Aspirin Resistance in Cardiovascular Disease: A Review

AbstractBackground. Aspirin is effective at reducing the cardiovascular event rate in defined patient groups. The introduction of antiplatelet therapies other than aspirin and the concept of aspirin resistance have led to critical reappraisal of current treatment. This review aims to clarify the evidence for aspirin resistance in patients with atherosclerosis.Methods. Medline search was performed to identify publications concerned with antiplatelet effects of aspirin and failure of aspirin therapy. Manual cross referencing was also performed.Results and conclusion. Wide variations in the rate of aspirin resistance (5.5–75%) have been reported. The lack of consensus on an appropriate definition and the number of different tests used to investigate aspirin resistance needs to be addressed. There are few studies where the primary aim was to document aspirin resistance or aspirin non-response. Further work should aim to investigate if aspirin resistance is clinically important and, if it is, what treatments may be beneficial to the at risk patient

Fluoropolymer coated Dacron or polytetrafluoroethylene for femoropopliteal bypass grafting: a multicentre trial

This trial was designed to compare graft patency between expanded polytetrafluoroethylene (PTFE) and fluoro­polymer coated Dacron for femoropopliteal bypass in patients in whom saphenous vein was unavailable. Methods: A multicentre prospective trial randomized 129 patients (74 men, 55 women) who underwent femoropopliteal bypass using either a PTFE or fluoropolymer coated Dacron graft. The indication for operation was disabling claudication in 68 (52.7%) and critical limb ischaemia in 61 (47.3%) patients. Distal anastomosis was above the knee in 76 (58.9%) and below the knee in 53 (41.1%) patients. Results: Primary patency at 6, 12 and 24 months was 71%, 56% and 47% for PTFE and 50%, 36% and 36% for fluoropolymer coated Dacron (P = 0.002), respectively. Secondary patency at 6, 12 and 24 months was 77%, 60% and 48% for PTFE and 66%, 49% and 46% for fluoropolymer coated Dacron (P = 0.13), respectively. The superior primary patency of PTFE over fluoropolymer coated Dacron was most evident in patients with poor prognostic indicators for graft survival: critical limb ischaemia (P = 0.001); below-knee anastomosis (P = 0.01); and smaller (6 mm) diameter grafts (P = 0.002). Graft thrombosis developed in the first month in 22 of 61 (36%) patients receiving fluoropolymer coated grafts compared to six of 68 (8.8%) patients receiving PTFE, which accounts for the difference in primary patency. Successful thrombectomy in 10 of the 22 fluoropolymer coated grafts resulted in similar secondary patency. Conclusion: Polytetrafluoroethylene has superior primary patency and similar secondary patency to fluoropolymer coated Dacron. These results support the preferential use of PTFE in patients with critical limb ischaemia, especially when a below-knee distal anastomosis and smaller diameter graft is required.A. Richardson, P. Tomlinson, R. Bell, C. Fisher, M. Condous, R. Ventura, A. Scott, D. Stary, R. Allen, E. Lippey, M. Appleberg, A. Chao, R. Fitridge, G. Frydman, S. Hazelton, B. King, P. Middleton, P. Pai, I. Thomson, B. Beiles, A. Gray-Wheale and R. Lan

Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages.

Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule proteins (AZP) were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane resulting in killing of mycobacteria. Exogenous addition of AZP to murine macrophage RAW 264.7, THP-1 and peripheral blood monocyte-derived macrophages significantly reduced the intracellular survival of mycobacteria without exhibiting cytotoxic activity on macrophages. Immunofluorescence studies showed that macrophages actively endocytose neutrophil granular proteins. Treatment with AZP resulted in increase in co-localization of BCG containing phagosomes with lysosomes but not in increase of autophagy. These data demonstrate that neutrophil azurophil proteins may play an important role in controlling intracellular survival of mycobacteria in macrophages