Obesity & Diabetes: New targets in heart failure management Rudolf A. de Boer, MD, FESC, FHFA University Medical Center Groningen Groningen, the Netherlands Novel concepts and treatments of comorbidities in Heart Failure with Preserved Ejection Fraction Sunday May 27, 12:45-14:00
Faculty Disclosure Declaration of financial interests For the last 3 years and the subsequent 12 months: I I have received a research grant(s)/ in kind support A From current sponsor(s) YES NO B From any institution YES NO II I have been a speaker or participant in accredited CME/CPD A From current sponsor(s) YES NO B From any institution YES NO III I have been a consultant/strategic advisor etc A For current sponsor(s) YES NO B For any institution YES NO IV I am a holder of (a) patent/shares/stock ownerships A Related to presentation YES NO B Not related to presentation YES NO
Faculty Disclosure: Rudolf A. de Boer MD PhD Declaration of non-financial interests: • University of Groningen, Groningen, the Netherlands • Professor of Cardiology, Cardiologist, Director of Experimental Cardiology • Dr. de Boer is supported by the Netherlands Heart Foundation (CVON DOSIS, grant 2014-40, CVON SHE-PREDICTS-HF, grant 2017-21, and CVON RED-CVD, grant 2017-11); and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). • Board member, Heart Failure Association (HFA) of the ESC • Chair, study group on HFpEF of the HFA • Member ESC Advocacy committee • Chair, working group of Heart Failure of the Dutch Society of Cardiology
Obesity Trends* Among U.S. Adults BRFSS, 1990, 1995, 2005 (*BMI 30, or about 30 lbs overweight for 5’4” person) 1995 1990 2005 No Data <10% 10% – 14% 15% – 19% 20% – 24% 25% –29% ≥30% University Medical Center Groningen
Overlapping risk factors University Medical Center Groningen
BMI and Diabetes: Predictors for new onset HFpEF • 28,820 individuals from the 4 large cohort studies, 12 years of FU • 811 new onset HFpEF (39%) • 200 new onset HFmrEF (10%) FHS/PREVEND/CVS/MESA • 1048 new onset HFrEF (51%) Bhambhani V, et al. Eur J Heart Fail. 2018; 20 :651-659 University Medical Center Groningen
Current pathophysiological paradigm: Obesity and DM are important drivers of HFpEF Shah, SJ et al. Circulation. 2016; 134 :73-90 University Medical Center Groningen
Treatment of obesity Neeland IJ, et al. Circulation. 2018; 137 :1391 – 1406 University Medical Center Groningen
Bariatric surgery and HFpEF Rodriguez Flores M, et al. Expert Rev Cardiovasc Ther. 2017; 15 :567-579 University Medical Center Groningen
Obesity-related HFpEF Speculation! Packer M. JACC: Heart Failure 2018 University Medical Center Groningen
Obesity paradox Padwal R, et al. Int J Obes (Lond). 2014; 38 :1110-1114 Carbone S, et al. Mayo Clin Proc. 2017; 92 :266-279 University Medical Center Groningen
Obesity: Contributor or confounder of HFpEF? Kitzman DW & Shah SJ. J Am Coll Cardiol HF. 2016; 68 :200-203 University Medical Center Groningen
Obesity: substantial heterogeneity Neeland IJ, et al. Circulation. 2018; 137 :1391 – 1406 University Medical Center Groningen
Carbone S, et al. Mayo Clin Proc. 2017; 92 :266-279 University Medical Center Groningen
Obese-HFpEF phenotype is clinically relevant • Obese HFpEF patients (N = 99) were compared to non-obese HFpEF patients (N = 96) and control subjects free of HF (N = 71) • Characteristics of obese HFpEF patients • Increased plasma volume • More concentric LV remodeling • Greater RV dilation and more RV dysfunction • Increased epicardial fat thickness • Greater total epicardial heart volume Obokata M, Circulation. 2017; 136 : 6-19 University Medical Center Groningen
Exercise capacity & hemodynamic reserve reduced in obese HFpEF patients Obokata M, Circulation. 2017; 136 : 6-19 University Medical Center Groningen
HF and Fitness: Role of BMI Low Cardiorespiratory Fitness High Cardiorespiratory Fitness Lavie CJ, et al. Mayo Clin Proc. 2013; 88 :251-258 University Medical Center Groningen
BMI stronger predictor for HFpEF than for HFrEF HF subtype by quartile of BMI HR for Incidence of HF subtype Men Women 4 P=<0.001 P<0.001 P<0.001 P=0.49 3 2 1 0 e n n W o m e n HFpEF HFrEF F HFpEF HFrEF H F r E o m e F M W E Savji N, et al. JACC Heart Fail. Accepted University Medical Center Groningen
Obesity and Sex: Effects on NT-proBNP PREVEND study: 8,592 subjects, mean age 49 years Suthahar N, et al. Eur J Heart Fail. 2018; in press University Medical Center Groningen
Summary 1 - Obesity • Important to have ‘ normal weight ’ • Once HFpEF: important to have sufficient lean mass • Losing fat mass: pharmacotherapy not useful, consider bariatric surgery when obesity is severe and intractable • We need to know much more about body weight, posture & sex differences University Medical Center Groningen
Diabetes: a call for action IDF Diabetes Atlas, 2015 University Medical Center Groningen
BMI and Diabetes: Strong predictors of new onset HFpEF • 28,820 individuals from the 4 large cohort studies, 12 years of FU • 811 new onset HFpEF (39%) • 200 new onset HFmrEF (10%) • 1048 new onset HFrEF (51%) Bhambhani V, et al. Eur J Heart Fail. 2018; 20 :651-659 University Medical Center Groningen
HF in T2DM trials & T2DM in HF trials Seferovic P, et al. Eur J Heart Fail. 2018; 20: 853-872 University Medical Center Groningen
Diabetes : Prognostic factor in prevalent HFpEF Kristensen, et al. Cardiovasc Drugs Ther. 2017; 31 :545-549 University Medical Center Groningen
Current pathophysiological paradigm: Obesity and DM are important drivers of HFpEF Shah, SJ et al. Circulation. 2016; 134 :73-90 University Medical Center Groningen
Pacher P, et al. Physiol Rev 2007; 87 :315-424 University Medical Center Groningen
Paulus & Da Canto. J Am Coll Cardiol HF. 2018; 6 :1 – 7. University Medical Center Groningen
Cardiovascular phenotype of patients with HFpEF with and without Diabetes • RELAX trial (216 stable outpatients with HF, EF > 50%) • Non-diabetic (N = 123); Diabetic (N = 93) • Diabetic patients were • Younger, more often male • More obese • Higher prevalence of hypertension, renal dysfunction, pulmonary disease & vascular disease Lindman BR, J Am Coll Cardiol. 2014; 64 : 541-9 University Medical Center Groningen
End points in HFpEF patients with and without diabetes Lindman BR, J Am Coll Cardiol. 2014; 64 : 541-9 University Medical Center Groningen
Treatment of T2DM in HF Seferovic P, et al. Eur J Heart Fail. 2018; 20: 853-872. University Medical Center Groningen
Treatment of T2DM in HF Seferovic P, et al. Eur J Heart Fail. 2018; 20: 853-872. University Medical Center Groningen
SGLT-2 trials in HFpEF Seferovic P, et al. Eur J Heart Fail. 2018; 20: 853-872. University Medical Center Groningen
Recognized Expanded Biological Effects of GLP-1 Seufert & Gallwitz ; Diabetes Obes Metab. 2014 Aug;16(8):673-88. University Medical Center Groningen
Meta-analysis: MACE-3 endpoint Bethel et al. Lancet Diabetes Endocrinol. 2017;6:105-113 University Medical Center Groningen
Meta-analysis: All-cause mortality Bethel et al. Lancet Diabetes Endocrinol. 2017;6:105-113 University Medical Center Groningen
Conclusion • Obesity and diabetes are amongst the most prevalent and dominant co-morbidities in HFpEF • We do not fully understand ‘obesity’ • No clear recommendations can be made for the treatment of T2DM, but SGLT-2 inhibitors and GLP1RA appear effective • Prospective RCTs are underway University Medical Center Groningen
Acknowledgements & Collaborations Experimental Cardiology Wiek H. van Gilst Medical Genetics University of Maastricht, the Netherlands Herman H. Silljé Jan Jongbloed Leon. J. de Windt Peter van der Meer Irene van Langen Stephane Heymans Laura M.G. Meems Yvonne Hoedemaekers Wouter C. Meijers University of Amsterdam, the Netherlands University of Wageningen, the Netherlands Tim Eijgenraam J. Peter van Tintelen Henk A. Schols Navin Suthahar Free University of Amsterdam, the Netherlands Imperial College, London, UK Salva Yurista Alexander Lyon Arnold Piek Jolanda van der Velden Aad Withaar Bianca J. Brundel Carolin Gehlken University of Utrecht, the Netherlands Janny Takens Frans Rutte Marloes Schouten Pieter Doevendans Clinical Cardiology Dirk J. van Veldhuisen University of Michigan, USA Pim van der Harst Bertram Pitt Hans L. Hillege Boxford, MA, USA Adriaan A. Voors Pieter Muntendam Maarten P. van den Berg Peter van der Meer University of California, San Diego, USA Internal Medicine Alan S. Maisel Stephan J. Bakker Ron T. Gansevoort Potential Conflicts of interest: Laboratory Medicine Speaker/consultancy fees: Medcon, Novartis, Servier, Mandalmed Research grants: NWO-VIDI, Netherlands Heart Fourndation, AstraZeneca, BMS, Trevena Anneke C. Muller Kobold Minority shareholder: scPharmaceuticals Medical Biology Ruud A. Bank Harry van Goor Peter Heeringa Marten Hofker † University Medical Center Groningen
University Medical Center Groningen
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