CLINICAL RESEARCH: HEART FAILURE
Atorvastatin Improves Left Ventricular Systolic Function and Serum Markers of Inflammation in Nonischemic Heart Failure
Srikanth Sola, MD*,
Muhammad Q.S. Mir, MD*,
Stamatios Lerakis, MD, FACC,
Neeraj Tandon, MD, FACC and
Bobby V. Khan, MD, PhD*,*
* Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia
Division of Cardiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
Manuscript received March 24, 2005;
revised manuscript received June 6, 2005,
accepted June 14, 2005.
* Reprint requests and correspondence to: Dr. Bobby V. Khan, Division of Cardiology, Department of Medicine, Emory University School of Medicine, 69 Jesse Hill Drive SE, C233, Atlanta, Georgia 30303. (Email: bkhan{at}emory.edu).
OBJECTIVES: This study examined the effect of statin therapy on vascular markers of inflammation and echocardiographic findings in patients with nonischemic forms of cardiomyopathy.
BACKGROUND: Despite advances in therapy, morbidity and mortality from heart failure (HF) remain high. We wished to determine whether treatment with atorvastatin affects left ventricular (LV) systolic function and markers of inflammation in patients with nonischemic HF.
METHODS: A total of 108 patients with nonischemic HF and a left ventricular ejection fraction (LVEF)  35% were randomized to either atorvastatin 20 mg/day or placebo in a double-blinded fashion for a 12-month period. The LVEF and LV end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were determined by echocardiography. Serum markers of inflammation and oxidation were also measured.
RESULTS: The LVEF increased from 0.33 ± 0.05 to 0.37 ± 0.04 (p = 0.01) in the atorvastatin group over the 12-month follow-up period, whereas those patients in the placebo group experienced a decline in ejection fraction during the same time period. In addition, LVEDD was reduced from 57.1 ± 5.9 mm to 53.4 ± 5.1 mm (p = 0.007) and LVESD was reduced from 42.4 ± 3.8 mm to 39.1 ± 3.8 mm (p = 0.02) in the cohort of patients treated with atorvastatin; these dimensions increased in the placebo group. There was an increase in erythrocyte superoxide dismutase (E-SOD) activity, and there were significant reductions in serum levels of high sensitivity C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-alpha receptor II (TNF- RII) in the atorvastatin group.
CONCLUSIONS: The use of atorvastatin in patients with nonischemic HF improves LVEF and attenuates adverse LV remodeling. The effects on soluble levels of several inflammatory markers with atorvastatin suggest, in part, mechanisms by which statins might exert their beneficial effects in nonischemic HF.
|
Abbreviations and Acronyms
| | CAD = coronary artery disease | | E-SOD = erythrocyte superoxide dismutase | | HDL = high-density lipoprotein | | HF = heart failure | | hsCRP = high sensitivity C-reactive protein | | IL = interleukin | | LDL = low-density lipoprotein | | LV = left ventricle/ventricular | | LVEDD = left ventricular end-diastolic diameter | | LVEF = left ventricular ejection fraction | | LVESD = left ventricular end-systolic diameter | | TNF- RII = tumor necrosis factor-alpha receptor II |
|
Related Article
-
The Emerging Role of Statins in the Treatment of Heart Failure
- Kumudha Ramasubbu and Douglas L. Mann
J. Am. Coll. Cardiol. 2006 47: 342-344.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
M. Alberton, P. Wu, E. Druyts, M. Briel, and E. J. Mills
Adverse events associated with individual statin treatments for cardiovascular disease: an indirect comparison meta-analysis
QJM,
February 1, 2012;
105(2):
145 - 157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Weeks, S. A. Glantz, T. De Marco, A. B. Rosen, and K. E. Fleischmann
Secondhand Smoke Exposure and Quality of Life in Patients With Heart Failure
Arch Intern Med,
November 28, 2011;
171(21):
1887 - 1893.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Cai, D. Zheng, Y. Dong, R. Qiu, Y. Huang, Y. Song, Z. Jiang, S. Rao, X. Liao, J. Kuang, et al.
Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction
Acta Biochim Biophys Sin,
November 1, 2011;
43(11):
857 - 866.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Chow, S. A. O'Barr, J. Peng, E. Chew, F. Pak, R. Quist, P. Patel, J. H. Patterson, and J. T. Heywood
Modulation of Novel Cardiorenal and Inflammatory Biomarkers by Intravenous Nitroglycerin and Nesiritide in Acute Decompensated Heart Failure: An Exploratory Study
Circ Heart Fail,
July 1, 2011;
4(4):
450 - 455.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Rahimi, J. Emberson, P. McGale, W. Majoni, A. Merhi, F. W. Asselbergs, V. Krane, P. W. Macfarlane, and PWM is acting on behalf of the PROSPER Executive
Effect of statins on atrial fibrillation: collaborative meta-analysis of published and unpublished evidence from randomised controlled trials
BMJ,
March 16, 2011;
342(mar16_2):
d1250 - d1250.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mithani, M. Kuskowski, Y. Slinin, A. Ishani, E. McFalls, and S. Adabag
Dose-Dependent Effect of Statins on the Incidence of Acute Kidney Injury After Cardiac Surgery
Ann. Thorac. Surg.,
February 1, 2011;
91(2):
520 - 525.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Mills, P. WU, G. Chong, I. Ghement, S. Singh, E. A. Akl, O. Eyawo, G. Guyatt, O. Berwanger, and M. Briel
Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170 255 patients from 76 randomized trials
QJM,
February 1, 2011;
104(2):
109 - 124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ghio, L. Scelsi, R. Latini, S. Masson, E. Eleuteri, M. Palvarini, O. Vriz, M. Pasotti, M. Gorini, R. Marchioli, et al.
Effects of n-3 polyunsaturated fatty acids and of rosuvastatin on left ventricular function in chronic heart failure: a substudy of GISSI-HF trial
Eur J Heart Fail,
December 1, 2010;
12(12):
1345 - 1353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Hong, S. C. Choi, J. S. Kim, W. J. Shim, S. M. Park, C. M. Ahn, J. H. Park, Y. H. Kim, and D. S. Lim
Low-dose versus moderate-dose atorvastatin after acute myocardial infarction: 8-month effects on coronary flow reserve and angiogenic cell mobilisation
Heart,
May 1, 2010;
96(10):
756 - 764.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Paulus and J. J.M. van Ballegoij
Treatment of Heart Failure With Normal Ejection Fraction: An Inconvenient Truth!
J. Am. Coll. Cardiol.,
February 9, 2010;
55(6):
526 - 537.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kaminsky, A. Suslikov, and E. Kosenko
Specific and Pronounced Impacts of Lisinopril and Lisinopril Plus Simvastatin on Erythrocyte Antioxidant Enzymes
J. Clin. Pharmacol.,
February 1, 2010;
50(2):
180 - 187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-A Chang, Y.-J. Kim, H.-W. Lee, D.-H. Kim, H.-K. Kim, H.-J. Chang, D.-W. Sohn, B.-H. Oh, and Y.-B. Park
Effect of Rosuvastatin on Cardiac Remodeling, Function, and Progression to Heart Failure in Hypertensive Heart With Established Left Ventricular Hypertrophy
Hypertension,
September 1, 2009;
54(3):
591 - 597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Schmechel, M. Grimm, A. El-Armouche, G. Hoppner, A. P. Schwoerer, H. Ehmke, and T. Eschenhagen
Treatment with atorvastatin partially protects the rat heart from harmful catecholamine effects
Cardiovasc Res,
April 1, 2009;
82(1):
100 - 106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Landmesser, K. C. Wollert, and H. Drexler
Potential novel pharmacological therapies for myocardial remodelling
Cardiovasc Res,
February 15, 2009;
81(3):
519 - 527.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Suzuki, V. Iyer, T. Cimato, and J. M. Canty Jr
Pravastatin Improves Function in Hibernating Myocardium by Mobilizing CD133+ and cKit+ Bone Marrow Progenitor Cells and Promoting Myocytes to Reenter the Growth Phase of the Cardiac Cell Cycle
Circ. Res.,
January 30, 2009;
104(2):
255 - 264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Hylek, L. Frison, L. E. Henault, and A. Cupples
Disparate Stroke Rates on Warfarin Among Contemporaneous Cohorts With Atrial Fibrillation: Potential Insights Into Risk From a Comparative Analysis of SPORTIF III Versus SPORTIF V
Stroke,
November 1, 2008;
39(11):
3009 - 3014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ye, Y. Lin, J. R. Perez-Polo, B. F. Uretsky, Z. Ye, B. C. Tieu, and Y. Birnbaum
Phosphorylation of 5-Lipoxygenase at Ser523 by Protein Kinase A Determines Whether Pioglitazone and Atorvastatin Induce Proinflammatory Leukotriene B4 or Anti-Inflammatory 15-Epi-Lipoxin A4 Production
J. Immunol.,
September 1, 2008;
181(5):
3515 - 3523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. H. Samson
The Role of Statin Drugs in the Management of the Peripheral Vascular Patient
Vascular and Endovascular Surgery,
August 1, 2008;
42(4):
352 - 366.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. C Parish and J. D Evans
Inflammation in Chronic Heart Failure
Ann. Pharmacother.,
July 1, 2008;
42(7):
1002 - 1016.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. G. Athyros, A. I. Kakafika, K. Tziomalos, A. Karagiannis, and D. P. Mikhailidis
CORONA, Statins, and Heart Failure: Who Lost the Crown?
Angiology,
March 1, 2008;
59(1):
5 - 8.
[PDF]
|
|
|
|
|
|
|
K. Ramasubbu, J. Estep, D. L. White, A. Deswal, and D. L. Mann
Experimental and Clinical Basis for the Use of Statins in Patients With Ischemic and Nonischemic Cardiomyopathy
J. Am. Coll. Cardiol.,
January 29, 2008;
51(4):
415 - 426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. Turner, R. S. Mughal, P. Warburton, D. J. O'Regan, S. G. Ball, and K. E. Porter
Mechanism of TNF{alpha}-induced IL-1{alpha}, IL-1{beta} and IL-6 expression in human cardiac fibroblasts: Effects of statins and thiazolidinediones
Cardiovasc Res,
October 1, 2007;
76(1):
81 - 90.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Zaca, S. Rastogi, M. Imai, M. Wang, V. G. Sharov, A. Jiang, S. Goldstein, and H. N. Sabbah
Chronic Monotherapy With Rosuvastatin Prevents Progressive Left Ventricular Dysfunction and Remodeling in Dogs With Heart Failure
J. Am. Coll. Cardiol.,
August 7, 2007;
50(6):
551 - 557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Del Porto, B. Lagana, S. Lai, I. Nofroni, F. Tinti, M. Vitale, E. Podesta, A. P. Mitterhofer, and R. D'Amelio
Response to anti-tumour necrosis factor alpha blockade is associated with reduction of carotid intima-media thickness in patients with active rheumatoid arthritis
Rheumatology,
July 1, 2007;
46(7):
1111 - 1115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Gupta, L. C. Plantinga, N. E. Fink, M. L. Melamed, J. Coresh, C. S. Fox, N. W. Levin, and N. R. Powe
Statin Use and Hospitalization for Sepsis in Patients With Chronic Kidney Disease
JAMA,
April 4, 2007;
297(13):
1455 - 1464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. K. Khush, D. D. Waters, V. Bittner, P. C. Deedwania, J. J.P. Kastelein, S. J. Lewis, and N. K. Wenger
Effect of High-Dose Atorvastatin on Hospitalizations for Heart Failure: Subgroup Analysis of the Treating to New Targets (TNT) Study
Circulation,
February 6, 2007;
115(5):
576 - 583.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.H. W. Tang and G. S. Francis
The Year in Heart Failure
J. Am. Coll. Cardiol.,
December 19, 2006;
48(12):
2575 - 2583.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Go, W. Y. Lee, J. Yang, J. C. Lo, and J. H. Gurwitz
Statin therapy and risks for death and hospitalization in chronic heart failure.
JAMA,
November 1, 2006;
296(17):
2105 - 2111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A F Leite-Moreira and P Castro-Chaves
Heart failure: statins for all?
Heart,
November 1, 2006;
92(11):
1537 - 1538.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Radaelli, M. Cazzaniga, A. Viola, G. Balestri, M. B. Janetti, M. G. Signorini, P. Castiglioni, A. Azzellino, G. Mancia, and A. U. Ferrari
Enhanced Baroreceptor Control of the Cardiovascular System by Polyunsaturated Fatty Acids in Heart Failure Patients
J. Am. Coll. Cardiol.,
October 17, 2006;
48(8):
1600 - 1606.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Sola and B. V. Khan
Reply
J. Am. Coll. Cardiol.,
September 19, 2006;
48(6):
1284 - 1284.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Goldberger, H. Subacius, A. Schaechter, A. Howard, R. Berger, A. Shalaby, J. Levine, A. H. Kadish, and for the DEFINITE Investigators
Effects of Statin Therapy on Arrhythmic Events and Survival in Patients With Nonischemic Dilated Cardiomyopathy
J. Am. Coll. Cardiol.,
September 19, 2006;
48(6):
1228 - 1233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bahl and D. S. Chongtham
Atorvastatin in Nonischemic Left Ventricular Systolic Dysfunction
J. Am. Coll. Cardiol.,
September 19, 2006;
48(6):
1283 - 1283.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. M. Scirica, D. A. Morrow, C. P. Cannon, K. K. Ray, M. S. Sabatine, P. Jarolim, A. Shui, C. H. McCabe, E. Braunwald, and for the PROVE IT-TIMI 22 Investigators
Intensive Statin Therapy and the Risk of Hospitalization for Heart Failure After an Acute Coronary Syndrome in the PROVE IT-TIMI 22 Study
J. Am. Coll. Cardiol.,
June 6, 2006;
47(11):
2326 - 2331.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G.F. Cleland, A. P. Coletta, N. P. Nikitin, and A. L. Clark
Clinical trials update from the American College of Cardiology: Darbepoetin alfa, ASTEROID, UNIVERSE, paediatric carvedilol, UNLOAD and ICELAND
Eur J Heart Fail,
May 1, 2006;
8(3):
326 - 329.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Statins for Nonischemic HF?
Journal Watch Cardiology,
February 23, 2006;
2006(223):
6 - 6.
[Full Text]
|
|
|
|
|
|
|
Statins for Patients with Nonischemic Heart Failure?
Journal Watch (General),
February 17, 2006;
2006(217):
7 - 7.
[Full Text]
|
|
|
|
|
|
|
K. Ramasubbu and D. L. Mann
The Emerging Role of Statins in the Treatment of Heart Failure
J. Am. Coll. Cardiol.,
January 17, 2006;
47(2):
342 - 344.
[Full Text]
[PDF]
|
|
|
|
