Correlation of Genetic Polymorphisms and Clinical Parameters With the Complexity of Coronary Artery Disease

Correlation of Genetic Polymorphisms and Clinical Parameters With the Complexity of Coronary Artery Disease in the Greek Population

The purpose of the research project is to investigate the potential association of 6 genetic polymorphisms with the complexity and the severity of coronary artery disease (SYNTAX score). The aim of the study is to combine genetic, clinical and laboratory data in order to create a prognostic tool that will enable an individualized therapeutic patient approach.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Coronary Arteriosclerosis; Cardiovascular Risk Factor
• Intervention / Treatment: Genetic: SNPs associated with CAD

Detailed Description

This study focus on the prediction of 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. Clinical and genetic patient information are systematically collected in a fashion that will enable also retrospective evaluation.

• Study Type: Observational
• Enrollment (Actual): 270

Contacts and Locations

Study Locations

• Greece
  • Thessaloníki, Greece, 54636
    • Ahepa University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients between 18 years to 90 years at entry, of both genders, who are admitted in the Department of Cardiology in the AHEPA University General Hospital of Thessaloniki and undergo coronary angiography for clinical purposes will be studied

Description

Inclusion Criteria:

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

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SYNTAX score = 0; Patients with nonobstructive CAD (≤50 % diameter stenosis)	Genetic: SNPs associated with CAD; Genotyping will be carried out by Real-Time PCR
0 < SYNTAX score < 23; Low SYNTAX group	Genetic: SNPs associated with CAD; Genotyping will be carried out by Real-Time PCR
SYNTAX score ≥ 23; Intermediate-High SYNTAX group	Genetic: SNPs associated with CAD; Genotyping will be carried out by Real-Time PCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between genetic risk variants and the SYNTAX score [All-comers population]	The investigators will evaluate the effects of 6 known genetic variants associated with risk of Coronary Artery Disease on the extend and severity of coronary atherosclerosis [as assessed by the SYNTAX score] in patients with significant CAD on coronary angiography, both individually and combined in a Genetic Risk Score	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACCEs	Cardiovascular death, myocardial infarction, stent thrombosis, any re-intervention and stroke	12 months
Predictive value of combining a Genetic Risk Score & SYNTAX score for the prediction of 1-year MACCEs	A Genetic Risk Score will be calculated as the weighted sum of alleles of 6 single nucleotide polymorphisms previously associated with CAD [The GRS will be constructed by summing the number of risk alleles (0/1/2) for each of the 6 SNPs weighted by their estimated effect sizes]. SYNTAX score is a coronary lesion complexity scoring system and represented by a single number.	12 months
Ankle-Brachial Index	A tool for diagnosing peripheral artery disease but also an indicator of systemic atherosclerosis [represented by a single number]	At hospital admission
Left Ventricular Ejection Fraction	LVEF [%] as assessed by echocardiography	At hospital admission & 12 months after discharge from hospital
Neutrophil to Lymphocyte Ratio	NLR [represented by a single number]	At hospital admission
Red Cell Distribution Width	RDW [%]	At hospital admission
Mean Platelet Volume	MPV [fL]	At hospital admission
Glomerular Filtration Rate	GFR as assessed by CKD-EPI formula [mL/min/1.73m²]	At hospital admission
High Density Lipoprotein	HDL [mg/dL]	At hospital admission

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki
• Collaborators: LABNET IAE - Private Reference Diagnostic Laboratory
• Investigators: Principal Investigator: Georgios Rampidis, MD, MSc, AHEPA University Hospital, 1st Cardiology Department - PhD candidate; Principal Investigator: Georgios Sianos, MD, PhD, FESC, AHEPA University Hospital, 1st Cardiology Department - PhD Supervisor 1; Principal Investigator: Charalambos Karvounis, MD, PhD, AHEPA University Hospital, 1st Cardiology Department, Director - PhD Supervisor 2; Principal Investigator: Ioannis Vizirianakis, PharmD, PhD, Aristotle University of Thessaloniki, School of Pharmacy - PhD Supervisor 3

Publications and helpful links

General Publications

• Rampidis GP, Benetos G, Benz DC, Giannopoulos AA, Buechel RR. A guide for Gensini Score calculation. Atherosclerosis. 2019 Aug;287:181-183. doi: 10.1016/j.atherosclerosis.2019.05.012. Epub 2019 May 10. No abstract available.
• Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, van den Brand M, Van Dyck N, Russell ME, Mohr FW, Serruys PW. The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention. 2005 Aug;1(2):219-27. No abstract available.
• Knowles JW, Zarafshar S, Pavlovic A, Goldstein BA, Tsai S, Li J, McConnell MV, Absher D, Ashley EA, Kiernan M, Ioannidis JPA, Assimes TL. Impact of a Genetic Risk Score for Coronary Artery Disease on Reducing Cardiovascular Risk: A Pilot Randomized Controlled Study. Front Cardiovasc Med. 2017 Aug 14;4:53. doi: 10.3389/fcvm.2017.00053. eCollection 2017.
• Howson JMM, Zhao W, Barnes DR, Ho WK, Young R, Paul DS, Waite LL, Freitag DF, Fauman EB, Salfati EL, Sun BB, Eicher JD, Johnson AD, Sheu WHH, Nielsen SF, Lin WY, Surendran P, Malarstig A, Wilk JB, Tybjaerg-Hansen A, Rasmussen KL, Kamstrup PR, Deloukas P, Erdmann J, Kathiresan S, Samani NJ, Schunkert H, Watkins H; CARDIoGRAMplusC4D; Do R, Rader DJ, Johnson JA, Hazen SL, Quyyumi AA, Spertus JA, Pepine CJ, Franceschini N, Justice A, Reiner AP, Buyske S, Hindorff LA, Carty CL, North KE, Kooperberg C, Boerwinkle E, Young K, Graff M, Peters U, Absher D, Hsiung CA, Lee WJ, Taylor KD, Chen YH, Lee IT, Guo X, Chung RH, Hung YJ, Rotter JI, Juang JJ, Quertermous T, Wang TD, Rasheed A, Frossard P, Alam DS, Majumder AAS, Di Angelantonio E, Chowdhury R; EPIC-CVD; Chen YI, Nordestgaard BG, Assimes TL, Danesh J, Butterworth AS, Saleheen D. Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. Nat Genet. 2017 Jul;49(7):1113-1119. doi: 10.1038/ng.3874. Epub 2017 May 22.
• Assimes TL, Roberts R. Genetics: Implications for Prevention and Management of Coronary Artery Disease. J Am Coll Cardiol. 2016 Dec 27;68(25):2797-2818. doi: 10.1016/j.jacc.2016.10.039.
• Vizirianakis IS, Fatouros DG. Personalized nanomedicine: paving the way to the practical clinical utility of genomics and nanotechnology advancements. Adv Drug Deliv Rev. 2012 Oct;64(13):1359-62. doi: 10.1016/j.addr.2012.09.034. Epub 2012 Sep 13. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): June 30, 2018
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 16, 2017
• First Posted (Actual): October 20, 2017

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 7, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Genetics; Coronary Artery Disease; Personalized Medicine; SNPs; Genetic Risk Score; Coronary Atherosclerosis; SYNTAX score
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Arteriosclerosis
• Other Study ID Numbers: CIP_PhD Rampidis Georgios_1.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Study Data/Documents

1. Clinical Study Report
   Information identifier: NCT03150680
   Information comments: GESS trial [ClinicalTrials.gov Identifier: NCT03150680] was designed exclusively based on the protocol of the study "Correlation of Genetic Polymorphisms and Clinical Parameters With the Complexity of Coronary Artery Disease" [CIP_PhD Rampidis Georgios_1.1]

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No