M. Prior

Vascular adhesion molecule-1 and markers of platelet function before and after a treatment with iloprost or a supervised physical exercise program in patients with peripheral arterial disease

Platelet function and levels of vascular adhesion molecule-1 (VCAM-1) were investigated in 24 patients with peripheral arterial disease at Fontaine stage II undergoing a 2 weeks treatment with iloprost (0.5-2 ng/kg/h i.v. infused, 6 h/day) or a 2 weeks supervised physical training, randomly assigned. Patients were studied before (T0) and after (T14) treatments and 10 days later (T24). The adhesion of washed platelets to fibrinogen coated microwells was reduced after treatment both with iloprost (1.9+/-0.4 vs 6.8+/-0.7%; T24 vs T0; M+/-SEM; p<0.05) and physical exercise (3.0+/-1.0 vs 6.7+/-0.7; p<0.05) while adhesion to human plasma coated microwells was reduced only after treatment with iloprost (1.9+/-0.8 vs 5.8+/-0.9; p<0.05). The expression of fibrinogen receptor (glycoprotein IIb/IIIa) on platelets, measured by flow-cytometry was also reduced after iloprost treatment (17.1+/-1.5 vs 31.8+/-4.8 AU; p<0.05) and physical exercise (14.6+/-1.5 vs 34.0+/-3.3; p<0.05). Theurinaryexcretion of platelet thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients treated with iloprost (154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1); p<0.05). Similarly plasma VCAM-1 was lower in patients who were treated with iloprost (827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1); p<0.05). In conclusion, both iloprost and physical exercise seem to act on reversible phenomena such as the expression of adhesion molecules or ex vivo adhesion, whereas only iloprost reduces thromboxane A2 biosynthesis in vivo. This anti-platelet activity seems to be extended in time and to be associated with an improvement in vascular function.

Young adults with coeliac disease may be at increased risk of early atherosclerosis

Accelerated progression of atherosclerosis and increased cardiovascular risk have been described in immune‐mediated disorders, but few data are available in coeliac disease.

Effects of nebivolol and atenolol on small arteries and microcirculatory endothelium-dependent dilation in hypertensive patients undergoing isometric stress.

Objective To examine the effects on small arteries and on the cutaneous microcirculatory system of nebivolol and atenolol in hypertensive patients. Design Twenty hypertensive patients were randomly assigned to receive nebivolol or atenolol in a single-blind, placebo-controlled cross-over study. Piezoelectric plethysmography on the third finger, laser Doppler on the third finger at rest and after iontophoretic administration of acetylcholine, and pressure–heart rate monitoring, were carried out both at rest and during handgrip. The tests were performed 45 min after 5 mg nebivolol or 100 mg atenolol administration, then repeated 2 days later with a placebo and, after a further 2 days, with atenolol or nebivolol again. Results Both atenolol and nebivolol reduced diastolic blood pressure values and heart rate, as well the increase of blood pressure and heart rate during handgrip. No change was recorded after placebo. Piezoelectric plethysmography showed a significant increase in the ratio between time to peak and total time (PT/TT), calculated on the sphygmic wave, during handgrip (0.295 ± 0.005 versus 0.231 ± 0.015, P < 0.005). After nebivolol, a decrease was recorded in rest conditions (0.185 ± 0.008 versus 0.231 ± 0.015, P < 0.005) with no statistically significant increase during handgrip, whereas atenolol showed an increase in the PT/TT ratio at rest, with a sustained response during handgrip. Laser Doppler showed an increased response to acetylcholine only after nebivolol. Conclusions Nebivolol and atenolol significantly reduced diastolic blood pressure and heart rate, favourably modulating response to handgrip. Nebivolol improved small artery distensibility index. Endothelium-dependent cutaneous vasodilation after acetylcholine demonstrated a lack of response with atenolol whereas nebivolol favourably acts on endothelial function.

Effect of Glutathione Infusion on Leg Arterial Circulation, Cutaneous Microcirculation, and Pain-Free Walking Distance in Patients With Peripheral Obstructive Arterial Disease: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE To assess the effects of glutathione on pain-free walking distance (PFWD) and hemodynamic parameters in patients with peripheral artery disease. PATIENTS AND METHODS Forty patients with Fontaine stage II peripheral artery disease who were seen between September 2000 and March 2001 at the vascular laboratory and ward of the Division of Vascular Medicine and Rehabilitation at Verona University were studied in a double-blind, placebo-controlled trial. The patients were randomly assigned (20 per group) to treatment with intravenous glutathione twice a day or saline solution twice a day for 5 days. Treatments were administered in a double-blind manner. The 2 groups of patients underwent measurement of PFWD by strain-gauge plethysmography and laser Doppler flowmetry (with postischemic test) of the symptomatic leg at rest and after treadmill test. All measurements and tests were repeated 12 hours after the last infusion. RESULTS Between the 2 groups, hemodynamic tests showed no differences in baseline values and at rest after treatment. At rest, no differences were observed between basal and posttreatment values; findings in the saline group were similar during tests before and after the infusion period. In the glutathione group, we observed increases in PFWD (196+/-15 vs 143+/-11 m; P<.04), macrocirculatory flow after treadmill test with plethysmography at the end of treatment (9.3+/-2 vs 2.8+/-0.5 mL per 100 mL/min; P<.002), and postischemic hyperemia with laser Doppler flowmetry, registered as perfusion units (PU), at the end of infusions (14.4+/-3.2 vs 6.18+/-1.5 PU; P<.005), with a greater area under the curve after treatment (705+/-103 vs 508+/-45 PU/s; P<.001) and reduced time to flow motion (32+/-4 vs 48+/-11 seconds; P<.05). CONCLUSION In patients with peripheral artery disease, glutathione prolongs PFWD and shows an improvement of macrocirculatory and microcirculatory parameters.

Effects of smoking on cardiopulmonary baroreceptor activation and peripheral vascular resistance

Patients and Methods  We studied 16 healthy smokers and 16 nonsmokers acting as controls. We subjected smokers and nonsmokers to cardiopulmonary baroreceptor stimulation by studying forearm and common carotid haemodynamic and sympathovagal balance. Smokers repeated the tests after smoking one cigarette. Smokers and controls were subjected to passive elevation of the legs and the trunk in a horizontal position with pressure monitoring and measurement of the calibre and flow in the brachial and common carotid arteries using a colourDoppler ultrasound. We calculated forearm resistance and carotid wall tension. We also studied R‐R variability, calculating the ratio between low frequency (LF) and high frequency (HF) R‐R interval variability.

Endothelial Progenitor Cells in Patients with Severe Peripheral Arterial Disease

The aims of this study were to investigate the interrelationships between endothelial progenitor cells (EPCs), peripheral arterial disease (PAD), and atherosclerotic risk factors, as only limited data are available regarding the EPCs in patients with PAD. The authors studied the number of EPCs by different methods in a carefully selected group of 45 patients with PAD along with 24 healthy subjects (HS). In patients with PAD, by utilizing the dual-binding method, the number of EPCs was significantly increased compared to HS (M +/- SD, PAD: 73 +/- 33, HS: 52 +/- 20 EPCs/high power field; p < .001). On the contrary, both CD34(+) cell count and CD133(+) cell count were significantly decreased compared to HS. Colony-forming units were significantly increased in PAD compared to HS (median and 25th and 75th percentiles, PAD: 7, 1, 9; HS: 1, 1, 4 CFU/well, respectively; Mann-Whitney, p = .006). In patients with PAD, the number and proliferative activity of circulating EPCs are increased with respect to HS even though EPC count by flourecence-activated cell sorting (FACS) analysis provided different results and this may explain the discrepancy in data collected using different methods. The regulation of the number and biological activity of EPCs in PAD remains unclear.

Ascorbic acid prevents vascular dysfunction induced by oral glucose load in healthy subjects.

OBJECTIVES To examine the effects of oral glucose load on forearm circulatory regulation before and after ascorbic acid administration in healthy subjects. DESIGN Microcirculation study with laser Doppler was performed at the hand in basal conditions, after ischemia and after acetylcholine and nitroprusside; strain gauge plethysmography was performed at basal and after ischemia. The tests were repeated in the same sequence 2 hour after oral administration of glucose (75 g). The subjects were randomised for administration of ascorbic acid (1 g bid) or placebo (sodium bicarbonate 1 g bid) for 10 days. After that, the tests were repeated before and after a new oral glucose load. Blood pressure and heart rate were monitored. RESULTS Macrocirculatory flux, pressure values and heart rate were unvaried throughout the study. The glucose load caused a reduction in the hyperemic peak flow with laser Doppler and plethysmography; it reduced flux recovery time and hyperemic curve area after ischemia; acetylcholine elicited a minor increase in flux with laser Doppler. The response to nitroprusside was unvaried after glucose load as compared to basal conditions. Treatment with ascorbic acid prevented the decrease in hyperemia after glucose, detected with laser Doppler and plethysmography. Ascorbic acid prevented the decreased response to acetylcholine after glucose, the response to nitroprusside was unaffected by ascorbic acid. Results after placebo were unvaried. CONCLUSIONS Oral glucose load impairs endothelium dependent dilation and hyperaemia at microcirculation, probably via oxidative stress; ascorbic acid can prevent it.

Biochemical Risk Factors for Cardiovascular Disease in an Aged Male Population: Emerging Vascular Pathogens

The progressive increase of deaths and morbidity from cardiovascular disease (CVD) in most developed societies has led to the formulation of preventive strategies and application of several diagnostic guidelines. However, there is emerging evidence that most panels and algo rithms are inadequate and require urgent revision and updating. Therefore, the aim of this study was the evaluation of a wide cardiovascular risk profile in elderly male patients with acute myocardial infarction (AMI) or peripheral occlusive disease (POD). The risk profile was assessed by measuring conventional serum lipid and lipoprotein levels and emerging parame ters : lipoprotein(a) (Lp[a]), homocysteine (Hcy), and C-reactive protein (CRP). The concentration of triglycerides, Lp(a), Hcy and the total cholesterol/high-density lipoprotein (TC/HDL) ratio were significantly higher in both classes of patients than in a popu lation of matched healthy controls and, similarly, patients with CVD displayed lower plasma values of HDL. No significant differences were observed for TC, low-density lipoprotein (LDL), and CRP. Patients with POD exhibited a marked atherogenic profile, as attested by substan tially increased values of Hcy, Lp(a), triglycerides, and TC/HDL ratio. The frequency distribu tions of Lp(a) and Hcy concentrations were markedly shifted toward upper values in both classes of patients than in controls. In multivariate regression analysis, Lp(a) and Hcy were the best predictors for AMI, whereas Lp(a), Hcy, and the TC/HDL ratio were the best predic tors for POD. Taken together, these data suggest that Lp(a) and Hcy excesses might exert a central role in the development of atherosclerotic disease in elderly male patients. Thereby, the inclusion of those tests, along with the TC/HDL ratio and other more conventional analyses in panels for the evaluation of the cardiovascular risk might be profitable in terms of effectual prevention.

Activity of cardiopulmonary baroreceptors, peripheral resistance and cutaneous microcirculation in patients with peripheral obstructive arterial disease.

Abstract. Arosio E, De Marchi S, Prior M, Zannoni M, Lucchese L, Lechi A (Division of Vascular Medicine and Rehabilitation, University of Verona, Italy). Activity of cardiopulmonary baroreceptors, peripheral resistance and cutaneous microcirculation in patients with peripheral obstructive arterial disease. J Intern Med 2000; 247: 471–478.

Commentary: coeliac disease and atherosclerosis – hand in hand? Authors' reply

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