The Oral Health Status of Patients with Peripheral Vascular Disorders : A Systematic Review

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: SAA was funded by the NHS Grampian Vascular Surgery Department, and MM was funded by the University of Aberdeen Institute of Dentistry through the Aberdeen Summer Research Scholarship as part of the Aberdeen Clinical Academic Training (ACAT).Peer reviewedPublisher PD

Introducing endovenous laser therapy ablation to a national health service vascular surgical unit e the aberdeen experience

Objectives: To report early clinical outcomes and learning experience following the introduction of endovenous laser ablation (EVLA) to an NHS vascular unit. Design: Prospective observational study. Results: Between February 2006 and January 2008, 631 consecutive patients underwent EVLA to 704 refluxing truncal veins e 579 GSV, 119 SSV and 6 straight segments of anterior accessory GSV. 275/631 (44%) patients had local anaesthesia (LA) plus sedation, 237 (38%) had LA only and 119 (18%) had general anaesthesia. All were treated using the 810 nm diode laser. Adjuvant procedures on-table included foam sclerotherapy 129/704 (18%), multiple stab avulsions 53/ 704 (8%) and 3 limbs had both. Three-month follow-up with duplex examination is complete in 635/704 limbs (90%). Complete occlusion was noted in 610 veins (96%), 14 (2.2%) were partially occluded and 11 (1.7%) showed no occlusion. 193 (30%) of the 635 limbs seen at follow-up required further treatment for residual varicosities using foam sclerotherapy. There has been one non-fatal pulmonary embolus associated with EVLA and no other complications. Conclusions: EVLA is safe and technically effective. It has a defined learning curve requiring new operator skills which can be readily acquired.peer-reviewe

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. Methods This was a double-blind randomized placebo-controlled trial. Some 132 patients were randomized to clopidogrel and aspirin or placebo and aspirin, with a loading dose 12 h before endovascular intervention. Flow cytometric measurements of platelet fibrinogen binding and P-selectin expression were taken as measures of platelet function at baseline, 12 h after the loading dose, and 1 h, 24 h and 30 days after intervention. Results Within 12 h of the loading dose, platelet activation in the clopidogrel group had decreased (P-selectin by 27·3 per cent, P = 0·017; fibrinogen binding by 34·7 per cent, P = 0·024; stimulated fibrinogen binding by 49·2 per cent, P < 0·001). No change was observed in the placebo group. Platelet function in the clopidogrel group was significantly suppressed compared with baseline at 1 h, 24 h and 30 days after endovascular intervention (stimulated fibrinogen binding by 53·9, 51·7 and 57·2 per cent respectively; all P < 0·001). Conclusion A combination of clopidogrel and aspirin inhibited platelet function more than aspirin alone in patients with claudication before and after angioplasty.peer-reviewe

Platelet activation is increased in peripheral arterial disease

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.peer-reviewe

Clopidogrel has no effect on D-dimer and thrombin-antithrombin III levels in patients with peripheral arterial disease undergoing peripheral percutaneous transluminal angioplasty

Objective: Coagulation activation markers are significantly elevated in patients with peripheral arterial disease compared with healthy controls. The more severe the disease, the higher the markers. Increased coagulation activation may contribute to the disease process and the risk of complications in patients with peripheral arterial disease, particularly after endovascular intervention. Animal studies have shown that clopidogrel significantly inhibits coagulation activation. The aim of this study was to determine whether combination of aspirin and clopidogrel affects thrombin-antithrombin III and D-dimer in patients with intermittent claudication undergoing angioplasty, compared with aspirin alone. Methods: This was a double blind, randomized placebo-controlled trial conducted in a vascular unit in a tertiary referral center. One hundred thirty-two patients with intermittent claudication were randomized to clopidogrel and aspirin or placebo and aspirin, with a loading dose 12 hours before endovascular intervention. D-dimer and thrombin-antithrom- bin III (TAT) levels were measured using enzyme-linked immunosorbent assay at baseline, 1 hour before, and 1 hour, 24 hours, and 30 days after intervention in 103 patients who underwent endovascular intervention. Results: There was a significant rise in D-dimer levels at 1 hour and 24 hours after angioplasty in both groups (placebo group: 63.69, 141.45, 122.18 ng/mL; clopidogrel group: 103.79, 159.95, 134.69 ng/mL), but no difference between the two groups (P .514). Similarly there was a significant rise in TAT levels at 1 hour after angioplasty in both groups (placebo group: 2.93, 6.16 g/L; clopidogrel group: 3.39, 5.27 g/L), with no significant difference between the two groups (P .746). Conclusion: Endovascular intervention results in a significant increase in TAT and D-dimer. The addition of clopidogrel to aspirin has no effect on TAT and D-dimer before or after endovascular intervention.peer-reviewe

Markers of coagulation activation, endothelial stimulation and inflammation in patients with peripheral arterial disease

Objectives. Patients with peripheral arterial disease have a significantly increased risk of cardiovascular and cerebrovascular mortality. Studies have shown that some haemostatic and inflammatory markers are elevated in these patients but the effect of the severity of the disease has not been fully documented. The aim of this study was to assess the level of coagulation activation, endothelial stimulation and inflammation in patients with claudication and critical limb ischaemia (CLI) compared to healthy controls. Design and methods. A prospective observational study was conducted amongst 202 subjects: 132 claudicants, 30 patients with critical ischaemia, and 40 controls. D-dimer (DD) and thrombin–antithrombin III (TAT) levels measured using ELISA as markers of coagulation activation. von Willebrand factor (vWF) and high-sensitivity C-reactive protein (CRP) levels were measured as markers of endothelial and inflammatory stimulation. Results. vWF and CRP levels were significantly higher in patients with intermittent claudication (1.9 U/ml, range 0.78– 4.05; p!0.001; 3.4 mg/l, range 0.15–24; pO0.001, respectively) and critical ischaemia (2.36 U/ml; range 1.03–5.69; p! 0.001; 7.17 mg/ml, range 0.15–174; p!0.001, respectively) compared to controls (1.28 U/ml, range 0.62–3.13; 1.04, range 0.15–7.59 mg/l). DD was also significantly higher in claudicants (48.6 mg/ml; range 2–1741; p!0.001) and in patients with CLI (61.1 mg/ml, range 3.65–1963; p!0.001) compared to controls (26.1 mg/ml, range 9.65–203.1). TAT levels were significantly higher in CLI (3.14 mg/l, range 2.09–58.11), compared to controls (2.36 mg/l, range 1.49–7.38; pZ0.004). Patients with CLI had significantly higher levels of CRP, vWF, and TAT than claudicants. Conclusions. Coagulation activation and endothelial stimulation are significantly increased in patients with peripheral arterial disease compared to healthy controls. Coagulation and endothelial activation increases with the severity of the arterial disease.peer-reviewe

Low intensity shockwave treatment modulates macrophage functions beneficial to healing chronic wounds

Acknowledgments: We acknowledge the University of Aberdeen Microscopy and Histology Facility and the qPCR facility for use of facilities and advice. We acknowledge Ehab Husain for scoring the patient wound biopsies. Funding: This research was funded by NHS Grampian Endowments, grant number 17/004 and by personal funding from JSH.Peer reviewedPublisher PD

Double-blind randomized placebo-controlled trial of the antiplatelet effects of aspirin-clopidogrel combination versus aspirin alone at endovascular intervention for intermittent claudication of the lower limb

Intermittent claudication is a common problem which causes significant impairment of quality of life and increased mortality. Endovascular recanalization, widely used for symptomatic relief, carries a high risk of reocclusion. Platelets play a central role in this process. Aspirin currently used in claudicants reduces the risk, and more potent antiplatelet strategies may reduce this further. The aim of this study was to investigate the antiplatelet effect of aspirin–clopidogrel versus aspirin alone in patients with claudication undergoing endovascular intervention. Methods: This was a double-blind randomized placebo-controlled trial; 132 patients were randomized to clopidogrel and aspirin or to placebo and aspirin with a loading dose 12 h before endovascular intervention. Flow cytometric measurement of platelet fibrinogen binding and P-selectin expression as measures of platelet activation status and of platelet responsiveness to stimulation at baseline, 12 h post-loading dose, 1 h, 24 h and 30 days postintervention. Results: Platelet activation was significantly diminished in the clopidogrel group at 12 h post-loading dose compared to baseline (P-selectin: 27·3 per cent reduction, P = 0·017; bound fibrinogen: 34·7 per cent reduction, P = 0·024; stimulated bound fibrinogen: 49 per cent, P < 0·001). No significant change was observed in the control group. Platelet function was significantly suppressed in the clopidogrel group at 1 h, 24 h and 30 days after endovascular intervention compared to the placebo group (P < 0·001). Conclusion: Clopidogrel–aspirin combination dramatically inhibits platelet function in claudicants before and after intervention. The combination treatment may help reduce reocclusion after endovascular recanalization.peer-reviewe

Management of secondary risk factors in patients with intermittent claudication

Objectives: the first line management of patients with intermittent claudication is "best medical therapy'' i.e., smoking cessation, exercise, antiplatelet therapy and risk factors modification. The aim of this study was to assess the current management of risk factors in primary care and to compare General Practitioner (GP) attitudes and actual management. Design and Methods: postal questionnaire of all 336 GPs in the referral area (Grampian, Scotland). Questionnaire and measurement of serum cholesterol, blood glucose and HbA1c of new clinic patients (n 104) with claudication referred by general practitioners. Results: a 73% GP response rate was obtained. Ninety-five percent of GPs would treat risk factors. The vast majority would prescribe aspirin, yet 28% of patients were on no anti-platelet therapy. Eighty-nine percent of GPs would advise an increase in exercise but only 14% of patients recalled being told to do so. One in seven of the GPs would not check serum cholesterol, 18% considered cholesterol lowering therapy to be primary prevention and 41% would only treat levels above 5.5 mmol/l. Eighty-five percent of patients were on a statin or had a cholesterol above 5 mmol/L. Seventy-seven percent of GPs would check glucose levels, and 14% of patients were found to be previously undiagnosed diabetics. Conclusions: risk factors in claudicants are suboptimally managed. Urgent guidelines for the specific management of claudicants by general practitioners, as well as strategies to ensure their implementation, are required.peer-reviewe

Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins

BACKGROUND Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain. METHODS In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants’ treatment costs and scores on the EuroQol EQ-5D questionnaire. RESULTS Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, −2.86; 95% confidence interval [CI], −4.49 to −1.22; P<0.001; and for surgery vs. foam sclerotherapy, −2.60; 95% CI, −3.99 to −1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2 CONCLUSIONS In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.