Early growth and coronary heart disease in later life

Editor—Eriksson et al concluded that in Finnish men born 60 years ago “low weight gain during infancy is associated with increased risk of coronary heart disease,” yet they did not analyse infant weight gain.1 All their references to infant growth relate to size at 1 year (table 3). Had they applied the key regression models that we have described2 to separate the effects of weight at different ages on later outcome, they would have found that infant weight gain was unrelated to risk of coronary heart disease. In their simultaneous analysis the hazard ratios for birth weight and weight at 1 year were similar and less than 1, showing that greater weight during infancy is protective. Weight gain is weight at 1 year less weight at birth, so if weight gain were protective it would appear as a protective effect of weight at 1 year and a relatively deleterious effect of weight at birth.2 But the two effects were equally protective, so weight gain in infancy (strictly, upwards centile crossing) is unrelated to later coronary heart disease. The hazard ratios for weight at birth and at 1 year can be rearranged as hazard ratios for mean weight and weight gain. The hazard ratio for weight gain is equal approximately to the square root of the ratio of the hazard ratios at 1 year and at birth—that is, . This is similar to the birthweight hazard ratio, which was not significant (95% confidence interval 0.83 to 1.06). During childhood, increasing fatness was related to increased risk of coronary heart disease, particularly in those who were initially thin.1 This corresponds to our interaction model.2 The hazard ratio for the change in body mass index from age 1 to age 12 is obtainable from our combined model. The hazard ratios for body mass index at ages 1 and 12 are 0.83 and 1.03 (table 4). On the assumption that they would be similar if fitted simultaneously, the square root of the ratio of hazard ratios gives the approximate hazard ratio for the change in body mass index, —not that different from 1.20. So we agree that infant thinness and subsequent increasing fatness are synergistic risk factors for coronary heart disease, as others have shown.3 But for centile crossing to relate to coronary heart disease the hazard ratios for body size at the start and end of the period should differ significantly, and this is not the case in infancy. Routine use of our approach2 would have avoided this confusion.