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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. The criteria required for the diagnosis identify various phenotypes, with different reproductive, metabolic, and cardiovascular (CV) risk characteristics. Emerging evidence links adipocyte-secreted hormones as candidates in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors. The aim of this review was to collect, analyze, and qualitatively resynthesize evidence on biomarkers of endothelial dysfunction (visfatin, vascular endothelial growth factor [VEGF], matrix metalloproteinase 9 [MMP-9]) in women with PCOS. Women with PCOS exhibit (a) increased plasma visfatin concentrations compared with controls with a similar body mass index; (b) increased VEGF production along with chronic, mild inflammation; and (c) increased MMP-9 concentrations, which might be related to either excessive CV risk or abnormalities of ovarian extracellular matrix remodeling, multiple cyst formation, follicular atresia, and chronic anovulation. As PCOS has been associated with CV risk, early identification of endothelial dysfunction is clinically relevant.

Smoking is associated with increased arterial stiffness. However, the impact of smoking cessation on arterial stiffness remains unknown. We investigated the effect of smoking cessation on arterial stiffness. Healthy participants (n = 209) were divided into nonsmoking (NSm, n = 96), quit smoking (QSm, n = 61), and maintained smoking groups (MSm, n = 52). Arterial stiffness indexes (ankle-brachial index [ABI] and brachial-ankle pulse wave velocity [baPWV]) were assessed at baseline, and after 6 and 12 months. Baseline, arterial stiffness was significantly higher in the MSm and QSm groups than in the NSm group (P < .001). In the QSm group, there was significant difference in ABI between baseline and 12 months (P = .03). No significant differences were shown in baPWV. Both ABI and baPWV were similar between QSm and MSm group at 12 months. However, there was significant difference between QSm and NSm groups (P < .001). This study shows that 12 months of smoking cessation is associated with improved arterial stiffness.

The aim of this study was to present clinical and paraclinical features of a rarely studied vascular syndrome that usually occurs after a minor traumatic injury. The prospective study of 25 patients identified a group of young subjects, mainly women, generally with history of vascular hyperactivity to cold, showing disseminated pain in a limb always combined with vasospasm, consecutive to a minor traumatic injury in general, and simulating acute ischemia of a limb. The patients' arterial and microcirculatory flows were restored after warming, which proved that they were suffering from intense, reversible but pathological vasospasm, because of its duration, diffusion, intensity, and disproportion as to the triggering event. The symptoms may recur, but they respond to physiotherapy. Patients' follow-up showed that microcirculatory function remains abnormal sometime after the initial episode with, in particular, an exacerbation of the venoarteriolar reflex.

Beyond the already well-established strong causative relationship with cancer, smoking increases the risk for vascular disease. Smoking may act directly or adversely influence risk factors contributing to the development of vascular disease. Smoking causes endothelial dysfunction, dyslipidemia (decreased high-density lipoprotein cholesterol levels, hypertriglyceridemia and increased oxidation of low-density lipoprotein cholesterol) and platelet activation leading to a prothrombotic state. Smoking increases emerging risk factors (eg, fibrinogen, homocysteine, and high-sensitivity C-reactive protein) and increases insulin resistance and the risk of developing type 2 diabetes mellitus. The beneficial effects of statins and antioxidants (eg, vitamins C and E, beta-carotene) are counteracted by smoking. Smoking-induced alterations in growth factors, adhesion molecules, and even in genes can accelerate the progression of atherosclerosis. The aim of this review is to consider the adverse consequences of smoking on the factors predisposing to vascular disease and to emphasize the beneficial effects of smoking cessation.

The literature investigating the association between vascular disorders and malignant neoplasms does not comprehensively review the full spectrum of vascular disorders associated with cancer, or provide proof that cancer is an etiologic factor in the development of these disorders. This paper investigates the causal role of cancer in the pathogenesis of vascular disorders, based on the Bradford-Hill criteria of causation. The Medline database was searched for articles on vascular disorders preceding the diagnosis of cancer (VDPCD). Included in the analysis were vascular disorders caused either by direct tumoral involvement of vessels or by paraneoplastic mechanisms. Vascular disorders caused by adverse reactions to anticancer therapy were excluded from analysis. Seven categories of VDPCDs were recognized: venous thromboembolism, arterial thrombosis and embolism, nonbacterial thrombotic endocarditis, migratory superficial thrombophlebitis, vasculitis, thrombotic microangiopathy, and leukothrombosis. To establish causality of the association between VDPCDs and malignancy, the degree of fulfillment of the Bradford-Hill criteria was assessed. A strong association was found in the literature between venous thromboembolism and cancer (OR 2.3-14.9 and SIR 1.3-4.4). Consistency and temporality of the association were confirmed in all VDPCD variants. Seven Bradford-Hill criteria were fulfilled for cancer associated with venous thromboembolism, six criteria for superficial phlebitis and cancer, and five criteria for each of the other VDPCDs. In conclusion, these data support the causal role of cancer in the pathogenesis of all seven categories of VDPCDs. Recognition of such a causal link between cancer and various vascular disorders may promote an earlier cancer diagnosis.

The efficacy of Pentoxifylline in vascular inner ear disease (VIED) was studied comparing PXF and placebo in a 4-week study; 40 patients with vascular disease and monolateral loss of hearing, vertigo, dizziness, tinnitus (analyzed with an analogue scale line), and cochlear flow reduction were included. The aims of the study were to study the effects of PXF (1600 mg daily) in VIED considering clinical outcome and cochlear flow. Of the 20 included patients, 19 completed the study. One dropout in the placebo group was due to low compliance. Intention-to-treat analysis indicated an improvement in cochlear flow (p<0.05) and a decrease in score in both groups. The cochlear flow increase was 287.5% in the PXF group vs 168% in the placebo group (119.5% difference; p<0.02). There was a difference in score decrease (44.1% larger) in the PXF group (p<0.05).Between-group analysis favors PXF considering blood flow and symptoms. Results indicate good efficacy and tolerability of PXF in VIED.

The efficacy of pentoxifylline (PXF) in vascular inner ear disease (VIED) was studied comparing PXF and placebo in a 4-week study; 60 patients with unilateral loss of hearing, vertigo, dizziness, tinnitus (analyzed with an analogue scale line), and cochlear flow reduction were included. The aim of the study was to study the effect of PXF (1800 mg/day) in VIED considering clinical outcome and cochlear flow. All patients completed the study. Improvement in cochlear flow (p<0.05) and a decrease in score in both groups were observed. The cochlear flow increase was 287.5% in the PXF group vs 168% in the placebo group (119.5% difference; p<0.02). There was a difference in score decrease (44.1% larger) in the PXF group (p<0.05). PXF was more effective considering flow and symptoms.

The aim of this study was to evaluate the effect of PXF (1800 mg daily) in patients with sudden loss of vision (SLV) in a 4-week trial, evaluating clinical outcome and retinal flow parameters. Inclusion criteria were SLV associated with thrombosis of the retinal artery; decrease in retinal blood flow (PSF: peak-systolic flow; EDF: end-diastolic flow velocity) and asymmetry between the two retinal arteries (>40%) documented by duplex scanning. All 10 included patients completed the study. The groups were comparable. No side effects were reported. A significant improvement in flow velocity (p<0.05) and a decrease in analogue score in both groups were observed. PSF increase was 550% in the PXF group vs 288% in the placebo group (262% difference). EDF increase was 400% in the PXF group vs 200% in the placebo group (200% difference). There was a significant difference in the analogue score decrease (33.3% difference larger in the PXF group; p<0.05). In conclusion, PXF treatment improved retinal flow after retinal artery occlusion better than placebo and should be considered as an important option in this condition.

Neurofibromatosis regroups at least two different autosomal dominant genetic disorders: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Vascular disease is an underestimated complication of NF1. Few studies are available on this, all based on case reports. Neurofibromin, NF1 protein product, has also been detected in aortic smooth muscle. The purpose of this study was to evaluate the physical properties of the vessels, by measuring the carotid-femoral pulse wave velocity (PWV). This parameter was assessed by the Complior, a new noninvasive, validated device, used to screen a large population. The authors studied 64 neurofibromatosis patients (34 boys and 30 girls) with a mean age of 12 years (range 5-25 years). To investigate the presence of vascular lesions, aortic stiffness was evaluated by carotid-femoral PWV by using an automatic processor (Complior). They compared data from the PWV with a control group (30 healthy children, 17 boys and 13 girls, mean age 11 years, range 5-23 years). The calculated mean PWV in the control group was 6.5 +/- 1.15 m/s. The mean PWV of the 64 young patients with NF1 was 6.3 +/- 1.02 m/s. There was no difference between the two groups (p=0.39). Nevertheless, analysis of the linear regression has shown a linear relationship between systolic blood pressure (SBP) and PWV in the control group, while in NF1 patients this relationship is not present. The authors suggest that the coexistence of different factors, such as intimal proliferation, thinning media, fragmentation of the elastic tissue, irregularity, stenosis and tortuosity of the vessels, dysplasia of the small vessels, that counterbalance PWV, normalize the mean value. They emphasize the importance of a careful vascular evaluation, using noninvasive method, such as Complior. This device is well accepted by NF1 patients.

The aim of this study was to evaluate the macrocirculatory and microcirculatory effects of treatment with lercanidipine, a new antihypertensive agent acting both on blood pressure and microcirculation in patients with moderate essential hypertension and without vascular disease and in patient with hypertension and vascular disease. In hypertensive subjects target-organ damage associated with high blood pressure may now be objectively documented by noninvasive tests. These alterations constitute a model to evaluate not only the pressure effects of antihypertensive treatment but also the normalization of the peripheral microcirculatory network. With color duplex scanning, flow velocity in the central retinal artery and retinal flow velocity can be measured and with use of laser-Doppler-flowmetry, it is also possible to evaluate microcirculation alterations in hypertensive subjects. These evaluation methods are completely noninvasive and may be used to assess the microcirculatory effects of antihypertensive drugs.

Vibration white finger (VWF) is an occupational disorder associated with long-term exposure to hand-transmitted vibration. The condition exhibits features of secondary Raynaud's phenomenon. The etiology is unknown. The aim of this study was to examine the role of leukocyte rheology in the pathogenesis of VWF. Fifty-two male subjects divided into two groups were exposed to controlled acute hand-transmitted vibration. One group consisted of 29 workers who have all had occupational exposure to handheld vibration and all suffered from VWF (mean age 46.9 years, range 22-66). The second group consisted of 23 controls. Venous blood was analyzed from the dorsum of the hand before and after vibration to determine granulocyte deformability, granulocyte morphology, and white blood cell count with differential. There was a subpopulation of hard and poorly deformable granulocytes in the VWF group when compared with controls (p < 0.05). Acute hand-transmitted vibration had no in vitro effect on leukocyte rheology in either group. Leukocyte rheology may play a role in the pathogenesis of microvascular disease and tissue ischemia in VWF, although whether this is a cause or an effect of the disorder is not clear.

The authors describe the case of a 60-year-old man with POEMS syndrome associated with vascular lesions. The patient had osteosclerotic myeloma IgA (lambda), polyneuropathy, endocrinopathy, and skin changes. Subsequently, he developed gangrene of the lower limbs with no response to heparin therapy. The humoral study showed thrombocythemia, high levels of interleukin-1beta (IL-1beta) and IL-6 and of some coagulative/fibrinolytic and endothelial factors (von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator, and endothelial adhesion molecule ICAM-1). The authors suggest that these factors, induced by the increased levels of cytokines, could be responsible for microvascular damage, gangrene, and heparin resistance.

The morphologic changes in the walls of hollow viscera caused by contraction and relaxation of smooth muscle cells were studied from autopsy and surgical specimens. The specimens studied included: esophageal spasm (corkscrew and nutcracker esophagus), contraction of the lower esophageal sphincter with marked esophageal dilatation, gaseous distension of the stomach, contraction of the gastric pylorus, bladder and anal sphincter, physiological segmental constriction of the small and large intestines, constriction and distension of the gallbladder, urinary bladder and bronchi, and postpartum contraction of the uterus. In contrast to distension, the constriction of hollow viscera shows marked reduction of the external circumference and diameter with thickening of the wall, contraction of smooth muscle cells, thickening of muscle bundles, remodeling of wall structure, and narrowing or obliteration of the lumen. Morphologic evidence of contraction of smooth muscle cells is demonstrated by varying degrees of typical lengthwise shortening of the cells and squeezing and folding of the nuclei depending on the degree of cytoplasmic contraction of the smooth muscle cells. Using these same classic morphologic signs, we have attempted to study constriction and distension of arteries and arterioles. We can demonstrate contraction of smooth muscle cells and remodeling of arterial and arteriolar walls in patients with spastic coronary artery thrombosis, cocaine-induced coronary artery thrombosis, acute constriction of mesenteric arteries with lacerations of arterial wall, and dissecting hemorrhages induced by large doses of intravenous infusion of vasoconstrictors for hemorrhagic shock, and in patients with sustained, accelerated, or malignant hypertension.

To assess endothelin-1 (ET-1) response to cold stimulation in essential acrocyanosis (EA), the authors measured ET-1 plasma concentrations in 6 patients with EA (6 women, age range seventeen to thirty-seven years) and in 6 controls (5 women, 1 man, age range twenty-one to thirty-seven years) before and after cold challenge by unilateral hand immersion in water bath at 13 degrees C for five minutes. The contralateral upper limb was considered as control. Blood samples were simultaneously drawn from an antecubital vein in the cooled side and in the contralateral upper limb at baseline, at the end of cooling, and at ten and ninety minutes after cooling was begun. Plasma ET-1 was determined by a radioimmunoassay system. Results are mean +/- SD. Baseline ET-1 was higher in patients with EA (5.1 +/- 0.3 pmol/L) than in controls (1.9 +/- 0.1 pmol/L, P < 0.001). After hand cooling, ET-1 in the cold-exposed upper limb rose in patients with EA to a peak value of 7.2 +/- 0.7 pmol/L, which was greater than that observed in healthy subjects (2.7 +/- 0.4 pmol/L, P < 0.001). The absolute increase in ET-1 plasma concentrations from baseline to peak value was significantly higher in patients with EA than in controls (2.1 +/- 0.3 vs 0.8 +/- 0.2 pmol/L, respectively, P < 0.001). In patients with EA, but not in controls, the rise in ET-1 plasma concentrations was still detected ninety minutes after cooling. The same time course of the plasma ET-1 concentrations was observed in the noncooled upper limb, but the increases in ET-1 at different times after cold stimulus were smaller than in the cold-challenged upper limb in both groups (P < 0.001). In conclusion, the results demonstrate that in patients with EA, baseline plasma levels of ET-1 are enhanced and are further increased by cooling until ninety minutes after cold challenge. This rise in plasma ET-1 could contribute to potentiating and prolonging cold-induced vasoconstriction/vasospasm and/or could be a marker for endothelial damage in EA.

Traditionally leukocytes have been regarded as beneficial cells, owing to their immunologic and antimicrobial activity. Recent evidence suggests, however, an additional role of granulocytes and monocytes as mediators of cardiovascular complications, such as ischemia, reperfusion, diabetes, physiologic shock, venous ulceration, and other conditions. Granulocytes and monocytes have a large volume, and stiff cytoplasm; they have the ability to adhere to endothelium and to other substrates; and they exert several forms of cytotoxicity. Granulocytes and monocytes may be trapped in the microcirculation, may obstruct capillaries and thereby induce a no-reflow phenomenon, and may initiate organ dysfunction via oxygen free radical production and proteolytic cleavage. Few organs seem to be spared from the potential destructive actions of these cells, and novel approaches are required to interfere with leukocyte accumulation in local regions of the peripheral circulation.

Whole blood filterability was monitored in 16 nondiabetic peripheral vascular disease (PVD) patients within forty-eight hours of onset of bacterial infection, after ten to seventeen days antibiotic therapy and again, ten days later, after convalescence. The whole blood filterability rate was constantly disturbed before infection in these patients; the impairment worsened significantly (as was expected during infection), but after convalescence the whole blood filterability rate did not return to preinfection levels. This further significant impairment in whole blood filterability was inversely correlated with a reduction in the patients' pain-free walking time as determined by a standard treadmell test performed after convalescence and compared with their average times before infection.

Transcutaneous oxygen (tcPO2) and carbon dioxide (tcPCO2) measurements were used before, during, and after intermittent pneumatic compression (IPC) to assess lower limb skin perfusion in 21 healthy adult volunteers and 23 elderly patients. The temperature of the sensors was set at 44 degrees C during calibration and maintained throughout all tests. Resting tcPO2 was significantly lower (p less than 0.01) in patients than in controls. In all subjects tcPO2 decreased and tcPCO2 increased during compression. Patients showed a highly significant increase (p less than 0.001) in tcPCO2 during and after the treatment. Results of this study indicate that the symptomatic improvement, in peripheral vascular disease and wound healing following IPC, is not due to improved skin perfusion or enhancement of oxygenation and CO2 removal.

An observational study was made of the localization of experimental calcification of blood vessels induced by hypervitaminosis D in 15 stock rabbits, in 10 rabbits with arteriovenous fistulae, and in 6 rabbits with experimental saccular aneurysms. An arteriotomy and a phlebotomy were performed on several animals from each group. The pulmonary trunk, aorta, common carotid arteries, and external jugular veins were dissected and stained with silver nitrate to demonstrate calcification macroscopically. The first major bifurcation from 37 renal arteries from these animals was examined by the serial section technique to localize calcification about the arterial forks histologically. There was evidence that early calcification was flow related with a predilection for sites where atrophic lesions occur. Proliferative lesions in which matrix vesicles are abundant exhibited no such predisposition. It was concluded that matrix vesicles do not appear to be susceptible to vitamin D calcification. The topography of the experimental calcification differed from that of diet-induced lipid deposition.

Intra-arterial pressure measurements have been made in a group of vascular patients using two different methods. The pull-through method, without systemic pressure monitoring, is compared with a technique employing simultaneous radial and femoral arterial puncture. In both techniques, pressures are measured at resting flow and during papaverine induced hyperaemia.

Hyperbaric oxygen therapy (HBT) consists of inhaling 100% oxygen under pressure exceeding atmospheric pressure. Patients with various degrees of peripheral vascular disease (stages II, III, and IV according to Fontaine's classification) were treated with HBT. Clinical symptoms improved in 70%. Ankle/brachial index increased by more than 0.10 in 47%. Photoplethysmographic pulse appearance has been detected in roughly one third of patients. Transcutaneous oxygen tension did not, however, improve significantly. Plasma malondialdehyde (MDA) was evaluated as a marker of lipid peroxidation, possibly influenced by hyperbaric oxygen. Surprisingly, the authors found that MDA levels decreased after HBT, probably as a result of the activation of antioxidant systems. These results show that HBT represents a useful approach in the treatment of peripheral vascular disease, since it improves clinical and hemodynamic parameters, with no potentially harmful side effects, such as enhanced lipid peroxidation, at least in the short term.

Skin blood flow in the microcirculation of the distal foot was evaluated in patients with vascular disease and diabetes and compared with that in normal volunteers by use of laser-Doppler flowmetry. Resting flow (RF) and the flow on standing (SF) were measured in a room at constant temperature (20-22 degrees C). RF was significantly different in the five groups, being increased in patients with diabetes (in comparison with normal volunteers) and decreased in patients with intermittent claudication, rest pain, and ischemic limbs. The venoarteriolar reflex (in response to standing) was also decreased or abolished in diabetic and in all vascular patients. After treatment of all vascular patients with nifedipine (10 mg tid) for one week, there was a significant increase in RF in all patients. The venoarteriolar reflex was improved but still remained below the normal limit. In conclusion laser-Doppler flowmetry is useful both for differentiating classes of different vascular patients and for evaluating the microcirculatory changes induced by nifedepine.

The authors calculated 442 values of resting ankle-arm indices in 222 patients, of whom 114 reported exercise pain of the lower extremities (51.3%) and 34 reported rest pain (15.3%). Tissue necrosis was diagnosed in 55 patients (24.8%) and other disorders in 19 (8.6%). Obliterating atherosclerosis was found in 186 patients (83.8%), Buerger's disease in 16 (7.2%), and other vascular diseases in 20 patients (9%). The studied index value in 262 examined lower extremities was 1.3-1.0 in 54, 0.9-0.8 in 29, 0.7-0.6 in 66, 0.5-0.4 in 55, and 0.3-0.0 in 58 lower extremities. Respective values for contralateral lower extremities (180) were the following: 69, 54, 33, 14, and 10.

The product of heart rate and blood pressure, (HR x BP), index of the myocardial oxygen consumption, was evaluated on 37 individuals with ages of between 32 and 65 years; 24 had ischemic heart disease with a disease of 1, 2 or 3 vessels, and 13 had non-significant lesions of 1 vessel (less than 75%) or no coronary heart disease (CHD). From the HR x BP correlation with the study of the angiograms of the coronary arteries, we verified that there was no distinction between patients. with CHD with or without an ejection fraction less than 50% or, with or without disturbances of myocardial contractility, and normal individuals. Thus, we believe that in patients with CHD, an excessive increase in the oxygen requirements of the myocardium is not the sole pathogenic mechanism of ischemia.

In peripheric arteriopathies, alterations occur to the venous system with a particular swelling of the veins of the foot-top, in the subjects (sclerotic or diabetic) at the 2nd and 3rd Fontaine stage, which gradually decreases until the collapse in the most advanced levels of the arterious affection (4th stage). In order to verify all that, we examined 40 artheriopathic subjects at the different Fontaine stages through a c.w. doppler apparatus and an impedence plethysmograph. Together with the modification of the arterious doppler velocitogram and the reduction of the Winsor index, we noticed that the velocity of the venous flow increases together with a venous hypertension that reaching the highest values at the 3rd stage, while at the 4th stage they are reduced because of the progress of the sclerosis. The impedence plethysmogram shows a reduction of the systodiastolic sphygmic excursion with a variation of the basic line, depending on the respiration, proportional at the clinic stage. In diabetic subjects the progress of the disease is more precocious because of the quicker implication of the microcirculation.

Skin blood flow in the distal foot was evaluated in patients with peripheral vascular disease and diabetes and compared with skin blood flow in normal volunteers by use of laser Doppler flowmetry. Resting blood flow (RBF) and standing blood flow (SBF) were recorded in a room at a constant temperature (20-22 degrees C). The RBF was found to be different in the five groups (normal, diabetics, patients with intermittent claudication, those with rest pain and those with impending gangrene. In diabetics RBF was significantly higher than in normal subjects. Even on standing, SBF in diabetics was higher and not different from RBF, indicating an ineffective venoarteriolar response (VAR). The VAR was also reduced in patients with claudication and was abolished in patients with rest pain and impending gangrene. In patients with rest pain SBF was increased. Laser Doppler flowmetry is a useful technique for evaluating skin perfusion in patients with peripheral arterial disease and for discriminating among different classes of patients.

Although it is universally accepted that the grade of reduction of district blood flow in PVD is directly correlated to alteration of the haemorheological pattern, there is still no uniformity of opinion regarding the existence of a specific rheological alteration in PVD. The scope of our study was to discover the existence of possible PVD-specific markers; we thus carried out a comparative evaluation of the rheological characteristics in blood of controls and patients affected with PVD. Eighty-nine males between the ages of 50 and 65 years (median 58 +/- 1 SE) were studied, all with a stage II vascular pathology with clinical onset of less than three months. Exclusion criteria were: diabetes mellitus, hyperlipaemia, stable hypertension, presence of vascular disease in other districts, cardio-circulatory problems and serious medical or surgical pathologies, previous vascular surgery, a history of acute thrombo-embolic episodes, and chronic alcoholism. Each patient, after a drug wash-out of 20 days, was monitored for haemorheological parameters. At the same time, the above parameters were measured in a group of 50 male controls of the same age range. All 139 subjects were smokers (10-15 cigarettes average per day). Our results indicate that modification in the bio-humoral (fibrinogen and plasma globulins) parameters, a reduced red blood cell filterability and a relative increase in the number of activated polymorphonucleate cells are probably specific haemorheological markers of the clinical onset of PVD.