Fausto Avanzini

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.

N-3 fatty acids in patients with multiple cardiovascular risk factors

BACKGROUND Trials have shown a beneficial effect of n-3 polyunsaturated fatty acids in patients with a previous myocardial infarction or heart failure. We evaluated the potential benefit of such therapy in patients with multiple cardiovascular risk factors or atherosclerotic vascular disease who had not had a myocardial infarction. METHODS In this double-blind, placebo-controlled clinical trial, we enrolled a cohort of patients who were followed by a network of 860 general practitioners in Italy. Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction. Patients were randomly assigned to n-3 fatty acids (1 g daily) or placebo (olive oil). The initially specified primary end point was the cumulative rate of death, nonfatal myocardial infarction, and nonfatal stroke. At 1 year, after the event rate was found to be lower than anticipated, the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes. RESULTS Of the 12,513 patients enrolled, 6244 were randomly assigned to n-3 fatty acids and 6269 to placebo. With a median of 5 years of follow-up, the primary end point occurred in 1478 of 12,505 patients included in the analysis (11.8%), of whom 733 of 6239 (11.7%) had received n-3 fatty acids and 745 of 6266 (11.9%) had received placebo (adjusted hazard ratio with n-3 fatty acids, 0.97; 95% confidence interval, 0.88 to 1.08; P=0.58). The same null results were observed for all the secondary end points. CONCLUSIONS In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. (Funded by Società Prodotti Antibiotici and others; ClinicalTrials.gov number, NCT00317707.).

Effects of vitamin E on clinic and ambulatory blood pressure in treated hypertensive patients

Abstract A randomized controlled open trial studied the effect of vitamin E supplementation (300 mg/day) on clinic and 24-h ambulatory blood pressure (BP) in 142 treated hypertensive patients. After 12 weeks, clinic BP decreased whether or not patients were randomized to vitamin E. Ambulatory BP showed no change in systolic BP and a small decrease in diastolic BP (−1.6 mm Hg, 95% confidence intervals from −2.8 to −0.4 mm Hg), approaching statistical significance in comparison to the control group (P = .06). Vitamin E supplementation thus seems to have no clinically relevant effect on BP in hypertensive patients already under controlled treatment.

Prognostic value of a history of hypertension in 11,483 patients with acute myocardial infarction treated with thrombolysis. GISSI-2 Investigators. Gruppo Italiano per lo Studio della, Sopravvivena nell'Infarto Miocardico.

Objective To assess the prognostic value of a history of hypertension in patients with acute myocardial infarction (AMI) treated with thrombolysis. Design Retrospective adjusted analysis of outcome data of patients with AMI randomly allocated to treatment in a controlled study of alteplase versus streptokinase and heparin versus no heparin. Setting A highly representative sample (about 90%) of Italian Coronary Care Units. Patients Patients with (n=3306) and without (n=7406) a history of treated hypertension. Main outcome measures Morbidity and mortality during hospital stay and the next 6 months. Results Patients with a history of hypertension had a significantly higher mortality, both in hospital and during the next 6 months. The difference persisted also after a multivariate analysis including all major prognostic factors for in-hospital and 6-month mortality, respectively. Left ventricular failure and recurrent ischaemic events (angina and re-infarction) were also significantly more frequent in hypertensives both during their hospital stay and during follow-up study. Conclusions A history of hypertension is a negative independent prognostic factor after acute myocardial infarction treated with thrombolysis.

Prevalence, incidence and mortality of diagnosed diabetes: Evidence from an Italian population-based study

Diabet. Med. 29, 385–392 (2012)

Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients

Abstract Nonsteroidal antiinflammatory drugs may affect blood pressure (BP) control in hypertensive patients receiving drug treatment, but data on the effects of low-dose aspirin are scanty. This study assessed the effects of chronic treatment with low doses of aspirin (100 mg/day) on clinic and ambulatory systolic (SBP) and diastolic (DBP) BP in hypertensives on chronic, stable antihyper- tensive therapy. The study was conducted in the framework of the Primary Prevention Project (PPP), a randomized, controlled factorial trial on the preventive effect of aspirin or vitamin E in people with one or more cardiovascular risk factors. Fifteen Italian hypertension units studied 142 hypertensive patients (76 men, 66 women; mean age 59 ± 5.9 years) treated with different antihypertensive drugs: 71 patients were randomized to aspirin and 71 served as controls. All patients underwent a clinic BP evaluation with an automatic sphygmomanometer and a 24-h ambulatory BP monitoring, at baseline and after 3 months of aspirin treatment. At the end of the study the changes in clinic SBP and DBP were not statistically different in treated and untreated subjects. Ambulatory SBP and DBP after 3 months of aspirin treatment were similar to baseline: ΔSBP −0.5 mmHg (95% confidence intervals [CI] from −1.9 to +2.9 mm Hg) and ΔDBP −1.1 mm Hg (95% CI from −2.5 to +0.3 mm Hg). The pattern was similar in the control group. No interaction was found between aspirin and the most used antihypertensive drug classes (angiotensin converting enzyme inhibitors and calcium antagonists). Despite the relatively small sample size our results seem to exclude any significant influence of low-dose aspirin on BP control in hypertensives under treatment.

Trends in drug prescriptions to diabetic patients from 2000 to 2008 in Italy's Lombardy Region: A large population-based study

OBJECTIVE To analyze the prescribing patterns of antidiabetic and cardiovascular medications among diabetics in the most highly populated Italian Region, from 2000 to 2008. METHODS Data were obtained from the Lombardy Region administrative health databases. The standardized prevalence of antidiabetic and cardiovascular drugs use was calculated within each study year. The prescription trends of initial treatment with antidiabetic drugs were also analyzed. RESULTS From 2000 to 2008 there was an increase in the proportion of patients treated with biguanides (from 53.4% to 66.5%; p<0.0001) while those receiving sulfonylurea decreased (from 78.6% to 56.4%; p<0.0001). A sharp increase of metformin (as monotherapy) as initial treatment was also observed (from 15.2% to 48.8%; p<0.0001). The percentage of patients receiving renin-angiotensin system inhibitors, lipid-lowering drugs and antiplatelets increased between 2000 and 2008, from respectively 45.1% to 63.3%, 13.6% to 43.2% and 21.6% to 40.9 (p<0.0001). Multivariate analyses indicated that changes in prescriptions were statistically significant for both antidiabetic and cardiovascular drugs. CONCLUSION This study documents progressive changes in the prescription of antidiabetic and cardiovascular drugs in accordance with guidelines. However, the use of metformin as first line therapy was still suboptimal and cardiovascular preventive strategies were only partially implemented in community practice.

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

Summary.  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.

Transition From Intravenous to Subcutaneous Insulin: Effectiveness and safety of a standardized protocol and predictors of outcome in patients with acute coronary syndrome

OBJECTIVE The study objectives were 1) to assess the effectiveness and safety of a standardized protocol for the transition to subcutaneous insulin and oral feeding in diabetic or hyperglycemic patients with acute coronary syndrome (ACS) who were receiving intravenous insulin and glucose at the time of the transfer from the intensive cardiac care unit to a general ward and 2) to identify predictors of transition outcome. RESEARCH DESIGN AND METHODS This was a prospective observational study. The protocol specifies that patients receive a 100% of their daily subcutaneous insulin requirement from the first day of oral feeding, calculated from the intravenous insulin rate during the final 12 h divided into two: 50% basal and 50% prandial. RESULTS In 142 patients (93 male, 49 female, age range 47–88 years, 135 with known diabetes) the first day after transition, 44.8% of blood glucose (BG) measurements were within the strict range of 100–140 mg/dL before meals and 100–180 mg/dL after meals, and 70.8% were within the broader ranges of 80–160 mg/dL and 80–200 mg/dL, respectively. Pre- or postprandial hypoglycemia (BG <70 mg/dL) occurred in 11 patients (7.7%) on the first day and in 38 patients (26.8%) on the first 3 days after transition. Old age, high doses of intravenous insulin, and wide BG variations in the 24 h before insulin infusion was stopped were predictive of poor BG control after transition. CONCLUSIONS This study shows the effectiveness and safety of a standardized protocol for the transition from intravenous to subcutaneous insulin in patients with ACS when regular oral feeding was resumed.

High pulse pressure and low mean arterial pressure : two predictors of death after a myocardial infarction

Objectives Although the negative prognostic implication of a clinical history of arterial hypertension in myocardial infarction (MI) survivors is well known, the predictive role of the blood pressure (BP) regimen after MI is not well defined. The aim of this study was to investigate the prognostic significance of different BP indices in post-MI. Methods and results We evaluated the relationship between baseline systolic, diastolic, pulse and mean arterial pressure (MAP), measured by sphygmomanometry at discharge from hospital or within 3 months of an MI, and total and cardiovascular mortality in 11 116 patients enrolled in the GISSI-Prevenzione trial. Over 3.5 years of follow-up, 999 patients died, 657 of them from cardiovascular causes. Low mean and high pulse pressure were significantly associated with total and cardiovascular mortality after controlling for potential confounders in the multivariate analysis. As compared with patients with less extreme BP values, patients with MAP of 80 mmHg or less (n = 1241; 11.2%) had a 48% higher risk of cardiovascular death [95% confidenceinterval (CI) 1.16–1.87; P = 0.001] and those with pulse pressure greater than 60 mmHg (n = 958; 8.6%) had a 35% higher risk (95% CI 1.09–1.69; P = 0.007); only four subjects (0.04%) had both a high pulse pressure and a low MAP (relative risk of cardiovascular death 3.48; 95% CI 0.48–25.88; P = 0.218). Conclusions Our results show for the first time an additional prognostic importance of two easily measurable components of BP, definitely high pulse pressure (> 60 mmHg) and low MAP (≤ 80 mmHg), in a large sample of non-selected patients surviving MI who entered a modern programme of cardiovascular prevention.