Determinants of thromboxane biosynthesis in patients with moderate to severe chronic kidney disease.

BACKGROUND: Mechanisms of accelerated atherothrombosis in patients with chronic kidney disease (CKD) are only partly characterized. The aims of this study were to evaluate the extent of thromboxane (TX)-dependent platelet activation in patients with CKD, and to characterize the determinants of altered TX biosynthesis in this setting, with particular reference to enhanced lipid peroxidation, low grade inflammation and CKD-related anemia. PATIENTS AND METHODS: A cross sectional comparison between urinary 8-iso-PGF2α and 11-dehydro-TXB2, in vivo markers of oxidative stress and platelet activation, respectively, was performed in 115 patients with stage 1-4 CKD. RESULTS: Levels of both urinary 11-dehydro-TXB2 and 8-iso-PGF2α increased sequentially across the four CKD stages (P<0.0001, Kruskal-Wallis test). Both urinary prostanoids were inversely associated with either estimated glomerular filtration rate (eGFR, P<0.0001) or hemoglobin levels (P<0.0001). A significant direct correlation was also observed between urinary 11-dehydro-TXB2 and 8-iso-PGF2α (Rho=0.620, P<0.0001). On multivariate analysis, urinary 8-iso-PGF2α (ß=0.459, P<0.0001), hemoglobin levels (ß=- 0.261, P=0.002) and eGFR (ß=-0.172, P=0.032) were independent predictors of urinary 11-dehydro-TXB2 (adjusted R(2)=0.488). CONCLUSIONS: This study provides biochemical evidence of persistent platelet activation in patients with CKD. This condition occurs early in the natural history of the disease and is related to kidney function and oxidative stress. Moreover, we found an independent inverse relationship between hemoglobin levels and TX-dependent platelet activation. This finding may provide a mechanistic link between CKD-related anemia and increased cardiovascular risk.

Aspirin overprescription in primary cardiovascular prevention.

INTRODUCTION: Aspirin overprescription is of some concern, especially in still-healthy individuals, and estimates of the magnitude of this problem are lacking. We evaluated the inappropriateness of aspirin prescription by primary care physicians in primary cardiovascular prevention. MATERIALS AND METHODS: Out of 20,599 patients screened by 16 primary care physicians in the Abruzzi region, central Italy, 400 patients were on treatment with aspirin for primary prevention. For each such patient, the absolute cardiovascular and coronary risks were assessed according to the Italian Cardiovascular Risk Chart for Primary Prevention and the European Society of Cardiology Coronary Risk Chart, respectively. Patients with a cardiovascular and/or coronary risk <1.0 event/100 patients/year were considered as treated inappropriately (aspirin overprescription), on the basis of previous literature. RESULTS: Overall, as many as 12% and 18% of patients had a cardiovascular and/or coronary risk <1.0 event/100 patients/year according to the European and the Italian charts, respectively, and therefore were defined as treated inappropriately. Patients with and without inappropriate treatment were similar with respect to smoking habits, family history and body max index. However, inappropriately treated patients had significantly lower levels of blood pressure and total cholesterol, and were more likely to be female, younger and non-diabetic than patients appropriately treated. CONCLUSIONS: A non-negligible proportion-up to 18%-of subjects in primary prevention is currently more likely to derive harm than benefit from inappropriate aspirin use. A wider use of Cardiovascular Risk Charts should guide primary care physicians in prescribing aspirin for primary prevention.