Abstract-The thrombotic microangiopathy observed in malignant hypertension is similar to that of thrombotic thrombocytopenic purpura, which is associated with a deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving protease that cleaves large prothrombogenic multimers. We hypothesized that ADAMTS13 is deficient in malignant hypertension and that the severity of thrombotic microangiopathy is associated with decreased ADAMTS13 activity. We included 20 patients with malignant and 20 patients with severe hypertension, and 20 matched normotensive individuals served as control subjects. VWF, active VWF, and free hemoglobin were assessed to explore predictors of ADAMTS13 activity. Patients with malignant hypertension had lower ADAMTS13 activity (80%; interquartile range: 53% to 130%) compared with control subjects (99% interquartile range: 82% to 129%; PϽ0.01) but not compared with patients with severe hypertension (Pϭ0.14). ADAMTS13 activity negatively correlated with lactic dehydrogenase levels after logarithmic transformation (rϭϪ0.65; PϽ0.001) and was associated with platelet count (rϭ0.34; Pϭ0.04) and the presence of schistocytes (rϭϪ0.37; Pϭ0.02). Apart from the association with thrombotic microangiopathy, ADAMTS13 was inversely associated with creatinine (rϭϪ0.42; Pϭ0.008). Increasing levels of VWF were associated with a decrease in ADAMTS13 activity (rϭϪ0.34; Pϭ0.03). There was no significant association between ADAMTS13 activity and other parameters, including blood pressure. In conclusion, ADAMTS13 is decreased in malignant hypertension and associated with the severity of thrombotic microangiopathy, likely because of the release of VWF after endothelium stimulation. Key Words: hypertensive crisis Ⅲ thrombotic microangiopathy Ⅲ coagulation Ⅲ kidney failure Ⅲ endothelium M alignant hypertension is a condition characterized by severe hypertension and acute ischemic complications and frequently complicated by a thrombotic microangiopathy (TMA). TMA is characterized by thrombosis of small vessels, intravascular hemolysis with fragmentation of red blood cells (schistocytes), elevated lactic dehydrogenase (LDH) levels, and consumption of platelets. TMA was observed in 27% of patients with malignant hypertension presenting at the emergency department of our hospital and was associated with renal impairment at presentation but an increased recovery of renal function during follow-up. 1 The pathogenesis of TMA in malignant hypertension is incompletely understood. Several mechanisms may lead to the TMA associated with malignant hypertension.Malignant hypertension bears resemblance to thrombotic thrombocytopenic purpura (TTP). TTP is associated with a congenital or acquired deficiency of ADAMTS13, a zinccontaining metalloprotease that cleaves large von Willebrand factor (VWF) multimers, thereby decreasing their prothrombogenic properties. 2,3 Deficiency of ADAMTS13 (activity) leads to the appearance of unusually large prothrombogenic multimers (UL-VWF) in the circulation resulting in thrombocytopenia, intravascu...

There are currently few recommendations on how to assess inter-arm blood pressure (BP) differences. The authors compared simultaneous with sequential measurement on mean BP, inter-arm BP differences, and within-visit reproducibility in 240 patients stratified according to age (<50 or ≥60 years) and BP (<140/90 mm Hg or ≥140/90 mm Hg). Three simultaneous and three sequential BP measurements were taken in each patient. Starting measurement type and starting arm for sequential measurements were randomized. Mean BP and inter-arm BP differences of the first pair and reproducibility of inter-arm BP differences of the first and second pair were compared between both methods. Mean systolic BP was 1.3AE7.5 mm Hg lower during sequential compared with simultaneous measurement (P<.01). However, the first sequential measurement was on average higher than the second, suggesting an order effect. Absolute systolic inter-arm BP differences were smaller on simultaneous (6.2AE6.7/3.3AE3.5 mm Hg) compared with sequential BP measurement (7.8AE7.3/4.6AE5.6 mm Hg, P<.01 for both). Within-visit reproducibility was identical (both r=0.60). Simultaneous measurement of BP at both arms reduces order effects and results in smaller inter-arm BP differences, thereby potentially reducing unnecessary referral and diagnostic procedures. J Clin Hypertens (Greenwich). 2013;15:839-844. ª2013 Wiley Periodicals, Inc.Inter-arm blood pressure (BP) differences have been established since the early 20s of the last century.1 The importance of assessing inter-arm BP differences is to prevent underestimation and undertreatment of hypertension because the arm with the highest BP should be taken as a reference. Therefore, guidelines on BP measurement recommend bilateral BP measurement at a patient's first visit.2,3 In addition, large inter-arm BP differences in systolic BP (SBP) may indicate the presence of atherosclerotic plaques and other vascular occlusive diseases and are associated with increased cardiovascular risk. 4,5 A recent meta-analysis of studies assessing the inter-arm BP differences showed that a SBP difference ≥15 mm Hg was associated with an increased risk of cardiovascular mortality.6 This is in line with another recent prospective study in hypertensive primary care patients, which showed that a BP difference of ≥10 mm Hg was an independent predictor of cardiovascular events and all-cause mortality after 10 years of follow-up.

Hypertensive crisis with retinopathy confers a prothrombotic state characterized by endothelial dysfunction, platelet activation and increased thrombin generation, whereas fibrinolytic activity is enhanced. The observed changes in prothrombotic and antithrombotic pathways may contribute to the increased risk of ischaemic and haemorrhagic complications in this extreme hypertension phenotype.

The survival of patients with malignant hypertension (MHT) has considerably improved over the past decades. Data regarding the excess risk of mortality and the contribution of conventional cardiovascular risk factors are lacking. The authors retrospectively assessed cardiovascular risk factors and all-cause mortality in 120 patients with a history of MHT and compared them with 120 normotensive and 120 hypertensive age-, sex-, and ethnicity-matched controls. Total cholesterol, low-density lipoprotein cholesterol, and body mass index were lower in MHT patients compared with hypertensive controls, whereas blood pressure, high-density lipoprotein cholesterol, and smoking habit were similar. Median estimated glomerular filtration rate was lower in MHT patients compared with normotensive and hyperten-sive controls (both P<.01). The annual incidence of all-cause mortality per 100 patient-years was higher in MHT patients (2.6) compared with normotensive (0.2) and hypertensive (0.5) controls (both P<.01). Mortality of patients with a history of MHT remains high compared with normotensive and hypertensive controls. Patients with MHT had a more favorable cardiovascular risk profile compared with hyper-tensive controls but a higher prevalence of renal insufficiency. J Clin Hypertens (Greenwich). 2014;16:122-126. ª2013 Wiley Periodicals, Inc. Malignant hypertension (MHT) is a hypertensive emergency characterized by severe hypertension and acute microvascular complications including grade III or IV hypertensive retinopathy. If left untreated, the 5-year survival rate is <5% mainly because of stroke, myocar-dial infarction, congestive heart failure, and end-stage renal disease. 1-3 With the availability of antihyperten-sive drugs and improved patient care, mortality has been markedly reduced to approximately 10% after 5 years. 2,4 This is still considerable, however, given the relatively young study populations, with an average age varying between 40 and 50 years at presentation. 2,5 Previous cohort studies, including our own, have shown that renal dysfunction is an important predictor of mortality in patients with MHT, 2,4 while other studies suggest a role of traditional cardiovascular risk factors such as excess smoking, decreased levels of high-density lipoprotein (HDL), and poor blood pressure (BP) control. 6-9 However, most of these studies lack a control population thereby limiting the internal validity. Nonetheless, insight into the excess risk of cardiovas-cular disease and mortality in patients with a history of MHT is required to identify which preventive measures may further improve outcome of this extreme phenotype of hypertension-related organ damage. Therefore, the principle aim of this study was to quantify the excess mortality risk in patients with a history of MHT. The second aim was to investigate whether traditional cardiovascular risk factors contribute to the increased risk. To this end, we compared cardiovascular risk factors and all-cause mortality of patients with a history of MHT with age-, sex-, and ...