Skip to content
2000
Volume 20, Issue 2
  • ISSN: 1573-4021
  • E-ISSN:

Abstract

Introduction

A previous meta-analysis reported the positive effects of statin therapy on endothelial function. However, the obtained result had several limitations that necessitated updating the information in this field. Therefore, a systematic and meta-analysis review was conducted to determine whether statin therapy could improve endothelial function, as assessed by flow-mediated dilation (FMD).

Methods

MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science were searched to identify randomized placebo-controlled trials assessing the impact of statin therapy on FMD. A random-effects model was used for meta-analysis to calculate the mean difference in weight. Meta-regression and subgroup analyses were used to identify sources of heterogeneity. In addition, nonlinear dose-response, quality of evidence, influence analysis, and publication bias evaluation were assessed using standard methods.

Results

Thirty-five trials (41 arms) involving 2178 participants were included in the meta-analysis study. Statin treatment significantly improved FMD [weighted mean difference (WMD): 1.7%, 95% CI: 1.3-2.2, p < 0.001). However, significant heterogeneity was observed (I2=97.9%, p < 0.001). The results of the subgroup analysis showed that health status can contribute to heterogeneity. Non-linear dose-response analysis revealed the most significant improvement in FMD with atorvastatin at a dose of 20 mg/day and simvastatin at 80 mg/day.

Conclusion

Statin therapy significantly improved endothelial function, as assessed by FMD. These changes are clinically significant, but their use should be approached with caution.

Loading

Article metrics loading...

/content/journals/chyr/10.2174/0115734021280797240212091416
2024-02-21
2024-11-26
Loading full text...

Full text loading...

References

  1. WidlanskyM.E. GokceN. KeaneyJ.F.Jr VitaJ.A. The clinical implications of endothelial dysfunction.J. Am. Coll. Cardiol.20034271149116010.1016/S0735‑1097(03)00994‑X14522472
    [Google Scholar]
  2. RossR. Atherosclerosis--an inflammatory disease.N. Engl. J. Med.1999340211512610.1056/NEJM1999011434002079887164
    [Google Scholar]
  3. VitaJ.A. KeaneyJ.F.Jr Endothelial function: A barometer for cardiovascular risk?Circulation20021066640642
    [Google Scholar]
  4. BonettiP.O. LermanL.O. LermanA. Endothelial dysfunction.Arterioscler. Thromb. Vasc. Biol.200323216817510.1161/01.ATV.0000051384.43104.FC12588755
    [Google Scholar]
  5. ChruścielP. SahebkarA. Rembek-WieliczkoM. SerbanM.C. UrsoniuS. MikhailidisD.P. JonesS.R. MosteoruS. BlahaM.J. MartinS.S. RyszJ. TothP.P. LipG.Y.H. PencinaM.J. RayK.K. BanachM. Impact of statin therapy on plasma adiponectin concentrations: A systematic review and meta-analysis of 43 randomized controlled trial arms.Atherosclerosis201625319420810.1016/j.atherosclerosis.2016.07.89727498397
    [Google Scholar]
  6. SahebkarA. KotaniK. SerbanC. UrsoniuS. MikhailidisD.P. JonesS.R. RayK.K. BlahaM.J. RyszJ. TothP.P. MuntnerP. LipG.Y.H. BanachM. Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials.Atherosclerosis2015241243344210.1016/j.atherosclerosis.2015.05.02226074317
    [Google Scholar]
  7. SerbanC. SahebkarA. UrsoniuS. MikhailidisD.P. RizzoM. LipG.Y.H. Kees HovinghG. KasteleinJ.J.P. KalinowskiL. RyszJ. BanachM. A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations.Sci. Rep.201551990210.1038/srep0990225970700
    [Google Scholar]
  8. SahebkarA. SerbanC. MikhailidisD.P. UndasA. LipG.Y.H. MuntnerP. BittnerV. RayK.K. WattsG.F. HovinghG.K. RyszJ. KasteleinJ.J. BanachM. Association between statin use and plasma D-dimer levels. A systematic review and meta-analysis of randomised controlled trials.Thromb. Haemost.2015114354655726017749
    [Google Scholar]
  9. SahebkarA. SerbanC. UrsoniuS. MikhailidisD.P. UndasA. LipG.Y.H. BittnerV. RayK.K. WattsG.F. HovinghG.K. RyszJ. KasteleinJ.J.P. BanachM. The impact of statin therapy on plasma levels of von Willebrand factor antigen.Thromb. Haemost.2016115352053210.1160/th15‑08‑062026632869
    [Google Scholar]
  10. BahramiA. BoS. JamialahmadiT. SahebkarA. Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ageing: Molecular mechanisms.Ageing Res. Rev.20205810102410.1016/j.arr.2020.10102432006687
    [Google Scholar]
  11. SohrevardiS. NasabF. MirjaliliM. BagherniyaM. TaftiA. JarrahzadehM. AzarpazhoohM. SaeidmaneshM. BanachM. JamialahmadiT. SahebkarA. Effect of atorvastatin on delirium status of patients in the intensive care unit: A randomized controlled trial.Arch. Med. Sci.20191751423142810.5114/aoms.2019.8933034522273
    [Google Scholar]
  12. Vahedian-AzimiA MohammadiSM BanachM BeniFH GuestPC Al-RasadiK Improved COVID-19 outcomes following statin therapy: An updated systematic review and meta-analysis.Biomed Res Int202120211901772
    [Google Scholar]
  13. GorabiA.M. KiaieN. PirroM. BianconiV. JamialahmadiT. SahebkarA. Effects of statins on the biological features of mesenchymal stem cells and therapeutic implications.Heart Fail. Rev.20212651259127210.1007/s10741‑020‑09929‑932008148
    [Google Scholar]
  14. BlandA.R. PayneF.M. AshtonJ.C. JamialahmadiT. SahebkarA. The cardioprotective actions of statins in targeting mitochondrial dysfunction associated with myocardial ischaemia-reperfusion injury.Pharmacol. Res.202217510598610.1016/j.phrs.2021.10598634800627
    [Google Scholar]
  15. RuszkowskiP. Masajtis-ZagajewskaA. NowickiM. Effects of combined statin and ACE inhibitor therapy on endothelial function and blood pressure in essential hypertension - a randomised double-blind, placebo controlled crossover study.J. Renin Angiotensin Aldosterone Syst.2019203147032031986889010.1177/147032031986889031486700
    [Google Scholar]
  16. DobruckiL.W. KalinowskiL. DobruckiI.T. MalinskiT. Statin-stimulated nitric oxide release from endothelium.Med. Sci. Monit.20017462262711433186
    [Google Scholar]
  17. RidkerP.M. RifaiN. PfefferM.A. SacksF. BraunwaldE. Long-term effects of pravastatin on plasma concentration of C-reactive protein.Circulation1999100323023510.1161/01.CIR.100.3.23010411845
    [Google Scholar]
  18. EndresM. LaufsU. HuangZ. NakamuraT. HuangP. MoskowitzM.A. LiaoJ.K. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase.Proc. Natl. Acad. Sci.199895158880888510.1073/pnas.95.15.88809671773
    [Google Scholar]
  19. ParizadehS.M.R. AzarpazhoohM.R. MoohebatiM. NematyM. Ghayour-MobarhanM. TavallaieS. RahseparA.A. AminiM. SahebkarA. MohammadiM. FernsG.A.A. Simvastatin therapy reduces prooxidant-antioxidant balance: Results of a placebo-controlled cross-over trial.Lipids201146433334010.1007/s11745‑010‑3517‑x21207250
    [Google Scholar]
  20. BahramiA. ParsamaneshN. AtkinS.L. BanachM. SahebkarA. Effect of statins on toll-like receptors: A new insight to pleiotropic effects.Pharmacol. Res.201813523023810.1016/j.phrs.2018.08.01430120976
    [Google Scholar]
  21. FerrettiG. BacchettiT. SahebkarA. Effect of statin therapy on paraoxonase-1 status: A systematic review and meta-analysis of 25 clinical trials.Prog. Lipid Res.201560507310.1016/j.plipres.2015.08.00326416579
    [Google Scholar]
  22. KandeloueiT AbbasifardM ImaniD AslaniS RaziB FasihiM Effect of statins on serum level of hs-CRP and CRP in patients with cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials.Mediators Inflamm.20222022873236010.1155/2022/8732360
    [Google Scholar]
  23. BanachM. ReinerZ. CiceroA. SabouretP. ViigimaaM. SahebkarA. PostadzhiyanA. GaitaD. PellaD. PensonP. 2022: The year in cardiovascular disease - the year of upfront lipid lowering combination therapy.Arch. Med. Sci.20221861429143410.5114/aoms/15614736457968
    [Google Scholar]
  24. SahebkarA. ChewG.T. WattsG.F. Recent advances in pharmacotherapy for hypertriglyceridemia.Prog. Lipid Res.2014561476610.1016/j.plipres.2014.07.00225083925
    [Google Scholar]
  25. RerianiM.K. DunlayS.M. GuptaB. WestC.P. RihalC.S. LermanL.O. LermanA. Effects of statins on coronary and peripheral endothelial function in humans: A systematic review and meta-analysis of randomized controlled trials.Eur. J. Cardiovasc. Prev. Rehabil.201118570471610.1177/174182671139843021450596
    [Google Scholar]
  26. HigginsJ.P.T. AltmanD.G. GøtzscheP.C. JüniP. MoherD. OxmanA.D. SavovicJ. SchulzK.F. WeeksL. SterneJ.A.C. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.BMJ2011343oct18 2d592810.1136/bmj.d592822008217
    [Google Scholar]
  27. BorensteinM. HedgesL.V. HigginsJ.P. RothsteinH.R. Introduction to meta-analysis.John Wiley & Sons202110.1002/9781119558378
    [Google Scholar]
  28. HozoS.P. DjulbegovicB. HozoI. Estimating the mean and variance from the median, range, and the size of a sample.BMC Med. Res. Methodol.2005511310.1186/1471‑2288‑5‑1315840177
    [Google Scholar]
  29. DerSimonianR. LairdN. Meta-analysis in clinical trials.Control. Clin. Trials19867317718810.1016/0197‑2456(86)90046‑23802833
    [Google Scholar]
  30. HigginsJ.P.T. ThompsonS.G. Quantifying heterogeneity in a meta‐analysis.Stat. Med.200221111539155810.1002/sim.118612111919
    [Google Scholar]
  31. GuyattG.H. OxmanA.D. VistG.E. KunzR. Falck-YtterY. Alonso-CoelloP. SchünemannH.J. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations.BMJ2008336765092492610.1136/bmj.39489.470347.AD18436948
    [Google Scholar]
  32. CerielloA. AssaloniR. Da RosR. MaierA. PiconiL. QuagliaroL. EspositoK. GiuglianoD. Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients.Circulation2005111192518252410.1161/01.CIR.0000165070.46111.9F15867169
    [Google Scholar]
  33. ChelloM. GoffredoC. PattiG. CanduraD. MelfiR. MastrobuoniS. Di SciascioG. CovinoE. Effects of atorvastatin on arterial endothelial function in coronary bypass surgery.Eur. J. Cardiothorac. Surg.200528680581010.1016/j.ejcts.2005.09.01316274999
    [Google Scholar]
  34. FábiánE. VargaA. PicanoE. VajoZ. RónaszékiA. CsanádyM. Effect of simvastatin on endothelial function in cardiac syndrome X patients.Am. J. Cardiol.200494565265510.1016/j.amjcard.2004.05.03515342302
    [Google Scholar]
  35. GrigoreL. RaselliS. GarlaschelliK. RedaelliL. NorataG.D. PirilloA. CatapanoA.L. Effect of treatment with pravastatin or ezetimibe on endothelial function in patients with moderate hypercholesterolemia.Eur. J. Clin. Pharmacol.201369334134610.1007/s00228‑012‑1345‑z22777149
    [Google Scholar]
  36. KohK.K. SonJ.W. AhnJ.Y. JinD.K. KimH.S. ChoiY.M. KimD.S. JeongE.M. ParkG.S. ChoiI.S. ShinE.K. Comparative effects of diet and statin on NO bioactivity and matrix metalloproteinases in hypercholesterolemic patients with coronary artery disease.Arterioscler. Thromb. Vasc. Biol.2002229e19e2310.1161/01.ATV.0000030997.02059.BB12231575
    [Google Scholar]
  37. KohK.K. QuonM.J. HanS.H. LeeY. AhnJ.Y. KimS.J. KohY. ShinE.K. Simvastatin improves flow-mediated dilation but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients.Diabetes Care200831477678210.2337/dc07‑219918184901
    [Google Scholar]
  38. YunK.H. ShinI.S. ParkE.M. RheeS.J. LeeE.M. YooN.J. KimN-H. OhS.K. JeongJ-W. Effect of additional statin therapy on endothelial function and prognosis in patients with vasospastic angina.Korean Circ. J.2008381263864310.4070/kcj.2008.38.12.638
    [Google Scholar]
  39. BeishuizenE.D. TamsmaJ.T. JukemaJ.W. van de ReeM.A. van der VijverJ.C.M. MeindersA.E. HuismanM.V. The effect of statin therapy on endothelial function in type 2 diabetes without manifest cardiovascular disease.Diabetes Care20052871668167410.2337/diacare.28.7.166815983318
    [Google Scholar]
  40. WoutersC.W. WeverK.E. BronckersI. HopmanM.T.E. SmitsP. ThijssenD.H.J. RongenG.A. Short-term statin treatment does not prevent ischemia and reperfusion-induced endothelial dysfunction in humans.J. Cardiovasc. Pharmacol.2012591222810.1097/FJC.0b013e318232b1a421885990
    [Google Scholar]
  41. van VenrooijF.V. van de ReeM.A. BotsM.L. StolkR.P. HuismanM.V. BangaJ.D. Aggressive lipid lowering does not improve endothelial function in type 2 diabetes: the Diabetes Atorvastatin Lipid Intervention (DALI) Study: A randomized, double-blind, placebo-controlled trial.Diabetes Care20022571211121610.2337/diacare.25.7.121112087021
    [Google Scholar]
  42. BankA.J. KellyA.S. KaiserD.R. CrawfordW.W. WaxmanB. SchowD.A. BillupsK.L. The effects of quinapril and atorvastatin on the responsiveness to sildenafil in men with erectile dysfunction.Vasc. Med.200611425125710.1177/1358863x0607222117390549
    [Google Scholar]
  43. BleskeB.E. NicklasJ.M. BardR.L. BrookR.D. GurbelP.A. BlidenK.P. RajagopalanS. PittB. Neutral effect on markers of heart failure, inflammation, endothelial activation and function, and vagal tone after high-dose HMG-CoA reductase inhibition in non-diabetic patients with non-ischemic cardiomyopathy and average low-density lipoprotein level.J. Am. Coll. Cardiol.200647233834110.1016/j.jacc.2005.06.08716412857
    [Google Scholar]
  44. SteinJ.H. MerwoodM.A. BellehumeurJ.L. AeschlimannS.E. KorcarzC.E. UnderbakkeG.L. MaysM.E. SosmanJ.M. Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors.Am. Heart J.2004147471310.1016/j.ahj.2003.10.01815077088
    [Google Scholar]
  45. EconomidesP.A. CaselliA. TianiE. KhaodhiarL. HortonE.S. VevesA. The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes.J. Clin. Endocrinol. Metab.200489274074710.1210/jc.2003‑03111614764790
    [Google Scholar]
  46. InancM.T. KalayN. HeyitT. OzdogruI. KayaM.G. DoganA. DuranM. KasapkaraH.A. GunebakmazO. BorluM. YarlıogluesM. OguzhanA. Effects of atorvastatin and lisinopril on endothelial dysfunction in patients with Behçet’s disease.Echocardiography2010278997100310.1111/j.1540‑8175.2010.01180.x20545993
    [Google Scholar]
  47. KayikciogluM. PayzinS. YavuzgilO. KultursayH. CanL.H. SoydanI. Benefits of statin treatment in cardiac syndrome-X.Eur. Heart J.200324221999200510.1016/S0195‑668X(03)00478‑014613735
    [Google Scholar]
  48. TikizC. UtukO. PirildarT. BayturanO. BayindirP. TaneliF. TikizH. TuzunC. Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis.J. Rheumatol.200532112095210116265685
    [Google Scholar]
  49. AlberH.F. FrickM. SüssenbacherA. DörlerJ. DichtlW. StockerE.M. PachingerO. WeidingerF. Effect of atorvastatin on peripheral endothelial function and systemic inflammatory markers in patients with stable coronary artery disease.Wien. Med. Wochenschr.20071573-4737810.1007/s10354‑007‑0377‑y17340064
    [Google Scholar]
  50. DograG.K. WattsG.F. ChanD.C. StantonK. Statin therapy improves brachial artery vasodilator function in patients with Type 1 diabetes and microalbuminuria.Diabet. Med.200522323924210.1111/j.1464‑5491.2004.01382.x15717868
    [Google Scholar]
  51. DograG. IrishA. ChanD. WattsG. A randomized trial of the effect of statin and fibrate therapy on arterial function in CKD.Am. J. Kidney Dis.200749677678510.1053/j.ajkd.2007.03.00317533020
    [Google Scholar]
  52. KondurackaE. Galicka-LatalaD. CieslikG. RostoffP. FedakD. SieradzkiJ. NaskalskiJ. PiwowarskaW. Effect of atorvastatin on endothelial function and inflammation in long‐duration type 1 diabetic patients without coronary heart disease and arterial hypertension.Diabetes Obes. Metab.200810971972510.1111/j.1463‑1326.2007.00798.x17941871
    [Google Scholar]
  53. DupuisJ. TardifJ.C. CernacekP. ThérouxP. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial.Circulation199999253227323310.1161/01.CIR.99.25.322710385495
    [Google Scholar]
  54. LiuniA. LucaM.C. GoriT. ParkerJ.D. Rosuvastatin prevents conduit artery endothelial dysfunction induced by ischemia and reperfusion by a cyclooxygenase-2-dependent mechanism.J. Am. Coll. Cardiol.201055101002100610.1016/j.jacc.2009.11.04620202516
    [Google Scholar]
  55. GargN. KrishanP. SyngleA. Rosuvastatin improves endothelial dysfunction in ankylosing spondylitis.Clin. Rheumatol.20153461065107110.1007/s10067‑015‑2912‑325771851
    [Google Scholar]
  56. LiuP.Y. LiuY.W. LinL.J. ChenJ.H. LiaoJ.K. Evidence for statin pleiotropy in humans: Differential effects of statins and ezetimibe on rho-associated coiled-coil containing protein kinase activity, endothelial function, and inflammation.Circulation2009119113113810.1161/CIRCULATIONAHA.108.81331119075102
    [Google Scholar]
  57. LiuM. WangF. WangY. JinR. Atorvastatin improves endothelial function and cardiac performance in patients with dilated cardiomyopathy: the role of inflammation.Cardiovasc. Drugs Ther.200923536937610.1007/s10557‑009‑6186‑319636689
    [Google Scholar]
  58. TanK.C.B. ChowW.S. TamS.C.F. AiV.H.G. LamC.H.L. LamK.S.L. Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus.J. Clin. Endocrinol. Metab.200287256356810.1210/jcem.87.2.824911836286
    [Google Scholar]
  59. ZhaoJ. YanH. LiY. WangJ. HanL. WangZ. TangM. ZhangW. ZhangY. ZhongM. Pitavastatin calcium improves endothelial function and delays the progress of atherosclerosis in patients with hypercholesterolemia.J. Zhejiang Univ. Sci. B201516538038710.1631/jzus.B140018125990055
    [Google Scholar]
  60. TantikosoomW. ThinkhamropB. KiatchusakulS. JarernsiripornkulN. SrinakarinJ. OjongpianS. Randomized trial of atorvastatin in improving endothelial function in diabetics without prior coronary disease and having average cholesterol level.J. Med. Assoc. Thai.200588339940615962651
    [Google Scholar]
  61. MagenE. ViskoperR. MishalJ. PrilukR. BerezovskyA. LasztA. LondonD. YosefyC. Resistant arterial hypertension and hyperlipidemia: Atorvastatin, not vitamin C, for blood pressure control.Isr. Med. Assoc. J.200461274274615609886
    [Google Scholar]
  62. ErbsS. BeckE.B. LinkeA. AdamsV. GielenS. KränkelN. Möbius-WinklerS. HöllriegelR. ThieleH. HambrechtR. SchulerG. High-dose rosuvastatin in chronic heart failure promotes vasculogenesis, corrects endothelial function, and improves cardiac remodeling — Results from a randomized, double-blind, and placebo-controlled study.Int. J. Cardiol.20111461566310.1016/j.ijcard.2010.02.01920236716
    [Google Scholar]
  63. HausbergM. KoschM. StamF. HeidenreichS. KistersK. RahnK.H. BarenbrockM. Effect of fluvastatin on endothelium-dependent brachial artery vasodilation in patients after renal transplantation.Kidney Int.20015941473147910.1046/j.1523‑1755.2001.0590041473.x11260410
    [Google Scholar]
  64. TanevaE. BoruckiK. WiensL. MakarovaR. Schmidt-LuckeC. LuleyC. WestphalS. Early effects on endothelial function of atorvastatin 40 mg twice daily and its withdrawal.Am. J. Cardiol.20069771002100610.1016/j.amjcard.2005.10.03216563905
    [Google Scholar]
  65. Gómez-DoblasJ.J. Jiménez-NavarroM.F. García-PinillaJ.M. Rodríguez-BailónI. RobledoJ. CabreraF. EspinosaS. de TeresaE. Effect of statin treatment begun early after acute myocardial infarction on endothelial function in patients with normal levels of cholesterol. VAATOPE Study (VAlue of ATOrvastatin in Postinfarction Endothelium).Med. Clin.2006126932532816650363
    [Google Scholar]
  66. MullenM.J. WrightD. DonaldA.E. ThorneS. ThomsonH. DeanfieldJ.E. Atorvastatin but not l-arginine improves endothelial function in type I diabetes mellitus: A double-blind study.J. Am. Coll. Cardiol.200036241041610.1016/S0735‑1097(00)00743‑910933350
    [Google Scholar]
  67. NagashimaH. EndoM. Pitavastatin prevents postprandial endothelial dysfunction via reduction of the serum triglyceride level in obese male subjects.Heart Vessels201126442843410.1007/s00380‑010‑0071‑721132308
    [Google Scholar]
  68. YoshidaO. KondoT. Kureishi-BandoY. SugiuraT. MaedaK. OkumuraK. MuroharaT. Pitavastatin, an HMG-CoA reductase inhibitor, ameliorates endothelial function in chronic smokers.Circ. J.201074119520210.1253/circj.CJ‑09‑034519926918
    [Google Scholar]
  69. KaratzisE. LekakisJ. PapamichaelC. AndreadouI. CimponeriuA. AznaouridisK. PapaioannouT.G. ProtogerouA. MavrikakisM. Rapid effect of pravastatin on endothelial function and lipid peroxidation in unstable angina.Int. J. Cardiol.20051011657010.1016/j.ijcard.2004.03.06015860385
    [Google Scholar]
  70. ZhangL. GongD. LiS. ZhouX. Meta-analysis of the effects of statin therapy on endothelial function in patients with diabetes mellitus.Atherosclerosis20122231788510.1016/j.atherosclerosis.2012.01.03122326029
    [Google Scholar]
  71. Cholesterol Treatment Trialists’ CollaborationEfficacy and safety of statin therapy in older people: A meta-analysis of individual participant data from 28 randomised controlled trials.Lancet20193931017040741510.1016/S0140‑6736(18)31942‑130712900
    [Google Scholar]
  72. CasinoP.R. KilcoyneC.M. CannonR.O.III QuyyumiA.A. PanzaJ.A. Impaired endothelium-dependent vascular relaxation in patents with hypercholesterolemia extends beyond the muscarinic receptor.Am. J. Cardiol.1995751404410.1016/S0002‑9149(99)80524‑47528464
    [Google Scholar]
  73. LawsP.E. SparkJ.I. CowledP.A. FitridgeR.A. The role of statins in vascular disease.Eur. J. Vasc. Endovasc. Surg.200427161610.1016/j.ejvs.2003.09.01414652831
    [Google Scholar]
  74. OgitaH. LiaoJ.K. Endothelial function and oxidative stress.Endothelium200411212313210.1080/1062332049048266415370071
    [Google Scholar]
  75. JiangH. ZhouY. NabaviS.M. SahebkarA. LittleP.J. XuS. WengJ. GeJ. Mechanisms of oxidized LDL-mediated endothelial dysfunction and its consequences for the development of atherosclerosis.Front. Cardiovasc. Med.2022992592310.3389/fcvm.2022.92592335722128
    [Google Scholar]
  76. AthyrosV. KakafikaA. TziomalosK. KaragiannisA. MikhailidisD. Pleiotropic effects of statins--clinical evidence.Curr. Pharm. Des.200915547948910.2174/13816120978731572919199976
    [Google Scholar]
  77. HadiH.A. SuwaidiJ.A. Endothelial dysfunction in diabetes mellitus.Vasc. Health Risk Manag.20073685387618200806
    [Google Scholar]
  78. KatsikiN. ReinerŽ. Tedeschi ReinerE. Al-RasadiK. PirroM. MikhailidisD.P. SahebkarA. Improvement of endothelial function by pitavastatin: A meta-analysis.Expert Opin. Pharmacother.201819327928610.1080/14656566.2018.142856029334477
    [Google Scholar]
  79. BullanoM.F. WertzD.A. YangG.W. KamatS. BorokG.M. GandhiS. McDonoughK.L. WilleyV.J. Effect of rosuvastatin compared with other statins on lipid levels and National Cholesterol Education Program goal attainment for low-density lipoprotein cholesterol in a usual care setting.Pharmacotherapy200626446947810.1592/phco.26.4.46916553504
    [Google Scholar]
  80. BanachM. SerbanC. UrsoniuS. RyszJ. MuntnerP. TothP.P. JonesS.R. RizzoM. GlasserS.P. WattsG.F. BlumenthalR.S. LipG.Y.H. MikhailidisD.P. SahebkarA. Statin therapy and plasma coenzyme Q10 concentrations—A systematic review and meta-analysis of placebo-controlled trials.Pharmacol. Res.20159932933610.1016/j.phrs.2015.07.00826192349
    [Google Scholar]
  81. GaoL. MaoQ. CaoJ. WangY. ZhouX. FanL. Effects of coenzyme Q10 on vascular endothelial function in humans: A meta-analysis of randomized controlled trials.Atherosclerosis2012221231131610.1016/j.atherosclerosis.2011.10.02722088605
    [Google Scholar]
  82. RasR.T. StreppelM.T. DraijerR. ZockP.L. Flow-mediated dilation and cardiovascular risk prediction: A systematic review with meta-analysis.Int. J. Cardiol.2013168134435110.1016/j.ijcard.2012.09.04723041097
    [Google Scholar]
  83. NormanG.R. SloanJ.A. WyrwichK.W. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation.Med. Care200341558259210.1097/01.MLR.0000062554.74615.4C12719681
    [Google Scholar]
/content/journals/chyr/10.2174/0115734021280797240212091416
Loading
/content/journals/chyr/10.2174/0115734021280797240212091416
Loading

Data & Media loading...

Supplements

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test