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Prospective, randomized, single-blind comparison of effects of 6 months' treatment with atorvastatin versus pravastatin on leptin and angiogenic factors in patients with coronary artery disease

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Abstract

Leptin has been reported to exert an atherosclerotic effect by regulating expression of angiogenic factors that have been implicated in the pathogenesis of coronary artery disease (CAD). The purpose of this study was to investigate whether lipid-lowering therapy (LLT) with statins could affect leptin levels and angiogenic factors in patients with CAD. This study included 76 patients with CAD and 15 subjects without CAD (non-CAD). CAD patients were randomized to 6 months of intensive LLT with atorvastatin or moderate LLT with pravastatin. Plasma leptin, angiopoetin-2 (Ang-2), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels were measured prior to statin therapy (baseline) and after 6 months. Baseline levels of leptin, Ang-2, HGF and VEGF were higher in the CAD group than in the non-CAD group (all P < 0.05). Treatment with intensive LLT decreased leptin, Ang-2, HGF and VEGF levels, whereas moderate LLT did not change these levels. This study suggests that LLT with atorvastatin decreases leptin levels and angiogenic factors in patients with CAD, possibly contributing to the beneficial effects of LLT with atorvastatin in CAD.

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References

  1. Woods AJ, Stock MJ (1996) Leptin activation in hypothalamus. Nature 381:745

    Article  PubMed  CAS  Google Scholar 

  2. Beltowski J (2006) Leptin and atherosclerosis. Atherosclerosis 189:47–60

    Article  PubMed  CAS  Google Scholar 

  3. Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, Flores-Riveros JR (1998) Biological action of leptin as an angiogenic factor. Science 281:1683–1686

    Article  PubMed  CAS  Google Scholar 

  4. La Cava A, Matarese G (2004) The weight of leptin in immunity. Nat Rev Immunol 4:371–379

    Article  PubMed  CAS  Google Scholar 

  5. Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A, Sattar N (2001) Plasma leptin and the risk of cardiovascular disease in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 104:3052–3056

    Article  PubMed  CAS  Google Scholar 

  6. Lee KW, Lip GYH, Blann AD (2004) Plasma angiopoietin-1, angiopoietin-2, angiopoietin receptor tie-2, and vascular endothelial growth factor levels in acute coronary syndromes. Circulation 110:2355–2360

    Article  PubMed  CAS  Google Scholar 

  7. Satani K, Konya H, Hamaguchi T, Umehara A, Katsuno T, Ishikawa T, Kohri K, Suehiro A, Kakishita E, Namba M (2003) Clinical significance of circulating hepatocyte growth factor, a new risk marker of carotid atherosclerosis in patients with type 2 diabetes. Diabet Med 23:617–622

    Article  Google Scholar 

  8. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN (2004) Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 291:1071–1080

    Article  PubMed  CAS  Google Scholar 

  9. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM (2004) Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 350:1495–1504

    Article  PubMed  CAS  Google Scholar 

  10. Nissen SE (2005) Effect of intensive lipid lowering on progression of coronary atherosclerosis: evidence for an early benefit from the reversal of atherosclerosis with aggressive lipid lowering (REVERSAL) trial. Am J Cardiol 96:61F–68F

    Article  PubMed  CAS  Google Scholar 

  11. Djoba Siawaya JF, Roberts T, Babb C, Black G, Golakai HJ, Stanley K, Bapela NB, Hoal E, Parida S, van Helden P, Walzl G (2008) An evaluation of commercial fluorescent bead-based luminex cytokine assays. PLoS ONE 3:e2535

    Article  PubMed  Google Scholar 

  12. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    PubMed  CAS  Google Scholar 

  13. Soderberg S, Ahren B, Jansson JH, Johnson O, Hallmans G, Asplund K, Olsson T (1999) Leptin is associated with increased risk of myocardial infarction. J Intern Med 246:409–418

    Article  PubMed  CAS  Google Scholar 

  14. Wallerstedt SM, Eriksson AL, Nikiason A, Ohisson C, Hedner T (2004) Serum leptin and myocardial infarction in hypertension. Blood Press 13:243–246

    Article  PubMed  CAS  Google Scholar 

  15. Singhal A, Farooqi SI, Cole TJ, O’Rahilly S, Fewtrell M, Kattenhorn M, Lucas A, Deanfield J (2002) Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease? Circulation 106:1919–1924

    Article  PubMed  CAS  Google Scholar 

  16. Peelman F, Waelput W, Iserentant H, Lavens D, Eyckerman S, Zabeau L, Tavernier J (2004) Leptin: linking adipocyte metabolism with cardiovascular and autoimmune diseases. Prog Lipid Res 43:283–301

    Article  PubMed  CAS  Google Scholar 

  17. Park HY, Kwon HM, Lim HJ, Hong BK, Lee JY, Park BE, Jang Y, Cho SY, Kim HY (2001) Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro. Exp Mol Med 33:95–102

    PubMed  CAS  Google Scholar 

  18. Cao R, Brakenhieim E, Wahlestedt C, Thyberg J, Cao Y (2001) Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc Natl Acad Sci USA 98:6390–6395

    Article  PubMed  CAS  Google Scholar 

  19. Bouloumie A, Marumo T, Lafontan M, Busse R (1999) Leptin induces oxidative stress in human endothelial cells. FASEB J 13:1231–1238

    PubMed  CAS  Google Scholar 

  20. Mavri A, Poredoš P, Suran D, Gaborit B, Juhan-Vague I, Poredoš P (2011) Effect of diet-induced weight loss on endothelial dysfunction: early improvement after the first week of dieting. Heart Vessels 26:31–38

    Article  PubMed  Google Scholar 

  21. Chiba T, Shinozaki S, Nakazawa T, Kawakami A, Ai M, Kaneko E, Kitagawa M, Kondo K, Chait A, Shimokado K (2008) Leptin deficiency suppresses progression of atherosclerosis in apoE-deficient mice. Atherosclerosis 196:68–75

    Article  PubMed  CAS  Google Scholar 

  22. Cao Y (2007) Angiogenesis modulates adipogenesis and obesity. J Clin Invest 117:2362–2368

    Article  PubMed  CAS  Google Scholar 

  23. Davignon J (2004) Beneficial cardiovascular pleiotropic effects of statins. Circulation 109 (Suppl 1):III39–43

    Google Scholar 

  24. Oka H, Ikeda S, Koga S, Miyahara Y, Kohno S (2008) Atorvastatin induces associated reductions in platelet P-selectin, oxidized low-density lipoprotein, and interleukin-6 in patients with coronary artery diseases. Heart Vessel 23:249–256

    Article  Google Scholar 

  25. Zhao SP, Wu ZH (2005) Atorvastatin reduces serum leptin concentration in hypercholesterolemic rabbits. Clin Chim Acta 360:133–140

    Article  PubMed  CAS  Google Scholar 

  26. von Eynatten M, Schneider JG, Hadziselimovic S, Hamman A, Bierhaus A, Nawroth P, Dugi KA (2005) Adipocytokines as a novel target for the anti-inflammatory effect of atorvastatin in patients with type 2 diabetes. Diabetes Care 28:754–755

    Article  Google Scholar 

  27. Shamsuzzaman AS, Winnicki M, Wolk R, Svatikova A, Phillips BG, Davison DE, Berger PB, Somers VK (2004) Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 109:2181–2185

    Article  PubMed  CAS  Google Scholar 

  28. Söderberg S, Colquhoun D, Keech A, Yallop J, Barnes EH, Pollicino C, Simes J, Tonkin AM, Nestel P, Study Investigators LIPID (2008) Leptin, but not adiponectin, is a predictor of recurrent cardiovascular events in men: results from the LIPID study. Int J Obes (Lond) 33:123–130

    Article  Google Scholar 

  29. Strandberg TE, Vanhangen H, Tikkanen MJ (1999) Effect of statins on C-reactive protein in patients with coronary artery disease. Lancet 353:118–119

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by a Grant-in-Aid for General Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture (no. 20590886) and a grant from the Keiryokai Research Foundation (no. 98).

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Correspondence to Mamoru Satoh.

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Takahashi, Y., Satoh, M., Tabuchi, T. et al. Prospective, randomized, single-blind comparison of effects of 6 months' treatment with atorvastatin versus pravastatin on leptin and angiogenic factors in patients with coronary artery disease. Heart Vessels 27, 337–343 (2012). https://doi.org/10.1007/s00380-011-0156-y

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  • DOI: https://doi.org/10.1007/s00380-011-0156-y

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