Correlation of Genetic Polymorphisms and Clinical Parameters With the Complexity of Coronary Artery Disease
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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 Design
Arms and Interventions
| Arm | 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
|
Outcome Measures
Primary Outcome Measures
- Relationship between genetic risk variants and the SYNTAX score [All-comers population] [12 months]
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
Secondary Outcome Measures
- MACCEs [12 months]
Cardiovascular death, myocardial infarction, stent thrombosis, any re-intervention and stroke
- Predictive value of combining a Genetic Risk Score & SYNTAX score for the prediction of 1-year MACCEs [12 months]
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.
- Ankle-Brachial Index [At hospital admission]
A tool for diagnosing peripheral artery disease but also an indicator of systemic atherosclerosis [represented by a single number]
- Left Ventricular Ejection Fraction [At hospital admission & 12 months after discharge from hospital]
LVEF [%] as assessed by echocardiography
- Neutrophil to Lymphocyte Ratio [At hospital admission]
NLR [represented by a single number]
- Red Cell Distribution Width [At hospital admission]
RDW [%]
- Mean Platelet Volume [At hospital admission]
MPV [fL]
- Glomerular Filtration Rate [At hospital admission]
GFR as assessed by CKD-EPI formula [mL/min/1.73m²]
- High Density Lipoprotein [At hospital admission]
HDL [mg/dL]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients who are admitted in the Department of Cardiology in the AHEPA University General Hospital of Thessaloniki and undergo coronary angiography for clinical purposes
-
Patients giving voluntary written consent to participate in the study
-
Male or female patients between 18 years to 90 years at entry
-
Patients without previous history of CAD
Exclusion Criteria:
-
Patients < 18 years old and > 90 years old at time of coronary angiography
-
Patients with a previous history of CAD
-
Cardiac Arrest at admission
-
Patients with serious concurrent disease and life expectancy of < 1 year
-
Patients who refuse to give written consent for participation in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AHEPA University Hospital | Thessaloníki | Greece | 54636 |
Sponsors and Collaborators
- Aristotle University Of Thessaloniki
- 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
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- CIP_PhD Rampidis Georgios_1.1