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Family history of premature coronary heart disease and risk prediction in the EPIC-Norfolk prospective population study
  1. Suthesh Sivapalaratnam1,
  2. S Matthijs Boekholdt1,2,
  3. Mieke D Trip1,2,
  4. Manjinder S Sandhu3,4,
  5. Robert Luben3,
  6. John J P Kastelein1,
  7. Nicholas J Wareham5,
  8. Kay-Tee Khaw3
  1. 1Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
  2. 2Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands
  3. 3Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  4. 4Department of Genetic Epidemiology, Wellcome Trust Sanger Institute, Hinxton, UK
  5. 5Medical Research Council Epidemiology Unit, Cambridge, UK
  1. Correspondence to Dr S M Boekholdt, Department of Cardiology, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, The Netherlands; s.m.boekholdt{at}


Objective The value of a family history for coronary heart disease (CHD) in addition to established cardiovascular risk factors in predicting an individual's risk of CHD is unclear. In the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, the authors tested whether adding family history of premature CHD in first-degree relatives improves risk prediction compared with the Framingham risk score (FRS) alone.

Methods and results This study comprised 10 288 men and 12 553 women aged 40–79 years participating in the EPIC-Norfolk cohort who were followed for a mean of 10.9±2.1 years (mean±SD). The authors computed the FRS as well as a modified score taking into account family history of premature CHD. A family history of CHD was indeed associated with an increased risk of future CHD, independent of established risk factors (FRS-adjusted HR of 1.74 (95% CI 1.56 to 1.95) for family history of premature CHD). However, adding family history of CHD to the FRS resulted in a negative net reclassification of 2%. In the subgroup of individuals estimated to be at intermediate risk, family history of premature CHD resulted in an increase in net reclassification of 2%. The sensitivity increased with 0.4%, and the specificity decreased 0.8%.

Conclusion Although family history of CHD was an independent risk factor of future CHD, its use did not improve classification of individuals into clinically relevant risk categories based on the FRS. Among study participants at intermediate risk of CHD, adding family history of premature CHD resulted in, at best, a modest improvement in reclassification of individuals into a more accurate risk category.

  • Epidemiology
  • CAD
  • genetics
  • risk stratification
  • coronary artery disease (CAD)

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  • Funding EPIC-Norfolk is supported by programme grants from the Medical Research Council UK and Cancer Research UK.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by the Norfolk Local Research Ethics Committee.

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

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