Review
Fetal programming of coronary heart disease

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Abstract

People who develop coronary heart disease grow differently from other people both in utero and during childhood. Slow growth during fetal life and infancy is followed by accelerated weight gain in childhood. Two disorders that predispose to coronary heart disease, type 2 diabetes and hypertension, are preceded by similar paths of growth. Mechanisms underlying this are thought to include the development of insulin resistance in utero, reduced numbers of nephrons associated with small body size at birth and altered programming of the micro-architecture and function of the liver. Slow fetal growth might also heighten the body's stress responses and increase vulnerability to poor living conditions in later life. Coronary heart disease appears to be a developmental disorder that originates through two widespread biological phenomena, developmental plasticity and compensatory growth.

Section snippets

Growth and hypertension and type 2 diabetes

There is now a substantial body of evidence showing that people who were small at birth remain biologically different to people who were larger. The differences include an increased susceptibility to hypertension and type 2 diabetes mellitus (T2DM), two disorders that are closely linked to coronary heart disease 11., 12., 13., 14., 15. and which are associated with the same general pattern of growth as coronary heart disease. The risks for each disease fall with increasing birthweight and rise

Biological mechanisms

The association between altered growth and coronary heart disease has led to the suggestion that the disease might originate in two phenomena associated with development – ‘developmental, or phenotypic plasticity’ and ‘compensatory growth’. Phenotypic plasticity is the phenomenon whereby one genotype gives rise to a range of different physiological or morphological states in response to different environmental conditions during development [17]. Such gene–environment interactions are ubiquitous

Responses to adult living standards

Observations on animals show that the environment during development permanently changes not only the body's structure and function but also its responses to environmental influences encountered in later life [34]. Table 5 shows the effect of low income in adult life on coronary heart disease among men in Helsinki [35]. As expected, men who had a low taxable income had higher rates of the disease 36., 37.. There is no agreed explanation for this and it is a major component of the social

Interactions

New studies, especially those of the two exceptionally well-documented cohorts in Helsinki, increasingly suggest that coronary heart disease and the disorders related to it develop through a series of interactions. The effects of genes are conditioned by fetal growth [20]: the effects of small body size at birth are conditioned by growth during childhood [1], and by living conditions in childhood [16] and adult life [35]. Any one influence, such as low income, does not have a single

Conclusion

The associations between slow fetal, infant and childhood growth and later coronary heart disease are strong and graded. Boys who at birth had a ponderal index above 26 kg m−3 and who at one year of age were above the cohort average for BMI (17.7 kg m−3) and height (76.2 cm) were at half the risk of developing coronary heart disease before the age of 65 years [1]. Such findings confirm the strong effects of early growth on later disease [41].

The principal determinant of growth rates in early

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