Thrombomodulin and von Willebrand factor: relation to endothelial dysfunction and disease outcome in children with acute lymphoblastic leukemia.

The severe endothelial dysfunction in children with acute lymphoblastic leukemia (ALL) can result from the disease itself, from treatment, or from other conditions (e.g. sepsis). The aim of this study was to determine the levels of markers of endothelial activation in children with ALL and to assess their potential prognostic value. Fifty-two children with ALL, 19 children with ALL 1-10 years after the completion of therapy, and 28 healthy children were studied. In children with ALL, there was a significant increase in thrombomodulin (TM) and von Willebrand factor (vWF) levels during the acute phase of the disease and during treatment. Children with an unfavorable outcome had higher levels of TM. In conclusion, severe endothelial dysfunction is present during the acute phase of ALL and during treatment and appears to result from the disease itself. Serum TM and vWF levels might represent additional, but not independent, prognostic markers in childhood ALL.

Targeting vascular risk in patients with metabolic syndrome but without diabetes.

There are no prospective data on the effect of a multitargeted treatment approach on cardiovascular disease (CVD) risk reduction in nondiabetic patients with metabolic syndrome (MetS). Furthermore, the optimal hypolipidemic drug treatment in these patients remains controversial. In this prospective, randomized, open-label, intention-to-treat, and parallel study, 300 nondiabetic patients with MetS, free of CVD at baseline, were studied for a period of 12 months. Age- and sex-matched subjects without MetS (n = 100) acted as controls. All patients received lifestyle advice and a stepwise-implemented drug treatment of hypertension, impaired fasting glucose, and obesity. For hypolipidemic treatment, the patients were randomly allocated to 3 treatment groups: atorvastatin (n = 100, 20 mg/d), micronized fenofibrate (n = 100, 200 mg/d), and both drugs (n = 100). Clinical and laboratory parameters, including the lipid profile and C-reactive protein (CRP), were assessed at the baseline and at the end of the study. The primary end point was the proportion of patients not having MetS or its component features at the end of the 12-month treatment period. The secondary end points were the difference in 10-year CVD risk (Prospective Cardiovascular Munster risk calculator) and the degree of CRP reduction. By the end of the study, 76% of the patients no longer had MetS, and 46% had only one diagnostic MetS factor. The estimated 10-year (Prospective Cardiovascular Munster) risk of all patients with MetS at baseline was 14.6%. This was reduced in the atorvastatin group to 6.4%, in the fenofibrate group to 9.2%, and in the combination group to 5.5% (P < .0001 for all vs baseline). The 10-year risks of the atorvastatin and combination groups were not different from that of the control group (5.0%). C-reactive protein was significantly reduced in all treatment groups, with the atorvastatin and combination groups having the greatest reduction (65% and 68%, respectively, P < .01 vs the fenofibrate group, 44%). Lipid values were significantly improved in all 3 treatment groups, with those on the combined treatment attaining lipid targets to a greater extent than those in the other 2 groups. A target-driven and intensified intervention aimed at multiple risk factors in nondiabetic patients with MetS substantially offsets its component factors and significantly reduces the estimated CVD risk. The atorvastatin-fenofibrate combination had the most beneficial effect on all lipid parameters and significantly improved their CVD risk status. Atorvastatin and combination treatment were more effective than fenofibrate alone in reducing CRP levels.