Predictive, Preventive and Personalized Medicine & Molecular Diagnostics

Biography

Biography: Malakoudis

Abstract

Abstract:

Genomics in the prediction of adverse cardiac events is strongly demonstrated in the literature. Stent thrombosis, in-stent restenosis and dual antiplatelet therapy tolerance seem to be the fields of the early prediction of relevant dependence of the human genomic status. Coronary angioplasty is the interventional approach of the inner lumen of the coronary arteries after a severe thrombus blockage. An intraluminal prothesis is advanced percutaneously through a wire to the target vessel and after a successful expansion is restoring the physiological anatomy of the lumen maintaining the proper blood flow.

The European Guidelines are suggesting Dual AntiPlatelet Therapy (DAPT) from 6 to 12 months. Despite of the effectiveness of the DAPT to avoid thrombus formation, one limitation is severe bleeding and of course patients with stent thrombosis (ST).

The second limitation is in-stent restenosis (ISR). In-stent restenosis is the phenomenon of the reclosure of the stent implants in the target vessel after a successful angioplasty.The last projected topic about the prediction of an adverse cardiac event is to improve coronary heart disease through genetic profiling.

1. CYP2C19*2 and CYP2C9*3 alleles are associated with stent thrombosis: a case– control study. (by A. Harmsze et al., doi:10.1093/eurheartj/ehq321) This case–control study aimed to determine the influence of genetic variations related to the pharmacokinetics and pharmacodynamics of clopidogrel on the occurrence of ST in patients who were on clopidogrel and aspirin treatment at the time of the event. The conclusion is that carriers of the CYP2C19*2 and CYP2C9*3 loss-of-function alleles were at a 1.7- and 2.4-fold increased risk of developing ST, respectively. The influence of these genetic variants was most profound on the risk of subacute ST. Personalized therapy targeting patients who carry these genetic variants might help to improve the clinical outcome after stent implantation.

2. The Cardio Gene Study: genomics of in-stent restenosis. The Cardio Gene Study is designed to understand ISR. Global gene and protein expression profiling define molecular phenotypes of patients. Well-defined clinical phenotypes will be paired with genomic data to define analyses aimed to achieve several goals. These include determining blood gene and protein expression in patients with ISR, investigating the genetic basis of ISR, developing predictive gene and protein biomarkers, and the identification of new targets for treatment.

Genomics in Action: Seeking To Improve Coronary Stent Therapy Through Genetic Profiling (Elizabeth G. Nabel, M.D.) Coronary heart disease is the leading cause of death in the United States and other industrialized countries. To improve the outlook for the 13 million Americans suffering from this common disorder, a laboratory that recently joined the National Human Genome Research Institute (NHGRI) is tapping into the power of genomics to develop better therapies. Of course further investigation and larger trials have to be scheduled and the researchers have to focus on the personalization of the molecular and genomic level