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Original research
Discordances between predicted and actual risk in obese patients with suspected cardiac ischaemia
  1. Sheldon E Litwin1,2,
  2. Adrian Coles3,
  3. C Larry Hill3,
  4. Brooke Alhanti3,
  5. Neha Pagidipati3,
  6. Kerry L Lee3,
  7. Patricia A Pellikka4,
  8. Daniel B Mark3,
  9. James E Udelson5,
  10. Lawton Cooper6,
  11. Jean-Claude Tardif7,
  12. Udo Hoffmann8,
  13. Pamela S Douglas3
  14. On behalf of the PROMISE investigators
  1. 1 Division of Cardiology, Department of Medicine, Ralph H Johnson VA Medical Center, Charleston, South Carolina, USA
  2. 2 Division of Cardiology, Medical University of South Carolina, Charleston, SC, USA
  3. 3 Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
  4. 4 Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
  5. 5 Division of Cardiology, Tufts University Medical Center, Tufts University School of Medicine, Boston, MA, USA
  6. 6 National Heart, Lung and Blood institute, Bethesda, MD, United States
  7. 7 Division of Cardiology, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada
  8. 8 Department of Radiology, Massachusetts General Hospital, Boston, MA, United States
  1. Correspondence to Dr Sheldon E Litwin, Department of Internal Medicine, Medical University of South Carolina, Charleston, South Carolina, USA; litwins{at}


Objectives To test the relationship between increasing severity of obesity, calculated risk and observed outcomes.

Methods Patients with symptoms suggestive of coronary artery disease (CAD) (n=10 003) were stratified according to body mass index (BMI). We compared risk factors, pooled risk scores and physicians’ perception of risk. Cox regression tested the association between BMI and (1) presence of obstructive CAD and (2) composite clinical endpoints (death, cardiovascular death, unstable angina hospitalisation and myocardial infarction).

Results BMI was ≥30 kg/m2 in 48% of patients and ≥35 in 20%. Increasingly obese patients were younger, female and non-smoking but with higher prevalence of hypertension, diabetes, black race and sedentary lifestyle. Pooled risk estimates of CAD were highest in those with mid-range BMI. In contrast, physicians’ estimation of the likelihood of significant CAD based on clinical impression increased progressively with BMI. For a 10% increase in the Diamond-Forrester probability of CAD, the adjusted OR for obstructive CAD was 1.5 (95% CI 1.4 to 1.5) in patients with BMI <35, but only 1.2 (95% CI 1.1 to 1.3) in those with BMI ≥35 (interaction p<0.001). Framingham Risk Score increased across increasing BMI categories. However, there was a strong and consistent inverse relationship between degree of obesity and all three composite clinical endpoints over a median 25 months of follow-up.

Conclusions Despite perceptions of higher risk and higher risk scores, increasingly obese patients had obstructive CAD less frequently than predicted and had fewer adverse clinical outcomes. There is a need for risk assessment tools and guidelines that account for obesity.

Trial registration number NCT01174550.

  • Obesity
  • Chest pain
  • Coronary artery disease
  • Angina
  • Risk score
  • Mortality

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  • Contributors SEL: conception, design, writing of manuscript and final approval. AC: statistical analysis, design, critical revision and final approval. NP, KLL, PAP, DBM, JEU, LC, J-CT and UH: drafting of manuscript, critical revision and final approval. PSD: conception, design, drafting of manuscript, critical revision and final approval.

  • Funding The PROMISE trial was funded by National Heart, Lung, and Blood Institute grants R01 HL098237, R01 HL098236, R01 HL098305, and R01 HL098235.

  • Competing interests SEL reports receiving fees for events adjudication committee from CVRx. NP reports ownership in Freedom Health, Inc; Physician Partners, LLC; RXAdvance, LLC; and Florida Medical Associates, LLC. KLL reports receiving grants from the National Institutes of Health. DM reports receiving grants from the National Institutes of Health, as well as personal fees from CardioDx, Medtronic, Inc and St. Jude Medical, and grants from Eli Lilly and Company, Bristol-Myers Squibb, Gilead Sciences, Inc, AGA Medical Corporation, Merck & Company, Oxygen Therapeutics and AstraZeneca. JEU reports receiving consulting fees/honoraria from Lantheus Medical Imaging; service on a data safety monitoring board for Gilead, GSK; service as an officer, director, trustee or other fiduciary role for HFSA Executive Council; other support from or service for Abbott Laboratories, Circulation/AHA – Associate Editor, Editor – Circulation Heart Failure, Pfizer/GlaxoSmithKline, Sunshine Heart; and receiving research grants from NHLBI, Otsuka. J-CT reports receiving grants from Amarin, AstraZeneca, DalCor, Esperion, Ionis, Merck, Pfizer, Sanofi and Servier; honoraria from DalCor, Pfizer, Sanofi and Servier; and owns a minor equity interest in DalCor. UH reports receiving grants from the American College of Radiology Imaging Network, HeartFlow Inc and Siemens Healthcare. PSD reports receiving grant support from HeartFlow and service on a data and safety monitoring board for GE HealthCare. The other authors report no potential conflicts of interest.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository.