Short Stature and Heart Disease: Nature or Nurture? FRANK KEE,* VIVIANE NICAUD,** LAURENCE TIRET,** ALUN EVANS,* DENIS O’REILLY† AND GUY DE BACKER‡ FOR THE EARS GROUP§

A number of case-control and cohort studies, from Britain, Europe, and more recently from north America have demonstrated that adult height is a risk factor for coronary heart disease (CHD). The association persists even after adjusting for other risk factors such as smoking, blood pressure, serum cholesterol, body mass index and lung function. While it is clear that early environment influences attained height, the relationship between height and CHD risk survives adjustment for childhood socioeconomic circumstances. Birthweight is also related to adult height and body mass index, but few of the studies relating CHD risk and adult height have adjusted directly for birthweight. It has been suggested that the inverse relationship between adult height and CHD risk could be attributable to the fetal origins of CHD. However, the fetal origins hypothesis, as proposed by Barker, refers to fetal undernutrition as the main cause of impaired fetal growth. While it has been demonstrated, particularly in animal studies, that undernutrition in utero leads to persisting changes in a range of metabolic and physiological parameters, it is very likely that genetic factors influence fetal growth and participate in the ‘early programming’ of CHD. Their possible role has not yet been properly examined, even in two recent twin studies. The height-risk relationship could, on the other hand, be somewhat artefactual if disease processes in adult life were responsible for loss of height. For example, the height-CHD risk association in the Whitehall Civil Servants’ Study was eliminated after exclusion of subjects with cardiovascular disease at baseline, offering, it was claimed, indirect support for a ‘shrinkage’ hypothesis. The European Atherosclerosis Research Study (EARS I & II) offers a design to investigate whether the relationship between height and CHD risk has a transmissible component. As part of a large case-control study of transmissible risk factors for CHD, healthy This paper was prepared on behalf of the group by: Frank Kee, Laurence Tiret, Viviane Nicaud, A Evans, Denis O’Reilly, Guy de Backer. * Department of Epidemiology, the Queen’s University of Belfast, Mulhouse, Royal Victoria Hospital, Belfast BT12 6BJ, Northern Ireland. ** INSERM U258, Paris, France. † Department of Clinical Biochemistry, Glasgow Royal Infirmary, Scotland. ‡ Department of Public Health, University of Ghent, Belgium. § Members of the EARS Group are given in the Appendix. Short Stature and Heart Disease: Nature or Nurture?