CORRELATES OF FAMILY HISTORY OF CORONARY-ARTERY DISEASE IN CHILDREN

The atherosclerotic process begins in childhood but, in general, does not reach the clinical horizon until after the fifth decade of life, a t which point the best opportunities for prevention and intervention h ave been lose. In order to identify children with a high risk of devel oping coronary artery disease (CAD), risk factors measured in children that are the most informative indicators of future risk must be ident ified. Using a novel analytical strategy chat incorporates a continuum oi information about context dependency, we investigated whether ther e were significant differences in intermediate biochemical and physiol ogical traits between children (189 females and 188 males, ages 5-20.5 pears) with and without a strong family history of clinically-defined CAD at three levels of context dependency (coarse grain, medium grain , and fine grain). In the coarse-grained analysis we tested for differ ences in mean levels of nine intermediate traits (lipids, apolipoprote ins, blood pressure traits) and indices of external and internal envir onmental context (age, body mass index, smoking status). Female childr en with a strong family history had higher average levels for total ch olesterol, triglyceride, Apo B, and systolic blood pressure and were o n average older and weighed more than female children with a weak fami ly history of CAD. Male children with a strong family history of CAD h ad higher average levels of triglycerides and were on average older th an male children with a weak family history. In the medium-grained ana lysis we investigated whether the regression relationships between eac h intermediate trait and each measure of environmental context was sig nificantly different between children with and without a strong family history of CAD. Our results indicate that children with a strong fami ly history of CAD have a significantly different relationship between their intermediate traits and environmental contexts than children wit h a weak family history. In the fine-grained analysis, we stratified t he sample into age, BMI, and smoking subgroups and tested for mean dif ferences in the intermediate traits between children with and without a strong family history. For seven of the nine intermediate traits we found evidence of significant mean differences between children with a nd without a strong family history of CAD in particular age and BMI su bgroups in nonsmokers that were not expected given the results from se parate age-dependent or BMI-dependent marginal analyses. From these an alyses, we conclude that the inferences about intermediate biochemical and physiological trait associations with family history of CAD depen d on where on the coarse-grain to fine-grain continuum of context depe ndency the analysis is performed. In many cases, inferences at one lev el of investigation are different than the inferences made at a coarse r or finer level. This study documents the complexity of the associati ons between intermediate traits and risk of CAD and raises the questio n of how many models are needed to maximize disease prediction and whe re these models should fall on the coarse-to fine-grain continuum. (C) 1998 Elsevier Science Inc.