Abstract 15094: Inflammatory Genotype-Phenotype Interaction Moderates Response to a Cardiovascular Disease Risk Reduction Intervention in Rural Adults at-Risk for Cardiovascular Disease

Abstract

Introduction: Systemic inflammation and inflammatory genotypes have been associated with cardiovascular disease (CVD) risk, with associations between C-reactive protein (CRP), a marker of systemic inflammation, the rs1205 polymorphism on the CRP gene, and CVD risk among the most well-studied. However, little is known about the effect of systemic inflammation and associated genotypes on response to CVD risk reducing interventions. The purpose of this study was to examine whether high sensitivity C-reactive protein (hsCRP) moderated the association between rs1205 genotype and response to a CVD lifestyle-focused risk-reduction intervention. Methods: Participants were 400 rural adults with 2+ CVD risk factors participating in the HeartHealth in Rural Kentucky study. At baseline, we measured serum hsCRP and genotyped participants for the rs1205 polymorphism. Genotypes were categorized as CC or CT/TT. Response to the HeartHealth intervention was estimated by the pre-to-post intervention percent change in Framingham Risk Score (FRS). A moderation analysis with subsequent floodlight analysis was conducted using PROCESS macro for SPSS. Analyses were adjusted for body mass index, education, financial status, marital status, and insurance status. Results: Participants were aged 51.2±13.3 years and predominantly female (73.6%). The rs1205 genotype’s effect on FRS change was moderated by hsCRP (p=.004). Subsequent floodlight analysis revealed that rs1205 genotype had a larger effect on FRS change among those with lower (<0.54 mg/L; p=.05) and higher (>7.67 mg/L; p=.05) hsCRP as compared to those with hsCRP ranging from 0.54-7.67 mg/L (p >.05). Among those with lower hsCRP, those with the CC genotype had a larger decrease in FRS than those with CT/TT genotypes. Among those with high hsCRP, those with the CT/TT genotypes experienced a larger decrease in FRS to those with the CC genotype. Conclusion: Findings suggest that inflammatory phenotype moderates the relationship between inflammatory genotype and response to a CVD risk reduction intervention. This highlights the need to examine additional inflammatory markers and inflammatory genotypes to determine the impact of inflammation and genetics on responsiveness to CVD risk reduction interventions.