My current research interests focus on studies of cardiovascular disease risk in human populations using non-traditional statistical approaches, especially as related to risk associations involving novel biomarkers as well as genetic markers. Underlying our approach is the hypothesis that particular blood and genetic risk markers are most efficacious in particular patient subgroups and that, in general, different patient subgroups have different markers of risk. As such, we have recently developed a 3-dimensional graphical exploratory data analysis technique that we call "outcome event mapping"
that allows identification of high-risk patient subgroups not constrained by traditional rectilinear approaches to subgroup identification and allowing subgroup identification even in unexpected regions of risk parameter domains. With it, we have demonstrated a high-risk subgroup in post-MI patients based upon high levels of serum C-reactive protein (CRP) and total cholesterol. Interestingly, we have shown the counter-intuitive result that within this subgroup elevated high-density lipoprotein (HDL) cholesterol, the so-called "good cholesterol", is a risk factor for recurrent events, a finding that we ascribe to transformation of the usual anti-inflammatory HDL into pro-inflammatory HDL. We have also been able to adapt outcome event mapping to delineate subgroup-specific risk in association with single-nucleotide polymorphism (SNP) variants. For example, we have shown that a variant of a SNP in the p22phox subunit of NAD(P)H oxidase (an enzyme playing a critical role in generation of reactive oxygen species and thus potentially in the transformation of HDL) is associated with risk along with elevated HDL in this subgroup. We plan future studies to delineate mechanisms involved in elevated HDL-associated risk using outcome event mapping with additional genetic markers together with advanced statistical techniques to elucidate causal pathways; and to fully characterize the physico-chemical nature of changes at the molecular level in HDL mediating transformation of HDL from anti-inflammatory to pro-inflammatory in nature.