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.
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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
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
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
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
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
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
Dessi-Fulgheri P, Sarzani R, Rappelli A (1998) The natriuretic peptide system in obesity-related hypertension: new pathophysiological aspects. J Nephrol 11:296–299
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
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
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
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
De Bold AJ (1985) Atrial natriuretic factor: a hormone produced by the heart. Science 230:427–470
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
Goetze JP (2010) Biosynthesis of cardiac natriuretic peptides. Results Probl Cell Differ 50:12–97
De Bold AJ, Bruneau BG, Kuroski de Bold ML (1996) Mechanical and neuroendocrine regulation of the endocrine heart. Cardiovasc Res 31:7–18
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
McGrath MF, de Bold AJ (2005) Determinants of natriuretic peptide gene expression. Peptides 26:933–943
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
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
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
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
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
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
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
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
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
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
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
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)
Ramos H, de Bold AJ (2006) Gene expression, processing, and secretion of natriuretic peptides: physiologic and diagnostic implications. Heart Fail Clin 2:255–268
De Bold AJ (2009) Cardiac natriuretic peptides gene expression and secretion in inflammation. J Investig Med 57:29–32
Kuwahara K, Nakao K (2010) Regulation and significance of atrial and brain natriuretic peptides as cardiac hormones. Endocr J 57:555–565
Goetze JP, Georg B, Jørgensen HL, Fahrenkrug J (2010) Chamber-dependent circadian expression of cardiac natriuretic peptides. Regul Pept 160:140–145
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
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
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
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
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
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
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
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
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
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
Preventing and Managing the Global Epidemic of Obesity (1997) Report of the world health organization consultation of obesity. WHO, Geneva
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
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
Goetze JP (2004) Biochemistry of pro-B-type natriuretic peptide-derived peptides: the endocrine heart revisited. Clin Chem 50:1503–1510
Goetze JP, Rehfeld JF (2009) Peptide hormones and their prohormones as biomarkers. Biomark Med 3:335–338
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
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
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
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
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
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
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
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
Mattsson C, Olsson T (2007) Estrogens and glucocorticoid hormones in adipose tissue metabolism. Curr Med Chem 14:2918–2924
Blouin K, Boivin A, Tchernof A (2008) Androgens and body fat distribution. J Steroid Biochem Mol Biol 108:272–280
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
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
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
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
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
Kuroski de Bold ML (1999) Estrogen, natriuretic peptides and the renin-angiotensin system. Cardiovasc Res 41:524–531
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
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
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
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
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
Marin P (1995) Testosterone and regional fat distribution. Obes Res 3(Suppl. 4):609S–612S
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
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
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
Glazer G (1991) Atherogenic effects of anabolic steroids on serum lipid levels. A literature review. Arch Intern Med 151:1925–1933
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
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
Traish AM, Saad F, Feeley RJ, Guay A (2009) The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl 30:477–494
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
Zitzmann M (2009) Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol 5:673–681
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
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
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
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
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
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
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
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
Wende AR, Abel ED (2010) Lipotoxicity in the heart. Biochim Biophys Acta 1801:311–319
Shimabukuro M (2010) Cardiac adiposity and global cardio metabolic risk. New concept and clinical implications. Circ J 73:27–34
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
Wozniak SE, Gee LL, Wachted MS, Frezza EE (2009) Adipose tissue: the new endocrine organ? A review article. Dig Dis Sci 54:1847–1856
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
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
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
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
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
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
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
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
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
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
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
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
Canoy D (2010) Coronary heart disease and body fat distribution. Curr Atheroscler Rep 12:125–133
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Royston P, Altman DG, Sauerbrei W (2006) Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med 25:127–141
Altman DG, Royston P (2006) The cost of dichotomising continuous variables. Br Med J 332:1080
Lee SY, Gallagher D (2008) Assessment methods in human body composition. Curr Opin Clin Nutr Metab Care 11:566–572
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
Wikipedia, the free encyclopedia. Arnold Alois Schwarzenegger. (http://en.wikipedia.org/wiki/ArnoldSchwarzenegger#cite_note-mrever-10)
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
Kalantar-Zadeh K, Kilpatrick RD, Kuwae N, Wu DY (2005) Reverse epidemiology: a spurious hypothesis or a hardcore reality? Blood Purif 23:57–63
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
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)
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
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
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
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
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
Arena R, Lavie CJ (2010) The obesity paradox and outcome in heart failure: is excess bodyweight truly protective? Future Cardiol 6:1–6
Hedayat M, Mahmoudi MJ, Rose NR, Rezari N (2010) Proinflammatory cytokines in heart failure: double-edged sword. Heart Fail Rev 15:543–562
Tostain JL, Blanc F (2008) Testosterone deficiency: a common, unrecognized syndrome. Nat Clin Pract Urol 5:388–396
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
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
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
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
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
Wallen T, Landahl S, Hedner T, Nakao K, Saito Y (1997) Brain natriuretic peptide predicts mortality in the elderly. Heart 77:264–267
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Ryding AD, Kumar S, Worthington A, Burgess D (2009) Prognostic values of brain natriuretic peptide in noncardiac surgery. Anesthesiology 111:311–319
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
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
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
Barabási AL (2009) Scale-free networks: a decade and beyond. Science 325:412–413
Barabási AL (2007) Network medicine—From obesity to the “diseasome”. N Engl J Med 357:404–407
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
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
Rosen R (2000) Essays on life itself. Columbia University Press, New York, pp 306–307
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
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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
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DOI: https://doi.org/10.1007/s10741-011-9249-z