Total burden of intraplaque hemorrhage in coronary arteries relates to the use of coumarin-type anticoagulants but not platelet aggregation inhibitors.

Intraplaque hemorrhage (IPH) is a crucial factor in progression and destabilization of an atherosclerotic plaque. Anti-thromboembolic drugs are widely used as prophylactic treatment against arterial and venous thrombotic diseases, but a major complication is bleeding. We investigated the association between exposure to anti-thromboembolic therapy and IPH in postmortem coronary arteries. Coronary arteries with postmortem angiographically confirmed extensive atherosclerosis were obtained at autopsy from patients who had received oral anticoagulants (n = 10), platelet aggregation inhibitors (n = 10), or no anti-thrombotic drugs (n = 10) before death. Coronary arteries were cut at 3-mm interval, and all plaque-containing segments were immunohistochemically screened for IPH and microvessels. These data were related to overall plaque composition and the use of anti-thromboembolic therapies. IPH was found in 483 out of 904 (53 %) coronary segments with advanced atherosclerotic plaques and more frequently in patients on oral anticoagulants (174/284, 61 %) than in patients on anti-platelets (198/376, 53 %) or without therapy (111/244, 46 %) (P = 0.02 and P = 0.001, respectively). Also, intraplaque microvascular leakage was more frequently observed in patients on anticoagulants than in non-treated patients (P = 0.03). Finally, the IPH appeared to be larger in plaques of patients on anticoagulant treatment (P < 0.001). Density of intraplaque microvessels was highest in plaques of patients on platelet inhibitors (P < 0.05), but this was not associated with increased hemorrhagic burden. Prophylactic therapy with oral coumarin-type anticoagulants appears to be associated with a higher hemorrhagic burden in atherosclerotic coronary arteries, which may lead to increase in plaque volume over time, in this selected subgroup of patients.

Microvascular endoglin (CD105) expression correlates with tissue markers for atherosclerotic plaque vulnerability in an ageing population with multivessel coronary artery disease.

AIMS: Vulnerable atherosclerotic plaques are lesions with a high propensity to develop plaque disruption and superimposed thrombosis. No systematic studies have been carried out on tissue markers for plaque vulnerability throughout the entire coronary artery system at the end stages of coronary atherosclerosis. METHODS AND RESULTS: Nine autopsied patients (mean age 77 years) with angiographically severe trivascular coronary atherosclerosis were selected for this study. All visible lesions in postmortem coronary angiograms (n = 125) were histologically and immunohistochemically screened for the presence of intraplaque haemorrhages (activated) microvessels and inflammatory infiltrates. Intraplaque haemorrhages were observed in 76/125 plaques (61%). Chronic inflammation was found superficially in 59/125 plaques (47%) and deeply inside the plaque tissue in 103/125 plaques (83%). Microvessels were found in 100/125 lesions (80%), of which 58% showed endothelial expression of the vascular activation marker CD105. Moreover, microvascular CD105 positivity correlated positively with plaque haemorrhage and deeply seated plaque inflammation. CONCLUSIONS: Plaque inflammation and haemorrhages can be found at a high frequency throughout the coronary artery system of elderly patients with multivessel coronary atherosclerosis. Microvascular expression of endoglin (CD105), which correlates positively with both of these features of plaque vulnerability, can serve as a marker of the risk of developing coronary thrombotic complications.