A Test for Heavy Alcohol Consumption in First Episode Coronary Heart Disease

Bd Holding, Inc., Iowa City IA

Investigators

Abstract

Excessive alcohol consumption (EAC) is often a silent killer that manifests its deleterious effects through its effects through other disease processes. Heavy alcohol consumption (HAC), which we define as drinking 6 or more drinks per day, is probably the best studied form of EAC and is a known to be substantial risk factor for CHD. But the exact frequency of HAC in those with CHD and the relationship of lesser levels of alcohol consumption to risk for CHD is not well established. However, if EAC is significantly contributing to the pathogenesis of CHD, quantifying then addressing EAC in clinical treatment plans may be critical for the prevention of the alcohol induced CHD deaths. Recently, we have developed an epigenetic tool known as the Alcohol T Score (ATS) to quantify steady state alcohol consumption. Using this tool, we show that in young adults, ATS values predict a large portion of the variance for developing the epigenetic signature of CHD. Then, in a second set of older adults with acute coronary syndrome (ACS), we show that ATS levels significantly predict survival (p<0.02) with those at the 90th percentile of ATS values being 2.4 fold more likely to die in the follow-up period than those at the 10th percentile of ATS values. In essence, these findings show that ATS values predict the development of CHD and death in those with CHD, but do they predict CHD itself? If so, this suggests that clinicians could prevent perhaps as many as 25% of all cardiac deaths by simply treating EAC before the first heart attack. Therefore, in this R43, we plan on extending our examinations to those with new onset CHD. Specifically, we hypothesize that HAC is more frequent in those with first episode CHD. To test that hypothesis, we will examine ATS, ZSCAN25 and phosphatidylethanolamine (PEth) levels in those with first episode CHD. We will then compare those levels to those in 75 age and sex matched controls to determine whether HAC is more frequent in those with new onset CHD. This project is innovative because excessive alcohol consumption is generally not considered in assessment of new onset CHD. It is high impact because HAC may be a significant contributor to related morbidity and mortality at all stages of CHD. The team is well prepared to conduct the research and includes board-certified cardiologist, statisticians and a leading expert on DNA methylation. The institution at which the study will be based evaluates thousands of patients annually for new onset CHD and Behavioral Diagnostics controls the IP for this technology which includes recently filed claims for this specific purpose. As a direct result of this research, we will determine whether new onset CHD is associated with HAC. As an indirect outcome, we will demonstrate the potential value of DNA methylation assessments of alcohol consumption as part of routine primary and secondary prevention assessments of cardiovascular disease. If the value of the testing appears significant, this will set up an R44 to determine the utility of our epigenetic alcohol testing for in routine assessments of CHD.