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Original research article
Impact of age on excess risk of coronary heart disease in patients with familial hypercholesterolaemia
  1. Liv J Mundal1,2,
  2. Jannicke Igland3,
  3. Marit B Veierød4,
  4. Kirsten Bjørklund Holven2,5,
  5. Leiv Ose1,2,
  6. Randi Marie Selmer6,
  7. Torbjorn Wisloff6,
  8. Ivar S Kristiansen7,
  9. Grethe S Tell8,
  10. Trond P Leren9,
  11. Kjetil Retterstøl1,2
  1. 1 Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Lipid Clinic, Oslo, Norway
  2. 2 Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
  3. 3 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  4. 4 Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
  5. 5 National Advisory Unit for Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway
  6. 6 Department of Infectious Disease Epidemiology and Modelling, Norwegian Institute of Public Health, Oslo, Norway
  7. 7 Department of Health Management and Health Economics, University of Oslo, Oslo, Norway
  8. 8 Department of Health Registries, Norwegian Institute of Public Health, Oslo, Norway
  9. 9 Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Oslo, Norway
  1. Correspondence to Prof Kjetil Retterstøl, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo 0317, Norway; kjetil.retterstol{at}medisin.uio.no

Abstract

Objective The primary objective was to study the risk of acute myocardial infarction (AMI) and coronary heart disease (CHD) in patients with familial hypercholesterolaemia (FH) and compare with the risk in the general population.

Methods Patients with an FH mutation but without prior AMI (n=3071) and without prior CHD (n=2795) were included in the study sample during 2001–2009. We obtained data on all AMI and CHD hospitalisations in Norway. We defined incident cases as first time hospitalisation or out-of-hospital death due to AMI or CHD. We estimated standardised incidence ratios (SIRs) with 95% CIs with indirect standardisation using incidence rates for the total Norwegian population stratified by sex, calendar year and 1 year age groups as reference rates.

Results SIRs for AMI (95% CIs) were highest in the age group 25–39 years; 7.5 (3.7 to 14.9) in men and 13.6 (5.1 to 36.2) in women and decreased with age to 0.9 (0.4 to 2.1) in men and 1.8 (0.9 to 3.7) in women aged 70–79 years. Similarly, SIRs for CHD were highest among patients 25–39 years old; 11.1 (7.1–17.5) in men and 17.3 (9.6–31.2) in women and decreased 2.4 (1.4–4.2) in men and 3.2 (1.5–7.2) in women at age 70–79. For all age groups, combined SIRs for CHD were 4.2 (3.6–5.0) in men and 4.7 (3.9–5.7) in women.

Conclusion Patients with FH are at severely increased risk of AMI and CHD compared with the general population. The highest excess risk was in the youngest group aged 25–39 years, in both sexes.

  • acute myocardial infarction
  • lipoproteins and hyperlipidemia
  • coronary artery disease
  • genetics
  • cardiac risk factors and prevention

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Footnotes

  • Contributors LJM, JI and KBH were responsible for the conceptual design of the study. LJM, JI, MBV, KBH, LO, RMS, TW, ISK, GST, TPL and KR were responsible for analysing and interpreting data. TPL was responsible for providing data from the UCCG registry. GST and JI were responsible for the CVDNOR data. LO, KBH and others contributed with blood samples from the Lipid Clinic. JI, MBV, RMS, ISK, TW and GST were responsible for the statistical analyses. LJM, KR and JI had the major responsibility of reviewing the study and input on revisions. All authors read and approved the final manuscript.

  • Funding This work was supported by the South-Eastern Norway Regional Health Authority, Oslo, Norway, Throne Holst Foundation for Nutrition Research, University of Oslo and Aktieselskabet Freia Chocolade Fabriks Medisinske Fond.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study was performed in accordance with the Declaration of Helsinki and approved by the Regional Committee for Medical and Health Research Ethics, South-East Norway (case no. 2011/1343) and the Data Protection Official at Oslo University Hospital.

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

  • Data sharing statement The corresponding author has the right to grant on behalf of all authors, and does grant on behalf of all authors, an exclusive licence (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in Heart editions and any other BMJPGL products to exploit all subsidiary rights.

  • Author note All participants signed an informed consent for genetic testing for diagnostic purpose. All participants received a letter with information that they could refuse their data to be linked to other registries. Those who refused were not included. The letter with information about the register linkage and the study as well as this procedure was approved by the local ethical committee prior to study start. This letter is uploaded as a supplementary file. The original language is Norwegian and it is uploaded in its original form; however, we will translate it if needed.

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