Clinical use of C-reactive protein for prognostic stratification in ischemic stroke: has the time come for including it in the patient risk profile?
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Biomarkers↗
Biomedical subjects
Mario Di Napoli
Publications and source records attributed to Mario Di Napoli.
MLN-519. Millennium/PAION.
Millennium Pharmaceuticals Inc (formerly LeukoSite Inc) and PAION GmbH are developing MLN-519, a ubiquitin/proteasome enzyme inhibitor, for the potential treatment of inflammatory diseases and stroke. MLN-519 is currently undergoing phase I clinical trials in acute stroke and myocardial infarction, and is poised to enter phase II trials.
Acetylcysteine↗
NCX-4016 NicOx.
NCX-4016 is a nitric oxide-aspirin conjugate non-steroidal anti-inflammatory drug that is under investigation by NicOx for the potential treatment of cardiovascular disorders and colon cancer. In April 2002, a phase II clinical trial was initiated in symptomatic peripheral arterial disease, and in March 2003, the University of Michigan was awarded a grant by the NIH to conduct a phase II trial in individuals at risk of colon cancer.
Animals↗
The proteasome system and proteasome inhibitors in stroke: controlling the inflammatory response.
The ubiquitin-proteasome pathway (UPP) is a predominantly non-lysosomal protein degradation pathway responsible for degrading many critical regulatory proteins (e.g., nuclear factor-kappa B). This pathway is widely known for its ubiquitous role in immune and inflammatory responses, control of cell growth and apoptosis. These roles are apparent in the nervous system, but neurons and their neighboring cells also employ the UPP for distinct functions, ranging from development to the co-ordination of cellular responses, injury of the nervous system and brain-specific processes such as aging and memory. Promising results from preclinical studies in animal models indicate that the use of specific proteasome inhibitors to manipulate UPP may prove valuable in treating such conditions as ischemic stroke.
Animals↗
Inflammation, hemostatic markers, and antithrombotic agents in relation to long-term risk of new cardiovascular events in first-ever ischemic stroke patients.
BACKGROUND AND PURPOSE: The measurement of markers of inflammation or thrombosis has been proposed as a method to improve the prediction of risk in patients with vascular disease. We evaluated the usefulness of these markers as predictors of cardiovascular events in ischemic stroke patients. METHODS: We analyzed levels of C-reactive protein (CRP), fibrinogen, and D-dimer within the first 24 hours after stroke onset in 473 first-ever ischemic stroke patients and determined the cumulative survival curves free of cardiovascular events in relation to the level of each of these markers according to the Kaplan-Meier method. We adjusted for possible confounding variables using a multivariate Cox proportional-hazards model. RESULTS: Patients in the highest tertiles of D-dimer, fibrinogen, and CRP were associated with an excess risk of new cardiovascular events of 36% (P=0.0134), 63% (P<0.0001), and 72% (P<0.0001), respectively, compared with patients in the lowest tertile. The patients in the highest tertile of CRP had 4 times the risk (hazard ratio, 4.04; P<0.0001) of a new cardiovascular event. Smoking, age, sex, and body mass index did not modify risk, and risk was independent of other confounding variables and of D-dimer and fibrinogen levels. The use of ticlopidine was associated with a significant risk reduction among patients with lower (86%, P=0.0159) and middle (69%, P<0.0001) levels of CRP, whereas a nonsignificant excess risk (27%, P=0.3896) was evident among those with the highest levels. CONCLUSIONS: Elevated levels of CRP, more than of D-dimer and fibrinogen, are related to the risk of new cardiovascular events after ischemic stroke. The efficacy of antiplatelet therapy in secondary prevention appears to be directly related to level of inflammatory and thrombotic markers.
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