EDICA_2019
Research type
Research Study
Full title
Early Detection of Myocardial Ischaemia in Suspected Acute Coronary Syndromes by Apo J-Glyc as a Novel Pathologically-based Ischaemia Biomarker.
IRAS ID
265793
Contact name
Diana Gorog
Contact email
Sponsor organisation
Glycardial Diagnostics
Duration of Study in the UK
1 years, 8 months, 1 days
Research summary
Research Summary
Chest pain may be due to reduced blood flow to the heart (coronary ischaemia) or due to non-heart related conditions such as acid reflux or muscular pain.The only currently available blood test (troponin) is only useful to detect a heart attack, namely permanent damage to the heart, but not simply reduced blood flow. This observational study aims to test whether measuring a protein in blood called Apo J-Glyc in patients presenting with chest pain can identify which patients have chest pain due to reduced blood flow to the heart, and which patients have non-cardiac pain.
Blood samples will be taken from persons who present to hospital with chest pain. Blood samples will be taken at hospital admission, throughout different post-admission times (1h, 3h, 24h and 72h or discharge) as well as at follow-up (3, 6, 9 and 12 months).
The quantity of Apo J-Glyc levels will be measured to provide information about how useful it is to allow early detection of patients who have reduced blood flow to the heart. Such a new marker could help identify patients who have pain due to heart disease who are at higher risk than patients with non-cardiac pain. This would allow high risk patients to be treated earlier with treatments to improve the blood flow to the heart, and provide reassurance and earlier discharge of low risk patients.Summary of Results
Based on clinical diagnostic tests, 291 patients were given a final diagnosis of “non-ischaemic” event and 113 patients were considered to have had an ischaemic event (33 STEMI, 48 NSTEMI, 27 Unstable Angina and 5 “unclassifiable” ACS). ApoJ-GlycA6 levels were significantly lower on admission in ischaemic patients, compared with non-ischaemic patients (66 [46-90] μg/ml vs. 73 [56-95] μg/ml, respectively; P=0.04). Ischaemic patients who underwent PCI and had a pre-PCI TIMI 0-2 flow showed significantly lower levels of ApoJ-GlycA6 at admission compared with non-ischaemic patients (64 [37-81] μg/ml vs. 73 [56-95] μg/ml; P=0.01). Reduced ApoJ-Glyc concentrations were present before any hs-Tn elevation took place or even in the absence of troponin elevation in a large proportion of patients 69% and 62% for ApoJ-GlycA2 and ApoJ-GlycA6, respectively vs. 56% for hs-Tn at admission in patients with documented ischemia (TIMI flow 0-2 pre-PCI).
In the presence of myocardial ischaemia, time 0 ApoJ-GlycA2 and ApoJ-GlycA6 serum levels decreased by 34% and 48%, respectively in STEMI patients, compared with non-ischaemic patients, i.e. ApoJ-GlycA2 in STEMI: 66 [52-95] μg/ml vs. non-ischaemic: 100 [72-131] μg/ml; P=0.0002; ApoJ-GlycA6 STEMI: 38 [34-67] vs. non-ischaemic: 73 [56-95] μg/ml; P<0.0001. ApoJ-GlycA6 showed a discriminating ability for the presence of STEMI with a 67% sensitivity and a 83% specificity (AUC=0.747, cut-off of 50μg/ml). In STEMI patients in whom PPCI successfully restored TIMI 3 flow, ApoJ-Glyc levels increased rapidly and significantly compared with time 0 levels (ApoJ-GlycA2: P=0.02 and P=0.003 for 1h and 3h; ApoJ-GlycA6: P=0.02 and P=0.002 for 1h and 3h) and compared to patients in whom PPCI was not performed.
Among the patients in the ischaemic group, 8.8% had MACE at 6-months follow-up and these showed a 26% (mean) reduction in ApoJ-GlycA2 serum levels 3h post-admission compared with levels at presentation. This reduction was not observed in patients who did not experience MACE. Patients in the highest GRACE Risk Score tertile (>118 points) showed a progressive decrease in ApoJ-GlycA2 levels after presentation compared with patients in the lower risk tertiles (41% mean decrease at 1h and 35% mean decrease at 3h when compared with admission levels; P=0.01 and P=0.02, respectively).Conclusions:
1. The EDICA study showed that ApoJ-Glyc detects both the presence of reversible ischaemia and the restoration of myocardial perfusion in those subjects undergoing successful revascularization.
2. ApoJ-Glyc appears to be able to map the dynamics of the ischaemic process (transient/reversible ischaemia) and complements the diagnostic role of cTn.
3. ApoJ-Glyc provides prognostic information thus supporting previous findings in experimental clinical work and can be a marker of risk in different IHD clinical settings.
4. Even in a subgroup of patients attending ED with chest pain suggestive of ACS and diagnosed as having a non-ischemic episode, reduced serum concentrations of ApoJ-Glyc correlated with impaired clinical outcomes during follow up, thus suggesting a role for this marker in the identification of patients with subclinical ischaemia and increased cardiovascular risk.
5. Each ApoJ-Glyc variant appears to provide complementary and perhaps synergistic information, with A6 being more sensitive for the early detection of ischemia and A2 providing information about the evolution of the ischaemic process and clinical outcomes.
6. Preliminary findings in EDICA, supporting data from previous clinical research studies, suggest that ApoJ-Glyc may have clinical applications beyond the diagnosis of ischaemia in the ED setting.REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
19/EM/0263
Date of REC Opinion
4 Oct 2019
REC opinion
Further Information Favourable Opinion