Paul Bachoo

Platelet activation is increased in peripheral arterial disease

OBJECTIVE Platelet activation was assessed in patients with peripheral arterial disease compared with healthy control subjects. METHODS This prospective comparative study included 100 subjects: 40 consecutive patients with intermittent claudication, 20 consecutive patients with critical ischemia and tissue loss, and 40 healthy control subjects. Whole blood flow cytometric analysis was performed to determine resting and stimulated platelet P-selectin expression and resting and stimulated platelet fibrinogen binding. Results are presented as platelet percentage and also as mean fluorescence intensity. RESULTS P-selectin expression was significantly increased in patients with intermittent claudication (median, 0.85%; range, 0.31%-4.77%; P =.023) and critical ischemia (median, 1.11%; range, 0.2%-3.26%; P =.028) compared with control subjects (median, 0.59%; range, 0.16%-4.58%). The percentage of platelets binding fibrinogen was also significantly higher in patients with intermittent claudication (median, 2.89%; range, 1.08%-9.59%; P <.001) compared with control subjects (median, 1.57%; range, 0.17%-10.7%). There was no significant difference in percentage of platelet fibrinogen binding between control subjects and patients with critical ischemia. Fibrinogen binding by stimulated platelets was significantly diminished in patients with critical limb ischemia compared with control subjects (67.2% vs 77.9%; P =.006). CONCLUSIONS Platelet activation is increased in patients with peripheral arterial disease, suggesting an underlying prothrombotic state. Platelets from patients with critical limb ischemia are less responsive to in vitro stimulation.

A Randomized Trial Comparing Treatments for Varicose Veins

BACKGROUND Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins, but their comparative effectiveness and safety remain uncertain. METHODS In a randomized trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of foam, laser, and surgical treatments. Primary outcomes at 6 months were disease-specific quality of life and generic quality of life, as measured on several scales. Secondary outcomes included complications and measures of clinical success. RESULTS After adjustment for baseline scores and other covariates, the mean disease-specific quality of life was slightly worse after treatment with foam than after surgery (P=0.006) but was similar in the laser and surgery groups. There were no significant differences between the surgery group and the foam or the laser group in measures of generic quality of life. The frequency of procedural complications was similar in the foam group (6%) and the surgery group (7%) but was lower in the laser group (1%) than in the surgery group (P<0.001); the frequency of serious adverse events (approximately 3%) was similar among the groups. Measures of clinical success were similar among the groups, but successful ablation of the main trunks of the saphenous vein was less common in the foam group than in the surgery group (P<0.001). CONCLUSIONS Quality-of-life measures were generally similar among the study groups, with the exception of a slightly worse disease-specific quality of life in the foam group than in the surgery group. All treatments had similar clinical efficacy, but complications were less frequent after laser treatment and ablation rates were lower after foam treatment. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN51995477.).

Systematic review of chimney and periscope grafts for endovascular aneurysm repair

Conventional endovascular aneurysm repair (EVAR) needs a proximal aortic seal zone that is free from aortic branch vessels. The modified application of conventional EVAR devices using adjuvant chimney or periscope grafts is described as a pragmatic alternative to custom‐made fenestrated and branched endografts. This systematic review examined the application and outcomes of chimney or periscope grafts for aortic aneurysm.

Platelet count and the outcome of operation for ruptured abdominal aortic aneurysm

PURPOSE The purpose of this study was to determine the relationship between admission and postoperative platelet count (PC) and mortality and morbidity rates after emergency surgery for ruptured abdominal aortic aneurysm (AAA). METHODS We performed a case record review of 65 consecutive patients admitted with ruptured AAA. RESULTS Five patients did not undergo operation because of poor clinical condition, 12 patients died at operation, 13 patients died after operation, and 35 patients survived (operative mortality rate of 58%). Fifteen patients had an admission PC of less than 150 x 10(9)/L, of whom 14 (93%) died; 27 patients had an admission PC of 150 to 250 x 10(9)/L, of whom 8 (30%) died; and 18 patients had an admission PC of greater than 250 x 10(9)/L of whom 3 (17%) died. At the end of operation 29 patients had a PC of less than 100 x 10(9)/L, of whom 13 (45%) died, 20 (69%) had development of multiorgan failure (MOF), and 6 (21%) required relaparotomy for bleeding complications. By contrast, all 19 patients having a PC of 100 x 10(9)/L or greater at the end of the operation survived, three (16%) had development of MOF, and none required further surgery for bleeding. There was a significant inverse correlation between PC at the end of the operation and the number of postoperative days spent on a ventilator, in the intensive therapy unit, and in hospital. After operation, 15 patients had development of thrombocytosis (PC > 400 x 10(9)/L), of whom 10 had development of deep venous thrombosis and 8 had development of pulmonary embolism. There were no deep venous thromboses or pulmonary embolisms in patients who did not have development of a postoperative thrombocytosis. CONCLUSIONS There is a direct correlation between PC on admission to the hospital and death after emergency repair of ruptured AAA. Thrombocytopenia at the end of the operation is associated with a high risk of morbidity from continuing hemorrhage or MOF. The development of postoperative thrombocytosis is associated with a high risk of thromboembolic complications. PC provides a simple marker of outcome in patients diagnosed with and undergoing operation for ruptured AAA.

Randomized clinical trial of the antiplatelet effects of aspirin–clopidogrel combination versus aspirin alone after lower limb angioplasty

There is a high risk of reocclusion after successful lower limb angioplasty. Platelets play a central role in this process. The aim of this study was to investigate the antiplatelet effect of a combination of aspirin and clopidogrel compared with aspirin alone in patients with claudication undergoing endovascular revascularization.

Platelet activation, myocardial ischemic events and postoperative non-response to aspirin in patients undergoing major vascular surgery.

Summary.  Objectives: Myocardial ischemia is the leading cause of postoperative mortality and morbidity in patients undergoing major vascular surgery. Platelets have been implicated in the pathogenesis of acute thrombotic events. We hypothesized that platelet activity is increased following major vascular surgery and that this may predispose patients to myocardial ischemia.Methods: Platelet function in 136 patients undergoing elective surgery for subcritical limb ischemia or infrarenal abdominal aortic aneurysm repair was assessed by P‐selectin expression and fibrinogen binding with and without adenosine diphosphate (ADP) stimulation, and aggregation mediated by thrombin receptor‐activating peptide and arachidonic acid (AA). Cardiac troponin‐I (cTnI) was performed.Results: P‐selectin expression increased from days 1 to 3 after surgery [median increase from baseline on day 3: 53% (range: −28% to 212%, P < 0.01) for unstimulated and 12% (range: −9% to 45%, P < 0.01) for stimulated]. Fibrinogen binding increased in the immediate postoperative period [median increase from baseline: 34% (range: −46% to 155%, P < 0.05)] and decreased on postoperative day 3 (P < 0.05). ADP‐stimulated fibrinogen binding increased on day1 (P < 0.05) and thereafter decreased. Platelet aggregation increased on days 1–5 (P < 0.05). Twenty‐eight (21%) patients had a postoperative elevation (> 0.1 ng mL−1) of cTnI. They had significantly increased AA‐stimulated platelet aggregation in the immediate postoperative period and on day 2 (P < 0.05), and non‐response to aspirin (48% vs. 26%, P = 0.036).Conclusions: This study has shown increased platelet activity and the existence of non‐response to aspirin following major vascular surgery. Patients with elevated postoperative cTnI had significantly increased AA‐mediated platelet aggregation and a higher incidence of non‐response to aspirin compared with patients who did not.

N-terminal pro B-type natriuretic peptide is an independent predictor of postoperative myocardial injury in patients undergoing major vascular surgery

OBJECTIVE Myocardial ischemia and infarction after surgery remain leading causes of morbidity and mortality in patients undergoing major vascular surgery. B-type natriuretic peptide has been shown to predict early postoperative cardiac events in patients undergoing major noncardiac surgery. We aimed to determine if N-terminal pro B-type natriuretic peptide (NT-pro-BNP), with its longer half-life and greater plasma stability, can predict postoperative myocardial injury in vascular patients. METHODS Recruited were 136 patients undergoing elective surgery for subcritical limb ischemia or abdominal aortic aneurysm (AAA) repair. Plasma NT-pro-BNP was measured preoperatively, and troponin-I was measured immediately after surgery and on postoperative days 1, 2, 3, and 5. RESULTS Twenty-eight patients (20%) sustained postoperative myocardial injury (troponin-I rise of >0.1 ng/mL). The median NT-pro-BNP level of those with myocardial injury was significantly higher than those who did not (380 pg/mL [interquartile range (IQR), 223-967] vs 209 pg/mL [109-363]; P = .003). NT-pro-BNP predicted this outcome with an area under the receiver operating characteristic (ROC) curve of 68% (95% confidence interval [CI] 0.56%-0.78%). In a multivariate analysis, a NT-pro-BNP value of >/=308 pg/mL (the optimal ROC curve-derived cutoff) was associated with an increased incidence of myocardial injury (odds ratio, 3.4; 95% CI, 1.41-9.09, P =.01). CONCLUSION Elevated preoperative plasma NT-pro-BNP levels independently predict postoperative myocardial injury, which is associated with adverse outcome in the short- and long-term regardless of the presence of symptoms of acute coronary syndrome.

Effect of Omega-3 fatty acid supplementation on markers of platelet and endothelial function in patients with peripheral arterial disease

OBJECTIVE Omega-3 fatty acids have been shown to reduce platelet and endothelial activation in patients with or at risk of cardiac disease. We aimed to determine if Omega-3 fatty acid supplementation in addition to best medical therapy can reduce the increased platelet and endothelial activity that is present in patients with intermittent claudication. METHODS One hundred and fifty patients who were receiving aspirin and statin therapy were recruited into a randomised cross-over double blind study involving 6 week supplementation with OMACOR fish oil (850-882 mg eicosapentaenoic and docosahexaenoic acid) versus placebo. A 12 week washout period occurred between treatments. Patients with diabetes were excluded. For each outcome a random effects model was fitted in which treatment and period were fixed effects and patients were random effects. RESULTS Omega-3 supplementation had no effect on the primary outcome measure von Willebrand factor. Similarly Omega-3 supplementation resulted in no change in unstimulated or stimulated P-selectin expression and fibrinogen binding, or platelet aggregation (Ultegra point of care). Pulse wave velocity was also unchanged. High-sensitivity C-reactive protein, s-ICAM and IL-6 were also unchanged. CONCLUSION Supplementation with Omega-3 fatty acids had no affect on platelet and endothelial activation or markers of inflammation in patients with peripheral arterial disease.

Influence of rurality, deprivation and distance from clinic on uptake in men invited for abdominal aortic aneurysm screening.

Effective abdominal aortic aneurysm (AAA) screening requires high uptake. The aim was to assess the independent association of screening uptake with rurality, social deprivation, clinic type, distance to clinic and season.

Randomized controlled trial of aspirin and clopidogrel versus aspirin and placebo on markers of smooth muscle proliferation before and after peripheral angioplasty.

OBJECTIVE In peripheral arterial disease (PAD) patients, a limiting factor in the success of percutaneous transluminal angioplasty (PTA) is the development of restenosis secondary to vascular smooth muscle cell (SMC) proliferation. Following endothelial damage and platelet activation, there is release of factors and adhesion molecules which affect SMC proliferation. The aim of this study was to determine the effect of combination antiplatelet therapy (clopidogrel and aspirin compared with aspirin and placebo) on the ability of plasma from PAD patients undergoing PTA to stimulate SMCs in vitro. We further aimed to investigate the effect of combination treatment on the levels of circulating adhesion molecules and factors, which are known to mediate SMC proliferation in experimental models. METHODS Fifty patients were randomized to receive blinded clopidogrel or placebo, for thirty days, in addition to their daily 75 mg aspirin. To measure proliferative capacity, diluted plasma was incubated for 15 minutes with 24 hour-growth-arrested rat vascular smooth muscle cells, and extracellular regulated kinase (ERK)1/2 activation was analyzed by Western blotting at baseline, one hour pre-PTA, one hour, 24 hours and 30 days post-PTA. Plasma platelet-derived growth factor (PDGF), sE-selectin, intracellular adhesion molecule-1 (sICAM-1), and von Willebrand factor (vWF) were measured by ELISA, at the same five timepoints. Platelet activation was measured by flow cytometry of ADP-stimulated platelet fibrinogen binding at baseline and one hour post-PTA. RESULTS ADP-stimulated platelet fibrinogen binding was significantly inhibited by clopidogrel before and after PTA. ERK 1/2 activation was significantly increased post-PTA in both the aspirin/clopidogrel and aspirin/placebo groups (P < .001). There was a statistically significant decrease in PDGF (P = .004), and increase in vWF (P = .026), following loading with clopidogrel. sICAM-1 levels significantly decreased (P = .016) in the aspirin/placebo group following PTA. There were no other significant changes and also there was no statistically significant difference between the two treatment groups for each of ERK 1/2, sICAM-1, sE-selectin, or vWF. CONCLUSIONS This is the first study to show in-vitro ERK 1/2 activation (a surrogate marker of SMC proliferation) increases post-PTA. Combination antiplatelet therapy had no significant effect on this, although it did reduce PDGF. Further work is required to evaluate potential therapeutic treatments, which may reduce peripheral PTA-induced smooth muscle cell activation. CLINICAL RELEVANCE High rates of restenosis remain the major limitation of peripheral arterial angioplasty and stenting.The restenotic lesion occurs secondary to platelet activation, released circulating factors, and subsequent smooth musclecell proliferation and migration into the intima. Methods to limit the restenotic lesion are poorly understood. This paperinvestigates the effect of PTA on smooth muscle cell activation and the release of factors in plasma which mediate SMCproliferation. It also examines the effect of combination antiplatelet therapy as a potential therapeutic strategy.