Persistent platelet activation in patients with type 2 diabetes treated with low doses of aspirin.

BACKGROUND: The percentage of diabetic patients who do not benefit from the protective effect of aspirin is larger than in other populations at cardiovascular risk. OBJECTIVE: We compared the ability of aspirin to suppress TxA2 and platelet activation in vivo, in type-2 diabetics vs. high-risk non-diabetic patients. METHODS: Urinary 11-dehydro-TXB2, plasma sCD40 L, and sP-selectin were measured, together with indices of low-grade inflammation, glycemic control, and lipid profile, in 82 patients with type-2 diabetes and 39 without diabetes, treated with low doses of aspirin. RESULTS: Urinary 11-dehydro-TxB2, plasma sCD40L and sP-selectin were significantly higher in diabetics than in controls: [38.9 (27.8-63.3) vs. 28.5 (22.5-43.9) ng mmol(-1) of creatinine, P = 0.02], [1.06 (0.42-3.06) vs. 0.35 (0.22-0.95) ng mL(-1); P = 0.0001], [37.0 (16.8-85.6) vs. 20.0 (11.2-35.6) ng mL(-1), P = 0.0001], respectively. The proportion of individuals with diabetes increased across quartiles of 11-dehydro-TxB2, sCD40L, and sP-selectin, with the highest quartiles of 11-dehydro-TxB2, sCD40L and sP-selectin, including 66%, 93.3%, and 93.3% of individuals with diabetes. Markers of platelet activation positively correlated with indices of glycemic control but not with markers of low-grade inflammation. CONCLUSIONS: Platelet dysfunction associated with insufficient glycemic control, may mediate persistent platelet activation under aspirin treatment.

PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans.

BACKGROUND: Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS: Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Physical activity and the risk of acute myocardial infarction. GISSI-EFRIM Investigators. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-Epidemiologia dei Fattori di Rischio dell'Infarto Miocardico.

The relationship between physical activity and acute myocardial infarction (AMI) was examined in a case-control study conducted in Italy in 1988 to 1989 within the framework of the GISSI-2 trial of streptokinase versus alteplase and heparin versus no heparin in the treatment of AMI. A total of 916 case patients admitted to coronary care units from various Italian regions for AMI were interviewed. Control subjects were 1106 patients admitted to the same network of hospitals for a broad spectrum of acute diseases not related to known or potential risk factors for myocardial infarction. Among various types of physical activity (occupational activity, walking, stair climbing, and sport and leisure-time physical activity), occupational physical exercise emerged as the most protective. Multivariate odds ratios (ORs) were 1.4 (95% confidence interval (CI), 1.0 to 2.0) and 1.6 (95% CI, 1.2 to 2.1) for the two lowest levels of occupational physical activity. The trends of increasing risk with decreasing activity were consistent, although less strong, when other types of activity were considered. The protection conveyed by occupational physical activity was similar across various strata of sex, age, education, smoking habits, and diabetes, and was not explained by serum cholesterol, body weight, or hypertension. This study therefore confirms that low physical activity is an indicator of subsequent risk of AMI.

Ibopamine kinetics after a single oral dose in patients with congestive heart failure.

The kinetics of ibopamine, the 3,4-diisobutyryl ester of N-methyldopamine (epinine), was assessed in 27 patients with congestive heart failure (CHF) and 8 healthy normal subjects (NS). Nine patients were in functional class IV according to the NYHA definition, 9 in class III and 9 in class II. Ibopamine was administered at a single oral dose of 100 mg. Epinine, both free and total (mainly conjugated), plasma concentrations and urinary recoveries of total epinine, HVA and DOPAC were studied. The results showed that ibopamine kinetics is not substantially different in CHF patients and in NS. In both groups the absorption of the drug was equally prompt and elevated. Mean Cmax, tmax and AUC infinity values of total epinine in CHF patients did not differ significantly from those in NS. In CHF patients t 1/2 of total epinine was significantly higher than in NS (4.1 +/- 0.2 h vs 3.1 +/- 0.2 h, mean +/- SE). Mean Cmax, tmax, AUCt and MRT values of free epinine in CHF patients were not significantly different from those in NS. The urinary recovery of the 3 metabolites considered together was comparable in CHF patients and in NS. The mean +/- SE total urinary recoveries in the 24 h after dosing, expressed as percentages of the administered dose, were 60 +/- 3 in CHF patients and 69 +/- 4 in NS. Conjugated epinine in urine was found to be constituted by 3-O-sulfate (84%) and 4-O-sulfate (16%).