Peripheral blood gene expression signatures which reflect smoking and aspirin exposure are associated with cardiovascular events

James A Wingrove,Steven Rosenberg,Deepak Voora,Karen Fitch,Brian Rhees

doi:10.1186/s12920-017-0318-6

James A Wingrove, Steven Rosenberg + Show 3 more

Open Access

https://doi.org/10.1186/s12920-017-0318-6

Copy DOI

Abstract

BackgroundCardiovascular disease and its sequelae are major causes of global mortality, and better methods are needed to identify patients at risk for future cardiovascular events. Gene expression analysis can inform on the molecular underpinnings of risk factors for cardiovascular events. Smoking and aspirin have known opposing effects on platelet reactivity and MACE, however their effects on each other and on MACE are not well described.MethodsWe measured peripheral blood gene expression levels of ITGA2B, which is upregulated by aspirin and correlates with platelet reactivity on aspirin, and a 5 gene validated smoking gene expression score (sGES) where higher expression correlates with smoking status, in participants from the previously reported PREDICT trial (NCT 00500617). The primary outcome was a composite of death, myocardial infarction, and stroke/TIA (MACE). We tested whether selected genes were associated with MACE risk using logistic regression.ResultsGene expression levels were determined in 1581 subjects (50.5% female, mean age 60.66 +/−11.46, 18% self-reported smokers); 3.5% of subjects experienced MACE over 12 months follow-up. Elevated sGES and ITGA2B expression were each associated with MACE (odds ratios [OR] =1.16 [95% CI 1.10–1.31] and 1.42 [95% CI 1.00–1.97], respectively; p < 0.05). ITGA2B expression was inversely associated with self-reported smoking status and the sGES (p < 0.001). A logistic regression model combining sGES and ITGA2B showed better performance (AIC = 474.9) in classifying MACE subjects than either alone (AIC = 479.1, 478.2 respectively).ConclusionGene expression levels associated with smoking and aspirin are independently predictive of an increased risk of cardiovascular events.

Highlights

Cardiovascular disease and its sequelae are major causes of global mortality, and better methods are needed to identify patients at risk for future cardiovascular events
Given the potential molecular interactions between smoking, aspirin, and platelet reactivity, we investigated the use of these gene expression signatures as predictors of MACE risk in a population of patients referred for elective, invasive coronary angiography [22]
Neither selfreported smoking nor aspirin use showed a significant association with MACE in univariate analyses (Table 1)

Summary

Introduction

Cardiovascular disease and its sequelae are major causes of global mortality, and better methods are needed to identify patients at risk for future cardiovascular events. Cardiovascular and cerebrovascular disease (CVD) and their complications continue to be a leading cause of morbidity, mortality, and cost in both the United States and world-wide [1]. CVD is a complex, multifactorial disease; its development and progression is driven by the interplay of genetics, environment, and diet. The transition from stable, atherosclerotic disease to a major adverse cardiovascular event (MACE, e.g. unstable angina, myocardial infarction, or stroke) is poorly understood though it is likely to be driven, in part, by platelet mediated thrombosis of the coronary or cerebral vessels [2,3,4]. Genome wide association studies are unraveling the genetic architecture of such events [5, 6] but are limited in the consideration of environmental effects

Methods

Results

Discussion

Conclusion