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.

Safety and efficacy of low-dose fondaparinux (1.5 mg) for the prevention of venous thromboembolism in acutely ill medical patients with renal impairment: the FONDAIR study.

BACKGROUND: Renal impairment is common, affecting around 40% of acutely ill medical patients, and is associated with an increased risk of both venous thromboembolism (VTE) and bleeding. The clinical benefit of effective thromboprophylactic strategies may be outweighed in these patients by an excessive rate of hemorrhage. OBJECTIVE: To assess the safety and efficacy of lower prophylactic doses of fondaparinux in acutely ill medical patients with renal impairment. PATIENTS/METHODS: We carried out a multicenter, investigator-initiated, prospective cohort study. Patients at risk of VTE with a creatinine clearance between 20 and 50 mL min(-1) were treated with fondaparinux 1.5 mg qd for a minimum of 6 to a maximum of 15 days. The primary outcome was the incidence of major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB) and symptomatic VTE. RESULTS: We enrolled 206 patients with a mean age of 82 years, mean creatinine clearance of 33 mL min(-1) , and a mean Charlson co-morbidity index of 8.2. One patient had major bleeding (0.49%, 95% confidence interval [CI] 0.03-3.10), eight had CRNMB (3.88%, 95% CI 1.81-7.78) and three developed symptomatic VTE (1.46%, 0.38-4.55). Twenty-three patients (11.17%, 7.36-16.48) died. No independent predictors of bleeding were found at univariate analysis. CONCLUSIONS: The addition of moderate to severe renal impairment to patients with traditional risk factors for VTE identified a population of very elderly acutely ill medical patients potentially at high risk of both VTE and bleeding complications. The recently approved lower prophylactic dose of fondaparinux appears to be a safe and relatively effective strategy in these patients.

Endocrine arterial hypertension: diagnostic approach in clinical practice.

Endocrine arterial hypertension (EAH) a condition in which hormone excess results in clinically significant hypertension is a rare cause of hypertension. However in the last years its prevalence has increased, mostly due to the improvement of diagnostic work-up. In clinical practice, hypertensive subjects with suspicion of EAH currently undergo hormonal screening of the renin-aldosterone and catecholamines and glucocorticoids excess. This paper reviews current understanding for earlier recognition of the main forms of EAH and discusses screening laboratory methods and localization techniques that have enhanced the clinician's ability to make the diagnosis of EAH. Primary aldosteronism (PA) has recently been recognised as the most frequent cause of EAH. The aldosterone to renin ratio (ARR) is a highly recommended screening test for PA. When ARR is increased, confirmatory tests as saline infusion or fludrocortisone suppression are required. Differential diagnosis of PA requires adrenal gland imaging by computed tomography (CT) or magnetic resonance imaging (MRI), biochemical testing of the aldosterone response to posture, and selective adrenal venous sampling to differentiate unilateral aldosterone-producing adenoma from bilateral hyperplasia. Hypertension is frequently found in endogenous Cushing's Syndrome (CS). Twenty-four-hour urinary free cortisol measurement is the gold standard for the diagnosis of CS, but it must be confirmed by the overnight dexamethasone suppression test. CT and MRI are the primary imaging studies to perform, while scintigraphy is a useful confirmatory method. The most specific and sensitive diagnostic test for catecholamine-producing neoplasms is determination of urinary metanephrine levels; the neoplasms can be located by CT, MRI and metaiodo-benzylguanidine scintigraphy.

Pulse hypertension: a new component of the metabolic syndrome in elderly women?

The classification of arterial hypertension (HT) to define metabolic syndrome (MS) is unclear in that different cutoffs of blood pressure (BP) have been proposed. We evaluated the categorization of HT most qualified to define MS in relationship with coronary heart disease (CHD) mortality at a population level. A total of 3257 subjects aged > or =65 years were followed up for 12 years. MS was defined according to the criteria of the National Education Cholesterol Program using three different categories of HT: MS-1 (systolic blood pressure (SBP) > or =130 and diastolic blood pressure (DBP) > or =85 mm Hg), MS-2 (SBP > or =130 or DBP > or =85 mm Hg) and MS-3 (pulse pressure (PP) > or =75 mm Hg in men and > or =80 mm Hg in women). Gender-specific adjusted hazard ratio (HR) with 95% confidence intervals (CI) for CHD mortality was derived from Cox analysis in the three MS groups, both including and excluding antihypertensive treatment. In women with MS untreated for HT, the risk of CHD mortality was always significantly higher than in those without MS, independent of categorization; the HR of MS was 1.73 (CI 1.12-2.67) using MS-1, 1.75 (CI 1.10-2.83) using MS-2 and 2.39 (CI 3.71-1.31) using MS-3. In women with MS treated for HT, the HR of CHD mortality was significantly increased only in the MS-3 group (1.92, CI 1.1-2.88). MS did not predict CHD in men. In conclusion, MS can predict CHD mortality in elderly women with untreated HT but not in those with treated HT; in the latter, PP is the most predictive BP value.

The long-term clinical course of acute deep venous thrombosis.

BACKGROUND: In patients who have symptomatic deep venous thrombosis, the long-term risk for recurrent venous thromboembolism and the incidence and severity of post-thrombotic sequelae have not been well documented. OBJECTIVE: To determine the clinical course of patients during the 8 years after their first episode of symptomatic deep venous thrombosis. DESIGN: Prospective cohort study. SETTING: University outpatient thrombosis clinic. PATIENTS: 355 consecutive patients with a first episode of symptomatic deep venous thrombosis. MEASUREMENTS: Recurrent venous thromboembolism, the post-thrombotic syndrome, and death. Potential risk factors for these outcomes were also evaluated. RESULTS: The cumulative incidence of recurrent venous thromboembolism was 17.5% after 2 years of follow-up (95% CI, 13.6% to 22.2%), 24.6% after 5 years (CI, 19.6% to 29.7%), and 30.3% after 8 years (CI, 23.6% to 37.0%). The presence of cancer and of impaired coagulation inhibition increased the risk for recurrent venous thromboembolism (hazard ratios, 1.72 [CI, 1.31 to 2.25] and 1.44 [CI, 1.02 to 2.01], respectively). In contrast, surgery and recent trauma or fracture were associated with a decreased risk for recurrent venous thromboembolism (hazard ratios, 0.36 [CI, 0.21 to 0.62] and 0.51 [CI, 0.32 to 0.87], respectively). The cumulative incidence of the post-thrombotic syndrome was 22.8% after 2 years (CI, 18.0% to 27.5%), 28.0% after 5 years (CI, 22.7% to 33.3%), and 29.1% after 8 years (CI, 23.4% to 34.7%). The development of ipsilateral recurrent deep venous thrombosis was strongly associated with the risk for the post-thrombotic syndrome (hazard ratio, 6.4; CI, 3.1 to 13.3). Survival after 8 years was 70.2% (CI, 64.7% to 75.6%). The presence of cancer increased the risk for death (hazard ratio, 8.1; CI, 3.6 to 18.1). CONCLUSION: Patients with symptomatic deep venous thrombosis, especially those without transient risk factors for deep venous thrombosis, have a high risk for recurrent venous thromboembolism that persists for many years. The post-thrombotic syndrome occurs in almost one third of these patients and is strongly related to ipsilateral recurrent deep venous thrombosis. These findings challenge the widely adopted use of short-course anticoagulation therapy in patients with symptomatic deep venous thrombosis.

Failure of thrombin-antithrombin III complexes in the diagnosis of deep vein thrombosis.

Plasma thrombin-antithrombin III (T-AT) complexes are reputed to be an indirect manifestation of thrombin generation, and a role for their determination in the diagnosis of deep vein thrombosis (DVT) has been advocated. In order to evaluate the accuracy of T-AT complexes assay for DVT diagnosis, in 166 consecutive outpatients with clinical suspicion of the disease, plasma concentration of T-AT complexes was measured immediately before venography by means of an enzyme-linked immunosorbent assay kit. The result of the T-AT complexes assay was elevated in 29 of the 48 patients with DVT (sensitivity, 60%). The T-AT complexes levels were within the normal range in 104 of the 118 patients with normal venograms (specificity, 88%). The positive and the negative predictive value were 67% and 85%, respectively. The authors conclude that the T-AT complexes assay is of little value for the diagnosis of DVT in outpatients.

Deep-vein thrombosis and the incidence of subsequent symptomatic cancer.

BACKGROUND: In contrast to the established relation between overt cancer and subsequent venous thromboembolism, it is unclear whether symptomatic deep-vein thrombosis is associated with a risk of subsequent overt malignant disease. METHODS: Two hundred sixty consecutive patients with symptomatic, venographically proved deep-vein thrombosis were enrolled in a study, of whom 250 were followed during a two-year period. Among those assessed during follow-up, the incidence of subsequently detected cancer in the 105 patients with secondary venous thrombosis (i.e., thrombosis associated with a well-recognized risk factor other than cancer) was compared with the incidence of cancer in the 145 patients with idiopathic venous thrombosis. RESULTS: Routine examination at the time of diagnosis of the venous thrombosis revealed cancer in 5 of the 153 enrolled patients with idiopathic venous thrombosis (3.3 percent) and in none of the 107 enrolled patients with secondary venous thrombosis. During follow-up, overt cancer developed in 2 of the 105 patients with secondary venous thrombosis (1.9 percent) and in 11 of the 145 patients with idiopathic venous thrombosis (7.6 percent; odds ratio, 2.3; 95 percent confidence interval, 1.0 to 5.2; P = 0.043). Of the 145 patients with idiopathic venous thrombosis, 35 had confirmed recurrent thromboembolism. Overt cancer subsequently developed in 6 of the 35 (17.1 percent). The incidence of cancer in the patients with recurrent idiopathic venous thrombosis was higher than that in the patients with secondary venous thrombosis (P = 0.008; odds ratio, 9.8; 95 percent confidence interval, 1.8 to 52.2) or in the patients with idiopathic venous thrombosis that did not recur (P = 0.024; odds ratio, 4.3; 95 percent confidence interval, 1.2 to 15.3). CONCLUSIONS: There is a statistically significant and clinically important association between idiopathic venous thrombosis and the subsequent development of clinically overt cancer, especially among patients in whom venous thromboembolism recurs during follow-up.

Dermatan sulphate: a safe approach to prevention of postoperative deep vein thrombosis.

To assess the efficacy and safety of dermatan sulphate (MF 701) in preventing postoperative deep vein thrombosis (DVT), 324 patients aged 40 years or over undergoing elective major general surgical operations were included in a randomized trial comparing MF 701 (100 mg intramuscularly once a day) with unfractionated calcium heparin (UFH, 5000 units subcutaneously three times daily). Both treatments were initiated before operation and continued until discharge. In all, 316 patients were included in the analysis (MF 701, 157; UFH, 159). Serial impedance plethysmography was performed in all patients; a 125I-radiolabelled fibrinogen uptake test was added to impedance plethysmography in a randomized subsample of 62 patients (MF 701, 28; UFH, 34). Positivity in either test was confirmed where possible by venography. DVT was diagnosed by venography or, when this could not be performed, by positivity of either impedance plethysmography or fibrinogen uptake test. The incidence of DVT was 3.1 per cent (patients receiving MF 701) and 1.6 per cent (those receiving UFH) in patients undergoing impedance plethysmography alone, and 7.1 and 11.8 per cent, respectively, in those undergoing both impedance plethysmography and fibrinogen uptake test; in neither case was the difference between treatments statistically significant. There were five in-hospital deaths, two in patients receiving MF 701 and three in patients on UFH. The incidence of clinically overt haemorrhage was 5.7 per cent in patients on MF 701 and 17.6 per cent in those on UFH (P less than 0.01). Postoperative transfusions and reoperations due to bleeding were significantly less frequent in patients receiving MF 701. Mortality rates at 3 months were similar for the two treatment groups. Compared with standard prophylaxis using UFH, MF 701 showed a similar efficacy with a significantly greater safety.

Deep vein thrombosis and fibrinolysis. Defective urokinase type plasminogen activator release.

In the present study 57 consecutive patients with a first episode of venographically proven deep vein thrombosis were investigated to evaluate the release of tissue-type plasminogen activator (t-PA) and of urokinase-type plasminogen activator (u-PA) in response to DDAVP stimulation as well as the resting plasminogen activator inhibitor (PAI) concentration, comparing this to the results obtained in 66 similar patients with a clinical suspicion of thrombosis but with a normal venogram. All assays were performed without knowledge of the patient's status. Four patients in the deep vein thrombosis-group (7%) had an absent u-PA antigen response upon DDAVP infusion, while a normal response was observed in all control subjects. Patients and controls showed similar increases in t-PA antigen level upon DDAVP. High resting PAI antigen levels were encountered in 5 patients in the deep vein thrombosis-group (9%) and in 6 subjects in the control group (9%). The results from this controlled study indicate that a defective release of u-PA may occur in patients with deep vein thrombosis and may have pathogenetic significance. Furthermore it is concluded that elevation of PAI levels cannot be considered as a specific risk factor for venous thrombosis.

Failure of computerized impedance plethysmography in the diagnostic management of patients with clinically suspected deep-vein thrombosis.

Before a new diagnostic modality can be introduced in clinical medicine, the validity of both a normal and abnormal test result have to be assessed prospectively in an appropriate patient group. We have evaluated the clinical validity of a new computerized impedance plethysmography (CIP) in the diagnostic management of 381 consecutive patients with clinically suspected venous thrombosis. In patients with serially normal CIP results, the diagnosis of venous thrombosis was refuted and, consequently, they were not treated with anticoagulant therapy and all were followed up for a period of 6 months to estimate the occurrence of symptomatic venous thromboembolism. The study was prematurely terminated by the safety monitoring committee because of an unacceptably high incidence of confirmed venous thromboembolism (10 patients, 3.2%; 95% confidence interval: 1.6% to 6%), including 4 episodes of fatal pulmonary embolism. In a subsequent explanatory study using ultrasonography in 29 other symptomatic patients who had at least 2 repeated normal CIP test results, the failure of CIP to detect proximal vein thrombosis was confirmed in 4 patients (14%). The reasons for this failure are probably related to the use of a modified device to measure impedance in the CIP apparatus, resulting in a lower ability to separate patients without venous thrombosis from those with the disease. We concluded that CIP is insensitive for the detection of proximal vein thrombosis and, therefore, not clinically useful in the diagnostic management of patients with suspected venous thrombosis.

[Occult pulmonary embolism in patients with proximal deep venous thrombosis]. / Embolia polmonare occulta in pazienti con trombosi venosa profonda prossimale.

It is known that proximal deep-vein thrombosis (DVT) of the lower limbs is associated with a high risk of pulmonary embolism (PE). However, only a few patients presenting with clinically symptomatic DVT exhibit symptoms or signs suggestive of this complication. The prevalence of silent PE in these patients is unknown. In order to assess the true prevalence of PE in a patient population presenting with venographically proven proximal DVT but without symptoms of PE, a perfusion lung scan was performed in 100 consecutive patients at presentation. Fifty-nine patients (59%) had a high probability lung scan (segmental or larger perfusion defects in lung areas free from abnormalities as shown by conventional chest x-ray) at the initiation of heparin treatment. At repeated lung scanning, performed after 10 days of anticoagulant treatment, complete to partial improvement was observed in 41 of these patients (71%), whereas in 13 (23%) the picture was unchanged and in 3 (5.2%) it worsened. In 6 patients who developed symptoms suggestive of PE during the study period, a lung scan was immediately repeated and correct interpretation of the clinical manifestation was permitted by comparison with the initial scan. It is concluded that lung-scan--detected asymptomatic PE occurs frequently in patients with proximal DVT, and that the majority of these emboli resolve within 10 days of anticoagulant treatment. In order to manage correctly patients who develop clinical manifestations suggestive of PE while undergoing therapy for venous thrombosis, a baseline lung scan is strongly recommended in all patients with proven proximal DVT.

Enzymatic patterns in reptilian brain. Histochemical characterization of the optic tectum.

The enzymatic patterns present in the optic tectum of 4 species belonging to different reptilian orders seem related to the degree of structural and functional organization reached by the nervous centre, as in other vertebrates. In particular the AChE localization in reptiles is representative of a evolutionary sequence in the distribution of this enzyme in the optic tectum along the tetrapode series.