Skip to main content

Advertisement

SpringerLink
Log in

The paradox of low BNP levels in obesity

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

The aim of this review is to analyze in detail some possible pathophysiological mechanisms linking obesity and cardiac endocrine function, in order to try to explain the negative association previously observed between BMI and BNP values in both healthy subjects and patients with cardiovascular diseases. In particular, we discuss the hypothesis that the response of the cardiac endocrine system is the integrated resultant of several and contrasting physiological and pathological interactions, including the effects of peptide and steroid hormones, cytokines, cardiovascular hemodynamics, clinical conditions, and pharmacological treatment. Several studies suggested that gonadal function regulates both body fat distribution and cardiac endocrine function. Visceral fat expansion can increase the clearance of active natriuretic peptides by means of an increased expression of clearance receptors on adipocytes, and in this way, it may contribute to decrease the activity of the cardiac endocrine system. Moreover, obesity is associated with ectopic lipid deposition even in the heart, which may directly exert a lipotoxic effect on the myocardium by secreting in loco several cytokines and adipokines. Obese subjects are frequently treated for hypertension and coronary artery disease. Pharmacological treatment reduces plasma level of cardiac natriuretic peptides, and this effect may explain almost in part the lower BNP levels of some asymptomatic subjects with increased BMI values. At present time, it is not possible to give a unique and definitive answer to the crucial question concerning the inverse relationship between the amount of visceral fat distribution and BNP levels. Our explanation for these unsatisfactory results is that the cardiac endocrine response is always the integrated resultant of several pathophysiological interactions. However, only few variables can be studied together; as a result, it is not possible to perform a complete evaluation of pathophysiological mechanisms under study. We are still not able to well integrate these multiple information together; therefore, we should learn to do it.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Sarzani R, Salvi F, Dessì-Fulgheri P, Rappelli A (2008) Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, hypertension: an integrated view in humans. J Hypertens 26:831–843

    PubMed  CAS  Google Scholar 

  2. Sarzani R, Marcucci P, Salvi F, Bordicchia M, Espinosa E, Mucci L et al (2008) Angiotensin II stimulates and atrial natriuretic peptide inhibits human visceral adipocyte growth. Int J Obes 32:259–267

    CAS  Google Scholar 

  3. Licata G, Volpe M, Scaglione R, Rubattu S (1994) Salt-regulating hormones in young normotensive obese subjects: effects of saline load. Hypertension 23(1 Suppl):I20–I124

    PubMed  CAS  Google Scholar 

  4. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW et al (2004) Impact of obesity on plasma natriuretic peptide levels. Circulation 109:594–600

    PubMed  CAS  Google Scholar 

  5. Sugisawa T, Kishimoto I, Kokubo Y, Makino H, Miyamoto Y, Yoshimasa Y (2010) Association of plasma B-type natriuretic peptide levels with obesity in a general urban Japanese population: the Suita Study. Endocr J 57:727–733

    PubMed  CAS  Google Scholar 

  6. Mehra MR, Uber PA, Park MH, Scott RL, Ventura HO, Harris BC et al (2004) Obesity and suppressed B-type natriuretic peptide levels in heart failure. J Am Coll Cardiol 43:1590–1595

    PubMed  CAS  Google Scholar 

  7. Dessi-Fulgheri P, Sarzani R, Rappelli A (1998) The natriuretic peptide system in obesity-related hypertension: new pathophysiological aspects. J Nephrol 11:296–299

    PubMed  CAS  Google Scholar 

  8. Daniels LB, Clopton P, Bhalla V, Krishnaswamy P, Nowak RM, McCord J et al (2006) How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure: results from the breathing not properly multinational study. Am Heart J 151:999–1005

    PubMed  CAS  Google Scholar 

  9. Krauser D, Lloyd-Jones D, Chae C, Cameron R, Anwaruddin S, Baggish AL et al (2005) Effect of body mass index on natriuretic peptide levels in patients with acute congestive heart failure: a ProBNP investigation of dyspnea in the emergency department (PRIDE) substudy. Am Heart J 149:744–750

    PubMed  CAS  Google Scholar 

  10. McCord J, Mundy BJ, Hudson MP, Maisel AS, Hollander JE, Abraham WT et al (2004) Breathing not properly multinational study investigators. Relationship between obesity and B-type natriuretic peptide levels. Arch Intern Med 164:2247–2252

    PubMed  CAS  Google Scholar 

  11. Park SJ, Cho KI, Jung SJ, Choi SW, Choi JW, Lee DW et al (2009) N-terminal pro-B-type natriuretic Peptide in overweight and obese patients with and without diabetes: an analysis based on body mass index and left ventricular geometry. Korean Circ J 39:538–544

    PubMed  CAS  Google Scholar 

  12. De Bold AJ (1985) Atrial natriuretic factor: a hormone produced by the heart. Science 230:427–470

    Google Scholar 

  13. Clerico A, Recchia FA, Passino C, Emdin M (2006) Cardiac endocrine function is an essential component of the homeostatic regulation network: physiological and clinical implications. Am J Physiol Heart Circ Physiol 290:H17–H29

    PubMed  CAS  Google Scholar 

  14. Goetze JP (2010) Biosynthesis of cardiac natriuretic peptides. Results Probl Cell Differ 50:12–97

    Google Scholar 

  15. De Bold AJ, Bruneau BG, Kuroski de Bold ML (1996) Mechanical and neuroendocrine regulation of the endocrine heart. Cardiovasc Res 31:7–18

    PubMed  Google Scholar 

  16. De Bold AJ, Ma KKY, Zhang Y, Kuroski de Bold ML, Bensimon M, Khoshbaten A (2001) The physiological and pathophysiological modulation of the endocrine function of the heart. Can J Physiol Pharmacol 79:705–714

    PubMed  Google Scholar 

  17. McGrath MF, de Bold AJ (2005) Determinants of natriuretic peptide gene expression. Peptides 26:933–943

    PubMed  CAS  Google Scholar 

  18. Balion CM, Santaguida P, McKelvie R, Hill SA, McQueen MJ, Worster A et al (2008) Physiological, pathological, pharmacological, biochemical and hematological factors affecting BNP and NT-proBNP. Clin Biochem 41:231–239

    PubMed  CAS  Google Scholar 

  19. Clerico A, Emdin M (2004) Diagnostic accuracy and prognostic relevance of the measurement of the cardiac natriuretic peptides: a review. Clin Chem 50:33–50

    PubMed  CAS  Google Scholar 

  20. Doust JA, Glasziou PP, Pietrzak E, Dobson AJ (2004) A systematic review of the diagnostic accuracy of natriuretic peptides for heart failure. Arch Intern Med 164:1978–1984

    PubMed  CAS  Google Scholar 

  21. Clerico A, Fontana M, Zyw L, Passino C, Emdin M (2007) Comparison of the diagnostic accuracy of brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP immunoassays in chronic and acute heart failure: a systematic review. Clin Chem 53:813–822

    PubMed  CAS  Google Scholar 

  22. Balion CM, McKelvie RS, Reichert S, Santaguida P, Booker L, Worster A et al (2008) Monitoring the response to pharmacologic therapy in patients with stable chronic heart failure: is BNP or NT-proBNP a useful assessment tool? Clin Biochem 41:266–276

    PubMed  CAS  Google Scholar 

  23. Ewald B, Ewald D, Thakkinstian A, Attia J (2008) Meta-analysis of B type natriuretic peptide, N-terminal pro B natriuretic peptide in the diagnosis of clinical heart failure, population screening for left ventricular systolic dysfunction. Intern Med J 38:101–113

    PubMed  CAS  Google Scholar 

  24. Emdin M, Passino C, Prontera C, Fontana M, Poletti R, Gabutti A, Mammini C, Giannoni A, Zyw L, Zucchelli GC, Clerico A (2007) Comparison of brain natriuretic peptide (BNP) and amino-terminal ProBNP for early diagnosis of heart failure. Clin Chem 53:1264–1272

    Google Scholar 

  25. Tang WH, Francis GS, Morrow DA, Newby LK, Cannon CP, Jesse RL et al (2007) National academy of clinical biochemistry laboratory medicine practice guidelines: clinical utilization of cardiac biomarker testing in heart failure. Circulation 116:e99–e109

    PubMed  CAS  Google Scholar 

  26. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA et al (2008) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European society of cardiology. Eur Heart J 29:2388–2442

    PubMed  CAS  Google Scholar 

  27. Clerico A, Fontana M, Ripoli A, Emdin M (2009) Clinical relevance of BNP measurement in the follow-up of patients with chronic heart failure. Adv Clin Chem 48:163–179

    PubMed  CAS  Google Scholar 

  28. Felker GM, Hasselblad V, Hernandez AF, O’Connor CM (2009) Biomarker-guided therapy in chronic heart failure: a meta-analysis of randomized controlled trials. Am Heart J 158:422–430

    PubMed  CAS  Google Scholar 

  29. Felker GM, Pang PS, Adams KF, Cleland JG, Cotter G, Dickstein K et al (2010) Clinical trials of pharmacological therapies in acute heart failure syndromes. Lessons learned and directions forward. Cir Heart Fail 3:314–325 (on behalf of the International AHFS Working Group)

    Google Scholar 

  30. Ramos H, de Bold AJ (2006) Gene expression, processing, and secretion of natriuretic peptides: physiologic and diagnostic implications. Heart Fail Clin 2:255–268

    PubMed  Google Scholar 

  31. De Bold AJ (2009) Cardiac natriuretic peptides gene expression and secretion in inflammation. J Investig Med 57:29–32

    PubMed  Google Scholar 

  32. Kuwahara K, Nakao K (2010) Regulation and significance of atrial and brain natriuretic peptides as cardiac hormones. Endocr J 57:555–565

    PubMed  CAS  Google Scholar 

  33. Goetze JP, Georg B, Jørgensen HL, Fahrenkrug J (2010) Chamber-dependent circadian expression of cardiac natriuretic peptides. Regul Pept 160:140–145

    PubMed  CAS  Google Scholar 

  34. Sakata Y, Yamamoto K, Masuyama T, Mano T, Nishikawa N, Kuzuya T et al (2001) Ventricular production of natriuretic peptides and ventricular structural remodelling in hypertensive heart failure. J Hypertens 19:1905–1959

    PubMed  CAS  Google Scholar 

  35. Takahashi N, Saito Y, Kuwahara K, Harada M, Kishimoto I, Ogawa Y et al (2003) Angiotensin II-induced ventricular hypertrophy and extracellular signal-regulated kinase activation are suppressed in mice overexpressing brain natriuretic peptide in circulation. Hypertens Res 26:847–853

    PubMed  CAS  Google Scholar 

  36. Walther T, Klostermann K, Heringer-Walther S, Schultheiss HP, Tschope C, Stepan H (2003) Fibrosis rather than blood pressure determines cardiac BNP expression in mice. Regul Pept 116:95–100

    PubMed  CAS  Google Scholar 

  37. Toth M, Vuorinen KH, Vuolteenaho O, Hassinen IE, Uusimaa PA, Leppaluoto J et al (1994) Hypoxia stimulates release of ANP and BNP from perfused rat ventricular myocardium. Am J Physiol 266:H1572–H1580

    PubMed  CAS  Google Scholar 

  38. Hama N, Itoh H, Shirakami G, Nakagawa O, Suga S, Ogawa Y et al (1995) Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation 92:1158–1164

    Google Scholar 

  39. Goetze JP, Gore A, Moller CH, Steinbruchel DA, Rehfeld JF, Nielsen LB (2004) Acute myocardial hypoxia increases BNP gene expression. FASEB J 18:1928–1930

    PubMed  CAS  Google Scholar 

  40. Jernberg T, James S, Lindahl B, Johnston N, Stridsberg M, Venge P et al (2004) Natriuretic peptides in unstable coronary artery disease. Eur Heart J 25:1486–1493

    PubMed  CAS  Google Scholar 

  41. Casals G, Ros J, Sionis A, Davidson MM, Morales-Ruiz M, Jiménez W (2009) Hypoxia induces B-type natriuretic peptide release in cell lines derived from human cardiomyocytes. Am J Physiol Heart Circ Physiol 297:H550–H555

    PubMed  CAS  Google Scholar 

  42. Chiu CZ, Wang BW, Chung TH, Shyu KG (2010) Angiotensin II and the ERK pathway mediate the induction of myocardin by hypoxia in cultured rat neonatal cardiomyocytes. Clin Sci 119:273–282

    PubMed  CAS  Google Scholar 

  43. Tan T, Scholz PM, Weiss HR (2010) Hypoxia inducible factor-1 improves the negative functional effects of natriuretic peptide and nitric oxide signaling in hypertrophic cardiac myocytes. Lige Sci 80:9–16

    Google Scholar 

  44. Preventing and Managing the Global Epidemic of Obesity (1997) Report of the world health organization consultation of obesity. WHO, Geneva

    Google Scholar 

  45. Pi-Sunyer FX, Becker DM, Bouchard C, Colditz GA, Carleton RA, Dietz WH et al. (1998) Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. National Heart, Lung and Blood Institute

  46. Clerico A, Fontana M, Vittorini S, Emdin M (2009) The search for a pathophysiological link between gender, cardiac endocrine function, body mass regulation and cardiac mortality: proposal for a working hypothesis. Clin Chim Acta 405:1–7

    PubMed  CAS  Google Scholar 

  47. Goetze JP (2004) Biochemistry of pro-B-type natriuretic peptide-derived peptides: the endocrine heart revisited. Clin Chem 50:1503–1510

    PubMed  CAS  Google Scholar 

  48. Goetze JP, Rehfeld JF (2009) Peptide hormones and their prohormones as biomarkers. Biomark Med 3:335–338

    PubMed  CAS  Google Scholar 

  49. Giuliani I, Rieunier F, Larue C, Delagneau JF, Granier C, Pau B et al (2006) Assay for measurement of intact B-type natriuretic peptide prohormone in blood. Clin Chem 52:1054–1561

    PubMed  CAS  Google Scholar 

  50. Waldo SW, Beede J, Isakson S, Villard-Saussine S, Fareh J, Clopton P, Fitzegerald RL et al (2008) Pro-B-type natriuretic peptide levels in acute decompensated heart failure. J An Coll Cardiol 51:1874–1882

    CAS  Google Scholar 

  51. Wu AH, Smith A, Rame E, Wians F, Minard F, Giuliani I et al (2009) Analytical assay characterization for 1–108 pro-B-type natriuretic peptide on the BioPlex 2200 analyzer. Clin Chim Acta 408:143–144

    PubMed  CAS  Google Scholar 

  52. Dries DL, Ky B, Wu AH, Rame JE, Putt ME, Cappola TP (2010) Simultaneous Assessment of Unprocessed ProBNP1–108 in addition to processed BNP32 improves identification of high-risk ambulatory patients with heart failure. Circ Heart Fail 3:220–227

    PubMed  Google Scholar 

  53. Peleg A, Jaffe AS, Hasin Y (2009) Enzyme-linked immuno absorbent assay for detection of human protease corin in blood. Clin Chim Acta 409:85–89

    PubMed  CAS  Google Scholar 

  54. Rame JE, Drazner MH, Post W, Peshock R, Lima J, Cooper RS et al (2007) Corin I555(P568) allele is associated with enhanced cardiac hypertrophic response to increased systemic afterload. Hypertension 49:857–864

    PubMed  CAS  Google Scholar 

  55. Rame JE, Tam SW, McNamara D, Worcel M, Sabolinski ML, Wu AH et al (2009) Dysfunctional corin i555(p568) allele is associated with impaired brain natriuretic peptide processing and adverse outcomes in blacks with systolic heart failure: results from the genetic risk assessment in heart failure sub study. Circ Heart Fail 2:541–548

    PubMed  CAS  Google Scholar 

  56. Emdin M, Passino C, Clerico A (2011) Natriuretic peptide assays revisited. Do we need proB-type natriuretic peptide? J Am Coll Cardiol 57:1396–1398

    PubMed  Google Scholar 

  57. Mattsson C, Olsson T (2007) Estrogens and glucocorticoid hormones in adipose tissue metabolism. Curr Med Chem 14:2918–2924

    PubMed  CAS  Google Scholar 

  58. Blouin K, Boivin A, Tchernof A (2008) Androgens and body fat distribution. J Steroid Biochem Mol Biol 108:272–280

    PubMed  CAS  Google Scholar 

  59. Clerico A, Del Ry S, Maffei S, Prontera C, Emdin M, Giannessi D (2002) Circulating levels of cardiac natriuretic hormones in healthy adult subjects: effects of aging and sex. Clin Chem Lab Med 40:371–377

    PubMed  CAS  Google Scholar 

  60. Nir A, Lindinger A, Rauh M, Bar-Oz B, Laer S, Schwachtgen L et al (2009) NT-Pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies. Pediatr Cardiol 30:3–8

    PubMed  Google Scholar 

  61. Cantinotti M, Storti S, Parri MS, Prontera C, Murzi B, Clerico A (2010) Reference intervals for brain natriuretic peptide in healthy newborns and infants measured with an automated immunoassay platform. Clin Chem Lab Med 48:697–700

    PubMed  CAS  Google Scholar 

  62. Das SR, Drazner MH, Dries DL, Vega GL, Stanek HG, Abdullah SM et al (2005) Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas heart study. Circulation 112:2163–2168

    PubMed  CAS  Google Scholar 

  63. Chang AY, Abdullah SM, Jain T, Stanek HG, Das SR, McGuire DK et al (2007) Associations among androgens, estrogens, and natriuretic peptides in young women: observations from the Dallas heart study. J Am Coll Cardiol 49:109–116

    PubMed  CAS  Google Scholar 

  64. Kuroski de Bold ML (1999) Estrogen, natriuretic peptides and the renin-angiotensin system. Cardiovasc Res 41:524–531

    PubMed  CAS  Google Scholar 

  65. Maffei S, Del Ry S, Prontera C, Clerico A (2001) Increase in circulating levels of cardiac natriuretic peptides after hormone replacement therapy in postmenopausal women. Clin Sci 101:447–453

    PubMed  CAS  Google Scholar 

  66. Elbers JM, Asscheman H, Seidell JC, Gooren LJ (1999) Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals. Am J Physiol 276:E317–E325

    PubMed  CAS  Google Scholar 

  67. Elbers JM, Asscheman H, Seidell JC, Megens JA, Gooren LJ (1997) Long-term testosterone administration increases visceral fat in female to male transsexuals. J Clin Endocrinol Metab 82:2044–2047

    PubMed  CAS  Google Scholar 

  68. Elbers JM, Giltay EJ, Teerlink T, Scheffer PG, Asscheman H, Seidell JC et al (2003) Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Clin Endocrinol 58:562–571

    CAS  Google Scholar 

  69. Boyanov MA, Boneva Z, Christov VG (2003) Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 6:1–7

    PubMed  CAS  Google Scholar 

  70. Marin P (1995) Testosterone and regional fat distribution. Obes Res 3(Suppl. 4):609S–612S

    PubMed  CAS  Google Scholar 

  71. Schroeder ET, Zheng L, Ong MD, Martinez C, Flores C, Stewart Y et al (2004) Effects of androgen therapy on adipose tissue, metabolism in older men. J Clin Endocrinol Metab 89:4863–4872

    PubMed  CAS  Google Scholar 

  72. Lovejoy JC, Bray GA, Greeson CS, Klemperer M, Morris J, Partington C et al (1995) Oral anabolic steroid treatment, but not parenteral androgen treatment, decreases abdominal fat in obese, older men. Int J Obes Relat Metab Disord 19:614–624

    PubMed  CAS  Google Scholar 

  73. Blouin K, Després JP, Couillard C, Tremblay A, Prud’homme D, Bouchard C et al (2005) Contribution of age and declining androgen levels to features of the metabolic syndrome in men. Metabolism 54:1034–1040

    PubMed  CAS  Google Scholar 

  74. Glazer G (1991) Atherogenic effects of anabolic steroids on serum lipid levels. A literature review. Arch Intern Med 151:1925–1933

    PubMed  CAS  Google Scholar 

  75. Phillips GB, Jing T, Heymsfield SB (2003) Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction. Metabolism 52:784–790

    PubMed  CAS  Google Scholar 

  76. Traish AM, Saad F, Guay A (2009) The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl 30:23–32

    PubMed  CAS  Google Scholar 

  77. Traish AM, Saad F, Feeley RJ, Guay A (2009) The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl 30:477–494

    PubMed  CAS  Google Scholar 

  78. Dandona P, Dhindsa S, Chaudhuri A, Bhatia V, Topiwala S, Mohanty P (2008) Hypogonadotrophic hypogonadism in type 2 diabetes, obesity and the metabolic syndrome. Curr Mol Med 8:816–828

    Google Scholar 

  79. Zitzmann M (2009) Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol 5:673–681

    PubMed  CAS  Google Scholar 

  80. Costello-Boerrigter LC, Burnett JC Jr (2009) A new role for the natriuretic peptides: metabolic regulators of the adipocyte. J Am Coll Cardiol 53:2078–2079

    PubMed  Google Scholar 

  81. Garruti G, Giusti V, Nussberger J, Darimont C, Verdumo C, Amstutz C et al (2007) Expression and secretion of the atrial natriuretic peptide in human adipose tissue and preadipocytes. Obesity 15:2181–2189

    PubMed  CAS  Google Scholar 

  82. Sengenes C, Zakaroff-Girard A, Moulin A et al (2002) Natriuretic peptide-dependent lipolysis in fat cells is a primate specificity. Am J Physiol Regul Integr Comp Physiol 283:R257–R265

    PubMed  CAS  Google Scholar 

  83. Lafontan M, Moro C, Berlan M, Crampes F, Sengenes C, Galitzky J (2008) Control of lipolysis by natriuretic peptides and cyclic GMP. Trends Endocrinol Metab 19:130–137

    PubMed  CAS  Google Scholar 

  84. Licata G, Volpe M, Scaglione R, Rubattu S (1994) Salt-regulating hormones in young normotensive obese subjects: effects of saline load. Hypertension 23(1 Suppl):I20–I124

    PubMed  CAS  Google Scholar 

  85. Messerli FH, Ventura HO, Reisin E, Dreslinski GR, Dunn FG, MacPhee AA et al (1982) Borderline hypertension and obesity: two prehypertensive states with elevated cardiac output. Circulation 66:55–60

    PubMed  CAS  Google Scholar 

  86. Emdin M, Gastaldelli A, Muscelli E, Macerata A, Natali A, Camastra S et al (2001) Hyperinsulinemia and autonomic nervous system dysfunction in obesity: effects of weight loss. Circulation 103:513–519

    PubMed  CAS  Google Scholar 

  87. Tokudome T, Horio T, Yoshihara F, Suga S, Kawano Y, Kohno M et al (2004) Direct effects of high glucose and insulin on protein synthesis in cultured cardiac myocytes and DNA and collagen synthesis in cardiac fibroblasts. Metabolism 53:710–715

    PubMed  CAS  Google Scholar 

  88. Wende AR, Abel ED (2010) Lipotoxicity in the heart. Biochim Biophys Acta 1801:311–319

    PubMed  CAS  Google Scholar 

  89. Shimabukuro M (2010) Cardiac adiposity and global cardio metabolic risk. New concept and clinical implications. Circ J 73:27–34

    Google Scholar 

  90. Gualillo O, Gonzalez-Juanately JR, Lago F (2007) The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives. Trends Cardiovasc Med 17:275–283

    PubMed  CAS  Google Scholar 

  91. Wozniak SE, Gee LL, Wachted MS, Frezza EE (2009) Adipose tissue: the new endocrine organ? A review article. Dig Dis Sci 54:1847–1856

    PubMed  Google Scholar 

  92. Silswal N, Singh AK, Aruna B, Mukhopadhyay S, Ghosh S, Ehtesham NZ (2005) Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaBdependent pathway. Biochem Biophys Res Commun 334:1092–1101

    PubMed  CAS  Google Scholar 

  93. Vuolteenaho K, Koskinen A, Kukkonen M, Nieminen R, Päivärinta U, Moilanen T et al (2009) Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage–mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production. Mediators Inflamm 2009:345838

    PubMed  Google Scholar 

  94. Mattioli B, Giordani L, Quaranta MG, Viora M (2009) Leptin exerts an anti-apoptotic effect on human dendritic cells via the PI3 K-Akt signaling pathway. FEBS lett 583:1102–1106

    PubMed  CAS  Google Scholar 

  95. Tong KM, Shieh DC, Chen CP, Tzeng CY, Wang SP, Huang KC et al (2008) Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3 K, Akt cascade and promotion of NF-kappaB/p300 binding in human synovial fibroblasts. Cell Signal 20:1478–1488

    PubMed  CAS  Google Scholar 

  96. Aleffi S, Petrai I, Bertolani C, Parola M, Colombatto S, Novo E et al (2005) Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology 42:1339–1348

    PubMed  CAS  Google Scholar 

  97. Lappas M, Permezel M, Rice GE (2005) Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase 1/2. Endocrinology 146:3334–3342

    PubMed  CAS  Google Scholar 

  98. Adya R, Tan BK, Chen J, Randeva HS (2008) Nuclear factor-kappaB induction by visfatin in human vascular endothelial cells: its role in MMP-2/9 production and activation. Diabetes Care 31:758–760

    PubMed  CAS  Google Scholar 

  99. Mascareno E, Beckles D, Dhar-Mascareno M, Siddiqui MA (2009) Enhanced hypertrophy in ob/ob mice due to an impairment in expression of atrial natriuretic peptide. Vascul Pharmacol 51:198–204

    PubMed  CAS  Google Scholar 

  100. Yuan K, Yu J, Shah A, Gao S, Kim SY, Kim SZ et al (2010) Leptin reduces plasma ANP level via nitric oxide-dependent mechanism. Am J Physiol Regul Integr Comp Physiol 298:R1007–R1016

    PubMed  CAS  Google Scholar 

  101. Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A et al (2009) Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol 53:2070–2077

    PubMed  CAS  Google Scholar 

  102. Fain JN, Kanu A, Bahouth SW, Cowan GS, Lloyd Hiler M (2003) Inhibition of leptin release by atrial natriuretic peptide (ANP) in human adipocytes. Biochem Pharmacol 65:1883–1888

    PubMed  CAS  Google Scholar 

  103. Moro C, Klimcakova E, Lolmède K, Berlan M, Lafontan M, Stich V et al (2007) Atrial natriuretic peptide inhibits the production of adipokines and cytokines linked to inflammation and insulin resistance in human subcutaneous adipose tissue. Diabetologia 50:1038–1047

    PubMed  CAS  Google Scholar 

  104. Canoy D (2010) Coronary heart disease and body fat distribution. Curr Atheroscler Rep 12:125–133

    PubMed  Google Scholar 

  105. Christenson RH, Azzazy HM, Duh SH, Maynard S, Seliger SL, Defilippi CR (2010) Impact of increased body mass index on accuracy of B-type natriuretic peptide (BNP) and N-terminal proBNP for diagnosis of decompensated heart failure and prediction of all-cause mortality. Clin Chem 56:633–641

    PubMed  CAS  Google Scholar 

  106. Wang TJ, Larson MG, Levy D, Leip EP, Benjamin EJ, Wilson PW et al (2002) Impact of age and sex on plasma natriuretic peptide levels in healthy adults. Am J Cardiol 90:254–258

    PubMed  CAS  Google Scholar 

  107. Horwich TB, Hamilton MA, Fonarow GC (2006) B-type natriuretic peptide levels in obese patients with advanced heart failure. J Am Coll Cardiol 47:85–90

    PubMed  CAS  Google Scholar 

  108. Taylor JA, Christenson RH, Rao K, Jorge M, Gottlieb SS (2006) B-type natriuretic peptide and N-terminal pro B-type natriuretic peptide are depressed in obesity despite higher left ventricular end diastolic pressures. Am Heart J 152:1071–1076

    PubMed  CAS  Google Scholar 

  109. van Kimmenade RR, Januzzi JL Jr, Baggish AL, Lainchbury JG, Bayes-Genis A, Richards AM, Pinto YM (2006) Amino-terminal pro-brain natriuretic Peptide, renal function, and outcomes in acute heart failure: redefining the cardiorenal interaction? J Am Coll Cardiol 48:1621–1627

    PubMed  Google Scholar 

  110. St Peter JV, Hartley GG, Murakami MM, Apple FS (2006) 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 52:680–685

    PubMed  CAS  Google Scholar 

  111. Iwanaga Y, Kihara Y, Niizuma S, Noguchi T, Nonogi H, Kita T, Goto Y (2007) BNP in overweight and obese patients with heart failure: an analysis based on the BNP-LV diastolic wall stress relationship. J Card Fail 13:663–667

    PubMed  CAS  Google Scholar 

  112. Pervanidou P, Akalestos A, Sakka S, Kanaka-Gantenbein C, Papassotiriou I, Chrousos GP (2010) Gender dimorphic associations between N-terminal pro-brain natriuretic peptide, body mass index and blood pressure in children and adolescents. Horm Res Paediatr 73:341–348

    PubMed  CAS  Google Scholar 

  113. Kanda H, Kita Y, Okamura T, Kadowaki T, Yoshida Y, Nakamura Y et al (2005) What factors are associated with high plasma B-type natriuretic peptide levels in a general Japanese population? J Hum Hypertens 19:165–172

    PubMed  CAS  Google Scholar 

  114. Wang TJ, Larson MG, Keyes MJ, Levy D, Benjamin EJ, Vasan RS (2007) Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals. Circulation 115:1345–1353

    PubMed  CAS  Google Scholar 

  115. Latini R, Masson S, Wong M, Barlera S, Carretta E, Staszewsky L et al (2006) Incremental prognostic value of changes in B-type natriuretic peptide in heart failure. Am J Med 119:70.e23–70.e30

    Google Scholar 

  116. Masson S, Latini R, Anand IS, Barlera S, Angelici L, Vago T et al (2008) Prognostic value of changes in N-terminal pro-brain natriuretic peptide in Val-HeFT (Valsartan Heart Failure Trial). J Am Coll Cardiol 52:997–1003

    PubMed  CAS  Google Scholar 

  117. Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H (2010) B-type natriuretic peptide—guided heart failure therapy. A meta-analysis. Arch Int Med 170:507–514

    CAS  Google Scholar 

  118. Bosco JL, Silliman RA, Thwin SS, Geiger AM, Buist DS, Prout MN et al (2010) A most stubborn bias: no adjustment method fully resolves confounding by indication in observational studies. J Clin Epidemiol 63:64–74

    PubMed  Google Scholar 

  119. Royston P, Altman DG, Sauerbrei W (2006) Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med 25:127–141

    PubMed  Google Scholar 

  120. Altman DG, Royston P (2006) The cost of dichotomising continuous variables. Br Med J 332:1080

    Google Scholar 

  121. Lee SY, Gallagher D (2008) Assessment methods in human body composition. Curr Opin Clin Nutr Metab Care 11:566–572

    PubMed  Google Scholar 

  122. Shirley S, Davis LL, Carlson BW (2007) The relationship between body mass index/body composition and survival in patients with heart failure. J Am Acad Nurse Pract 20:326–332

    Google Scholar 

  123. Wikipedia, the free encyclopedia. Arnold Alois Schwarzenegger. (http://en.wikipedia.org/wiki/ArnoldSchwarzenegger#cite_note-mrever-10)

  124. Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow GC, Norris CM, McAlister FA (2008) Body mass index and mortality in heart failure: a meta-analysis. Am Heart J 156:13–22

    PubMed  Google Scholar 

  125. Kalantar-Zadeh K, Kilpatrick RD, Kuwae N, Wu DY (2005) Reverse epidemiology: a spurious hypothesis or a hardcore reality? Blood Purif 23:57–63

    PubMed  Google Scholar 

  126. Clerico A, Del Ry S, Giannessi D (2000) Measurement of natriuretic cardiac hormones (ANP, BNP, and related peptides) in clinical practice: the need for a new generation of immunoassay methods. Clin Chem 46:1529–1534

    PubMed  CAS  Google Scholar 

  127. Apple FS M, Panteghini M, Ravkilde J, Mair J, Wu AHB J, Tate J et al (2005) Quality specifications for B-type natriuretic peptide assays. Clin Chem 51:486–493 (On Behalf of the Committee on Standardization of Markers of Cardiac Damage of the IFCC)

    PubMed  Google Scholar 

  128. Apple FS, Wu AH, Jaffe AS, Panteghini M, Christenson RH, Cannon CP et al (2007) National academy of clinical biochemistry and IFCC committee for standardization of markers of cardiac damage laboratory medicine practice guidelines: analytical issues for biomarkers of heart failure. Circulation 116:e95–e98

    PubMed  CAS  Google Scholar 

  129. Prontera C, Zaninotto M, Giovannini S, Zucchelli GC, Pilo A, Sciacovelli L et al (2009) Proficiency testing project for brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP (NT-proBNP) immunoassays: the Cardio Ormocheck study. Clin Chem Lab Med 47:762–768

    PubMed  CAS  Google Scholar 

  130. Liang F, O’Rear J, Schellenberger U, Tai L, Lasecki M, Schreiner GF et al (2007) Evidence for functional heterogeneity of circulating B-type natriuretic peptide. J Am Coll Cardiol 49:1071–1078

    PubMed  CAS  Google Scholar 

  131. Kalantar-Zadeh K, Anker SD, Horwich TB, Fonarow GC (2008) Nutritional and anti-inflammatory interventions in chronic heart failure. Am J Cardiol 101(Suppl 11A):89E–103E

    PubMed  CAS  Google Scholar 

  132. Lavie CL, Milani RV, Ventura HO (2009) Obesity and cardiovascular disease. Risk factor, paradox, and impact of weigh loss. J Am Coll Cardiol 53:1925–1932

    PubMed  Google Scholar 

  133. Arena R, Lavie CJ (2010) The obesity paradox and outcome in heart failure: is excess bodyweight truly protective? Future Cardiol 6:1–6

    PubMed  Google Scholar 

  134. Hedayat M, Mahmoudi MJ, Rose NR, Rezari N (2010) Proinflammatory cytokines in heart failure: double-edged sword. Heart Fail Rev 15:543–562

    PubMed  CAS  Google Scholar 

  135. Tostain JL, Blanc F (2008) Testosterone deficiency: a common, unrecognized syndrome. Nat Clin Pract Urol 5:388–396

    PubMed  CAS  Google Scholar 

  136. Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K et al (2005) N-terminal pro brain natriuretic peptide is inversely related to metabolic cardiovascular risk factors and the metabolic syndrome. Hypertension 46:660–666

    PubMed  CAS  Google Scholar 

  137. Chainani-Wu N, Weidner G, Purnell DM, Frenda S, Merritt-Worden T, Kemp C et al (2010) Relation of B-type natriuretic peptide levels to body mass index after comprehensive lifestyle changes. Am J Cardiol 105:1570–1576

    PubMed  CAS  Google Scholar 

  138. Nielsen OW, McDonagh TA, Robb SD, Dargie HJ (2003) Retrospective analysis of the cost-effectiveness of using plasma brain natriuretic peptide in screening for left ventricular systolic dysfunction in the general population. J Am Coll Cardiol 41:113–120

    PubMed  Google Scholar 

  139. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T et al (2004) Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 350:655–663

    PubMed  CAS  Google Scholar 

  140. Kistorp C, Raymond I, Pedersen F, Gustafsson F, Faber J, Hildebrandt P (2005) N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA 293:1609–1616

    PubMed  CAS  Google Scholar 

  141. Wallen T, Landahl S, Hedner T, Nakao K, Saito Y (1997) Brain natriuretic peptide predicts mortality in the elderly. Heart 77:264–267

    PubMed  CAS  Google Scholar 

  142. McKie PM, Rodeheffer RJ, Cataliotti A, Martin FL, Urban LH, Mahoney DW et al (2006) Amino-terminal pro- B-type natriuretic peptide and B-type natriuretic peptide: biomarkers for mortality in a large community-based cohort free of heart failure. Hypertension 47:874–880

    PubMed  CAS  Google Scholar 

  143. Nakamura M, Tanaka F, Onoda T, Takahashi T, Sakuma M, Kawamura K et al (2010) Gender-specific risk stratification with plasma B-type natriuretic peptide for future onset of congestive heart failure and mortality in the Japanese general population. Int J Cardiol 143:124–129

    PubMed  Google Scholar 

  144. Tsutamoto T, Wada A, Maeda K, Hisanaga T, Mabuchi N, Hayashi M et al (1999) Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction. Comparison with plasma angiotensin II and endothelin-1. Eur Heart J 20:1799–1807

    PubMed  CAS  Google Scholar 

  145. Stanek B, Frey B, Hulsmann M, Berger R, Sturm B, Strametz-Juranek J et al (2001) Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction. J Am Coll Cardiol 38:436–442

    PubMed  CAS  Google Scholar 

  146. Anand IS, Fisher LD, Chiang YT, Latini R, Masson S, Maggioni AP et al (2003) Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan heart failure trial (Val-HeFT). Circulation 107:1278–1283

    PubMed  CAS  Google Scholar 

  147. Koseki Y, Watanabe J, Shinozaki T, Sakuma M, Komaru T, Fukuchi M et al (2003) The CHART Investigators. Characteristics and 1-year prognosis of medically treated patients with chronic heart failure in Japan. Circ J 67:431–436

    PubMed  Google Scholar 

  148. Omland T, Persson A, Ng L, O’Brien R, Karlsson T, Herlitz J et al (2002) N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes. Circulation 106:2913–2918

    PubMed  CAS  Google Scholar 

  149. Arakawa N, Nakamura M, Aoki H, Hiramori K (1996) Plasma brain natriuretic peptide concentrations predict survival after acute myocardial infarction. J Am Coll Cardiol 27:1561–1656

    Google Scholar 

  150. Darbar D, Davidson NC, Gillespie N, Choy AM, Lang CC, Shyr Y et al (1996) Diagnostic value of B-type natriuretic peptide concentrations in patients with acute myocardial infarction. Am J Cardiol 78:284–287

    PubMed  CAS  Google Scholar 

  151. Richards AM, Doughty R, Nicholls MG, MacMahon S, Sharpe N, Murphy J et al (2001) Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. J Am Coll Cardiol 37:1781–1787

    PubMed  CAS  Google Scholar 

  152. Sabatine MS, Morrow DA, de Lemos JA, Gibson CM, Murphy SA, Rifai N et al (2002) Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation 105:1760–1763

    PubMed  CAS  Google Scholar 

  153. Jernberg T, Stridsberg M, Lindahl B (2002) Usefulness of plasma N-terminal proatrial natriuretic peptide (proANP) as an early predictor of outcome in unstable angina pectoris or non-ST-elevation acute myocardial infarction. Am J Cardiol 89:64–66

    PubMed  CAS  Google Scholar 

  154. Morrow DA, de Lemos JA, Sabatine MS, Murphy SA, Demopoulos LA, DiBattiste PM et al (2003) Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18. J Am Coll Cardiol 41:1264–1272

    PubMed  CAS  Google Scholar 

  155. Galvani M, Ottani F, Oltrona L, Ardissino D, Gensini GF, Maggioni AP et al (2004) Italian working group on atherosclerosis, thrombosis, and vascular biology and the associazione nazionale medici cardiologi ospedalieri (ANMCO). N-terminal pro-brain natriuretic peptide on admission has prognostic value across the whole spectrum of acute coronary syndromes. Circulation 110:128–134

    PubMed  CAS  Google Scholar 

  156. Doust JA, Pietrzak E, Dobson A, Glasziou P (2005) How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. Br Med J 330:625

    CAS  Google Scholar 

  157. Galvani M, Ferrini D, Ottani T (2004) Natriuretic peptides for risk stratification of patients with acute coronary syndromes. Eur J Heart Fail 6:327–333

    PubMed  CAS  Google Scholar 

  158. Di Angelantonio E, Chowdhury R, Sarwar N, Ray KK, Gobin R, Saleheen D et al (2009) B-type natriuretic peptides and cardiovascular risk: systematic review and meta-analysis of 40 prospective studies. Circulation 120:2177–2187

    PubMed  CAS  Google Scholar 

  159. Karthikeyan G, Moncur RA, Levine O, Heels-Ansdell D, Chan MT, Alonso-Coello P, et al. (2009) Is a pre-operative brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide measurement an independent predictor of adverse cardiovascular outcomes within 30 days of noncardiac surgery? A systematic review and meta-analysis of observational studies. J Am Coll Cardiol 54:1599–1606

    Google Scholar 

  160. Ryding AD, Kumar S, Worthington A, Burgess D (2009) Prognostic values of brain natriuretic peptide in noncardiac surgery. Anesthesiology 111:311–319

    PubMed  CAS  Google Scholar 

  161. Kellett J (2004) Prediction of in-hospital mortality by brain natriuretic peptide levels and other independent variables in acutely ill patients with suspected heart disease. Can J Cardiol 20:686–690

    PubMed  Google Scholar 

  162. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. (2005) ACC/AHA 2005 Guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart association task force on practice guidelines (Writing committee to update the 2001 guidelines for the evaluation and management of heart failure): developed in collaboration with the American college of chest physicians and the international society for heart and lung transplantation: endorsed by the heart rhythm society. Circulation 112:e154–e235

    Google Scholar 

  163. Lavie CJ, Milani RV, Ventura HO (2010) Body composition and heart failure prevalence and prognosis: getting to the fat of the matter in the “obesity paradox”. Mayo Clin Porc 85:605–608

    Google Scholar 

  164. Barabási AL (2009) Scale-free networks: a decade and beyond. Science 325:412–413

    PubMed  Google Scholar 

  165. Barabási AL (2007) Network medicine—From obesity to the “diseasome”. N Engl J Med 357:404–407

    PubMed  Google Scholar 

  166. Goh KI, Cusik ME, Valle D, Childs B, Vidal M, Barabási AL (2007) The human disease network. Proc Natl Acad Sci USA 104:8685–8690

    PubMed  CAS  Google Scholar 

  167. Lee DS, Park J, Kay KA, Christakis NA, Oltvai ZN, Barabási AL (2008) The implications of human metabolic network topology for disease comorbidity. Proc Natl Acad Sci USA 105:9880–9885

    PubMed  CAS  Google Scholar 

  168. Rosen R (2000) Essays on life itself. Columbia University Press, New York, pp 306–307

    Google Scholar 

  169. Sugisawa T, Kishimoto I, Kokubo Y, Nagumo A, Makino H, Miyamoto Y, Yoshimasa Y (2010) Visceral fat is negatively associated with B-type natriuretic peptide levels in patients with advanced type 2 diabetes. Diabetes Res Clin Pract 89:174–180

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Cardiovascular Endocrinology and Cell Biology, Fondazione CNR—Regione Toscana Gabriele Monasterio, Scuola Superiore Sant’Anna, Via Trieste 41, 56126, Pisa, Italy

    Aldo Clerico, Alberto Giannoni, Simona Vittorini & Michele Emdin

  2. Scuola Superiore S. Anna, Pisa, Italy

    Aldo Clerico & Alberto Giannoni

Authors
  1. Aldo Clerico
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alberto Giannoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Simona Vittorini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michele Emdin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aldo Clerico.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clerico, A., Giannoni, A., Vittorini, S. et al. The paradox of low BNP levels in obesity. Heart Fail Rev 17, 81–96 (2012). https://doi.org/10.1007/s10741-011-9249-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-011-9249-z

Keywords

Search

Navigation