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Pleiotropic effects of statins–clinical evidence.
Abstract
The present review considers the potential pleiotropic effects of statins and the evidence indicative of the "real world" benefit from these effects in patients with cardiovascular disease (CVD). Some of these cholesterol-independent effects of statins involve improved endothelial function, stability of atherosclerotic plaques, attenuation of oxidative stress and inflammation, as well as inhibition of the thrombogenic response. Clinical evidence from early statin administration in acute coronary syndromes and in revascularisation procedures is reported. Moreover, the "metabolic" effects of statin treatment, such as renal function improvement and reduction in serum uric acid levels, in patients with stable coronary heart disease are discussed. Evidence suggests that in high CVD risk patient groups pleiotropic effects of statins may play a role in the reduction of morbidity and mortality. However, this concept requires proof in appropriately designed trials that will include clinically relevant end points in order to set specific targets in new CVD-related biomarkers, in addition to lipid levels, that should be used to fully assess the statin contribution to CVD treatment.
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“Statins have various pleiotropic effects that are independent of their serum cholestrol-lowering properties. Some of those reported have included antioxidative, anti-inflammatory and immunomodulatory capabilities (Athyros et al., 2009).”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as Athyros et al., 2009
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Items 101–154 of 154
Τζιόμαλος, Κ., Giampatzis, V., Bouziana, S. D., Spanou, M., Pavlidis, A., Papadopoulou, M., Boutari, C., Magkou, D., Savopoulos, C. G., & Hatzitolios, A. I. (2013) · International Journal of Stroke · doi:10.1111/ijs.12116 · Cited by 6
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“Controversy still exists as to whether the potential pleiotropic effects of statins will translate into true beneficial clinical outcomes independent of the statin lipid effects [3].”
BackgroundMyoglobin microplate assay to evaluate prevention of protein peroxidation
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Self-citationEditorial: Preventing Cardio-renal Syndrome Rather than Treating It: Could Statins Play A Role?
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“There is evidence that these factors could be controlled by the pleiotropic (cholesterol-lowering-independent) effects of statins [46].”
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“, anti-inflammatory, antioxidant, and antithrombotic actions) as well as the reduction in cardiovascular risk with these agents are clearly dose-dependent [11].”
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“Other pleiotropic effects such as anti-inflammatory and anti-oxidative effects may also be involved [1, 2].”
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“Although effective for atherosclerotic treatment, statins have been shown to lead to death or even non-fatal myocardial infarction (Athyros et al., 2009).”
BackgroundParaskevas, K. I., Tzovaras, A. A., Gentimi, F., Kyriakides, Z. S., & Mikhailidis, D. P. (2010) · Angiology · doi:10.1177/0003319709360526 · Cited by 4
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Kanda, D., Takumi, T., Tokushige, A., Ikeda, Y., & Ohishi, M. (2023) · BMC Cardiovascular Disorders · doi:10.1186/s12872-023-03547-7 · Cited by 3
“Furthermore, statins have also been reported to upregulate NO synthase [22, 23] and reduce oxidative stress, which may reduce the progression of renal dysfunction.”
BackgroundHao, P., Chen, Y., Wang, X., Xu, F., Wang, J., & Zhang, Y. (2009) · 中国科学通报：英文版 · doi:10.1007/s11434-009-0654-9 · Cited by 2
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Pittaras, A. E., Avranas, K., Imprialos, K. P., Faselis, C. J., & Kokkinos, P. F. (2014) · Springer eBooks · doi:10.1007/978-3-319-08272-1_13 · Cited by 2
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“Statins have both fundamental lipid-lowering capacity and additional pleiotropic actions [9].”
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Pachano-Bravo, A., Ganesan, O., Mueller, S., & Orgill, D. P. (2026) · Wound Repair and Regeneration · doi:10.1111/wrr.70133 · Cited by 1
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“Although the reduction in LDL-cholesterol concentration may represent the most important cardioprotective effect of these drugs, it has been proposed that statins also exert additional lipid-independent mechanisms of action that may alter the natural history of the atherosclerotic process [34].”
BackgroundSimulation and verification of macroscopic isotropy of hollow alginate-based microfibers
Djomehri, S. I., Zeid, H., Yavari, A., Mobed-Miremadi, M., Youssefi, K., & Liao-Chan, S. (2014) · Artificial Cells Nanomedicine and Biotechnology · doi:10.3109/21691401.2014.897629 · Cited by 1
“Conventional FDA-approved treatments include prescription of statins (Athyros et al. 2009), oral consumption of artificial cells encapsulating non-GMO-based probiotics (Jones et al.”
BackgroundMethodRahal, E. A. (2012) · IOSR Journal of Pharmacy (IOSRPHR) · doi:10.9790/3013-25105660 · Cited by 1
Sobhy, M. A., Badran, H. M., Hassanein, M., Rafla, S. M., Zawawy, T. E., Zaki, A. M., Loutfi, M. I., Sadaka, M. A., Ayad, S. W., Kamal, A., et al. (2025) · The Egyptian Heart Journal · doi:10.1186/s43044-025-00655-x · Cited by 1
“Additionally, it contributes to the regression of atherosclerotic plaque lipid content [28] and exerts multiple pleiotropic effects, including anti-inflammatory properties, endothelial function enhancement, and antioxidant activity [29, 30].”
Okumus, T., Pala, A. A., Taner, T., & Aydın, U. (2021) · Journal of College of Physicians And Surgeons Pakistan · doi:10.29271/jcpsp.2021.04.373 · Cited by 1
“Statins cause a decrease indirectly in CRP levels with their anti-inflammatory effects.(5,6) Statins reduce complications related to CPB in cardiac surgery with their anti-inflammatory, antioxidant, and indirect antiarrhythmic effects.”
BackgroundInflammation and LDL Reduction
Athyros, V. G., Sfikas, G., & Koumaras, C. (2022) · Current Vascular Pharmacology · doi:10.2174/1570161120666221004150503 · Cited by 1
Self-citationFarokhi, F. (2022) · Neurology & Neurotherapy Open Access Journal · doi:10.23880/nnoaj-16000165
Endothelial dysfunction as a common soil of lower urinary tract symptoms and cardiovascular disease
Yamagishi, S. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2018.03.033 · Cited by 1
Metabolic Regulation of Endothelial Dysfunction and Cardiovascular Risk
Young, J. M. (2012) · Otago University Research Archive (University of Otago)
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Perea, A., Guarín, C. J. M., & Hernández, P. (2012) · IATREIA · doi:10.17533/udea.iatreia.10549
“…y colaboradores en los que se demostró que los niveles de L-mevalonato en sangre disminuían dos horas después de la administración de estatinas por vía oral, mientras que los de colesterol LDL disminuían significativamente solo después de 6-7 días de iniciar la ingesta de estos medicamentos (11).”
BackgroundStiff Heart and Stiff Arteries. Could We Soften Both?
Athyros, V. G., Τζιόμαλος, Κ., Farganis, M. A., & Geleris, P. (2013) · The Open Hypertension Journal · doi:10.2174/1876526201305010094
“Statins may attenuate most if not all these adverse pathogenetic factors through their pleitropic effects [86,87].”
BackgroundSelf-citationAre antibodies against PCSK9 the statins of the 21st century?
Τζιόμαλος, Κ., & Athyros, V. G. (2014) · Clinical Lipidology · doi:10.2217/clp.14.1
Self-citationMohammed, S. S., Mustafa, W. W., & Hussain, S. A. (2018) · Asian Journal of Pharmaceutical and Clinical Research · doi:10.22159/ajpcr.2018.v11i12.28309
The Role of Statins in the Management of Heart Failure with Preserved Ejection Fraction
Alkagiet, S., Giannakoulas, G. A., Hatzitolios, A. I., & Τζιόμαλος, Κ. (2019) · Current Pharmacology Reports · doi:10.1007/s40495-019-00172-x
Kim, Y. H., Her, A., Jeong, M. H., Kim, B., Hong, S., Kim, S., Ahn, C., Kim, J., Ko, Y., Choi, D., et al. (2021) · Cardiology Journal · doi:10.5603/cj.a2021.0007
“Statins both reduce LDL-cholesterol and decrease the occurrences of cardiovascular death, non-fatal MI, and repeat coronary revascularization by inhibiting 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase activity, as well as other not fully understood processes [3, 18, 19].”
Backgroundal., I. E. (2021) · International Journal of ADVANCED AND APPLIED SCIENCES · doi:10.21833/ijaas.2021.03.014
“However, normalization of platelet hyperactivity after treatment with statins in hypercholesterolemic patients augment the hypothesis that statins have both lipid and non-lipid activity (Athyros et al., 2009).”
BackgroundБогдан, Т. В. (2021) · Reports of the National Academy of Sciences of Ukraine · doi:10.15407/dopovidi2021.03.104
Ranaiy, M. S., Farokhi, F., & Babaei-Balderlou, F. (2021) · Research Square · doi:10.21203/rs.3.rs-882972/v1
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Biletskyi, S. V., Kazantseva, T., Petrynych, O., & Petrynych, V. V. (2021) · Bukovinian Medical Herald · doi:10.24061/2413-0737.xxv.4.100.2021.19
“114 сприятливі ліпіднезалежні плейотропні ефекти, наприклад антиоксидантний та антитромботичний, а також здатний покращувати функцію ендотелію [24].”
Ranaiy, M. S., Farokhi, F., & Babaei-Balderlou, F. (2021) · Research Square · doi:10.21203/rs.3.rs-898243/v1
Low fat diets for acquired hypercholesterolemia
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Hadijah, S., Djabir, Y. Y., & Nainu, F. (2022) · Jurnal Mandala Pharmacon Indonesia · doi:10.35311/jmpi.v8i1.170
“Statin merupakan pilihan pertama dalam pengobatan dislipidemia secara umum, dimana statin bekerja menghambat 3-hydroxyl-3 methylglutaryl co-enzyme A (HMG-CoA) reduktase, serta memiliki efek pleiotropik dan meningkatkan fungsi endotel (Athyros et al., 2009).”
BackgroundDiabetes Mellitus Type 2 and Cardiovascular Disease
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Additional file 28 of Effectiveness of long-term using statins in COPD – a network meta-analysis
Lu, Y., Chang, R., Yao, J., Xu, X., 滕永军, & Cheng, N. (2020) · Figshare · doi:10.6084/m9.figshare.11981811
Additional file 32 of Effectiveness of long-term using statins in COPD – a network meta-analysis
Lu, Y., Chang, R., Yao, J., Xu, X., 滕永军, & Cheng, N. (2020) · Figshare · doi:10.6084/m9.figshare.11981826
Additional file 7 of Effectiveness of long-term using statins in COPD – a network meta-analysis
Lu, Y., Chang, R., Yao, J., Xu, X., 滕永军, & Cheng, N. (2020) · Figshare · doi:10.6084/m9.figshare.11981844
Additional file 24 of Effectiveness of long-term using statins in COPD – a network meta-analysis
Lu, Y., Chang, R., Yao, J., Xu, X., 滕永军, & Cheng, N. (2020) · Figshare · doi:10.6084/m9.figshare.11981799
Additional file 20 of Effectiveness of long-term using statins in COPD – a network meta-analysis
Lu, Y., Chang, R., Yao, J., Xu, X., 滕永军, & Cheng, N. (2020) · Figshare · doi:10.6084/m9.figshare.11981787
Additional file 16 of Effectiveness of long-term using statins in COPD – a network meta-analysis
Lu, Y., Chang, R., Yao, J., Xu, X., 滕永军, & Cheng, N. (2020) · Figshare · doi:10.6084/m9.figshare.11981772
Additional file 12 of Effectiveness of long-term using statins in COPD – a network meta-analysis
Lu, Y., Chang, R., Yao, J., Xu, X., 滕永军, & Cheng, N. (2020) · Figshare · doi:10.6084/m9.figshare.11981760
Metadata
- Authors
- Athyros, V., Kakafika, A., Tziomalos, K., Karagiannis, A., & Mikhailidis, D.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- Corresponding author
- Mikhailidis, Dimitri
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2009-02-01
- Volume
- 15
- Issue
- 5
- Pages
- 479-489
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W2116801503
- Cited by
- 154
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 10 · 2020: 12 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 15 · 2014: 9 · 2013: 13 · 2012: 16
- FWCI
- 21.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Pharmaceutical Design (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- statins, pleiotropy, cardiovascular disease, endothelial function, atherosclerotic plaque stability, oxidative stress, inflammation, acute coronary syndrome, revascularization, renal function, serum uric acid, coronary artery disease, cardiovascular risk reduction
- MeSH terms
- Animals, Cardiovascular Diseases, Clinical Trials as Topic, Humans, Hypercholesterolemia, Risk Factors, Biomarkers, Oxidative Stress, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atherosclerosis
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