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• W3146027852 abstract "HomeCirculationVol. 109, No. 5Short-Term Statin Therapy and Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBShort-Term Statin Therapy and Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy Pim van der Harst, Adriaan A. Voors and Dirk J. van Veldhuisen Pim van der HarstPim van der Harst Academic Hospital Groningen, Groningen, the Netherlands Search for more papers by this author , Adriaan A. VoorsAdriaan A. Voors Academic Hospital Groningen, Groningen, the Netherlands Search for more papers by this author and Dirk J. van VeldhuisenDirk J. van Veldhuisen Academic Hospital Groningen, Groningen, the Netherlands Search for more papers by this author Originally published10 Feb 2004https://doi.org/10.1161/01.CIR.0000115211.60667.A6Circulation. 2004;109:e34To the Editor:With great interest we read the article by Node et al1 concerning short-term statin therapy in patients with idiopathic dilated cardiomyopathy (IDC). The demonstrated improvement of left ventricular ejection fraction (LVEF) by simvastatin therapy is intriguing. The authors speculated on several possible mechanisms, including a decrease in plasma cytokines and neurohormones. Although this may certainly have played a role, we think that another potential mechanism should have been discussed. We hypothesize that improvement of LVEF by simvastatin in the present study might be caused by the beneficial effects on myocardial blood flow (MBF) reserve.In healthy subjects with hypercholesterolemia, statin treatment improves MBF reserve, as measured by positron emission tomography.2 In patients with IDC, MBF reserve is impaired in proportion to the severity of heart failure.3,4 Therefore, it is very likely that a decrease of cholesterol levels in patients with IDC will also lead to an improvement of MBF reserve. Whether such an improvement in MBF reserve in patients with IDC automatically translates into an increase in LVEF may be disputed. Nevertheless, recent work from our institution using positron emission tomography has demonstrated that regional impairment of MBF reserve is associated with decreases in contractile reserve and LVEF.4 The observed improvement in LVEF in the study by Node et al1 may well have been caused by improvement of MBF reserve leading to increased LVEF.1 Node K, Fujita M, Kitakaze M, et al. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation. 2003; 108: 839–843.LinkGoogle Scholar2 Gould KL, Martucci JP, Goldberg DI, et al. Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease: a potential noninvasive marker of healing coronary endothelium. Circulation. 1994; 89: 1530–1538.CrossrefMedlineGoogle Scholar3 van den Heuvel AF, van Veldhuisen DJ, van der Wall EE, et al. Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2000; 35: 19–28.CrossrefMedlineGoogle Scholar4 van den Heuvel AF, Bax JJ, Blanksma PK, et al. Abnormalities in myocardial contractility, metabolism and perfusion reserve in non-stenotic coronary segments in heart failure patients. Cardiovasc Res. 2002; 55: 97–103.CrossrefMedlineGoogle ScholarcirculationahaCirculationCirculationCirculation0009-73221524-4539Lippincott Williams & WilkinsResponseLiao James K., , Node Koichi, , Fujita Masashi, , Hori Masatsugu, , and Kitakaze Masafumi, 10022004We are pleased that Dr van Veldhuisen and colleagues found our study of interest.1 Although we speculated in our paper that the beneficial effects of statins on cardiac function in patients with idiopathic dilated cardiomyopathy may be due to improvements in endothelial function, neurohormonal imbalance, and inflammation, we agree that another potential mechanism may be due to improvement in myocardial blood flow (MBF) reserve. In experimental animals, we have found that statins upregulate coronary vascular endothelial nitric oxide production2 and decrease myocardial oxygen consumption.3 These effects could be the basis for the observed improvement in MBF reserve in hypercholesterolemic subjects with idiopathic dilated cardiomyopathy treated with statins.We would like to emphasize, however, that improvements in cardiac function with statin treatment probably occur independently of cholesterol lowering. Indeed, we have recently found that statins increase myocardial capillary density in normal and cardiomyopathic Syrian hamsters without significant alterations in serum cholesterol levels.4 This may reflect a preservation of the coronary microvasculature due to a direct vascular protective effect of statins and is consistent with recent studies demonstrating direct angiogenic effect of statins on ischemic limb vasculature.5 The ability of statins, therefore, to positively affect the coronary microvasculature may contribute, in part, to the observed improvements in MBF reserve and myocardial function in patients with heart failure. eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Wasim R, Ansari T, Ahsan F, Siddiqui M, Singh A, Shariq M and Parveen S (2022) Pleiotropic Benefits of Statins in Cardiovascular Diseases, Drug Research, 10.1055/a-1873-1978, 72:09, (477-486), Online publication date: 1-Nov-2022. Wang X, Zhang T, Hu L, Sun S, Zhang W, Sun Z, Shen L and He B (2017) Comparison of Effects of Different Statins on Contrast-Induced Acute Kidney Injury in Rats: Histopathological and Biochemical Findings, Oxidative Medicine and Cellular Longevity, 10.1155/2017/6282486, 2017, (1-10), . Desmaele S, Cornu P, Barbé K, Brouns R, Steurbaut S and Dupont A (2015) Relationship between pre-stroke cardiovascular medication use and stroke severity, European Journal of Clinical Pharmacology, 10.1007/s00228-015-2001-1, 72:4, (495-502), Online publication date: 1-Apr-2016. Stravodimou A and Voutsadakis I (2013) Statin use and peripheral blood progenitor cells mobilization in patients with multiple myeloma, Clinical and Translational Oncology, 10.1007/s12094-013-1046-9, 16:1, (85-90), Online publication date: 1-Jan-2014. Park K, Kim J, Noh E, Yu H, Kim S, Kim S, Kim S and Chung E (2013) Methyl β-cyclodextrin activates eNOS-cGMP pathway in endothelial cells, Molecular & Cellular Toxicology, 10.1007/s13273-013-0030-3, 9:3, (235-241), Online publication date: 1-Sep-2013. Jacob R, Walter M, Self-Medlin Y and Mason R (2013) Atorvastatin Active Metabolite Inhibits Oxidative Modification of Small Dense Low-Density Lipoprotein, Journal of Cardiovascular Pharmacology, 10.1097/FJC.0b013e318294998d, 62:2, (160-166), Online publication date: 1-Aug-2013. Wei Y, Li X, Xiong J, Abais J, Xia M, Boini K, Zhang Y and Li P (2013) Attenuation by Statins of Membrane Raft-Redox Signaling in Coronary Arterial Endothelium, Journal of Pharmacology and Experimental Therapeutics, 10.1124/jpet.112.201442, 345:2, (170-179), Online publication date: 1-May-2013. Won H, Kim S, Bang O, Lee S, Huh W, Ko J, Kim H, McLeod H, O’Connell T, Kim J and Lee S (2011) Differentially expressed genes in human peripheral blood as potential markers for statin response, Journal of Molecular Medicine, 10.1007/s00109-011-0818-3, 90:2, (201-211), Online publication date: 1-Feb-2012. Krikorian R, Eliassen J, Boespflug E, Nash T and Shidler M (2013) Improved cognitive-cerebral function in older adults with chromium supplementation, Nutritional Neuroscience, 10.1179/147683010X12611460764084, 13:3, (116-122), Online publication date: 1-Jun-2010. Roura S and Bayes-Genis A (2009) Vascular dysfunction in idiopathic dilated cardiomyopathy, Nature Reviews Cardiology, 10.1038/nrcardio.2009.130, 6:9, (590-598), Online publication date: 1-Sep-2009. Igarashi J and Michel T (2009) Sphingosine-1-phosphate and modulation of vascular tone, Cardiovascular Research, 10.1093/cvr/cvp064, 82:2, (212-220), Online publication date: 1-May-2009., Online publication date: 1-May-2009. Mason R, Kubant R, Heeba G, Jacob R, Day C, Medlin Y, Funovics P and Malinski T (2007) Synergistic Effect of Amlodipine and Atorvastatin in Reversing LDL-Induced Endothelial Dysfunction, Pharmaceutical Research, 10.1007/s11095-007-9491-1, 25:8, (1798-1806), Online publication date: 1-Aug-2008. Fujii T, Onimaru M, Yonemitsu Y, Kuwano H and Sueishi K (2008) Statins restore ischemic limb blood flow in diabetic microangiopathy via eNOS/NO upregulation but not via PDGF-BB expression, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00149.2008, 294:6, (H2785-H2791), Online publication date: 1-Jun-2008. Bifulco M, Malfitano A and Marasco G (2014) Potential therapeutic role of statins in neurological disorders, Expert Review of Neurotherapeutics, 10.1586/14737175.8.5.827, 8:5, (827-837), Online publication date: 1-May-2008. Carnicer R, Navarro M, Guillén N, Arbonés-Mainar J, Surra J, Acín S and Osada J (2008) Simvastatin reverses the hypertension of heterozygous mice lacking cystathionine β-synthase and apolipoprotein A-I, Naunyn-Schmiedeberg's Archives of Pharmacology, 10.1007/s00210-007-0247-6, 377:1, (35-43), Online publication date: 1-Mar-2008. (2008) Clinical Management of the Metabolic Syndrome The Metabolic Syndrome in Clinical Practice, 10.1007/978-1-84628-911-8_6, (154-223), . Cleaveland S, Haydon D and Taylor L (2007) Overviews of Pathogen Emergence: Which Pathogens Emerge, When and Why? Wildlife and Emerging Zoonotic Diseases: The Biology, Circumstances and Consequences of Cross-Species Transmission, 10.1007/978-3-540-70962-6_5, (85-111), . Webby R, Webster R and Richt J (2007) Influenza Viruses in Animal Wildlife Populations Wildlife and Emerging Zoonotic Diseases: The Biology, Circumstances and Consequences of Cross-Species Transmission, 10.1007/978-3-540-70962-6_4, (67-83), . Douglas K, Sattar N and Kitas G (2006) Potential role of statins and PPARs in rheumatoid arthritis, Future Rheumatology, 10.2217/17460816.1.2.259, 1:2, (259-274), Online publication date: 1-Apr-2006. Erdös B, Snipes J, Tulbert C, Katakam P, Miller A and Busija D (2006) Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00804.2005, 290:3, (H1264-H1270), Online publication date: 1-Mar-2006. Abeles A and Pillinger M (2006) Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?, Arthritis & Rheumatism, 10.1002/art.21521, 54:2, (393-407), Online publication date: 1-Feb-2006. Howes L (2006) The effects of lipid-lowering drug therapy on cardiovascular responsiveness in type 2 diabetic patients, Diabetes, Obesity and Metabolism, 10.1111/j.1463-1326.2005.00469.x, 8:1, (8-14), Online publication date: 1-Jan-2006. Becker S and Palsson B (2005) Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation, BMC Microbiology, 10.1186/1471-2180-5-8, 5:1, Online publication date: 1-Dec-2005. Juturu V and Komorowski J (2004) Dietary chromium picolinate: Efficacy and safety, The Journal of Trace Elements in Experimental Medicine, 10.1002/jtra.20008, 17:4, (291-293), . February 10, 2004Vol 109, Issue 5 Advertisement Article InformationMetrics https://doi.org/10.1161/01.CIR.0000115211.60667.A6PMID: 14769695 Originally publishedFebruary 10, 2004 PDF download Advertisement" @default.
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