Skip to main content
SpringerLink
Log in

Do Statins Have a Role in the Management of Diastolic Dysfunction?

  • Current Opinion
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Diastolic dysfunction of the left ventricle is an increasingly recognized clinical entity that may in some cases cause overt congestive heart failure. Currently, treatment of these patients is based on limited studies in patients with symptomatic heart failure. HMG-CoA reductase inhibitor (statin) drugs, which are primarily used for the treatment of hyperlipidemia, have been shown to have additional pharmacologic properties that may be beneficial in other disease states such as heart failure. Here, we wish to review the current knowledge of the mechanism of action of statins and the probable implications for asymptomatic patients with diastolic dysfunction. We discuss the causes and settings of diastolic dysfunction, the potential role of statin therapy in the treatment of diastolic dysfunction, and potential mechanisms by which statins may show benefit. The use of statins in the setting of diastolic dysfunction, both for treatment of established heart failure as well as to prevent progression of subclinical disease to overt symptomatic expression, is an area of substantial research interest with direct clinical application.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I

Similar content being viewed by others

References

  1. Kwan ML, Habel LA, Flick ED, et al. Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors. Breast Cancer Res Treat 2008 Jun; 109 (3): 573–9.

    Article  PubMed  CAS  Google Scholar 

  2. Khurana V, Bejjanki HR, Caldito G, et al. Statins reduce the risk of lung cancer in humans: a large case-control study of US veterans. Chest 2007 May; 131 (5): 1282–8.

    Article  PubMed  Google Scholar 

  3. Ishida W, Kajiwara T, Ishii M, et al. Decrease in mortality rate of chronic obstructive pulmonary disease (COPD) with statin use: a population-based analysis in Japan. Tohoku J Exp Med 2007 Jul; 212 (3): 265–73.

    Article  PubMed  Google Scholar 

  4. Girgis RE, Mozammel S, Champion HC, et al. Regression of chronic hypoxic pulmonary hypertension by simvastatin. Am J Physiol Lung Cell Mol Physiol 2007 May; 292 (5): L1105–10.

    Article  PubMed  CAS  Google Scholar 

  5. Chua D, Tsang RS, Kuo IF. The role of statin therapy in sepsis. Ann Pharmacother 2007 Apr; 41 (4): 647–52.

    Article  PubMed  Google Scholar 

  6. Kanda H, Yokota K, Kohno C, et al. Effects of low-dosage simvastatin on rheumatoid arthritis through reduction of Th1/Th2 and CD4/CD8 ratios. Mod Rheumatol 2007; 17 (5): 364–8.

    Article  PubMed  CAS  Google Scholar 

  7. Bauersachs J, Hiss K, Fraccarollo D, et al. Simvastatin improves left ventricular function after myocardial infarction in hypercholesterolemic rabbits by anti-inflammatory effects. Cardiovasc Res 2006 Dec 1; 72 (3): 438–46.

    Article  PubMed  CAS  Google Scholar 

  8. Raina A, Pickering T, Shimbo D. Statin use in heart failure: a cause for concern? Am Heart J 2006 Jul; 152 (1): 39–49.

    Article  PubMed  CAS  Google Scholar 

  9. Palmieri V, Russo C, Palmieri EA, et al. Isolated left ventricular diastolic dysfunction: implications for exercise left ventricular performance in patients without congestive heart failure. J Am Soc Echocardiogr 2006 May; 19 (5): 491–8.

    Article  PubMed  Google Scholar 

  10. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part I. Diagnosis, prognosis, and measurements of diastolic function. Circulation 2002; 105: 1387–93.

    Article  PubMed  Google Scholar 

  11. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part II. Causal mechanisms and treatment. Circulation 2002 Mar 26; 105 (12): 1503–8.

    Article  PubMed  Google Scholar 

  12. Arias MA, Sanchez-Gila J. Statins and diastolic heart failure. Int J Cardiol 2007 Jan 31; 115(1): 91–2.

    Article  PubMed  Google Scholar 

  13. Zile MR. Treating diastolic heart failure with statins: “phat” chance for pleiotropic benefits. Circulation 2005 Jul 19; 112 (3): 300–3.

    Article  PubMed  Google Scholar 

  14. Chen Y, Ohmori K, Mizukawa M, et al. Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes. Circ J 2007 Jan; 71 (1): 144–52.

    Article  PubMed  CAS  Google Scholar 

  15. Entok E, Unalir A, Cavusoglu Y, et al. Long-term effects of antilipidaemic therapy on left ventricular function in patients with dyslipidaemia: multigated radio-nuclide ventriculography study. Nucl Med Commun 2005 Sep; 26 (9): 773–9.

    Article  PubMed  CAS  Google Scholar 

  16. Fukuta H, Sane DC, Brucks S, et al. Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 2005 Jul 19; 112 (3): 357–63.

    Article  PubMed  CAS  Google Scholar 

  17. Silver MA, Langsjoen PH, Szabo S, et al. Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction. Am J Cardiol 2004 Nov 15; 94 (10): 1306–10.

    Article  PubMed  CAS  Google Scholar 

  18. Okura H, Asawa K, Kubo T, et al. Impact of statin therapy on systemic inflammation, left ventricular systolic and diastolic function and prognosis in low risk ischemic heart disease patients without history of congestive heart failure. Intern Med 2007; 46 (17): 1337–43.

    Article  PubMed  Google Scholar 

  19. Endo A, Kuroda M, Tanzawa K. Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B fungal metabolites, having hypocholesterolemic activity. FEBS Lett 1976 Dec 31; 72 (2): 323–6.

    Article  PubMed  CAS  Google Scholar 

  20. Van Aelst L, D’Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev 1997 Sep 15; 11 (18): 2295–322.

    Article  PubMed  Google Scholar 

  21. Moon SY, Zheng Y. Rho GTPase-activating proteins in cell regulation. Trends Cell Biol 2003 Jan; 13 (1): 13–22.

    Article  PubMed  CAS  Google Scholar 

  22. Inoue I, Goto S, Mizotani K, et al. Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells. Life Sci 2000 Jul 14; 67 (8): 863–76.

    Article  PubMed  CAS  Google Scholar 

  23. Inoue I, Itoh F, Aoyagi S, et al. Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun 2002 Jan 11; 290 (1): 131–9.

    Article  PubMed  CAS  Google Scholar 

  24. Roglans N, Sanguino E, Peris C, et al. Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. J Pharmacol Exp Ther 2002 Jul; 302 (1): 232–9.

    Article  PubMed  CAS  Google Scholar 

  25. Ortego M, Bustos C, Hernández-Presa MA, et al. Atorvastatin reduces NF-kappaB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. Atherosclerosis 1999 Dec; 147 (2): 253–61.

    Article  PubMed  CAS  Google Scholar 

  26. Garcia MJ, Thomas JD, Klein AL. New Doppler echocardiographic applications for the study of diastolic function. J Am Coll Cardiol 1998 Oct; 32 (4): 865–75.

    Article  PubMed  CAS  Google Scholar 

  27. Redfield MM, Jacobsen SJ, Burnett JC, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003; 289: 194–202.

    Article  PubMed  Google Scholar 

  28. Little CW. Assessment of normal and abnormal cardiac function. In: Braunwald E, Zipes D, Libby P, editors. Heart disease: a textbook of cardiovascular medicine. 6th ed. Orlando (FL): WB Saunders Company, 2001: 479–500.

    Google Scholar 

  29. Alpert NR, LeWinter M, Mulieri LA, et al. Chemomechanical energy transduction in the failing heart. Heart Failure Rev 1999 Oct; 4 (3): 1382–4147.

    Article  Google Scholar 

  30. Kramer BK, Smith TW, Kelly RA. Endothelin and increased contractility in adult rat ventricular myocytes: role of intracellular alkalosis induced by activation of the protein kinase C-dependent Na(+)-H+ exchanger. Circ Res 1991 Jan; 68 (1): 269–79.

    Article  PubMed  CAS  Google Scholar 

  31. Endoh M, Fujita S, Yang HT, et al. Endothelin: receptor subtypes, signal transduction, regulation of Ca2+ transients and contractility in rabbit ventricular myocardium. Life Sci 1998; 62 (17–18): 1485–9.

    Article  PubMed  CAS  Google Scholar 

  32. Apstein CS, Gravino FN, Haudenschild CC. Determinants of a protective effect of glucose and insulin on the ischemic myocardium: effects on contractile function, diastolic compliance, metabolism, and ultrastructure during ischemia and reperfusion. Circ Res 1983 May; 52 (5): 515–26.

    Article  PubMed  CAS  Google Scholar 

  33. Varma N, Morgan JP, Apstein CS. Mechanisms underlying ischemic diastolic dysfunction: relation between rigor, calcium homeostasis, and relaxation rate. Am J Physiol Heart Circ Physiol 2003 Mar; 284 (3): H758–71.

    PubMed  CAS  Google Scholar 

  34. Zheng X, Hu SJ. Effects of simvastatin on cardiac performance and expression of sarcoplasmic reticular calcium regulatory proteins in rat heart. Acta Pharmacol Sin 2005 Jun; 26 (6): 696–704.

    Article  PubMed  CAS  Google Scholar 

  35. Saka M, Obata K, Ichihara S, et al. Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure. J Cardiovasc Pharmacol 2006 Jun; 47 (6): 770–9.

    Article  PubMed  CAS  Google Scholar 

  36. Jguirim-Souissi I, Jelassi A, Addad F, et al. Plasma metalloproteinase-12 and tissue inhibitor of metalloproteinase-1 levels and presence, severity, and outcome of coronary artery disease. Am J Cardiol 2007 Jul 1; 100 (1): 23–7.

    Article  PubMed  CAS  Google Scholar 

  37. Chen J, Mehta JL. Angiotensin II-mediated oxidative stress and procollagen-1 expression in cardiac fibroblasts: blockade by pravastatin and pioglitazone. Am J Physiol Heart Circ Physiol 2006 Oct; 291 (4): H1738–45.

    Article  PubMed  CAS  Google Scholar 

  38. Riessen R, Axel DI, Fenchel M, et al. Effect of HMG-CoA reductase inhibitors on extracellular matrix expression in human vascular smooth muscle cells. Basic Res Cardiol 1999 Oct; 94 (5): 322–32.

    Article  PubMed  CAS  Google Scholar 

  39. Graf K, Kappert K, Stawowy P, et al. Statins regulate alpha2beta1-integrin expression and collagen I-dependent functions in human vascular smooth muscle cells. J Cardiovasc Pharmacol 2003 Jan; 41 (1): 89–96.

    Article  PubMed  CAS  Google Scholar 

  40. Jones SP, Teshima Y, Akao M, et al. Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ Res 2003 Oct 17; 93 (8): 697–9.

    Article  PubMed  CAS  Google Scholar 

  41. Lee TM, Lin MS, Tsai CH, et al. Effects of pravastatin on ventricular remodeling by activation of myocardial KATP channels in infarcted rats: role of 70-kDa S6 kinase. Basic Res Cardiol 2007 Mar; 102 (2): 171–82.

    Article  PubMed  CAS  Google Scholar 

  42. Lee TM, Chou TF, Tsai CH. Effects of pravastatin on cardiomyocyte hypertrophy and ventricular vulnerability in normolipidemic rats after myocardial infarction. J Mol Cell Cardiol 2003 Dec; 35 (12): 1449–59.

    Article  PubMed  CAS  Google Scholar 

  43. Sola S, Mir MQ, Lerakis S, et al. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol 2006 Jan 17; 47 (2): 332–7.

    Article  PubMed  CAS  Google Scholar 

  44. Ozkiris A, Erkilic K, Koc A, et al. Effect of atorvastatin on ocular blood flow velocities in patients with diabetic retinopathy. Br J Ophthalmol 2007 Jan; 91 (1): 69–73.

    Article  PubMed  CAS  Google Scholar 

  45. Nemes A, Neu K, Forster T, et al. Relationship between hypercholesterolemia, lipid-lowering therapy and coronary flow velocity reserve evaluated by stress transesophageal echocardiography in patients with a negative coronary angiogram. Echocardiography 2004 Jan; 21 (1): 37–41.

    Article  PubMed  Google Scholar 

  46. Brutsaert DL. Cardiac endothelial-myocardial signaling: its role in cardiac growth, contractile performance, and rhythmicity. Physiol Rev 2003 Jan; 83 (1): 59–115.

    PubMed  CAS  Google Scholar 

  47. Farhangkhoee H, Khan ZA, Kaur H, et al. Vascular endothelial dysfunction in diabetic cardiomyopathy: pathogenesis and potential treatment targets. Pharmacol Ther 2006 Aug; 111 (2): 384–99.

    Article  PubMed  CAS  Google Scholar 

  48. Rydén L, Standl E, Bartnik M, et al., on behalf of the Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary: the Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 2007 Jan; 28 (1): 88–136.

    Article  PubMed  Google Scholar 

  49. Ii M, Nishimura H, Kusano KF, et al. Neuronal nitric oxide synthase mediates statin-induced restoration of vasa nervorum and reversal of diabetic neuropathy. Circulation 2005 Jul 5; 112 (1): 93–102.

    Article  PubMed  CAS  Google Scholar 

  50. Schmeer C, Kretz A, Isenmann S. Therapeutic potential of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors for the treatment of retinal and eye diseases. CNS Neurol Disord Drug Targets 2007 Aug; 6 (4): 282–7.

    Article  PubMed  CAS  Google Scholar 

  51. Yamagishi S, Nakamura K, Matsui T, et al. Potential utility of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in diabetic retinopathy. Med Hypotheses 2006; 66 (5): 1019–21.

    Article  PubMed  CAS  Google Scholar 

  52. Danesh FR, Sadeghi MM, Amro N, et al. 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of Rho GTPase/ p21 signaling pathway: implications for diabetic nephropathy. Proc Natl Acad Sci U S A 2002 Jun 11; 99 (12): 8301–5.

    Article  PubMed  CAS  Google Scholar 

  53. Ota T, Takamura T, Ando H, et al. Preventive effect of cerivastatin on diabetic nephropathy through suppression of glomerular macrophage recruitment in a rat model. Diabetologia 2003 Jun; 46 (6): 843–51.

    Article  PubMed  CAS  Google Scholar 

  54. Tonolo G, Melis MG, Formato M, et al. Additive effects of Simvastatin beyond its effects on LDL cholesterol in hypertensive type 2 diabetic patients. Eur J Clin Invest 2000 Nov; 30 (11): 980–7.

    Article  PubMed  CAS  Google Scholar 

  55. Strazzullo P, Kerry SM, Barbato A, et al. Do statins reduce blood pressure? A meta-analysis of randomized, controlled trials. Hypertension 2007 Apr; 49 (4): 792–8.

    Article  PubMed  CAS  Google Scholar 

  56. Minami M, Atarashi K, Ishiyama A, et al. Effects of cholesterol-lowering therapy on pressor hyperreactivity to stress in hypercholesterolemic patients. Hypertens Res 2003 Apr; 26 (4): 273–80.

    Article  PubMed  CAS  Google Scholar 

  57. Tonstad S, Furu K, Rosvold EO, et al. Determinants of control of high blood pressure: the Oslo Health Study 2000–2001. Blood Press 2004; 13 (6): 343–9.

    Article  PubMed  Google Scholar 

  58. Terzoli L, Mircoli L, Raco R, et al. Lowering of elevated ambulatory blood pressure by HMG-CoA reductase inhibitors. J Cardiovasc Pharmacol 2005 Sep; 46 (3): 310–5.

    Article  PubMed  CAS  Google Scholar 

  59. Tonelli M, Sacks F, Pfeffer M, et al. Effect of pravastatin on blood pressure in people with cardiovascular disease. J Hum Hypertens 2006 Aug; 20 (8): 560–5.

    Article  PubMed  CAS  Google Scholar 

  60. Borghi C, Dormi A, Veronesi M, et al., for the Brisighella Heart Study Working Party. Association between different lipid-lowering treatment strategies and blood pressure control in the Brisighella Heart Study. Am Heart J 2004 Aug; 148 (2): 285–92.

    Article  PubMed  CAS  Google Scholar 

  61. Leibovitz E, Hazanov N, Zimlichman R, et al. Treatment with atorvastatin improves small artery compliance in patients with severe hypercholesterolemia. Am J Hypertens 2001 Nov; 14 (11 Pt 1): 1096–8.

    Article  PubMed  CAS  Google Scholar 

  62. Kanbay M, Yildirir A, Bozbas H, et al. Statin therapy helps to control blood pressure levels in hypertensive dyslipidemic patients. Ren Fail 2005; 27 (3): 297–303.

    PubMed  CAS  Google Scholar 

  63. Borghi C, Prandin MG, Costa FV, et al. Use of statins and blood pressure control in treated hypertensive patients with hypercholesterolemia. J Cardiovasc Pharmacol 2000 Apr; 35 (4): 549–55.

    Article  PubMed  CAS  Google Scholar 

  64. Danaoglu Z, Kultursay H, Kayikcioglu M, et al. Effect of statin therapy added to ACE-inhibitors on blood pressure control and endothelial functions in normolipidemic hypertensive patients. Anadolu Kardiyol Derg 2003 Dec; 3 (4): 331–7.

    PubMed  Google Scholar 

  65. Ferrier KE, Muhlmann MH, Baguet JP, et al. Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension. J Am Coll Cardiol 2002 Mar 20; 39 (6): 1020–5.

    Article  PubMed  CAS  Google Scholar 

  66. Zanchetti A, Crepaldi G, Bond MG, et al. Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study: PHYLLIS study group. J Hypertens 2001 Jan; 19 (1): 79–88.

    Article  PubMed  CAS  Google Scholar 

  67. Dilaveris P, Giannopoulos G, Riga M, et al. Beneficial effects of statins on endothelial dysfunction and vascular stiffness. Curr Vasc Pharmacol 2007 Jul; 5 (3): 227–37.

    Article  PubMed  CAS  Google Scholar 

  68. Verreth W, De Keyzer D, Davey PC, et al. Rosuvastatin restores superoxide dismutase expression and inhibits accumulation of oxidized LDL in the aortic arch of obese dyslipidemic mice. Br J Pharmacol 2007 Jun; 151 (3): 347–55.

    Article  PubMed  CAS  Google Scholar 

  69. Monetti M, Canavesi M, Camera M, et al. Rosuvastatin displays anti-atherothrombotic and anti-inflammatory properties in apoE-deficient mice. Pharmacol Res 2007 May; 55 (5): 441–9.

    Article  PubMed  CAS  Google Scholar 

  70. Abhayaratna WP, Barnes ME, O’Rourke MF, et al. Relation of arterial stiffness to left ventricular diastolic function and cardiovascular risk prediction in patients > or = 65 years of age. Am J Cardiol 2006 Nov 15; 98 (10): 1387–92.

    Article  PubMed  Google Scholar 

  71. Yambe M, Tomiyama H, Hirayama Y, et al. Arterial stiffening as a possible risk factor for both atherosclerosis and diastolic heart failure. Hypertens Res 2004 Sep; 27 (9): 625–31.

    Article  PubMed  Google Scholar 

  72. John S, Delles C, Jacobi J, et al. Rapid improvement of nitric oxide bioavailability after lipid-lowering therapy with cerivastatin within two weeks. J Am Coll Cardiol 2001 Apr; 37 (5): 1351–8.

    Article  PubMed  CAS  Google Scholar 

  73. John S, Schlaich M, Langenfeld M, et al. Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study. Circulation 1998 Jul 21; 98 (3): 211–6.

    Article  PubMed  CAS  Google Scholar 

  74. Hernández-Perera O, Perez-Sala D, Navarro-Antolin J, et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest 1998 Jun 15; 101 (12): 2711–9.

    Article  PubMed  Google Scholar 

  75. Aikawa M, Rabkin E, Sugiyama S, et al. An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro. Circulation 2001 Jan 16; 103 (2): 276–83.

    Article  PubMed  CAS  Google Scholar 

  76. Crisby M, Nordin-Fredriksson G, Shah PK, et al. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 2001 Feb 20; 103 (7): 926–33.

    Article  PubMed  CAS  Google Scholar 

  77. Kang L, Fang Q, Hu SJ. Regulation of phospholamban and sarcoplasmic reticulum Ca2+-ATPase by atorvastatin: implication for cardiac hypertrophy. Arch Pharm Res 2007 May; 30 (5): 596–602.

    Article  PubMed  CAS  Google Scholar 

  78. Saka M, Obata K, Ichihara S, et al. Attenuation of ventricular hypertrophy and fibrosis in rats by pitavastatin: potential role of the RhoA-extracellular signal-regulated kinase-serum response factor signalling pathway. Clin Exp Pharmacol Physiol 2006 Dec; 33 (12): 1164–71.

    Article  PubMed  CAS  Google Scholar 

  79. Senthil V, Chen SN, Tsybouleva N, et al. Prevention of cardiac hypertrophy by atorvastatin in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circ Res 2005 Aug 5; 97 (3): 285–92.

    Article  PubMed  CAS  Google Scholar 

  80. Rasburg S, Pras M, Lidar M, et al. Extremely high dose pravastatin may suppress amyloidogenesis in a mouse model. Ann Rheum Dis 2002 Jun; 61 (6): 572.

    Article  Google Scholar 

  81. Petanceska SS, DeRosa S, Sharma A, et al. Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol. J Mol Neurosci 2003; 20 (3): 395–406.

    Article  PubMed  CAS  Google Scholar 

  82. Kiechl S, Willeit J, Egger G, et al. Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 1997 Nov 18; 96 (10): 3300–7.

    Article  PubMed  CAS  Google Scholar 

  83. Iribarren C, Sempos CT, Eckfeldt JH, et al. Lack of association between ferritin level and measures of LDL oxidation: the ARIC study. Atherosclerosis risk in communities. Atherosclerosis 1998 Jul; 139 (1): 189–95.

    Article  PubMed  CAS  Google Scholar 

  84. de Sotomayor MA, Perez-Guerrero C, Herrrera MD, et al. Improvement of age-related endothelial dysfunction by simvastatin: effect on NO and COX pathways. Br J Pharmacol 2005 Dec; 146 (8): 1130–8.

    Article  PubMed  Google Scholar 

  85. Brouilette SW, Moore JS, McMahon AD, et al., West of Scotland Coronary Prevention Study Group. 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 Jan 13; 369 (9556): 107–14.

    Article  PubMed  CAS  Google Scholar 

  86. Ii M, Losordo DW. Statins and the endothelium. Vascul Pharmacol 2007 Jan; 46 (1): 1–9.

    Article  PubMed  CAS  Google Scholar 

  87. Jasińska M, Owczarek J, Orszulak-Michalak D. Statins: a new insight into their mechanisms of action and consequent pleiotropic effects. Pharmacol Rep 2007 Sep–Oct; 59 (5): 483–99.

    PubMed  Google Scholar 

  88. Mann DL, McMurray JJ, Packer M, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 2004 Apr 6; 109 (13): 1594–602.

    Article  PubMed  CAS  Google Scholar 

  89. Kiliszek M, Burzyńska B, Styczyński G, et al. A1166C polymorphism of the angiotensin AT1 receptor (AT1R) gene alters endothelial response to statin treatment. Clin Chem Lab Med 2007; 45 (7): 839–42.

    Article  PubMed  CAS  Google Scholar 

  90. Spyridopoulos I, Haendeler J, Urbich C, et al. Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation 2004 Nov 9; 110 (19): 3136–42.

    Article  PubMed  CAS  Google Scholar 

  91. Assmus B, Urbich C, Aicher A, et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Circ Res 2003 May 16; 92 (9): 1049–55.

    Article  PubMed  CAS  Google Scholar 

  92. Haendeler J, Hoffmann J, Diehl JF, et al. Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells. Circ Res 2004 Apr 2; 94 (6): 768–75

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Mid America Cardiology, The University of Kansas Hospital and Medical Center, G600 KU Medical Center, Mail Stop 4023, 3901 Rainbow Boulevard, Kansas City, KS, 66160-7200, USA

    Mazda Biria &  James Vaceks

  2. School of Pharmacy, The University of Kansas Hospital and Medical Center, Kansas City, Kansas, USA

    Patricia A. Howard

Authors
  1. Mazda Biria
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patricia A. Howard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James Vaceks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James Vaceks.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Biria, M., Howard, P.A. & Vaceks, J. Do Statins Have a Role in the Management of Diastolic Dysfunction?. Am J Cardiovasc Drugs 8, 297–303 (2008). https://doi.org/10.2165/00129784-200808050-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00129784-200808050-00002

Keywords

Search

Navigation