Abnormal ankle-brachial index (ABI) predicts primary and secondary cardiovascular risk and cancer mortality.

BACKGROUND: An abnormal ankle-brachial pressure index (ABI) is a marker of the risk for increased total and cardiovascular (CV) mortality. However, it is not clear whether it is associated with an even worse prognosis in patients with previous CV events or with cancer mortality. MATERIALS AND METHODS: Consecutive subjects undergoing ABI assessment for suspected peripheral artery disease or for stratification of CV risk in ten centers in the Veneto Region (northeast Italy), between 2011 and 2014 were enrolled. The ABI was expressed as normal ≥0.9 to ≤1.3, and abnormal <0.9 or >1.3. All-cause mortality and CV or cancer mortality and hospitalizations for CV disease were collected from administrative databases up to December 2018. RESULTS: The study enrolled 1,177 patients. ABI was abnormal in 57.2%. Median follow-up was 61.6 months (53.4-70.1). All-cause, CV and cancer mortality were higher in patients with abnormal than normal ABI, with hazard ratios (HR) respectively 2.0 (95% CI 1.48-2.69), 1.98 (95% CI 1.24-3.17) and 1.85 (95% CI 1.09-3.15). Among subjects with abnormal ABI, the risk of overall mortality, HR 1.57 (95% CI 1.17-2.12), and CV mortality, HR 2.39 (95% CI 1.43-3.99), was higher in those with previous CV events. These latter also had a higher risk of hospitalization for myocardial infarction and stroke: HR 1.85 (95% CI 1.023.37) and 2.17 (95% CI 1.10-4.28). CONCLUSIONS: The co-existence of abnormal ABI and a history of CV events identifies subjects at higher risk, who call for a more aggressive approach. Abnormal ABI is also a predictor of cancer mortality.

Medical management of patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is one of the most frequent manifestations of atherosclerosis and is associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of cardiovascular events. Major risk factors of PAD are similar to those that lead to atherosclerosis in other vascular beds. However, there are differences in the power of individual risk factors in the different vascular territories. Cigarette smoking and diabetes mellitus represent the greatest risks of PAD. For prevention of the progression of PAD and accompanying cardiovascular events similar preventative measures are used as in coronary artery disease (CAD). However, recent data indicate that there are some differences in the efficacy of drugs used in the prevention of atherothrombotic events in PAD. Antiplatelet treatment is indicated in virtually all patients with PAD. In spite of the absence of hard evidence- based data on the long term efficacy of aspirin, it is still considered as a first line treatment and clopidogrel as an effective alternative. The new antiplatelet drugs ticagrelol and prasugrel also represent promising options for treatment of PAD. Statin therapy is indicated to achieve the target low density lipoprotein cholesterol level of ≤2.5 mmol/L (100 mg/dL) and there is emerging evidence that lower levels are more effective. Statins may also improve walking capacity. Antihypertensive treatment is indicated to achieve the goal blood pressure (<140/90 mmHg). All classes of antihypertensive drugs including beta-blockers are acceptable for treatment of hypertension in patients with PAD. Diabetic patients with PAD should reduce their glycosylated haemoglobin to ≤7%. As PAD patients represent the group with the highest risk of atherothrombotic events, these patients need the most intensive treatment and elimination of risk factors of atherosclerosis. These measures should be as comprehensive as those in patients with established coronary and cerebrovascular disease.

Consensus Document on Intermittent Claudication from the Central European Vascular Forum (C.E.V.F.)-3rd revision (2013) with the sharing of the Mediterranean League of Angiology and Vascular Surgery, and the North Africa and Middle East Chapter of International Union of Angiology.

This paper is the review of the Consensus Document on Intermittent Claudication of the Central European Vascular Forum (CEVF), published in 2008, and and shared with the North Africa and Middle East Chapter of International Union of Angiology and the Mediterranean League of Angiology and Vascular Surgery. The Document presents suggestions for general practitioners and vascular specialists for more precise and appropriate management of PAD, particularly of intermittent claudication, and underlines the investigations that should be required by GPs and what the GP should expect from the vascular specialist (angiologist, vascular surgeon). The idea of the Faculty is to produce a short document, which is an easy reference in daily clinical practice, both for the GPs and vascular specialists.

Silent pulmonary embolism in patients with proximal deep vein thrombosis in the lower limbs.

BACKGROUND: One in every three patients with deep vein thrombosis (DVT) in the lower limbs may have silent pulmonary embolism (PE), but its clinical relevance has not been thoroughly studied. METHODS: We used the RIETE Registry data to study patients with proximal DVT and no PE symptoms, but with a systematic search for PE. We compared the outcome of DVT patients with silent PE and those with no PE. RESULTS: Of 2375 patients with DVT, 842 (35%) had silent PE and 1533 had no PE. During the first 15 days of anticoagulation, patients presenting with silent PE had a higher incidence of symptomatic PE events than those with no PE (0.95% vs. 0.13%; P = 0.015), with a similar incidence of major bleeding (0.95% vs. 1.63%; P = 0.09). In patients with silent PE, the incidence of PE events during the first 15 days was equal to the incidence of major bleeding (eight events each), but in those with no PE the incidence of PE events was eight times lower (3 vs. 25 bleeding events). Multivariate analysis confirmed that DVT patients with silent PE had a higher incidence of symptomatic PE events during the first 15 days than those with no PE (odds ratio, 4.80; 95% CI, 1.27-18.1), with no differences in bleeding. CONCLUSIONS: DVT patients with silent PE at baseline had an increased incidence of symptomatic PE events during the first 15 days of anticoagulant therapy. This effect disappeared after 3 months of anticoagulation.

Risk stratification and outcomes in hemodynamically stable patients with acute pulmonary embolism: a prospective, multicentre, cohort study with three months of follow-up.

BACKGROUND: The role of risk stratification in normotensive patients with acute pulmonary embolism (PE) is still unclear. OBJECTIVES: We evaluated, in these patients, the usefulness of six prognostic markers for predicting in-hospital adverse events related to PE and 3-month mortality. PATIENTS/METHODS: Two hundred and one consecutive patients with confirmed acute PE and normal blood pressure, who were administered conventional anticoagulation, were recruited in a multicentre prospective cohort study with 3 months of follow-up. At baseline, they received a comprehensive risk-evaluation including echocardiographic assessment of right ventricular dysfunction, determination of troponin I, brain natriuretic peptide and D-dimer, arterial blood gas analysis and a clinical score. Primary outcome of the study was PE-related in-hospital death or clinical deterioration. Secondary outcomes were in-hospital and 3-month all-cause mortality. RESULTS: The primary outcome occurred in one patient (0.5%), who died from PE during hospitalization. The in-hospital and 3-month all-cause mortality were 2% and 9%, respectively. None of the prognostic markers was predictive of the primary outcome. Clinical score, troponin I and hypoxemia predicted in-hospital all-cause mortality (P = 0.02, 0.01 and < 0.01, respectively). Clinical score (HR, 4.7; 95% CI, 1.9-12.0), D-dimer (4.8; 1.4-16.3), hypoxemia (5.7; 2.1-15.1) and troponin I (7.5; 2.5-22.7) were predictors of 3-month all-cause mortality on univariate analysis. On multivariate analysis clinical score and troponin I remained independently predictive. CONCLUSIONS: We did not find prognostic markers useful as predictors of in-hospital PE-related adverse events. Clinical score, troponin I and hypoxemia predicted in-hospital all-cause mortality. Clinical score and troponin I independently predicted 3-month all-cause mortality.

Isolated distal deep vein thrombosis: efficacy and safety of a protocol of treatment. Treatment of Isolated Calf Thrombosis (TICT) Study.

AIM: The optimal treatment of isolated distal deep vein thrombosis (ID-DVT) is still controversial. A complete anticoagulation as soon as the diagnosis is made is recommended by some authors. Alternatively, other authors suggest to perform serial ultrasonography assessments to detect the possible extension of DVT towards proximal veins. Only in this case the treatment should be initiated. Furthermore, the optimal duration of treatment is far from established. The Treatment of Isolated Calf Thrombosis (TICT) study was set up to assess the efficacy and safety of a particular treatment regimen of ID-DVT based on low molecular weight heparins (LMWH). METHODS: The drug treatment consisted of a twice-daily subcutaneous administration of a full dose of weight-adjusted LMWH for one week, followed by a half dose of LMWH administered once-daily for another three weeks. At the end of the four-week period of treatment, a colour-coded Doppler ultrasonography (CCDU) assessment was scheduled and after three months a follow-up visit was performed. If a patient was unable to attend the visit, he was contacted by a phone-call to assess if any adverse events occurred. The study enrolled 192 outpatients with ID-DVT confirmed by CCDU. Twenty-one out of 192 patients (10.9%) were excluded for violation of protocol. Thus 171 (39.9% men, mean age of 60.45 years ) were eligible and were included in the study. Sixty-one patients (36.6%) presented an unprovoked ID-DVT. RESULTS: Events during the period of treatment (4 weeks). Ten out of 171 patients (5.8%) had complications: five patients showed an extension proximal to the knee (2.9%) all with an unprovoked ID-DVT; two showed an extension of thrombus within the distal veins. Three patients (1.7%) suffered from minor bleeding; there was no major bleeding. Further events during three months of observation occurred. Five patients had thrombus recurrences: four patients showed a proximal DVT (3 with a previous unprovoked ID-DVT, 1 with a previous ID-DVT secondary to a traumatic leg fracture, with persistent difficulty of deambulation); one, with a previous secondary thrombosis, showed a ID-DVT. CONCLUSIONS: In our study only 2.9% of patients with ID-DVT showed a progression of thrombosis to proximal deep veins; the majority of thrombus progression, during the treatment period, was observed in patients with unprovoked ID-DVT. Our results support the usefulness of a prolonged treatment in unprovoked ID-DVT.

Porphyrin-photosensitized processes: their applications in the prevention of arterial restenosis.

Photodynamic therapy (PDT) is based on the use of a photozensitising compound which is accumulated by rapidly proliferating cells. Subsequent irradiation with light wavelengths specifically absorbed by the photosensitiser promotes the generation of reactive short-lived oxygen species which cause an irreversible and selective damage. Endovascular interventions to correct obstructive arterial disease have been developed worldwide with excellent short term results. However, long term patency is still limited by the onset of restenosis, due to subsequent intimal hyperplasia (IH). IH is characterized by proliferation and migration of smooth muscle cells (SMC) and extracellular matrix production. Targeting of SMC by photozensitisers can be efficiently achieved by taking advantage of the receptors for low density lipoproteins (LDL) expressed by such cells. Thus, preference is given to hydrophobic compounds which readily partition in the lipid matrix of LDL. We developed a liposomal formulation of a highly hydrophobic photozensitising agent, Zn(II)-phthalocyanine (ZnPc). The liposome-delivered ZnPc was readily taken up by cultured SMC cells and preferentially localized in the Golgi apparatus. Red light irradiation of incubated SMC induced cell death. Extension of these investigations to an in vivo rabbit model showed that ZnPc mainly accumulated in the media layer, where PDT induces the main damage through cellular depletion due to apoptosis of SMC, changes in the extracellular matrix with generation of a barrier to cellular migration, and acceleration of re-endothelization. Initial clinical applications showed that PDT safely and effectively prevents restenosis after angioplasty up to a 6 month follow-up.

Carotid plaque morphology and cerebrovascular events.

AIM: Beside the degree of stenosis, plaque morphology obtained by the B mode ultrasound technique has been considered to define the plaque at risk for cerebrovascular events, and a subset of patients who deserve more strict surveillance. Our aim was to evaluate the relationship between plaque morphology, progression of stenosis, and the development of new cerebrovascular events. METHODS: We followed up by carotid duplex scan 230 asymptomatic patients, evaluating the degree and progression of internal carotid (ICA) stenoses and plaque morphology of the atherosclerotic lesions. RESULTS: During the follow-up period (median 32 month, range 6-125 months) 7% of patients developed ischemic neurological events of which 1.7% was a stroke. Of these events, only 5.7% correlated with carotid lesions. The new neurological events correlated with the degree and progression of stenoses, with a non homogeneous echographic appearance and irregular surface. The progression of the degree of stenoses was the parameter that correlated the most with the development of new neurologic symptoms. Nevertheless, the lesions that progressed modified their echographic pattern from homogeneous to non homogeneous in 78% of cases. Irregular surface and high degree of stenoses more than the baseline echographic pattern seem to correlate with plaque progression. CONCLUSION: Our follow-up study confirmed that ICA stenosis is a benign condition: very few strokes clearly correlated to the stenosis were observed. Nevertheless, the major predictors of risk for cerebrovascular events, besides the degree of stenoses, are the progression of the degree of stenosis, irregular surface and non-homogeneous echographic appearance.

Local photodynamic therapy with Zn(II)-phthalocyanine in an experimental model of intimal hyperplasia.

Photodynamic therapy (PDT) appears to be a novel promising modality to prevent intimal hyperplasia (IH) and restenosis after angioplasty. Local PDT, that consists of local delivery of photosensitizing agents followed by intraluminal local irradiation, represents a recent advancement. This methodology requires optimization in order to achieve the best prompt outcome especially in terms of pharmacokinetics of the photosensitizing agent. We studied the pharmacokinetic properties by using the photosensitizing agent Zn(II)-phthalocyanine (ZnPc), locally released by a channeled balloon. The efficacy of local PDT in reducing IH was evaluated in an experimental rabbit model of arterial injury. The maximum accumulation of ZnPc was found at 30 min: the injured portion of the artery gave a ZnPc recovery of 1.18 micromol/mg, as compared with undetectable amounts of ZnPc in the non injured arteries; within 90 min after the local delivery, clearance of the agent was almost complete. Local PDT produced an effective reduction of IH in our vascular injury model: at 7, 14, 21 and 28 days IH and intima/media ratio (IMR) was significantly reduced as compared with balloon injured arteries. The local delivery of ZnPc showed favourable pharmacokinetic properties, that allow the performance of PDT immediately after the vascular injury. Local PDT performed in these conditions represents a promising approach to prevent IH after balloon injury. Further studies are needed to better clarify the biological response of the injured arterial wall to local PDT.

High grade phyllodes tumour of the prostate.

A case of malignant variant of prostatic phyllodes tumour in a 61-yr-old man is reported. This is an extremely rare neoplasm that closely resembles the not uncommon tumour of the female breast. Only 18 previous cases have been described. Although an initially benign clinical behavior has been presumed a high probability of local recurrence or aggressive behavior may occur.

Percutaneous excimer laser angioplasty of lower limb vessels: results of a prospective 24-month follow-up.

The aim of this prospective study was to assess the effectiveness and the long-term patency effect of excimer laser angioplasty in peripheral arterial obstructive disease. Seventy-eight patients referred for excimer laser angioplasty of lower limbs have been followed up for up to 24 months. Ankle/brachial systolic pressure index, color Doppler mapping, and arterial digital subtraction angiography were performed. Immediate procedural success was achieved in a high percentage of patients (97%). Balloon angioplasty was also used in 85% of patients. Early reocclusions occurred in 8% of patients. The cumulative patency rate was 47% at the 12-month interval and 40% at the 24-month interval. Poor runoff and the length of the lesions negatively influenced the outcome. Excimer laser angioplasty is an effective procedure, indicated in selected patients showing < 10 cm occlusions and good runoff.

[Prevalence of clinically silent pulmonary embolism in deep venous thrombosis of the legs]. / Prevalenza di embolia polmonare clinicamente silente nella trombosi venosa profonda degli arti inferiori.

BACKGROUND: Thromboembolic venous disease is a possible lethal condition which is very often present in clinical practice. The aim of this study was to evaluate the prevalence of clinically occult pulmonary embolism (PE) in a group of patients with recent proximal deep venous thrombosis (DVT), and the relationship between prevalence of PE and DVT extension, echographic features of the thrombi, anticoagulant therapy administered. MATERIALS AND METHODS: The study enrolled 93 patients with DVT of the proximal lower extremities, without clinical symptoms and signs of PE. All patients were submitted to echo color-Doppler and ventilation-perfusion lung scan. The results were analysed by a score system for the echographic scan and by a series of probability criteria, as recommended by the PIOPED investigators, for the lung scan. RESULTS: All patients were recognised to suffer from proximal DVT. High probability lung scans for PE were found in 43 subjects (46.2%), intermediate probability in 14 (15%), low probability in 7 (7.7%), very low-normal in 29 (31.1%). The prevalence of PE failed to show any significant difference with respect to DVT extension, ultrasonographic features of the thrombi and anticoagulant therapy administered. CONCLUSIONS: The results obtained show a high prevalence of asymptomatic PE in patients with DVT, and suggest the need of an extensive use of lung scan in this kind of patients, and the utility of an early detection of DVT, in order to establish an intense antithrombotic therapy, irrespective of the extension of the thrombus with US.

The characteristics of the thrombi of the lower limbs, as detected by ultrasonic scanning, do not predict pulmonary embolism.

OBJECTIVE: To evaluate whether pulmonary embolism (PE), as detected by perfusion lung scan, could be predicted by the ultrasonic (US) characteristics of the thrombi in patients with deep venous thrombosis (DVT) of the lower limbs. PATIENTS: Ninety-three consecutive patients with DVT and no symptoms of lung involvement (52 men, 41 women; mean age, 67 +/- 17 years). MEASUREMENTS AND RESULTS: The degree of thrombotic involvement of the lower limbs was assessed using a US score system ranging from 1 (indicating a subsegmental, nonocclusive thrombus) to 16 (massive, occlusive). According to the echographic and color-Doppler features, the thrombi were classified in terms of echoreflectivity, adhesiveness to the vein wall, and organization. The diagnosis of PE (PIOPED criteria) was highly probable in 46% of the patients, intermediate in 15%, low in 8%, and very low/normal in 31%. No correlations were found between the lung scan findings on one side and the venous scoring system or the US features of the thrombi on the other side. CONCLUSIONS: While confirming that the prevalence of PE in patients with DVT is elevated, we failed to define a subgroup of patients at higher risk. Our data imply that lung scan should be used extensively for the detection of silent PE and that anticoagulation should not be graded on US findings.

[The prevalence of carotid and coronary diseases in asymptomatic patients at high risk for atherosclerosis]. / Prevalenza di carotidopatia e coronaropatia in pazienti asintomatici ad elevato rischio per aterosclerosi.

To evaluate the prevalence of carotid lesions and silent coronary artery disease in asymptomatic patients, we studied 31 subjects with one or more risk factors for atherosclerosis. All patients have been studied by means of non invasive cardiologic evaluations and carotid echo color Doppler. The prevalence of carotid and or coronary artery disease was 80%. The prevalence of silent coronary artery disease was 19% and carotid artery disease 61%. Patients with more than one risk factor showed a higher prevalence of carotid lesions (84%) than those with only one risk factor (16%). In conclusion, the prevalence of carotid disease in asymptomatic patients, at risk for atherosclerosis, is high. The echo color Doppler system represents the best approach to study carotid atherosclerosis in vivo. When carotid lesions are present, a non invasive cardiological evaluation may be useful to reveal a silent coronary artery disease.

Intimal medial thickening of common carotid artery as indicator of coronary artery disease.

The authors investigated the relation between coronary atherosclerosis, angiographically detected, and intimal-medial (I-M) thickening of the common carotid artery (CCA), as measured by high-resolution B-mode ultrasound system. They studied 31 patients with coronary artery disease (CAD) and 23 healthy control subjects. I-M thickening of CCAs and atheromatous plaques at the carotid bifurcation were evaluated. A score system was defined (range 0-20) based on the absence or presence of atherosclerotic lesions at common and internal carotid arteries. A coronary angiography score was defined based on the presence of of atherosclerotic lesions at nine coronary arterial segments (range 0-36). The thickness of CCAs (M +/- SD) in CAD patients was significantly higher (1.45 +/- 0.95 mm) than in controls (0.87 +/- 0.10 mm, P < 0.005), and an I-M thickening of 1.1 mm or more was specific and positively predictive of CAD. A significant positive correlation between coronary and carotid score was observed (P < 0.028, r = 0.373). The study suggests that I-M thickening could be helpful for the identification of patients at risk for CAD.

Wall thickening of common carotid arteries in patients affected by noninsulin-dependent diabetes mellitus: relationship to microvascular complications.

This study evaluates the wall thickness of common carotid arteries and the atherosclerotic involvement of the carotid bifurcations in patients with noninsulin-dependent diabetes mellitus (NIDDM), with and without microvascular complications. Seventy subjects affected by NIDDM, and 17 healthy controls were evaluated by means of high-resolution echo-Doppler scan. Twenty-six diabetics (Group A) and complications (overnight proteinuria > 500 mg, background retinopathy, sensory neuropathy), while 44 (Group B) had no complications. The two groups were comparable for age, sex, plasma lipid profile, and smoking habit. Arterial hypertension was present in 15 of 26 (58%) complicated patients (Group A) and in 18 of 44 (41%) uncomplicated patients (Group B). None of the patients had a history of cerebrovascular disease. The authors found that the wall thickness of the common carotid artery was greater and atherosclerotic lesions of the carotid bifurcation were more frequent in diabetic patients with microvascular complications than in uncomplicated diabetics (who had a similar distribution of other risk factors for atherosclerosis) and in nondiabetic controls. These data on the one hand confirm the role of diabetes as an independent risk factor for carotid atherosclerosis and, on the other hand, indicate a correlation between microvascular lesions and early atherosclerosis in diabetes.