Statin administration is associated with higher IGF-1 levels in patients without diabetes mellitus

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Background: Research makes it clear that the IGF-1 level correlates with cardiovascular disease, chronic heart failure, and mortality. Yet, little is known about the effect of statins on IGF-1.

Aims: to evaluate the effect of statin treatment on IGF-1 and its association with a cardiovascular risk.

Material and methods: The study included 115 patients (mean age, 55.8±6.1 years) who either were overweight or had mild obesity (body mass index 28.6±3.8 kg/m2) without diabetes. Group 1 consisted of 70 patients with verified coronary artery disease receiving statin therapy; group 2 included 45 healthy subjects. Coronary angiography and treadmill test were used to diagnose coronary artery disease. Impaired glucose tolerance and total cholesterol, triglycerides, LPHD, LPLD, fibrinogen, and IGF-1 levels were evaluated in all the subjects. Heart chamber geometry was assessed by echocardiography.

Results: The IGF-1 level was significantly higher in group 1 compared to the control group (196 and 167 ng/ml, respectively; р=0.014). Serum levels of IGF-1 were associated with duration of statin therapy (R=0.311; p=0.000), stage of hypertension (R=0.187; p=0.04), fibrinogen (R=0.274; p=0.033), TG (R=0.316; p=0.006), total cholesterol (R=–0.213; p=0.016), LPLD (R=–0.184; p=0.038), smoking (R=0.3; p=0.009), ejection fraction (R=0.298; p=0.041), end-diastolic volume (R=0.422; p=0.036), end-systolic volume (R=0.407; p=0.042), end-diastolic dimension (R=0.27; p=0.014), interventricular septal thickness (R=0.247; p=0.02), and left ventricular posterior wall thickness (R=0.258; p=0.019). Rosuvastatin dose positively correlated with the IGF-1 level (R=0.521; p=0.028).

Conclusions: Statin administration is associated with higher IGF-1 levels in patients without diabetes. High IGF-1 level correlates with the risk factors of coronary artery disease: hypertension, lipid profile, and fibrinogen level and has an adverse effect on chronic heart failure by altering the cardiac remodeling.

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About the authors

Olga V. Shpagina

Endocrinology Research Centre

Author for correspondence.
ORCID iD: 0000-0002-9033-6354
SPIN-code: 3114-2272

MD, postgraduate student

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

Irina Z. Bondarenko

Endocrinology Research Centre

ORCID iD: 0000-0002-5178-6029
SPIN-code: 4524-4803


Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

Galina S. Kolesnikova

Endocrinology Research Centre

ORCID iD: 0000-0002-8698-0681
SPIN-code: 7716-9680


Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036


  1. Piepoli MF, Hoes AW, Agewall S, et al. European guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts) developed with the Special contribution of the European association for cardiovascular prevention & rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315-2381. doi: 10.1093/Eurheartj/Ehw106
  2. Salmon WDJr, Daughaday WH. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med. 1957;49(6):825-836.
  3. Puche JE, Castilla-Cortazar I. Human conditions of insulin-like growth factor-I (IGF-I) deficiency. J Transl Med. 2012;10:224. doi: 10.1186/1479-5876-10-224
  4. Higashi Y, Pandey A, Goodwin B, Delafontaine P. Insulin-like growth factor-1 regulates glutathione peroxidase expression and activity in vascular endothelial cells: implications for atheroprotective actions of insulin-like growth factor-1. Biochim Biophys Acta. 2013;1832(3):391-399. doi: 10.1016/J.Bbadis.2012.12.005
  5. Bach LA. Endothelial cells and the IGF system. J Mol Endocrinol. 2015;54(1):R1-R13. doi: 10.1530/JME-14-0215
  6. Higashi Y, Quevedo HC, Tiwari S, et al. Interaction between insulin-like growth factor-1 and atherosclerosis and vascular aging. Front Horm Res. 2014;43:107-124. doi: 10.1159/000360571
  7. Higashi Y, Sukhanov S, Shai SY, et al. Insulin-like growth factor-1 receptor deficiency in macrophages accelerates atherosclerosis and induces an unstable plaque phenotype in apolipoprotein E-deficient mice. Circulation. 2016;133(23):2263-2278. doi: 10.1161/Circulationaha.116.021805
  8. Caplice N, Devoe M, Choi J, et al. P2125 randomised placebo controlled trial evaluating the safety and efficacy of intracoronary insulin like growth factor 1 post percutaneous intervention for acute myocardial infarction. Eur Heart J. 2017;38(suppl_1). doi: 10.1093/eurheartj/ehx502.P2125
  9. Jang HJ, Hong EM, Park SW, et al. Statin induces apoptosis of human colon cancer cells and down regulation of insulin-like growth factor 1 receptor VIA proapoptotic ERK activation. Oncol Lett. 2016;12(1):250-256. doi: 10.3892/Ol.2016.4569
  10. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr. 1989;2(5):358-367. doi: 10.1016/S0894-7317(89)80014-8
  11. Bruce RA, Blackmon JR, Jones JW, Strait G. Exercising testing in adult normal subjects and cardiac patients. Pediatrics. 1963;32:Suppl:742-756.
  12. Judkins MP. Percutaneous transfemoral selective coronary arteriography. Radiol Clin North Am. 1968;6(3):467-492.
  13. Schneider HJ, Klotsche J, Saller B, et al. Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients. Eur J Endocrinol. 2008;158(2):153-161. doi: 10.1530/Eje-07-0600
  14. Friedrich N, Haring R, Nauck M, et al. Mortality and serum insulin-like growth factor (IGF)-I and IGF binding protein 3 concentrations. J Clin Endocrinol Metab. 2009;94(5):1732-1739. doi: 10.1210/Jc.2008-2138
  15. Siddals KW, Marshman E, Westwood M, Gibson JM. Abrogation of insulin-like growth factor-I (IGF-I) and insulin action by mevalonic acid depletion: synergy between protein prenylation and receptor glycosylation pathways. J Biol Chem. 2004;279(37):38353-38359. doi: 10.1074/Jbc.M404838200
  16. Narayanan RP, Gittins M, Siddals KW, et al. Atorvastatin administration is associated with dose-related changes in IGF bioavailability. Eur J Endocrinol. 2013;168(4):543-548. doi: 10.1530/Eje-12-0844
  17. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a metaanalysis. JAMA. 2011;305(24):2556-2564. doi: 10.1001/Jama.2011.860
  18. Schneider HJ, Friedrich N, Klotsche J, et al. Prediction of incident diabetes mellitus by baseline IGF1 levels. Eur J Endocrinol. 2011;164(2):223-229. doi: 10.1530/Eje-10-0963
  19. Ridker PM, Pradhan A, Macfadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the jupiter trial. Lancet. 2012;380(9841):565-571. doi: 10.1016/S0140-6736(12)61190-8
  20. Erlandsson MC, Doria Medina R, Toyra Silfversward S, Bokarewa MI. Smoking functions as a negative regulator of IGF1 and impairs adipokine network in patients with rheumatoid arthritis. Mediators Inflamm. 2016;2016:3082820. doi: 10.1155/2016/3082820
  21. Kaklamani VG, Linos A, Kaklamani E, et al. Age, sex, and smoking are predictors of circulating insulin-like growth factor 1 and insulin-like growth factor-binding protein 3. J Clin Oncol. 1999;17(3):813-817. doi: 10.1200/Jco.1999.17.3.813

Copyright (c) 2021 Shpagina O.V., Bondarenko I.Z., Kolesnikova G.S.

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