Cardiovascular autonomic dysfunction in patients with idiopathic diabetes insipidus.

INTRODUCTION: Central diabetes insipidus (DI) is a rare disease characterized by the excretion of excessive volumes of dilute urine due to reduced levels of the antidiuretic hormone arginine vasopressin (AVP), caused by an acquired or genetic defect in the neurohypophysis. The aim of this study was to identify any autonomic dysfunction (AD) in patients with DI as a possible cofactor responsible for their reportedly higher mortality. METHODS: The study involved 12 patients (6 females) with central idiopathic DI and a well-controlled electrolyte balance, and 12 controls matched for age, sex and cardiovascular risk factors, who were assessed using the tilt, lying-to-standing, hand grip, deep breath, Valsalva maneuver and Stroop tests. RESULTS: The tilt test showed a significantly more pronounced decrease in both systolic (- 20.67 ± 18 vs. - 1.92 ± 6.99 mmHg, p = 0.0009) and diastolic blood pressure (- 10.5 ± 14.29 vs. - 1.5 ± 5 mmHg, p = 0.012) in patients than in controls. Three patients with DI had to suspend the test due to the onset of syncope. The lying-to-standing test also revealed a marked reduction in blood pressure in patients with DI (1.05 ± 0.13 vs. 1.53 ± 0.14, p = 0.0001). Similar results emerged for the Valsalva maneuver (Valsalva ratio, 1.24 ± 0.19 vs. 1.79 ± 0.11, p < 0.0001) and deep breath test (1.08 ± 0.11 vs. 1.33 ± 0.08, p < 0.0001). CONCLUSIONS: All the principal autonomic tests performed in the study were concordant in indicating that patients with central DI have an impaired autonomic nervous system function despite a normal hydroelectrolytic balance under desmopressin therapy. This impairment may reflect damage to the autonomic system per se and/or the absence of any vasoactive effect of AVP on vascular smooth muscle. In our opinion, patients with central DI should be educated on how to prevent orthostatic hypotension, and pharmacological treatment should be considered for patients with a more marked impairment.

The impact of deep vein thrombosis on the risk of subsequent cardiovascular events: a 14-year follow-up study.

BACKGROUND: The association between deep vein thrombosis (DVT) and atherosclerosis is still controversial. METHODS: We examined the rate of subsequent symptomatic atherosclerosis in patients with unprovoked as compared to secondary DVT with a retrospectively follow-up of a cohort of patients who 14 years earlier had developed an episode of DVT not preceded by arterial cardiovascular events. We collected information on the development of coronary heart disease, ischemic stroke, peripheral artery disease or sudden otherwise unexplained death. RESULTS: We retrieved information from 138 patients with unprovoked and 123 with secondary DVT. The cumulative incidence of symptomatic atherosclerosis was 17.6% (95% CI, 8.3 to 26.0) in patients with unprovoked DVT, and 5.1% (95% CI: 0.0 to 10.7) in those with secondary DVT. After adjusting for age, sex, smoking, hypertension, diabetes and dyslipidemia, the hazard ratio (HR) for development of symptomatic atherosclerosis among patients with unprovoked DVT as compared to those with secondary DVT was 2.89 (95% CI, 1.06 to 7.88; P=0.038). CONCLUSIONS: The risk of subsequent symptomatic atherosclerosis among patients with unprovoked DVT is approximately three times as high as that of patients with secondary events.

Optimal duration of anticoagulation in patients with unprovoked venous thromboembolism: the impact of novel anticoagulants.

Once anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE) over years approaches 50% of all patients with a first episode of unprovoked VTE. The persistence of residual vein thrombosis at ultrasound assessment has consistently been shown to increase the risk, as do persistently high values of D-dimer. Although the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify a substantial proportion of subjects in whom anticoagulation can be safely discontinued. For those patients in whom anticoagulation cannot be discontinued, new opportunities are offered by the availability of low-dose anti-Xa compounds, which have been found to possess an extremely favourable benefit/risk profile.

Failure of old and new anticoagulants to prevent ischemic stroke in high-risk atrial fibrillation: a case report.

Rivaroxaban is an oral anticoagulant that acts as a direct, competitive factor Xa inhibitor. Large randomized clinical trials have shown that, at a daily dose of 20 mg, Rivaroxaban is at least as effective as dose-adjusted warfarin for the prevention of stroke or other embolic complications in patients with nonvalvular atrial fibrillation (AF). The safety and efficacy of combining Rivaroxaban with an antiplatelet agent for secondary stroke prevention has not been established. We report the case of an elderly patient with permanent AF and coronary heart disease, who had already suffered an ischemic stroke while on warfarin treatment, and was consequently switched to treatment with an association of Rivaroxaban and Aspirin. Her CHA2DS2-VASc score was 9. The patient developed a severe recurrent disabling ischemic stroke. This case goes to show that the novel direct anticoagulants may fail to prevent recurrent stroke in patients at particularly high risk, even when associated with antiplatelet drugs.

An unusual finding of massive pulmonary embolism in a patient during treatment with high-dose ibuprofen.

Non-steroidal anti-inflammatory drugs have been associated with an increased risk of venous thromboembolism. We report for the first time, the case of a patient who developed massive pulmonary embolism after a long period of treatment with high doses of ibuprofen. A 65-year-old woman was admitted with severe dyspnea while on treatment with high doses of ibuprofen for diffuse spine pain due to arthrosis. A spiral computed tomography showed a massive pulmonary embolism. No other explanation for the thromboembolic disorder was found. She was successfully treated with therapeutic doses of low-molecular-weight heparin followed by rivaroxaban. Ibuprofen was discontinued and replaced by tramadol. High-dose ibuprofen is likely to have accounted for the life-threatening thromboembolic disorder.

Incidence of arterial embolism in patients on treatment with old and new anticoagulants for venous thromboembolism.

The separate nature of venous and arterial thrombotic disorders has recently been challenged. Patients with venous thromboembolism (VTE) have an increased risk of subsequent symptomatic arterial cardiovascular events, the risk being higher in those with unexplained episodes. Among the implications of this association, there is the potential for old and new antithrombotic drugs to impact on the development of both venous and arterial cardiovascular events. According to the results of recent studies, aspirin in low doses, when administered for the long-term management of patients with unprovoked VTE, reduces by approximately 35% the risk of recurrent VTE while offering a considerable protection against the development of arterial cardiovascular events. By contrast, there is no room to expect a reduction in the risk of subsequent arterial cardiovascular events in patients treated with vitamin K antagonists (VKA) in comparison to patients in whom VKAs are discontinued. According to the results from recent randomized clinical trials, the likelihood of arterial cardiovascular events in patients on the novel direct factor Xa inhibitors is unlikely to differ from that of patients receiving conventional anticoagulation. As dabigatran has been associated with a slight increase in the risk of myocardial infarction over warfarin, its use should be discouraged in patients with coronary heart disease. The long-term use of low-dose apixaban beyond the first months in patients with unprovoked VTE may decrease the long-term risk of arterial, as well as venous, thrombotic events.

Further evidence in support of the association between venous thrombosis and atherosclerosis: a case-control study.

INTRODUCTION: Whether there is an association between venous thromboembolism (VTE) and atherosclerosis is still controversial. AIMS: In a case-control study conducted on subjects older than 50, we assessed the prevalence of symptomatic or subclinical atherosclerosis in a group of unselected patients with unprovoked VTE, and compared it with that of patients with secondary VTE and of matched control individuals free from VTE disorders. METHODS: Cases and controls were enquired about the presence of previous symptomatic manifestations of atherosclerosis. Those with a negative history underwent the ultrasound assessment of carotid arteries following a standardized procedure. An intima-media thickness higher than 0.9 mm or the detection of at least one carotid plaque was regarded as a subclinical manifestation of atherosclerosis. After adjusting for age, gender and risk factors for atherosclerosis, we calculated the odds ratio (OR) for symptomatic or subclinical atherosclerosis in patients with unprovoked VTE as compared to those with secondary VTE and controls. RESULTS: We recruited 100 patients with unprovoked VTE, 100 with secondary VTE and 100 control individuals. In patients with unprovoked VTE, the adjusted OR for symptomatic or subclinical atherosclerosis was 5.1 (95% CI, 2.0 to 13.1) in comparison to patients with secondary VTE, and 14.5 (95% CI, 5.8 to 36.3) in comparison to controls. The prevalence of atherosclerosis was higher in patients with secondary VTE than in controls (OR, 3.1; 95% CI, 1.6 to 6.1). CONCLUSION: The results of this study confirm the presence of a strong association between venous thrombosis and atherosclerosis.

Diagnosis and complications of Cushing's disease: gender-related differences.

OBJECTIVE: Cushing's disease (CD) presents a remarkable preponderance in female gender, with a female-to-male ratio of 3-8:1. The aim of this study was to evaluate gender-related differences in the presentation of CD, as regards: biochemical indices of hypercortisolism; sensitivity of diagnostic tests; clinical features and complications of disease. METHODS: We retrospectively studied 84 adult patients with CD, 67 women and 17 men, evaluated at diagnosis. We compared the features of the disease between the sexes and analysed the effect of gender on CD complications, adjusted for potential confounders (age, gonadal status, BMI, urinary free cortisol values). RESULTS: We observed no differences between males and females as regards age at diagnosis, disease duration and BMI. Men, compared with women, presented higher urinary free cortisol values (P < 0·001) and ACTH values (P < 0·05). As regards diagnostic tests, men presented a lower ACTH response to DDAVP stimulation (P < 0·05). The pituitary tumour itself was less easily visualized by pituitary MRI in males compared with females (P < 0·05). Furthermore, some complications of disease were more frequent or more severe in men, in particular hypokalaemia (P < 0·05), hypercoagulable state and osteoporosis at lumbar spine (P < 0·01), with consequent higher risk of vertebral fractures. Male gender was found to be an independent risk factor for dyslipidaemia, severity of hypertension, lumbar osteoporosis and fractures. CONCLUSIONS: Although CD is less frequent in male patients, in this gender, it presents with more florid clinical manifestations and may imply more diagnostic difficulties.

Autonomic dysfunction and primary antiphospholipid syndrome: a frequent and frightening correlation?

INTRODUCTION: the correlation between primary antiphospholipid syndrome (APS) and cardiovascular events is well known, but the correlation between APS and sudden death is not clear; it probably correlates with sympathetic alterations of the autonomic system. AIM: To compare the autonomic nervous system (ANS) in a group of subjects suffering from APS against that of a control group with no cardiovascular risk factors, matched for age, sex, and body mass index. SUBJECTS AND METHODS: An equal number (n = 31) of subjects with APS, and healthy controls, underwent autonomic evaluation: tilt test, deep breath, Valsalva maneuver, hand grip, lying-to-standing, Stroop, and sweat tests. RESULTS: Cases in the APS group were positive for the tilt test, relating to changes in respiratory rate intervals, by comparison with controls. Results of other tests were also altered significantly in APS cases, by comparison with controls. (The sweat and Stroop tests were only performed in 14 cases). Autonomic disease did not correlate with age, sex, history of disease, arterial or venous thrombosis, or antibody positivity; only their coagulation parameters correlated with autonomic dysfunction. CONCLUSION: Autonomic dysfunction in APS seems to correlate with coagulation parameters. APS patients should receive autonomic evaluation, to minimize the risks of fatal arrhythmias and sudden death.

Autonomic dysfunction in Hodgkin and non-Hodgkin lymphoma. A paraneoplastic syndrome?

We wanted to determine whether autonomic dysfunction in patients with lymphoma is related to chemotherapy or represent a paraneoplastic syndrome. 40 patients with current or cured Hodgkin or non-Hodgkin lymphoma and 40 healthy controls, matched for age, gender, hypertension and diabetes mellitus underwent autonomic evaluation (Deep Breath, Valsalva Maneuver, Hand Grip, Lying to Standing, Tilt Test). Current patients also suffering from diabetes or hypertension, or still on chemotherapy revealed autonomic changes, while cured or healthy subjects did not. Autonomic dysfunction in lymphoma is a transient manifestation of a paraneoplastic syndrome.

Flow-mediated arterial dilation in primary antiphospholipid syndrome.

OBJECTIVE: To investigate precocious alterations in the artery wall of patients with primary antiphospholipid syndrome (APS). METHODS: We evaluated flow-mediated dilation (FMD) of the brachial artery and intima-media thickness (IMT) of carotid arteries in 16 patients and 16 healthy controls matched for age, gender, and other cardiovascular risk factors. RESULTS: FMD of the brachial artery was significantly lower in patients than in controls (6.3 +/- 5.2% vs 18.2 +/- 2.7; P < .005). IMT was similar in the 2 groups. FMD was significantly reduced in patients with anticardiolipin antibodies IgM. CONCLUSIONS: APS correlates closely with precocious atherosclerosis, and the correlation with a type of anticardiolipin antibody may be predictive of more accelerated atherosclerosis.

Carotid and femoral atherosclerosis in chronic hepatitis C: a 5-year follow-up.

The objective of this study was to assess the progression of atherosclerosis in carotid and femoral arteries after a 5-year period using ultrasound in subjects with chronic hepatitis C and in controls matched for classic atherosclerotic risk factors. A total of 40 patients and 40 controls were assessed by echocolor Doppler in 2001 and in 2006 to evaluate plaque and intima-media thickness. The patients showed no changes in plaque and intima-media thickness during the 5-year period in all districts examined, whereas a significant increase in intima-media thickness in the carotid sections was recorded in the controls. Chronic hepatitis C seems to cause delay in the atherosclerotic process.

Type IIb von Willebrand disease: role of qualitative defects in atherosclerosis and endothelial dysfunction.

OBJECTIVE: To verify whether a hereditary bleeding tendency, such as von Willebrand disease (vWD) type IIB, protects against the onset of atherosclerosis. PARTICIPANTS AND METHODS: Twenty-four patients with vWD type IIB and 24 healthy controls, matched for common atherosclerotic risk factors. All patients were evaluated by color Doppler ultrasound of the common carotid, carotid bifurcation, common femoral artery, brachial artery, and abdominal aorta, investigating intima-media thickness (IMT) and presence of plaques in each arterial district. Flow mediated dilation (FMD) of the brachial artery was used to test endothelial function. RESULTS: vWD type IIB patients presented no significant difference in IMT in any arterial district. FMD showed no differences between the 2 groups. CONCLUSIONS: The quantitative clotting defect characteristic of vWD type IIB does not seem to protect against atherosclerosis.