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

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03315234
• Other study ID #: CIP_PhD Rampidis Georgios_1.1
• Status: Active, not recruiting
• Start date: September 1, 2016
• Est. completion date: June 30, 2021

Study information

• Verified date: June 2020
• Source: Aristotle University Of Thessaloniki
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 270
• Est. completion date: June 30, 2021
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Arteriosclerosis
• Cardiovascular Risk Factor
• Coronary Arteriosclerosis
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Genetic:
• SNPs associated with CAD
Genotyping will be carried out by Real-Time PCR

Locations

Country	Name	City	State
Greece	AHEPA University Hospital	Thessaloníki

Sponsors (2)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki	LABNET IAE - Private Reference Diagnostic Laboratory

Country where clinical trial is conducted

Greece, 

References & Publications (6)

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. Review. — View Citation

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, Tybjærg-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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	MACCEs	Cardiovascular death, myocardial infarction, stent thrombosis, any re-intervention and stroke	12 months
Secondary	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
Secondary	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
Secondary	Left Ventricular Ejection Fraction	LVEF [%] as assessed by echocardiography	At hospital admission & 12 months after discharge from hospital
Secondary	Neutrophil to Lymphocyte Ratio	NLR [represented by a single number]	At hospital admission
Secondary	Red Cell Distribution Width	RDW [%]	At hospital admission
Secondary	Mean Platelet Volume	MPV [fL]	At hospital admission
Secondary	Glomerular Filtration Rate	GFR as assessed by CKD-EPI formula [mL/min/1.73m²]	At hospital admission
Secondary	High Density Lipoprotein	HDL [mg/dL]	At hospital admission