Relationship between coronary stenosis severity and high shear thrombosis assessment in vitro

Abstract

Funding Acknowledgements Type of funding sources: None. Among stable outpatients presenting with suspected coronary artery disease, the presence and extent of coronary artery calcification (CAC) and the severity of disease on CT coronary angiography (CTCA) has been shown to be predictive of future major adverse cardiovascular events (MACE) including myocardial infarction (MI). In stable patients, high on-treatment platelet reactivity has also been shown to relate to an increased risk of MACE including MI. The relationship between thrombotic markers in peripheral blood and the extent of CAC and coronary disease severity, is unknown. It was the aim of this pilot study to assess the relationship between thrombotic status and the extent of CAC and severity of coronary stenosis on CT. Subjects with suspected coronary disease undergoing CTCA and CAC were invited to participate in this observational study. Venous blood was obtained to assess platelet reactivity to high shear (occlusion time, OT) and endogenous fibrinolysis (lysis time, LT) using the Global Thrombosis Test, and related to CAC and to maximum stenosis in any main coronary artery on CTCA. Eighty patients were recruited, specifically 20 patients from each CAC quartile (adjusted for age, gender and ethnicity), 58% were male, aged 61±10 y. Groups were matched for age, sex, diabetes, and hs-CRP. The median Agatson CAC score was 27 [interquartile range (IQR) 0.5-125.5] and in each quartile (Q) as follows: Q1 0[0-0]; Q2 17[6-51.5]; Q3 70.25[26-111.5] and Q4 192.6[70.5-413.5]. Patients were divided into 4 groups according to maximal severity of coronary stenosis on CTCA (0%, 1-49%, 50-69%, >70%). With increasing stenosis severity, we found patients exhibited less efficient endogenous fibrinolysis (longer LT) (LT 1728s[1512-2102] vs. 2028s[1687-2288] vs. 1728s[1634-1927] vs. 2524s[2425-2623] respectively, p=0.040) whilst platelet reactivity appeared unrelated to severity of coronary stenosis (438s[341-479] vs. 415s[357-484] vs. 444s[384-504] vs. 391s[357-425], p=0.907). Platelet reactivity (OT 430s[339-477] vs. 458s[391-499] vs. 409s[351-488] vs. 413s[354-496], p=0.76) and spontaneous fibrinolysis (LT 1754s[1548-2162] vs. 1809s[1635-2291] vs. 2111s[1838-2312] vs. 1846s[1666-2090], p=0.253) were similar between the quartiles. Furthermore, there was no difference in platelet reactivity (430s[339-477] vs. 413s[354-496], p=0.830) or spontaneous fibrinolysis (1754s[1548-2162] vs. 1846s[1666-2090], p=0.561) when comparing patients within the lowest and the highest quartiles of CAC. The severity of maximal coronary stenosis, but not the extent of CAC, is related to the effectiveness of spontaneous fibrinolysis at high shear in vitro, with patients with more severe stenoses exhibiting less efficient fibrinolysis. Further studies are required to investigate whether the extent of in vivo coronary shear (related to plaque morphology) can be reflected by the assessment of thrombosis and fibrinolysis in response to high shear in vitro.