischemic heart disease (IHD) risk by genetically predicted VEGF, ie, using Mendelian randomization.Methods and ResultsSingle nucleotide polymorphisms (SNPs) predicting VEGF level, at genome‐wide significance, were applied to the CARDIoGRAMplusC4D 1000 Genomes‐based genome‐wide association study IHD case (n=60 801)‐control (n=123 504) study. We obtained unconfounded estimates using instrumental variable analysis by combining the Wald estimates for each SNP using inverse variance weighting and Mendelian randomization–Egger regression. Based on 9 SNPs independently predicting VEGF (rs1740073 [C6orf223], rs2375981 [KCNV2], rs2639990 [ZADH2], rs4782371 [ZFPM1], rs6921438 [LOC100132354], rs7043199 [VLDLR‐AS1], rs10761741 [JMJD1C], rs6993770 [ZFPM2], and rs114694170 [MEF2C]), VEGF was unrelated to IHD (odds ratio 0.99 per log‐transformed pg/mL, 95%CI 0.96‐1.02) using inverse variance weighting. However, Mendelian randomization–Egger regression suggested an inverse relation of VEGF with IHD (odds ratio 0.95, 95%CI 0.91‐0.99), although the association was not evident after excluding the lead SNP (rs6921438) or additionally excluding the pleiotropic SNP (rs6993770).ConclusionsOur study does not provide strong evidence for a positive effect of VEGF on IHD but does not rule out the possibility that some specific types of VEGF, for which genetic predictors have not yet been identified, might play a role.

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“…It is an exploratory study in two small cohorts with no reference to quantitative funduscopy such as OCT parameters. Moreover, we failed to match patients for statin use, which has been shown to moderately reduce VEGF-A levels [10]. However, both groups, controls and patients, where comparable in terms of daily and seasonal VEGF fluctuations, which argues against a major effect of statins on the results in our patients.…”

Section: Discussionmentioning

confidence: 88%

Intra-individual variability and circadian rhythm of vascular endothelial growth factors in subjects with normal glucose tolerance and type 2 diabetes

et al. 2017

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Increased levels of systemic vascular endothelial growth factors (VEGFs) in patients with diabetes are associated with increased risk of microvessel disease. On the other hand, low VEGF levels after intravitreal antibody application may be associated with acute cardiovascular complications and treatment failure. Individual levels of systemic VEGF vary in a wide range depending on analytical methods and quality of diabetes control. So far only limited information exists on intraindividual fluctuations over longer periods and circadian rhythms. We analysed the intraindividual variance of VEGF-A, VEGF-C and placental growth factor (PLGF) in CTAD (citrate-theophylline-adenine-dipyridamol) plasma as well as VEGF-A in serum over a period of 6 months in patients with stable controlled type 2 diabetes (10 M, 10 F) and age and sex matched subjects with normal glucose tolerance (NGT). Furthermore, circadian levels of VEGFs were controlled hourly from 7:30 a.m. to 7:30 p.m. under standardized metabolic ward conditions. In addition, the relationship to metabolic, hormonal and inflammatory biomarkers was analyzed. VEGF-A, VEGF-C and PLGF remained stable in plasma and VEGF-A in serum over 6 months in both groups. No circadian change was observed in VEGF-A serum and plasma concentrations. A minor decrease of VEGF-C plasma levels was evident after 5 p.m. in both groups and a significant peak of PLGF concentrations occurred after lunch, which was more pronounced in T2DM. In multivariate analysis, only serum VEGF-A correlated to diabetes duration, whereas VEGF-C only correlated to HbA1c and fasting blood glucose. We did not observe significant intraindividual variances for VEGF-A in serum and VEGF-A, VEGF-C and PLGF in CTAD plasma over a period of 6 months. Taken together, a single morning measurement of systemic VEGF levels after 7:30 am appears to be a reliable parameter for the individual risk associated with abnormal VEGF concentrations in blood.Trial Registration: NCT02325271

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Does statin therapy reduce plasma VEGF levels in humans? A systematic review and meta-analysis of randomized controlled trials

Cited by 40 publications

References 67 publications

Circulating vascular endothelial growth factor and the risk of cardiovascular events

Circulating vascular endothelial growth factor and the risk of cardiovascular events

Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study

Intra-individual variability and circadian rhythm of vascular endothelial growth factors in subjects with normal glucose tolerance and type 2 diabetes

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