The association between small size at birth and increased risk of cardiovascular disease in adulthood is well established. This relationship is commonly interpreted according to the “thrifty phenotype hypothesis,” which states that the association is generated by a mismatch between fetal and postnatal nutrition. Empirical support for an interaction between impaired fetal growth and later overnutrition is, however, sparse and partly conflicting.
The Stockholm Heart Epidemiology Program is a population-based case-control study of risk factors for acute myocardial infarction (MI); data were available for 1058 cases and 1478 controls. Using logistic regression, we studied the effect of size at birth, and its interactive effect with body mass index (BMI), at 3 occasions in adulthood, on the risk of MI. Biologic interaction was estimated with the synergy index.
Very low birth weight for gestational age was associated with increased risk of MI (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.4–2.9; attributable fraction = 5%). In nonfatal cases, adjustment for waist-hip ratio, insulin resistance, blood pressure, and lipids reduced the point estimate somewhat. Low birth weight for gestational age in combination with high BMI at the time of the MI produced an OR of 10.8 (3.6–31.8) for MI compared with normal birth weight and normal BMI; the synergy index was 6.5 (95% CI = 1.8–24.0).
The synergism between small size at birth and high adult BMI supports the thrifty phenotype hypothesis. However, this mechanism seems to pertain to only a small fraction of the acute MI cases, implying minor public health importance.
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From the aCentre for Health Equity Studies (CHESS), Stockholm University/Karolinska Institutet, Stockholm, Sweden; bDepartment of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden; and cDepartment of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
Submitted 15 January 2010; accepted 17 August 2010; posted 28 October 2010.
The SHEEP study was supported by grants from the Swedish Council for Social Research, the Swedish Council for Work Life, and the County Council of Stockholm. Also, supported by fellowship grant 2006–1146 of the Swedish Council of Working Life and Social Research and by the Ansgarius Foundation (to I.J.).
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Editors' note: Related articles appear on pages 148 and 151.
Correspondence: Kristiina Rajaleid, Centre for Health Equity Studies (CHESS), Stockholm University/Karolinska Institutet, Sveavägen 160, 106 91 Stockholm, Sweden. E-mail: firstname.lastname@example.org.