Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema.

BACKGROUND AND OBJECTIVE: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of "vascular preconditioning" predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls. METHODS: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. RESULTS: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 µm), increased apical, internal, and external diameter (28 vs 22 µm; 22 vs 20 µm; and 81 vs 65 µm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. CONCLUSIONS: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema.

Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema: From Bed to Bench.

BACKGROUND AND OBJECTIVE: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. Objective: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE.

Metabolic disturbances and antihypertensive therapy.

Arterial hypertension is frequently associated with metabolic abnormalities. Hyperinsulinemia and insulin resistance are found in obese patients, in non-insulin-dependent diabetics and in some hypertensive patients, irrespective of whether the patients are overweight or have diabetes mellitus. Membrane transport abnormalities, such as increased sodium-lithium exchange associated with hypertension are also significantly related to disturbances in lipid metabolism. Increased sympathetic nervous system activity is a well established feature of arterial hypertension and this may also affect glucose and lipid metabolism. The possibility of these metabolic alterations in the hypertensive patient must be taken into account when deciding upon treatment. Attention to diet is mandatory and includes advice to reduce energy, salt and saturated fat intakes and to increase the intake of less digestible fiber and of potassium; alcohol consumption should be limited. Energy expenditure by regular aerobic physical exercise should be encouraged and continuous effort is necessary to help patients stop smoking. In patients with high blood pressure and abnormalities in lipid and glucose metabolism, it is wise to start pharmacological treatment with drugs that are known to be neutral in their metabolic effects, such as calcium antagonists, angiotensin converting enzyme inhibitors or alpha-blocking agents.