Mean BMI, visit-to-visit BMI variability and BMI changes during follow-up in patients with acute myocardial infarction with systolic dysfunction and/or heart failure: insights from the High-Risk Myocardial Infarction Initiative

  • Susan Stienen
  • João Pedro Ferreira
  • Nicolas Girerd
  • Kévin Duarte
  • Zohra Lamiral
  • John J. V. McMurray
  • Bertram Pitt
  • Kenneth Dickstein
  • Faiez Zannad
  • Patrick RossignolEmail author
  • For the High-Risk Myocardial Infarction Database Initiative
Original Paper



In patients with acute myocardial infarction (MI), BMI < 18.5 kg/m2 and a decrease in BMI during follow-up have been associated with poor prognosis. For BMI ≥ 25 kg/m2, an “obesity paradox” has been suggested. Recently, high visit-to-visit BMI variability has also been associated with poor prognosis in patients with coronary artery disease.


To simultaneously evaluate several BMI measurements and study their association with cardiovascular (CV) outcomes in a large cohort of patients with acute myocardial infarction (MI) and left ventricular (LV) systolic dysfunction, heart failure (HF) or both.


The high-risk MI dataset is pooled from four trials: CAPRICORN, EPHESUS, OPTIMAAL and VALIANT. Mean BMI, change from baseline, and variability were assessed during follow-up. The primary outcome was CV death. Cox-proportional hazard models were performed to study the association between the various BMI parameters and outcomes (median follow-up = 1.8 years).


A total of 12,719 patients were included (72% male, mean age 65 ± 11 years). Mean, change and visit-to-visit variability in BMI had a non-linear association with CV death (P < 0.001). Mean BMI < 26 kg/m2 (vs. ≥ 26–35 kg/m2) and BMI decrease during follow-up were independently associated with CV death (adjusted HR 1.32, 95% CI 1.16–1.51, P < 0.001 and adjusted HR 1.57, 95% CI 1.40–1.76, P < 0.001, respectively). Low and high BMI variability (< 2% and > 4%) were associated with increased event-rates, but lost statistical significance in sensitivity analysis including patients with ≥ 5 measurements or excluding patients with HF hospitalization, suggesting that BMI variability may be particularly associated with HF hospitalizations.


Mean BMI < 26 kg/m2 and a BMI decrease during follow-up were independently associated with CV death in patients with MI and LV systolic dysfunction, HF or both. These associations likely reflect poorer patient status and causality cannot be inferred.


Acute myocardial infarction Systolic dysfunction Body mass index Prognosis Variability 



The authors thank Pierre Pothier for editing the manuscript. SS, JF, NG, PR were supported by a Contrat de Plan Etat Lorraine, FEDER, and a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program (reference: ANR-15-RHU-0004), and GEENAGE Impact Lorraine Université d’Excellence—reference ANR-15-IDEX-04-LUE.

Supplementary material

392_2019_1453_MOESM1_ESM.docx (623 kb)
Supplementary material 1 (DOCX 623 KB)


  1. 1.
    Abdulla J, Kober L, Abildstrom SZ, Christensen E, James WP, Torp-Pedersen C (2008) Impact of obesity as a mortality predictor in high-risk patients with myocardial infarction or chronic heart failure: a pooled analysis of five registries. Eur Heart J 29:594–601CrossRefGoogle Scholar
  2. 2.
    Bucholz EM, Krumholz HA, Krumholz HM, Underweight (2016) Markers of cachexia, and mortality in acute myocardial infarction: a prospective cohort study of elderly medicare beneficiaries. PLoS Med 13:e1001998CrossRefGoogle Scholar
  3. 3.
    Gregory AB, Lester KK, Gregory DM, Twells LK, Midodzi WK, Pearce NJ (2017) The relationship between body mass index and the severity of coronary artery disease in patients referred for coronary angiography. Cardiol Res Pract 2017:5481671CrossRefGoogle Scholar
  4. 4.
    Herrmann J, Gersh BJ, Goldfinger JZ, Witzenbichler B, Guagliumi G, Dudek D, Kornowski R, Brener SJ, Parise H, Fahy M, McAndrew TC, Stone GW, Mehran R (2014) Body mass index and acute and long-term outcomes after acute myocardial infarction (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial). Am J Cardiol 114:9–16CrossRefGoogle Scholar
  5. 5.
    Bucholz EM, Beckman AL, Krumholz HA, Krumholz HM (2016) Excess weight and life expectancy after acute myocardial infarction: the obesity paradox reexamined. Am Heart J 172:173–181CrossRefGoogle Scholar
  6. 6.
    Niedziela J, Hudzik B, Niedziela N, Gasior M, Gierlotka M, Wasilewski J, Myrda K, Lekston A, Polonski L, Rozentryt P (2014) The obesity paradox in acute coronary syndrome: a meta-analysis. Eur J Epidemiol 29:801–812CrossRefGoogle Scholar
  7. 7.
    O’Brien EC, Fosbol EL, Peng SA, Alexander KP, Roe MT, Peterson ED (2014) Association of body mass index and long-term outcomes in older patients with non-ST-segment-elevation myocardial infarction: results from the CRUSADE Registry. Circ Cardiovasc Qual Outcomes 7:102–109CrossRefGoogle Scholar
  8. 8.
    Wienbergen H, Gitt AK, Juenger C, Schiele R, Heer T, Towae F, Gohlke H, Senges J, Group MPs (2008) Impact of the body mass index on occurrence and outcome of acute ST-elevation myocardial infarction. Clin Res Cardiol 97:83–88CrossRefGoogle Scholar
  9. 9.
    Fonarow GC, Srikanthan P, Costanzo MR, Cintron GB, Lopatin M, Committee ASA, Investigators (2007) An obesity paradox in acute heart failure: analysis of body mass index and inhospital mortality for 108,927 patients in the Acute Decompensated Heart Failure National Registry. Am Heart J 153:74–81CrossRefGoogle Scholar
  10. 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 156:13–22CrossRefGoogle Scholar
  11. 11.
    Chau K, Girerd N, Magnusson M, Lamiral Z, Bozec E, Merckle L, Leosdottir M, Bachus E, Frikha Z, Ferreira JP, Despres JP, Rossignol P, Boivin JM, Zannad F (2018) Obesity and metabolic features associated with long-term developing diastolic dysfunction in an initially healthy population-based cohort. Clin Res Cardiol 107(10):887–896CrossRefGoogle Scholar
  12. 12.
    Flegal KM, Kit BK, Orpana H, Graubard BI (2013) Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA 309:71–82CrossRefGoogle Scholar
  13. 13.
    Jacobs L, Efremov L, Ferreira JP, Thijs L, Yang WY, Zhang ZY, Latini R, Masson S, Agabiti N, Sever P, Delles C, Sattar N, Butler J, Cleland JGF, Kuznetsova T, Staessen JA, Zannad F, Heart OiAi (2017) Risk for incident heart failure: a subject-level meta-analysis from the Heart “OMics” in AGEing (HOMAGE) Study. J Am Heart Assoc 6(5):e005231. CrossRefGoogle Scholar
  14. 14.
    Kennedy LM, Dickstein K, Anker SD, James M, Cook TJ, Kristianson K, Willenheimer R (2006) Weight-change as a prognostic marker in 12 550 patients following acute myocardial infarction or with stable coronary artery disease. Eur Heart J 27:2755–2762CrossRefGoogle Scholar
  15. 15.
    Sierra-Johnson J, Romero-Corral A, Somers VK, Lopez-Jimenez F, Thomas RJ, Squires RW, Allison TG (2008) Prognostic importance of weight loss in patients with coronary heart disease regardless of initial body mass index. Eur J Cardiovasc Prev Rehabil 15:336–340CrossRefGoogle Scholar
  16. 16.
    Bangalore S, Fayyad R, Laskey R, DeMicco DA, Messerli FH, Waters DD (2017) Body-weight fluctuations and outcomes in coronary disease. N Engl J Med 376:1332–1340CrossRefGoogle Scholar
  17. 17.
    Dickstein K, Bebchuk J, Wittes J (2012) The high-risk myocardial infarction database initiative. Prog Cardiovasc Dis 54:362–366CrossRefGoogle Scholar
  18. 18.
    Dargie HJ (2000) Design and methodology of the CAPRICORN trial—a randomised double blind placebo controlled study of the impact of carvedilol on morbidity and mortality in patients with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail 2:325–332CrossRefGoogle Scholar
  19. 19.
    Dargie HJ (2001) Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 357:1385–1390CrossRefGoogle Scholar
  20. 20.
    Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M, Eplerenone Post-Acute Myocardial Infarction Heart Failure E and Survival Study I (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348:1309–1321CrossRefGoogle Scholar
  21. 21.
    Pitt B, Williams G, Remme W, Martinez F, Lopez-Sendon J, Zannad F, Neaton J, Roniker B, Hurley S, Burns D, Bittman R, Kleiman J (2001) The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure Efficacy and Survival Study. Cardiovasc Drugs Ther 15:79–87CrossRefGoogle Scholar
  22. 22.
    Dickstein K, Kjekshus J (1999) Comparison of the effects of losartan and captopril on mortality in patients after acute myocardial infarction: the OPTIMAAL trial design. Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist Losartan. Am J Cardiol 83:477–481CrossRefGoogle Scholar
  23. 23.
    Dickstein K, Kjekshus J, Group OSCotOS (2002) Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 360:752–760CrossRefGoogle Scholar
  24. 24.
    Pfeffer MA, McMurray J, Leizorovicz A, Maggioni AP, Rouleau JL, Van De Werf F, Henis M, Neuhart E, Gallo P, Edwards S, Sellers MA, Velazquez E, Califf R (2000) Valsartan in acute myocardial infarction trial (VALIANT): rationale and design. Am Heart J 140:727–750CrossRefGoogle Scholar
  25. 25.
    Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM, Valsartan in Acute Myocardial Infarction Trial I (2003) Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 349:1893–1906CrossRefGoogle Scholar
  26. 26.
    Coiro S, Girerd N, Rossignol P, Bauersachs J, Pitt B, Fay R, Ambrosio G, Solomon SD, Dickstein K, Zannad F (2017) Association of digitalis treatment with outcomes following myocardial infarction in patients with heart failure or evidence of left ventricular dysfunction: an analysis from the High-Risk Myocardial Infarction Database Initiative. Clin Res Cardiol 106:722–733CrossRefGoogle Scholar
  27. 27.
    von Lueder TG, Girerd N, Atar D, Agewall S, Lamiral Z, Kanbay M, Pitt B, Dickstein K, Zannad F, Rossignol P, High-Risk Myocardial Infarction Database Initiative I (2015) Serum uric acid is associated with mortality and heart failure hospitalizations in patients with complicated myocardial infarction: findings from the High-Risk Myocardial Infarction Database Initiative. Eur J Heart Fail 17:1144–1151CrossRefGoogle Scholar
  28. 28.
    Abdin A, Poss J, Fuernau G, Ouarrak T, Desch S, Eitel I, de Waha S, Zeymer U, Bohm M, Thiele H (2018) Revision: prognostic impact of baseline glucose levels in acute myocardial infarction complicated by cardiogenic shock-a substudy of the IABP-SHOCK II-trial. Clin Res Cardiol 107:517–523CrossRefGoogle Scholar
  29. 29.
    de Araujo Goncalves P, Ferreira J, Aguiar C, Seabra-Gomes R (2005) TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS. Eur Heart J 26:865–872CrossRefGoogle Scholar
  30. 30.
    Mogensen UM, Jhund PS, Abraham WT, Desai AS, Dickstein K, Packer M, Rouleau JL, Solomon SD, Swedberg K, Zile MR, Kober L, McMurray JJV, Paradigm HF, Investigators A and Committees (2017) Type of atrial fibrillation and outcomes in patients with heart failure and reduced ejection fraction. J Am Coll Cardiol 70:2490–2500CrossRefGoogle Scholar
  31. 31.
    Pocock SJ, Ariti CA, McMurray JJ, Maggioni A, Kober L, Squire IB, Swedberg K, Dobson J, Poppe KK, Whalley GA, Doughty RN, Meta-Analysis Global Group in Chronic Heart F (2013) Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies. Eur Heart J 34:1404–1413CrossRefGoogle Scholar
  32. 32.
    Zhang J, Begley A, Jackson R, Harrison M, Pellicori P, Clark AL, Cleland JGF (2019) Body mass index and all-cause mortality in heart failure patients with normal and reduced ventricular ejection fraction: a dose-response meta-analysis. Clin Res Cardiol 108(2):119–132CrossRefGoogle Scholar
  33. 33.
    Rossignol P, Masson S, Barlera S, Girerd N, Castelnovo A, Zannad F, Clemenza F, Tognoni G, Anand IS, Cohn JN, Anker SD, Tavazzi L, Latini R, Gissi HF, Val-He FTI (2015) Loss in body weight is an independent prognostic factor for mortality in chronic heart failure: insights from the GISSI-HF and Val-HeFT trials. Eur J Heart Fail 17:424–433CrossRefGoogle Scholar
  34. 34.
    Zamora E, Diez-Lopez C, Lupon J, de Antonio M, Domingo M, Santesmases J, Troya MI, Diez-Quevedo C, Altimir S, Bayes-Genis A (2016) Weight loss in obese patients with heart failure. J Am Heart Assoc 5:e002468CrossRefGoogle Scholar
  35. 35.
    Jamaly S, Carlsson L, Peltonen M, Jacobson P, Sjostrom L, Karason K (2016) Bariatric surgery and the risk of new-onset atrial fibrillation in Swedish obese subjects. J Am Coll Cardiol 68:2497–2504CrossRefGoogle Scholar
  36. 36.
    Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, Navaneethan SD, Singh RP, Pothier CE, Nissen SE, Kashyap SR, Investigators S (2017) Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. N Engl J Med 376:641–651CrossRefGoogle Scholar
  37. 37.
    Pack QR, Rodriguez-Escudero JP, Thomas RJ, Ades PA, West CP, Somers VK, Lopez-Jimenez F (2014) The prognostic importance of weight loss in coronary artery disease: a systematic review and meta-analysis. Mayo Clin Proc 89:1368–1377CrossRefGoogle Scholar
  38. 38.
    Shimada YJ, Tsugawa Y, Brown DF, Hasegawa K (2016) Bariatric surgery and emergency department visits and hospitalizations for heart failure exacerbation: population-based, self-controlled series. J Am Coll Cardiol 67:895–903CrossRefGoogle Scholar
  39. 39.
    Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimsky P, Group ESCSD (2018) 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 39:119–177CrossRefGoogle Scholar
  40. 40.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH van der, Meer P, Group ESCSD (2016) 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37:2129–2200CrossRefGoogle Scholar
  41. 41.
    Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, Webb-Peploe KM, Harrington D, Kox WJ, Poole-Wilson PA, Coats AJ (1997) Wasting as independent risk factor for mortality in chronic heart failure. Lancet 349:1050–1053CrossRefGoogle Scholar
  42. 42.
    Banack HR, Kaufman JS (2014) The obesity paradox: understanding the effect of obesity on mortality among individuals with cardiovascular disease. Prev Med 62:96–102CrossRefGoogle Scholar
  43. 43.
    Pi-Sunyer XF, Becker DM, Bouchard C, Carleton R, Colditz GA, Dietz WH, Foreyt JP, Garrison RJ, Grundy SM, Hansen BC, Higgins M, Hill JO, Howard BV, Kuczmarski RJ, Kumanyika S, Legako DR, Prewitt ET, Rocchini AP, Smith PL, Snetselaar LG, Sowers JR, Weintraub M, Williamson DF, Wilson TG (1998) Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Expert panel on the identification, evaluation, and treatment of overweight in adults. Am J Clin Nutr 68(4):899–917CrossRefGoogle Scholar
  44. 44.
    Coutinho T, Goel K, Correa de Sa D, Carter RE, Hodge DO, Kragelund C, Kanaya AM, Zeller M, Park JS, Kober L, Torp-Pedersen C, Cottin Y, Lorgis L, Lee SH, Kim YJ, Thomas R, Roger VL, Somers VK, Lopez-Jimenez F (2013) Combining body mass index with measures of central obesity in the assessment of mortality in subjects with coronary disease: role of “normal weight central obesity”. J Am Coll Cardiol 61:553–560CrossRefGoogle Scholar
  45. 45.
    Sze S, Zhang J, Pellicori P, Morgan D, Hoye A, Clark AL (2017) Prognostic value of simple frailty and malnutrition screening tools in patients with acute heart failure due to left ventricular systolic dysfunction. Clin Res Cardiol 106:533–541CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Susan Stienen
    • 1
  • João Pedro Ferreira
    • 1
    • 2
  • Nicolas Girerd
    • 1
  • Kévin Duarte
    • 3
    • 4
    • 5
  • Zohra Lamiral
    • 1
  • John J. V. McMurray
    • 6
  • Bertram Pitt
    • 7
  • Kenneth Dickstein
    • 8
  • Faiez Zannad
    • 1
  • Patrick Rossignol
    • 1
    Email author
  • For the High-Risk Myocardial Infarction Database Initiative
  1. 1.Université de Lorraine, INSERM, Centre d’Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)NancyFrance
  2. 2.Cardiovascular Research and Development Unit, Department of Physiology and Cardiothoracic Surgery, Faculty of MedicineUniversity of PortoPortoPortugal
  3. 3.Université de Lorraine, Institut Elie Cartan de Lorraine, UMR 7502Vandoeuvre-lès-NancyFrance
  4. 4.CNRS, Institut Elie Cartan de Lorraine, UMR 7502Vandoeuvre-lès-NancyFrance
  5. 5.Team BIGS, INRIAVillers-lès-NancyFrance
  6. 6.BHF Cardiovascular Research CentreUniversity of GlasgowGlasgowScotland, UK
  7. 7.Department of MedicineUniversity of Michigan School of MedicineAnn ArborUSA
  8. 8.Department of CardiologyUniversity of Bergen, Stavanger University HospitalStavangerNorway

Personalised recommendations