Neighborhood socioeconomic disadvantage is associated to increased individual risk of ischemic heart disease (IHD). However, the value of this association for causal inference is uncertain. Moreover, neighborhoods are often defined by available administrative boundaries without evaluating in which degree these boundaries embrace a relevant socio-geographical context that condition individual differences in IHD risk. Therefore, we performed an analysis of variance, and also compared the associations obtained by conventional multilevel analyses and by quasi-experimental family-based design that provides stronger evidence for causal inference. Linking the Swedish Multi-Generation Register to several other national registers, we analyzed 184,931 families embracing 415,540 full brothers 45-64 years old in 2004, and residing in 8408 small-area market statistics (SAMS) considered as "neighborhoods" in our study. We investigated the association between low neighborhood income (categorized in groups by deciles) and IHD risk in the next four years. We distinguished between family mean and intrafamilial-centered low neighborhood income, which allowed us to investigate both unrelated individuals from different families and full brothers within families. We applied multilevel logistic regression techniques to obtain odds ratios (OR), variance partition coefficients (VPC) and 95% credible intervals (CI). In unrelated individuals a decile unit increase of low neighborhood income increased individual IHD risk (OR = 1.04, 95% CI: 1.03-1.07). In the intrafamilial analysis this association was reduced (OR = 1.02, 95% CI: 1.02-1.04). Low neighborhood income seems associated with IHD risk in middle-aged men. However, despite the family-based design, we cannot exclude residual confounding by genetic and non-shared environmental factors. Besides, the low neighborhood level VPC = 1.5% suggest that the SAMS are a rather inappropriate construct of the socio-geographic context that conditions individual variance in IHD risk. In contrast the high family level VPC = 20.1% confirms the relevance of the family context for understanding IHD risk.
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