Development of a Risk Prediction Algorithm Through the Investigation of Genetic Risk Factors and the Complexity of Coronary Artery Disease to Estimate Future Risk of Cardiovascular Events: Angiographic (SYNTAX Score), Clinical and Pharmacogenetic Analysis.

Conditions

Coronary Artery Disease

Keywords

SYNTAX score, SNPs, Genetics, Pharmacogenetics, Genetic Risk Score, Precision Medicine

Brief summary

The purpose of the research project is to investigate the potential association of 207 genetic polymorphisms with the complexity and the severity of coronary artery disease (SYNTAX score), along with the patients' response to clopidogrel and statin therapy. The aim of the study is to combine genetic, pharmacogenetic, clinical and laboratory data in order to create an algorithm (GEnetic Syntax Score-GESS) that will enable an individualized therapeutic patient approach.

Detailed description

Regarding Greece, this is the first prospectively enrolling medical database of this magnitude. Clinical and genetic patient information are systematically collected in a fashion that will enable also future retrospective evaluation of clinical and genetic details from each patient. This study is a discrete arm of a series of research projects that focus on the development of personalized medical therapy and share a common purpose: predicting future risk of cardiovascular events, assessing the severity and complexity of coronary artery disease by incorporating genetic information into the SYNTAX score and providing personalized therapeutic guidance to patients. The ultimate goal of the study would be to identify, design and develop a panel of genetic markers that in combination with clinical and angiographic information will be a reliable tool for predicting cardiovascular risk for future adverse events.

Fani Chatzopoulou, Nikolaos Mittas, Efstratios Karagiannidis, Αndreas S. Papazoglou, Nikolaos Stalikas et al. (15 authors)

Circulation2023-11-071 citations

10.1161/circ.148.suppl_1.17570

Dissecting miRNA–Gene Networks to Map Clinical Utility Roads of Pharmacogenomics-Guided Therapeutic Decisions in Cardiovascular Precision Medicine

Fani Chatzopoulou, Konstantinos Kyritsis, Christos Papagiannopoulos, Eleftheria Galatou, Nikolaos Mittas et al. (14 authors)

Cells2022-02-1023 citations

10.3390/cells11040607

A Risk-Stratification Machine Learning Framework for the Prediction of Coronary Artery Disease Severity: Insights From the GESS Trial

Nikolaos Mittas, Fani Chatzopoulou, Konstantinos Kyritsis, Christos Papagiannopoulos, Nikoleta F. Theodoroula et al. (15 authors)

Frontiers in Cardiovascular Medicine2022-01-1822 citations

10.3389/fcvm.2021.812182

The GEnetic Syntax Score: a genetic risk assessment implementation tool grading the complexity of coronary artery disease—rationale and design of the GESS study

Ioannis S. Vizirianakis, Fani Chatzopoulou, Αndreas S. Papazoglou, Efstratios Karagiannidis, Georgios Sofidis et al. (18 authors)

BMC Cardiovascular Disorders2021-06-0816 citations

10.1186/s12872-021-02092-5

Interventions

GENETICSNPs associated with CAD, SNPs associated with pharmacological response to clopidogrel and statins

Genotyping will be carried out by Next-Generation Sequencing (NGS)

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to 90 Years

Healthy volunteers

No

Inclusion criteria

1. Patients giving voluntary written consent to participate in the study 2. Male or female patients between 18 years to 90 years at entry 3. Patients without previous history of CAD 4. Patients who are admitted in the Department of Cardiology in the AHEPA University General Hospital of Thessaloniki and undergo coronary angiography for clinical purposes

Exclusion criteria

1. Patients \< 18 years old and \> 90 years old at time of coronary angiography 2. Patients with a previous history of CAD 3. Cardiac Arrest at admission 4. Patients with serious concurrent disease and life expectancy of \< 1 year 5. Patients who refuse to give written consent for participation in the study

Design outcomes

Primary

Measure	Time frame	Description
Relationship between genetic risk variants and the SYNTAX score	12 months	All-comers population

Secondary

Measure	Time frame	Description
MACCEs	12 months	Cardiovascular death, myocardial infarction, stent thrombosis, any re-intervention and stroke
Predictive value of combining a Genetic Risk Score, SYNTAX score and clinical variables for the prediction of 1-year MACCEs	12 months	A multilocus Genetic Risk Score will be calculated as the weighted sum of alleles of 207 single nucleotide polymorphisms previously associated with CAD \[The investigators will construct a multilocus genetic risk score for each individual by summing the number of risk alleles (0/1/2) for each of the 207 SNPs weighted by their estimated effect sizes\]. SYNTAX score is a coronary lesion complexity scoring system and represented by a single number. Clinical variables include: 1. Major CV risk factors as defined according to ESC Guidelines \[as dichotomous variables-yes or no\] 2. Ankle-Brachial Index: a tool for diagnosing peripheral artery disease but also an indicator of systemic atherosclerosis \[measurement according to ESC Guidelines-represented by a single number\] 3. Left Ventricular Ejection Fraction (LVEF%) using echocardiography.
Any BARC (Bleeding Academic Research Consortium) bleeding	12 months	Bleeding Academic Research Consortium (BARC) recently proposed a novel standardized bleeding definition

Countries

Greece

Contacts

Primary ContactGeorgios Sianos, MD PhD FESC

gsianos@auth.gr0030 2310994830

Outcome results

None listed