Carotid plaque pathology: Thrombosis, ulceration, and stroke pathogenesis

Abstract

Conclusion:There is an increased risk of venous thrombosis in patients with cancer. The risk is greatest in the first few months after diagnosis and in the presence of distal metastasis. Patients also with Factor V Leiden and prothrombin 20210A mutations have even higher risk.Summary: This is a report of the Multiple Environmental and Genetic Assessment (MEGA) of Risk Factors for Venous Thrombosis Study. MEGA is a case controlled population based study evaluating risk of venous thrombosis with various risk factors. This report details risk of venous thrombosis with cancer and the joint effects of cancer and selected genetic mutations predisposing to venous thrombosis. Patients were identified at 6 anticoagulation clinics in the Netherlands between March 1, 1999, and May 31, 2002. Patients included were those 18-70 years of age with a first time diagnosis of pulmonary embolism or lower extremity deep venous thrombosis. Control patients, (partners of the patients with venous thrombosis) were also utilized in the study. Both patients and controls received a questionnaire to evaluate acquired risk factors for venous thrombosis. Once anticoagulation therapy had been discontinued for three months, patients and controls were interviewed and blood taken for analysis of Factor V Leiden and prothrombin 20210A mutations.In patients with malignancy, the overall risk of venous thrombosis was increased 7 times (odds ratio [OR], 6.7; 95% CI, 5.2-8.6). The highest risk was present in patients with hematologic malignancies (OR 28.0, 95% CI, 4.0-199.7). Risk was also substantially increased in patient with gastrointestinal cancers (OR 18.9; 95% CI, 4.6-77.8), and patients with pulmonary malignancies (OR 24.8; 95% CI, 3.4-181.1). Risk was highest in the first several months following malignancy diagnosis (adjusted OR 53.5; 95% CI, 8.6-334.3). In patients with cancer the presence of distal metastatic disease further increased the risk of venous thromboembolism (VTE) compared to patients without metastatic disease (adjusted OR, 19.8; 95% CI, 2.6-149.1). The combination of cancer and Factor V Leiden mutation increased the risk of VTE 12 times compared to patients with Factor V Leiden mutation and no diagnosed malignancy. Results were similar for patients with and without cancer with respect to the prothrombin 20210A mutation.Comment: The data raises the question as to whether patients with cancer should be screened for Factor V Leiden and prothrombin 20210A mutation and treated with prophylactic anticoagulation therapy if a mutation is present. Also the question arises whether prophylactic anticoagulation is indicated in patients with malignancies associated with an especially high risk for VTE. The cost effectiveness of such strategies and the ultimate ability of such strategies to prolong life or improve quality of life are clear in patients with cancer who are undergoing surgery or active chemotherapy (ACTA Haematol 2001;106:73-80). There is currently no data to suggest routine prophylaxis for VTE in all cancer patients would be...

Influence of CagA-positive Helicobacter pylori strains on atherosclerotic carotid disease

“…It could be due to the fact that positive immunoreactivity was better visualized in the symptomatic group. Previous histopathological studies of endarterectomy specimens disclosed plaque ulceration and rupture as morphological characteristics of symptomatic stenosis compared with asymptomatic plaques [35][36][37]. The plaque areas covered by inflammatory cells were significantly larger in symptomatic ICA plaques versus asymptomatic placques, indicating that acute inflammation could also be involved in plaque destabilization [36,[38][39][40].…”

2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease

“…Investigations of the relationship between cerebral symptoms and morphological characteristics of plaque defined by ultrasound found an association of clinical cerebral ischemic events with ulceration, echolucency, intraplaque hemorrhage, and high lipid content (86,87). Molecular and cellular processes responsible for plaque composition (86 -88) may be more important than the degree of stenosis in determining the risk of subsequent TIA and stroke, but the degree of carotid stenosis estimated by ultrasonography remains the main determinant of disease severity and forms the basis for most clinical decision making.…”

Development of 3D ultrasound techniques for carotid artery disease assessment and monitoring

“…These results indicate that factors other than stenosis severity are also important in identifying the sub-population at risk. There is now agreement that for event-free survival, the important question is not simply related to the presence of disease or the degree of stenosis, but rather related to indolent slow progression, followed by sudden plaque complications, leading to plaque rupture and consequent life-or brain-threatening thrombosis [10,11].…”

“…Although progress has been made, many questions still remain unanswered. As atherosclerosis is such a complex disease, it is clear that understanding the mechanisms of initiation, progression, and finally conversion of a stable to an unstable life-threatening atherothrombotic lesion (an event known as plaque fissuring, rupture, or disruption) [10,20] will require advances in many different fields.…”