ASSOCIATION AMONG STATIN, TELOMERE LENGTH AND CARDIOVASCULAR DISEASES
Background: Recent evidence has shown associations between cardiovascular diseases (CVDs) and telomere length (TL). Many factors affect telomerase activity (TA) and TL, and statin was recently found to be associated with TA and TL. This systematic review and meta-analysis was conducted to summarize the evidence on the effect of statin on TA and TL, and update the knowledge of association between TL and CVDs. Primary objective is to determine the effect of statin on TA and TL; Secondary objective, to assess the associations between TL and CVDs.
Methods: The MEDLINE and Scopus databases were searched to identify eligible studies and extracted data. Meta-analysis was done to see effects of statin on TA/TL [i.e., standardized/unstandardized mean difference (SMD/USMD)] and TL on CVDs using random-effects and fixed-effects model according to heterogeneity assessed by Q test and I2.
Results: Five and 18 studies were selected for the primary and secondary objectives, respectively. Pooled TA showed effect of statin on TA with SMD [95% confidence interval (CI)] of 1.90 (1.16, 2.64) TA. However, no significant effect on TL was seen. Increased risk of CHD among participants with shorter TL was estimated by a pooled risk ratio of 1.58 (1.19, 2.09). However, pooled hazard ratios (HRs) for CHD and stroke were non-significant; but shorter TL was significantly increased risk for unspecified CVDs with pooled HR of 1.33 (1.04, 1.70).
Conclusions: Our study showed association between statin and TA, but not for TL. In addition, shorter TL is more likely to be higher risk for CHD and unspecified CVDs. However, results were still inconclusive based on different pooled parameters. More studies are required to confirm the association of statin with TL, possibly to elucidate its protective effect on CVDs.
Keywords: Telomere, Telomerase, Statin, Cardiovascular diseases
Global atlas on cardiovascular disease prevention and control. 2011.
Mendis, S., P. Puska, and B. Norrving, Global atlas on cardiovascular disease prevention and control. 2011: World Health Organization.
Haycock, P.C., et al., Leucocyte telomere length and risk of cardiovascular disease: Systematic review and meta- Analysis. BMJ (Online), 2014. 349.
Blackburn, E.H., Switching and signaling at the telomere. Cell, 2001. 106(6): p. 661-673.
Fyhrquist, F., O. Saijonmaa, and T. Strandberg, The roles of senescence and telomere shortening in cardiovascular disease. Nat Rev Cardiol, 2013. 10(5): p. 274-83.
Boccardi, V., et al., A new pleiotropic effect of statins in elderly: modulation of telomerase activity. Faseb j, 2013. 27(9): p. 3879-85.
Janic, M., et al., Low-Dose Fluvastatin and Valsartan Rejuvenate the Arterial Wall Through Telomerase Activity Increase in Middle-Aged Men. Rejuvenation Res, 2016. 19(2): p. 115-9.
Saliques, S., et al., Circulating leukocyte telomere length and oxidative stress: a new target for statin therapy. Atherosclerosis, 2011. 219(2): p. 753-60.
Strazhesko, I.D., et al., Atorvastatin Therapy Modulates Telomerase Activity in Patients Free of Atherosclerotic Cardiovascular Diseases. Front Pharmacol, 2016. 7: p. 347.
Tran, P.T., A.K. Meeker, and E.A. Platz, Association between statin drug use and peripheral blood leukocyte telomere length in the National Health and Nutrition Examination Survey 1999-2002: a cross-sectional study. Ann Epidemiol, 2018.
Haycock, P.C., et al., Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis. Bmj, 2014. 349: p. g4227.
Jin, X., et al., Relationship between short telomere length and stroke: A meta-analysis. Medicine (Baltimore), 2018. 97(39): p. e12489.
Moher, D., et al., Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine, 2009. 151(4): p. 264-269.
Carty, C.L., et al., Leukocyte telomere length and risks of incident coronary heart disease and mortality in a racially diverse population of postmenopausal women. Arteriosclerosis, Thrombosis, and Vascular Biology, 2015. 35(10): p. 2225-2231.
Cawthon, R.M., et al., Association between telomere length in blood and mortality in people aged 60 years or older. Lancet, 2003. 361(9355): p. 393-5.
Brouilette, S.W., et al., Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet, 2007. 369(9556): p. 107-114.
Stefler, D., et al., Leukocyte telomere length and risk of coronary heart disease and stroke mortality: prospective evidence from a Russian cohort. Scientific reports, 2018. 8(1): p. 16627.
Madrid, A.S., et al., Short telomere length and ischemic heart disease: Observational and genetic studies in 290 022 individuals. Clinical Chemistry, 2016. 62(8): p. 1140-1149.
Mwasongwe, S., et al., Leukocyte telomere length and cardiovascular disease in African Americans: The Jackson Heart Study. Atherosclerosis, 2017. 266: p. 41-47.
Osthus, I.B.O., et al., Association of Telomere Length With Myocardial Infarction: A Prospective Cohort From the Population Based HUNT 2 Study. Prog Cardiovasc Dis, 2017. 59(6): p. 649-655.
Ye, S., et al., Relation between leukocyte telomere length and incident coronary heart disease events (from the 1995 Canadian Nova Scotia Health Survey). American Journal of Cardiology, 2013. 111(7): p. 962-967.
Weischer, M., et al., Short telomere length, myocardial infarction, ischemic heart disease, and early death. Arterioscler Thromb Vasc Biol, 2012. 32(3): p. 822-9.
Fitzpatrick, A.L., et al., Leukocyte telomere length and mortality in the cardiovascular health study. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 2011. 66 A(4): p. 421-429.
Ellehoj, H., L. Bendix, and M. Osler, Leucocyte Telomere Length and Risk of Cardiovascular Disease in a Cohort of 1,397 Danish Men and Women. Cardiology (Switzerland), 2016. 133(3): p. 173-177.
Willeit, P., et al., Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arterioscler Thromb Vasc Biol, 2010. 30(8): p. 1649-56.
Epel, E.S., et al., The rate of leukocyte telomere shortening predicts mortality from cardiovascular disease in elderly men. Aging (Albany NY), 2008. 1(1): p. 81-8.
Martin-Ruiz, C.M., et al., Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: A population-based study. Aging Cell, 2005. 4(6): p. 287-290.
Yuan, X., et al., Longitudinal changes in leukocyte telomere length and mortality in elderly Swedish men. Aging (Albany NY), 2018. 10(10): p. 3005.
Baragetti, A., et al., Telomere shortening over 6 years is associated with increased subclinical carotid vascular damage and worse cardiovascular prognosis in the general population. Journal of Internal Medicine, 2015. 277(4): p. 478-487.
Hammadah, M., et al., Telomere shortening, regenerative capacity, and cardiovascular outcomes. Circulation Research, 2017. 120(7): p. 1130-1138.
Needham, B.L., et al., Leukocyte Telomere Length and Mortality in the National Health and Nutrition Examination Survey, 1999-2002. Epidemiology, 2015. 26(4): p. 528-535.
Wells, G., et al., Newcastle-Ottawa quality assessment scale cohort studies. 2014.
Wells, G., et al., NewCastle–Ottawa quality assessment scale—case control studies. 2017.
NEWCASTLE - OTTAWA QUALITY ASSESSMENT SCALE(adapted for cross sectional studies).
Higgins, J., et al., Revised Cochrane risk of bias tool for randomized trials (RoB 2.0). 2016, Version.
Cawthon, R.M., Telomere measurement by quantitative PCR. Nucleic acids research, 2002. 30(10): p. e47-e47.
Shammas, M.A., Telomeres, lifestyle, cancer, and aging. Current opinion in clinical nutrition and metabolic care, 2011. 14(1): p. 28.
Wang, Z., et al., Characterization of oxidative guanine damage and repair in mammalian telomeres. PLoS genetics, 2010. 6(5): p. e1000951.
Haendeler, J., et al., Antioxidants Inhibit Nuclear Export of Telomerase Reverse Transcriptase and Delay Replicative Senescence of Endothelial Cells. Circulation Research, 2004. 94(6): p. 768-775.
Chen, J.-w., S.-b. Zhou, and Z.-m. Tan, Aspirin and pravastatin reduce lectin-like oxidized low density lipoprotein receptor-1 expression, adhesion molecules and oxidative stress in human coronary artery endothelial cells. Chinese medical journal, 2010. 123(12): p. 1553-1560.
Puccetti, L., et al., Effects of atorvastatin and rosuvastatin on thromboxane-dependent platelet activation and oxidative stress in hypercholesterolemia. Atherosclerosis, 2011. 214(1): p. 122-128.
Elissa Epel , E.B. Background Information and Our Views on Telomere Dynamics and Measurement. 2017; Available from: http://www.amecenter.ucsf.edu/telomeretesting.
How to Cite
Copyright (c) 2022 Each author(s) agree to transfer all copyrights and assign YAYASAN ALIANSI CENDEKIAWAN INDONESIA THAILAND, the Publisher of Proceedings of the International Conference on Applied Science and Health, for the full term of exclusive copyright and any extensions or renewals of that terms thereof throughout the world, including but not limited to publish, disseminate, transmit, store, translate, distribute, sell, republish and use the Contribution and material contained therein in print and electronic form of the journal and in other derivative works, in all languages and any form of media of expression available now or in the future and to license or permit others to do so.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.Proceedings of the International Conference on Applied Science and Health is an open access following Creative Commons License Deed – Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). Users are allowed to copy and redistribute the material in any medium or format as well as remix, transform, and build upon the material with one condition--appropriate credit is given to the journal.