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Published in: Cardiovascular Diabetology 1/2009

Open Access 01-12-2009 | Original investigation

Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment

Authors: Koichi Node, Teruo Inoue, Valentin Boyko, Ilan Goldberg, Enrique Z Fisman, Yehuda Adler, Ehud Schwammenthal, Zipora Matas, Solomon Behar, Alexander Tenenbaum

Published in: Cardiovascular Diabetology | Issue 1/2009

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Abstract

Background

The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment.

Methods

Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up.

Results

During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3).

Conclusion

Long-term treatment by bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment.
Literature
1.
go back to reference Fruchart JC, Staels B, Duriez P: The role of fibric acid in atherosclerosis. Curr Atheroscler Rep. 2001, 3: 83-92. 10.1007/s11883-001-0015-x.CrossRefPubMed Fruchart JC, Staels B, Duriez P: The role of fibric acid in atherosclerosis. Curr Atheroscler Rep. 2001, 3: 83-92. 10.1007/s11883-001-0015-x.CrossRefPubMed
2.
go back to reference Rovellini A, Sommmariva D, Branchi A, Maraffi F, Montalto C, Gandini R, Fasoli A: Effects of slow release bezafibrate on the lipid pattern and on blood glucose of type 2 diabetic patients with hyperlipidaemia. Pharmacol Res. 1992, 25: 237-245. 10.1016/S1043-6618(05)80072-6.CrossRefPubMed Rovellini A, Sommmariva D, Branchi A, Maraffi F, Montalto C, Gandini R, Fasoli A: Effects of slow release bezafibrate on the lipid pattern and on blood glucose of type 2 diabetic patients with hyperlipidaemia. Pharmacol Res. 1992, 25: 237-245. 10.1016/S1043-6618(05)80072-6.CrossRefPubMed
3.
go back to reference Taniguchi A, Fukushima M, Sakai M, Tokuyama K, Nagata I, Fukunaga A, Kishimoto H, Doi K, Yamashita Y, Matsuura T, Kitatani N, Okumura T, Nagasaka S, Nakaishi S, Nakai Y: Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients. Metabolism. 2001, 50: 477-480. 10.1053/meta.2001.21028.CrossRefPubMed Taniguchi A, Fukushima M, Sakai M, Tokuyama K, Nagata I, Fukunaga A, Kishimoto H, Doi K, Yamashita Y, Matsuura T, Kitatani N, Okumura T, Nagasaka S, Nakaishi S, Nakai Y: Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients. Metabolism. 2001, 50: 477-480. 10.1053/meta.2001.21028.CrossRefPubMed
4.
go back to reference Jonkers IJ, Mohrschladt MF, Westerndorp RG, Laase van der A, Smeit AH: Severe hypertriglyceridemia with insulin resistance is associated with systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial. Am J Med. 2002, 112: 275-280. 10.1016/S0002-9343(01)01123-8.CrossRefPubMed Jonkers IJ, Mohrschladt MF, Westerndorp RG, Laase van der A, Smeit AH: Severe hypertriglyceridemia with insulin resistance is associated with systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial. Am J Med. 2002, 112: 275-280. 10.1016/S0002-9343(01)01123-8.CrossRefPubMed
5.
go back to reference The BIP study group: Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000, 102: 21-27.CrossRef The BIP study group: Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000, 102: 21-27.CrossRef
6.
go back to reference Goldenberg I, Benderly M, Goldbourt U, for the BIP Study Group: Secondary prevention with bezafibrate therapy for the treatment of dyslipidemia: an extended follow-up of the BIP trial. J Am Coll Cardiol. 2008, 51: 459-465. 10.1016/j.jacc.2007.09.048.CrossRefPubMed Goldenberg I, Benderly M, Goldbourt U, for the BIP Study Group: Secondary prevention with bezafibrate therapy for the treatment of dyslipidemia: an extended follow-up of the BIP trial. J Am Coll Cardiol. 2008, 51: 459-465. 10.1016/j.jacc.2007.09.048.CrossRefPubMed
7.
go back to reference Wang CH, Weisel RD, Liu PP, Fedak PWM, Verma S: Glitazones and heart failure: critical appraisal for the clinician. Circulation. 2003, 107: 1350-1354. 10.1161/01.CIR.0000054675.30348.9A.CrossRefPubMed Wang CH, Weisel RD, Liu PP, Fedak PWM, Verma S: Glitazones and heart failure: critical appraisal for the clinician. Circulation. 2003, 107: 1350-1354. 10.1161/01.CIR.0000054675.30348.9A.CrossRefPubMed
8.
go back to reference Wooltorton E: Rosiglitazone (Avandia) and pioglitazone (Actos) and heart failure. Can Med Assoc J. 2002, 166: 219. Wooltorton E: Rosiglitazone (Avandia) and pioglitazone (Actos) and heart failure. Can Med Assoc J. 2002, 166: 219.
9.
go back to reference Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, Le Winter M, Porte D, Semenkovich CF, Smith S, Young LH, Kahn R: Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation. 2003, 108: 2941-2948. 10.1161/01.CIR.0000103683.99399.7E.CrossRefPubMed Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, Le Winter M, Porte D, Semenkovich CF, Smith S, Young LH, Kahn R: Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation. 2003, 108: 2941-2948. 10.1161/01.CIR.0000103683.99399.7E.CrossRefPubMed
10.
go back to reference Goldbourt U, Behar S, Reicher-Reiss H, Agmon J, Kaplinsky E, Graff E, Kishon Y, Capsi A, Weisbort J, Mandelzweig L, Abinader E, Aharon L, Braun S, David D, Flich M, Friedman Y, Kristal N, Leil N, Markiewicz W, Marmor A, Palant A, Pelled B, Rabinowitz B, Reisin L, Roguin N, Rosenfeld T, Schlesinger Z, Sclarovsky S, Sherf L, Tzivoni D, Zahavi I, Zion M, Brunner D, for the Bezafibrate Infarction Prevention Study Group: Rationale and design of a secondary prevention trial of increasing serum high-density lipoprotein cholesterol and reducing triglycerides in patients with clinically manifest atherosclerotic heart disease (the Bezafibrate Infarction Prevention Trial). Am J Cardiol. 1993, 71: 909-915. 10.1016/0002-9149(93)90905-R.CrossRefPubMed Goldbourt U, Behar S, Reicher-Reiss H, Agmon J, Kaplinsky E, Graff E, Kishon Y, Capsi A, Weisbort J, Mandelzweig L, Abinader E, Aharon L, Braun S, David D, Flich M, Friedman Y, Kristal N, Leil N, Markiewicz W, Marmor A, Palant A, Pelled B, Rabinowitz B, Reisin L, Roguin N, Rosenfeld T, Schlesinger Z, Sclarovsky S, Sherf L, Tzivoni D, Zahavi I, Zion M, Brunner D, for the Bezafibrate Infarction Prevention Study Group: Rationale and design of a secondary prevention trial of increasing serum high-density lipoprotein cholesterol and reducing triglycerides in patients with clinically manifest atherosclerotic heart disease (the Bezafibrate Infarction Prevention Trial). Am J Cardiol. 1993, 71: 909-915. 10.1016/0002-9149(93)90905-R.CrossRefPubMed
11.
go back to reference The Criteria Committee of the New York Heart Association: Nomenclature and Criteria for Diagnosis. 1994, Boston, Little, Brown, 9 The Criteria Committee of the New York Heart Association: Nomenclature and Criteria for Diagnosis. 1994, Boston, Little, Brown, 9
12.
go back to reference Tenenbaum A, Motro M, Fisman EZ, Leor J, Boyko V, Mandelzweig L, Behar S: Functional capacity impairment in patients with coronary artery disease: prevalence, risk factors and prognosis. Cardiology. 2003, 100: 207-215. 10.1159/000074814.CrossRefPubMed Tenenbaum A, Motro M, Fisman EZ, Leor J, Boyko V, Mandelzweig L, Behar S: Functional capacity impairment in patients with coronary artery disease: prevalence, risk factors and prognosis. Cardiology. 2003, 100: 207-215. 10.1159/000074814.CrossRefPubMed
13.
go back to reference Tenenbaum A, Fisman EZ, Boyko V, Benderly M, Tanne D, Haim M, Matas Z, Motro M, Behar S: Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate. Arch Intern Med. 2006, 166: 737-741. 10.1001/archinte.166.7.737.CrossRefPubMed Tenenbaum A, Fisman EZ, Boyko V, Benderly M, Tanne D, Haim M, Matas Z, Motro M, Behar S: Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate. Arch Intern Med. 2006, 166: 737-741. 10.1001/archinte.166.7.737.CrossRefPubMed
14.
go back to reference Tenenbaum A, Motro M, Fisman EZ, Tanne D, Boyko V, Behar S: Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med. 2005, 165: 1154-1160. 10.1001/archinte.165.10.1154.CrossRefPubMed Tenenbaum A, Motro M, Fisman EZ, Tanne D, Boyko V, Behar S: Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med. 2005, 165: 1154-1160. 10.1001/archinte.165.10.1154.CrossRefPubMed
15.
go back to reference Tenenbaum A, Motro M, Fisman EZ, Schwammenthal E, Adler Y, Goldenberg I, Leorr J, Boyko V, Mandelzweig L, Behar S: eroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease. Circulation. 2004, 109: 2197-2202. 10.1161/01.CIR.0000126824.12785.B6.CrossRefPubMed Tenenbaum A, Motro M, Fisman EZ, Schwammenthal E, Adler Y, Goldenberg I, Leorr J, Boyko V, Mandelzweig L, Behar S: eroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease. Circulation. 2004, 109: 2197-2202. 10.1161/01.CIR.0000126824.12785.B6.CrossRefPubMed
16.
go back to reference Tanne JH: FDA places "black box" warning on antidiabetes drugs. Br Med J. 2007, 334: 1237-10.1136/bmj.39244.394456.DB.CrossRef Tanne JH: FDA places "black box" warning on antidiabetes drugs. Br Med J. 2007, 334: 1237-10.1136/bmj.39244.394456.DB.CrossRef
17.
go back to reference Young ME, Laws FA, Goodwin GW, Taegtmeyer H: proliferators-activated receptor alpha is associated with contractile dysfunction in hyperprophied rat heart. J Biol Chem. 2003, 276: 44390-44395. 10.1074/jbc.M103826200.CrossRef Young ME, Laws FA, Goodwin GW, Taegtmeyer H: proliferators-activated receptor alpha is associated with contractile dysfunction in hyperprophied rat heart. J Biol Chem. 2003, 276: 44390-44395. 10.1074/jbc.M103826200.CrossRef
18.
go back to reference Vikramadithyan RK, Hirata K, Yagyu H, Hu Y, Augustus A, Homma S, Goldberg IJ: proliferators-activated receptor agonist modulate heart function in transgenic mice with lipotoxic cardiomyopathy. J Pharmacol Exp Ther. 2005, 313: 586-593. 10.1124/jpet.104.080259.CrossRefPubMed Vikramadithyan RK, Hirata K, Yagyu H, Hu Y, Augustus A, Homma S, Goldberg IJ: proliferators-activated receptor agonist modulate heart function in transgenic mice with lipotoxic cardiomyopathy. J Pharmacol Exp Ther. 2005, 313: 586-593. 10.1124/jpet.104.080259.CrossRefPubMed
19.
go back to reference Bettencourt P, Frioes F, Azevedo A, Dias P, Pimenta J, Rocha-Goncalves F, Ferreira A: Prognostic information provided by serial measurements of brain natriuretic peptide in heart failure. Int J Cardiol. 2004, 93: 45-48. 10.1016/S0167-5273(03)00115-3.CrossRefPubMed Bettencourt P, Frioes F, Azevedo A, Dias P, Pimenta J, Rocha-Goncalves F, Ferreira A: Prognostic information provided by serial measurements of brain natriuretic peptide in heart failure. Int J Cardiol. 2004, 93: 45-48. 10.1016/S0167-5273(03)00115-3.CrossRefPubMed
20.
go back to reference Gardner RS, Chong KS, Morton JJ, McDonagh TA: A change in N-terminal pro-brain natriuretic peptide is predictive of outcome in patients with advanced heart failure. Eur J Heart Fail. 2007, 9: 266-271. 10.1016/j.ejheart.2006.07.002.CrossRefPubMed Gardner RS, Chong KS, Morton JJ, McDonagh TA: A change in N-terminal pro-brain natriuretic peptide is predictive of outcome in patients with advanced heart failure. Eur J Heart Fail. 2007, 9: 266-271. 10.1016/j.ejheart.2006.07.002.CrossRefPubMed
21.
go back to reference Latini R, Masson S, Wong M, Barlera S, Carretta E, Staszewsky L, Vago T, Maggioni AP, Anand IS, Tan LB, Tognoni G, Cohn JN: Incremental prognostic value of changes in B-type natriuretic peptide in heart failure. Am J Med. 2006, 119: 70-10.1016/j.amjmed.2005.08.041.CrossRefPubMed Latini R, Masson S, Wong M, Barlera S, Carretta E, Staszewsky L, Vago T, Maggioni AP, Anand IS, Tan LB, Tognoni G, Cohn JN: Incremental prognostic value of changes in B-type natriuretic peptide in heart failure. Am J Med. 2006, 119: 70-10.1016/j.amjmed.2005.08.041.CrossRefPubMed
22.
go back to reference Schou M, Gustafsson F, Kjaer A, Hildebrandt PR: Long-term clinical variation of NT-proBNP in stable chronic heart failure patients. Eur Heart J. 2007, 28: 177-182. 10.1093/eurheartj/ehl449.CrossRefPubMed Schou M, Gustafsson F, Kjaer A, Hildebrandt PR: Long-term clinical variation of NT-proBNP in stable chronic heart failure patients. Eur Heart J. 2007, 28: 177-182. 10.1093/eurheartj/ehl449.CrossRefPubMed
23.
go back to reference Schou M, Gustafsson F, Nielsen PH, Madsen LH, Kjaer A, Hildebrandt PR: Unexplained week-to-week variation in BNP and NTproBNP is low in chronic heart failure patients during steady state. Eur J Heart Fail. 2007, 9: 68-74. 10.1016/j.ejheart.2006.05.001.CrossRefPubMed Schou M, Gustafsson F, Nielsen PH, Madsen LH, Kjaer A, Hildebrandt PR: Unexplained week-to-week variation in BNP and NTproBNP is low in chronic heart failure patients during steady state. Eur J Heart Fail. 2007, 9: 68-74. 10.1016/j.ejheart.2006.05.001.CrossRefPubMed
24.
go back to reference Rivera M, Cortes R, Salvador A, Bertomeu V, de Burgos FG, Paya R, Portoles M, Talens-Visconti R, Martinez-Dolz L, Valero R, Sevilla B, Climent V: Obese subjects with heart failure have lower N-terminal pro-brain natriuretic peptide plasma levels irrespective of aetiology. Eur J Heart Fail. 2005, 7: 1168-1170. 10.1016/j.ejheart.2005.04.003.CrossRefPubMed Rivera M, Cortes R, Salvador A, Bertomeu V, de Burgos FG, Paya R, Portoles M, Talens-Visconti R, Martinez-Dolz L, Valero R, Sevilla B, Climent V: Obese subjects with heart failure have lower N-terminal pro-brain natriuretic peptide plasma levels irrespective of aetiology. Eur J Heart Fail. 2005, 7: 1168-1170. 10.1016/j.ejheart.2005.04.003.CrossRefPubMed
25.
go back to reference Das SR, Drazner MH, Dries DL, Vega GL, Stanek HG, Abdullah SM, Canham RM, Chung AK, Leonard D, Wians FH, de Lemos JA: Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation. 2005, 112: 2163-2168. 10.1161/CIRCULATIONAHA.105.555573.CrossRefPubMed Das SR, Drazner MH, Dries DL, Vega GL, Stanek HG, Abdullah SM, Canham RM, Chung AK, Leonard D, Wians FH, de Lemos JA: Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation. 2005, 112: 2163-2168. 10.1161/CIRCULATIONAHA.105.555573.CrossRefPubMed
26.
go back to reference St Peter JV, Hartley GG, Murakami MM, Apple FS: B-type natriuretic peptide (BNP) and N-terminal pro-BNP in obese patients without heart failure: relationship to body mass index and gastric bypass surgery. Clin Chem. 2006, 52: 680-685. 10.1373/clinchem.2005.062562.CrossRefPubMed St Peter JV, Hartley GG, Murakami MM, Apple FS: B-type natriuretic peptide (BNP) and N-terminal pro-BNP in obese patients without heart failure: relationship to body mass index and gastric bypass surgery. Clin Chem. 2006, 52: 680-685. 10.1373/clinchem.2005.062562.CrossRefPubMed
27.
go back to reference Masson S, Latini R: Amino-terminal pro-B-Type natriuretic peptides and prognosis in chronic heart failure. Am J Cardiol. 2008, 101: 56A-60A. 10.1016/j.amjcard.2007.11.024.CrossRef Masson S, Latini R: Amino-terminal pro-B-Type natriuretic peptides and prognosis in chronic heart failure. Am J Cardiol. 2008, 101: 56A-60A. 10.1016/j.amjcard.2007.11.024.CrossRef
Metadata
Title
Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment
Authors
Koichi Node
Teruo Inoue
Valentin Boyko
Ilan Goldberg
Enrique Z Fisman
Yehuda Adler
Ehud Schwammenthal
Zipora Matas
Solomon Behar
Alexander Tenenbaum
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2009
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-8-5

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