Giancarlo Marenzi

Centro Cardiologico Monzino, Milano, Lombardy, Italy

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Publications (122)741.11 Total impact

  • Giancarlo Marenzi, Nicola Cosentino, Carlo Guastoni
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    ABSTRACT: Chronic kidney disease (CKD) is associated with a high burden of coronary artery disease (CAD), which remains the most common cause of morbidity and mortality in CKD patients. Although the management of CAD is more challenging in patients with CKD than in the general population, and coupled with concerns about further deterioration of renal function and therapy-related toxic effects, CKD patients and those receiving dialysis have not traditionally been included in randomized trials evaluating either medical or revascularization therapies. Thus, only scant data from small prospective studies or retrospective analyses of controlled trials and registries are available, and to date no optimal treatment approach has been defined for this subgroup of patients. However, they potentially have much to gain from the pharmacological, interventional, and surgical strategies used in the general population. Thus, the objective of this review is to summarize the current evidence regarding the management of CAD in CKD patients, in particular with respect to uncertainties regarding coronary revascularization options, and their risk-benefit relationship in such a high-risk population.
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    ABSTRACT: Most patients hospitalized for acutely decompensated heart failure (ADHF) present with symptoms and signs of volume overload, which are also associated with high rates of death and re-hospitalization. Several studies have investigated the possible use of extracorporeal ultrafiltration in the management of ADHF, evaluating potential clinical benefits in terms of hospitalization and survival rates versus those of conventional diuretic therapy. Though ultrafiltration remains an extremely appealing therapeutic option for patients with AHDF, some of the most recent studies have reported conflicting results. Differences in the selection of study population, heterogeneity of the indications for the use of ultrafiltration, disparity in the ultrafiltration protocols, and high variability in the pharmacologic therapies used for the control group could explain some of these contradictory findings. The purpose of the present review is to provide an overview and an update on the mechanisms and clinical effects of ultrafiltration and on currently available evidence supporting its use in ADHF.
    American Journal of Cardiovascular Drugs 02/2015; 15(2). DOI:10.1007/s40256-015-0107-6 · 2.20 Impact Factor
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    ABSTRACT: We assessed whether short-term, pre-procedural, intensive statin treatment may reduce contrast-induced acute kidney injury (CI-AKI) incidence in patients with and without acute coronary syndromes (ACS) undergoing coronary angiography (CA) and percutaneous coronary intervention (PCI). Statins may exert renal-protective effects through their pleiotropic properties. However, there have been conflicting reports on the CI-AKI preventive effect of pre-procedural statin administration. Randomized controlled trials published between January 1st, 2003 and February 28th, 2014 comparing the preventive effects against CI-AKI of pre-procedural statins vs. control (lower statin dose, no statin, or placebo) in patients undergoing CA/PCI were included. Data were combined from 9 clinical trials enrolling 5212 patients (age 65±5years, 63% males). Pooled analysis showed that intensive, short-term statin pre-treatment significantly reduced the risk of CI-AKI as compared to control (relative risk [RR] 0.50; 95% confidence interval [CI] 0.39 to 0.64; P<0.001). Pre-specified subgroup analysis showed that intensive statin pre-treatment significantly reduced CI-AKI risk in patients with ACS (RR 0.37; 95% CI 0.25 to 0.55; P<0.0001), with only a non-significant positive trend in patients without ACS (RR 0.65; 95% CI 0.41 to 1.03; P=0.07). No evidence of publication bias was detected. Short-term, pre-procedural, intensive statin treatment significantly reduced CI-AKI incidence in ACS patients, and may contribute to the overall clinical benefit associated with the early use of these drugs in this clinical setting. Its role in non-ACS patients warrants further investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International Journal of Cardiology 01/2015; 183C:47-53. DOI:10.1016/j.ijcard.2015.01.046 · 6.18 Impact Factor
  • Giancarlo Marenzi, Amir Kazory, Piergiuseppe Agostoni
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    ABSTRACT: To provide an overview on the most recent evidence for the use of extracorporeal and peritoneal ultrafiltration in heart failure, focusing on the major publications from the last few years. There have been several studies investigating the possible use of extracorporeal and peritoneal ultrafiltration in the management of acute and chronic heart failure. These trials have investigated the potential benefits and advantages of ultrafiltration over conventional medical therapy, in terms of clinical outcomes. Although ultrafiltration remains an extremely appealing therapeutic option for patients with heart failure and congestion, with several theoretical beneficial effects, some of the most recent studies have reported inconsistent findings. Differences in the selection of the study population, heterogeneity of the indications for use of ultrafiltration, variation in the ultrafiltration protocols, and high variability in the pharmacologic therapy used for the control group could explain some of these conflicting findings.
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    ABSTRACT: In acute coronary syndromes (ACS), serum creatinine (sCr) levels have short- and long-term prognostic value. However, it is possible that repeated evaluations of sCr during hospitalization, rather than measuring sCr value at admission only, might improve risk assessment. We investigated the relationship between sCr baseline value, its changes, and in-hospital mortality in patients hospitalized with ACS. In 2,756 ACS patients, sCr was measured at hospital admission and then daily, until discharge from coronary care unit. Patients were grouped according to the maximum sCr change observed: <0.3 mg/dL change from baseline (stable renal function [SRF] group), ≥0.3 mg/dL decrease (improved renal function [IRF] group), and ≥0.3 mg/dL increase (worsening renal function [WRF] group). Of the 2,756 patients, 2,163 (78%) had SRF, 292 (11%) had IRF, and 301 (11%) had WRF. In-hospital mortality in the 3 groups was 0.5%, 2%, and 14% (P < .001), respectively. Peak sCr value was a more powerful predictor of mortality (area under the curve 0.86, 95% CI 0.81-0.92) than the initial sCr value (area under the curve 0.69, 95% CI 0.63-0.77; P < .001). When sCr and its change patterns during coronary care unit stay were evaluated together, improved mortality risk stratification was found. In ACS patients, daily sCr value and its change pattern are stronger predictors of in-hospital mortality than the initial sCr value only; thus, their combined evaluation provides a more accurate and dynamic stratification of patients' risk. Finally, the intermediate mortality risk of IRF patients possibly reflects acute kidney injury started before hospitalization. Copyright © 2014 Elsevier Inc. All rights reserved.
    American Heart Journal 12/2014; 169(3). DOI:10.1016/j.ahj.2014.11.019 · 4.56 Impact Factor
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    ABSTRACT: Objectives We investigated the use of a 3-hr treatment with hemodiafiltration, initiated soon after emergency or urgent coronary angiography in acute coronary syndrome (ACS) patients with associated severe renal and cardiac dysfunction.Background Patients with ACS and severe combined renal and cardiac dysfunction have a particularly high mortality risk. In them, the ideal strategy to both optimize treatment of coronary disease and minimize renal injury risk is currently unknown.Methods This was an interventional study. ACS patients (STEMI and NSTEMI) with associated severe renal (eGFR ≤30 ml/min/1.73 m2) and cardiac (LVEF ≤40%) dysfunction, admitted at La Spezia Hospital <24 hr from symptoms onset, underwent a prophylactic 3-hr hemodiafiltration treatment, which was started soon after urgent or emergency coronary procedure. Controls were patients matched for age, gender, Mehran's risk score, and kind of ACS, admitted at the Centro Cardiologico Monzino Milan. In-hospital and 1-year outcomes were evaluated.ResultsSixty patients (30% STEMI), 30 hemodiafiltration-treated patients and 30 controls, with similar baseline characteristics, were included. In-hospital and cumulative 1-year mortality rates were significantly lower in hemodiafiltration-treated patients than in controls (3% vs. 23%; P = 0.05, and 10% vs. 53%; P < 0.001, respectively). Moreover, they had a lower incidence of severe AKI (10% vs. 40%; P = 0.015) and lower need for rescue renal replacement therapy during hospitalization (7% vs. 27%; P = 0.04).Conclusions Our pilot study suggests that, in ACS patients with severe renal and cardiac insufficiency, treatment with an aggressive prophylactic hemodiafiltration session after urgent or emergency coronary angiography seems to be associated with a relevant improvement in survival. © 2014 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 10/2014; 85(3). DOI:10.1002/ccd.25694 · 2.40 Impact Factor
  • Ivana Marana, Giancarlo Marenzi, Amir Kazory
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    ABSTRACT: Despite major advances in pharmacological therapy and cardiac devices, heart failure patients continue to be frequently (re-)hospitalized with signs and symptoms of fluid overload. Diuretics improve the symptoms of fluid overload, but their effectiveness is reduced by a number of factors including excess salt intake, underlying chronic kidney disease, renal adaptation to their actions and neurohormonal activation. Ultrafiltration (UF) is a mechanical method of fluid removal with several potential advantages over diuretic-based conventional therapies: several recent studies have demonstrated favorable clinical response to UF therapy. Such studies have shown that removal of large amounts of isotonic fluid, in addition to relieving symptoms of congestion, can improve exercise capacity, reduce cardiac filling pressures, restore diuretic responsiveness, and portend a favorable effect on cardio-pulmonary, cardiorenal interactions, and neurohormonal hyperactivation. However, despite these proposed benefits, so far, no clinical study has yet been carried out to explore the impact of UF therapy on hard clinical endpoints such as long-term mortality. In this article, we review a number of mechanistic aspects of UF therapy, with particular emphasis on cardio-pulmonary and cardiorenal interactions, and revisit the results of more recent clinical trials in order to highlight the characteristics that can help identify patients who are more likely to benefit from this therapeutic modality.
    Néphrologie & Thérapeutique 07/2014; 10(4). DOI:10.1016/j.nephro.2014.02.006 · 0.55 Impact Factor
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    ABSTRACT: There are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration vs. conventional therapy in patients hospitalized for HF and overt fluid overload. Patients with congestive HF were randomized to receive standard medical therapy (Control group) or ultrafiltration (Ultrafiltration group). The primary end point of the study was re-hospitalizations for congestive HF during a 1-year follow-up. Fifty-six patients were randomized to ultrafiltration (n=27) or standard therapy (n=29). Despite similar body weight reduction at hospital discharge in the two groups (7.5±4.5 and 7.9±5.0 kg, respectively; P=0.75), a lower incidence of re-hospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04-0.48; P=0.002). Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower BNP levels. At one year, 7 (30%) deaths occurred in the ultrafiltration group, and 11 (44%) in the Control group (P=0.33). In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from re-hospitalization for congestive HF.
    Journal of cardiac failure 11/2013; DOI:10.1016/j.cardfail.2013.11.004 · 3.07 Impact Factor
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    ABSTRACT: We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina. An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated. Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA. This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.
    PLoS ONE 11/2013; 8(11):e80345. DOI:10.1371/journal.pone.0080345 · 3.53 Impact Factor
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    ABSTRACT: To investigate whether admission B-type natriuretic peptide levels predict the development of acute kidney injury in acute coronary syndromes. Prospective study. Single-center study, 13-bed intensive cardiac care unit at a University Cardiological Center. Six-hundred thirty-nine acute coronary syndromes patients undergoing emergency and urgent percutaneous coronary intervention. None. We measured B-type natriuretic peptide at hospital admission in acute coronary syndromes patients (55% ST-elevation myocardial infarction and 45% non-ST-elevation myocardial infarction). Acute kidney injury was classified according to the Acute Kidney Injury Network criteria: stage 1 was defined as a serum creatinine increase greater than or equal to 0.3 mg/dL from baseline; stage 2 as a serum creatinine increase greater than two- to three-fold from baseline; stage 3 as a serum creatinine increase greater than three-fold from baseline, or greater than or equal to 4.0 mg/dL with an acute increase greater than 0.5 mg/dL, or need for renal replacement therapy. Acute kidney injury was developed in 85 patients (13%) and had a higher in-hospital mortality than patients without acute kidney injury (14% vs 1%; p < 0.001). B-type natriuretic peptide levels were higher in acute kidney injury patients than in those without acute kidney injury (264 [112-957] vs 98 [44-271] pg/mL; p < 0.001) and showed a significant gradient according to acute kidney injury severity (224 [96-660] pg/mL in stage 1 and 939 [124-1,650] pg/mL in stage 2-3 acute kidney injury; p < 0.001). The risk of developing acute kidney injury increased in parallel with B-type natriuretic peptide quartiles (5%, 9%, 15%, and 24%, respectively; p < 0.001). When B-type natriuretic peptide was evaluated, in terms of capacity to predict acute kidney injury, the area under the curve was 0.702 (95% CI, 0.642-0.762). In patients hospitalized with acute coronary syndromes, B-type natriuretic peptide levels measured at admission are associated with acute kidney injury as well as its severity.
    Critical care medicine 11/2013; DOI:10.1097/CCM.0000000000000025 · 6.15 Impact Factor
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    ABSTRACT: Rationale: Four monocentric studies reported that circadian rhythms can affect left ventricular infarct size after ST-segment-elevation acute myocardial infarction (STEMI). Objective: To further validate the circadian dependence of infarct size after STEMI in a multicentric and multiethnic population. Methods and Results: We analyzed a prospective cohort of subjects with first STEMI from the First Acute Myocardial Infarction study that enrolled 1099 patients (ischemic time <6 hours) in Italy, Scotland, and China. We confirmed a circadian variation of STEMI incidence with an increased morning incidence (from 6:00 am till noon). We investigated the presence of circadian dependence of infarct size plotting the peak creatine kinase against time onset of ischemia. In addition, we studied the patients from the 3 countries separately, including 624 Italians; all patients were treated with percutaneous coronary intervention. We adopted several levels of analysis with different inclusion criteria consistent with previous studies. In all the analyses, we did not find a clear-cut circadian dependence of infarct size after STEMI. Conclusions: Although the circadian dependence of infarct size supported by previous studies poses an intriguing hypothesis, we were unable to converge toward their conclusions in a multicentric and multiethnic setting. Parameters that vary as a function of latitude could potentially obscure the circadian variations observed in monocentric studies. We believe that, to assess whether circadian rhythms can affect the infarct size, future study design should not only include larger samples but also aim to untangle the molecular time-dynamic mechanisms underlying such a relation.
    Circulation Research 05/2013; 112(10):e110-4. DOI:10.1161/CIRCRESAHA.112.300778 · 11.09 Impact Factor
  • Giancarlo Marenzi, Nadia Aspromonte
    Journal of the American College of Cardiology 03/2013; DOI:10.1016/j.jacc.2012.11.065 · 15.34 Impact Factor
  • Marenzi G, Aspromonte N
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    ABSTRACT: letter
    Journal of the American College of Cardiology 01/2013; 13. DOI:10.1016/j.jacc.2012.11.065. · 15.34 Impact Factor
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    ABSTRACT: Acute kidney injury (AKI) occurs frequently in patients with acute coronary syndromes (ACS) and is associated with adverse short- and long-term outcomes. To date, however, no standardized definition of AKI has been used for patients with ACS. As a result, information on its true incidence and the clinical and prognostic relevance according to the severity of renal function deterioration are still lacking. We retrospectively studied 3,210 patients with ACS. AKI was identified on the basis of the changes in serum creatinine during hospitalization according to the AKI Network criteria. Overall, 409 patients (13%) developed AKI: 262 (64%) had stage 1, 25 (6%) stage 2, and 122 (30%) stage 3 AKI. In-hospital mortality was greater in patients with AKI than in those without AKI (21% vs 1%; p <0.001). The adjusted risk of death increased with increasing AKI severity. Compared to no AKI, the adjusted odds ratio for death was 3.5 (95% confidence interval 1.79 to 6.83) with stage 1 AKI and 31.2 (95% confidence interval 16.96 to 57.45) with stage 2 to 3 AKI. A significant parallel increase in major adverse cardiac events was also observed comparing patients without AKI and those with stage 2 to 3 AKI. In conclusion, in patients with ACS, AKI is a frequent complication, and the graded increase of its severity, as assessed using the AKI Network classification, is associated with a progressive increased risk of in-hospital morbidity and mortality.
    The American journal of cardiology 12/2012; 111(6). DOI:10.1016/j.amjcard.2012.11.046 · 3.43 Impact Factor
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    ABSTRACT: Mechanisms linking chronic kidney disease (CKD) and adverse outcomes in acute coronary syndromes (ACS) are not fully understood. Among potential key players, reduced nitric oxide (NO) synthesis due to its endogenous inhibitors, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine could be involved. We measured plasma concentration of arginine, ADMA and SDMA and investigated their relationship with CKD and long-term outcome in non-ST-elevation myocardial infarction (NSTEMI). We prospectively measured arginine, ADMA, and SDMA at hospital admission in 104 NSTEMI patients. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2). We considered a primary end point of combined cardiac death and re-infarction at a median follow-up of 21 months. In CKD (n = 33) and no-CKD (n = 71) patients, arginine and ADMA were similar, whereas SDMA was significantly higher in CKD patients (0.65±0.23 vs. 0.42±0.12 µmol/L; P<0.0001). Twenty-four (23%) patients had an adverse cardiac event during follow-up: 12 (36%) were CKD and 12 (17%) no-CKD patients (P = 0.02). When study population was stratified according to arginine, ADMA and SDMA median values, only SDMA (median 0.46 µmol/L) was associated with the primary end-point (P = 0.0016). In models adjusted for age, hemoglobin and left ventricular ejection fraction, the hazard ratio (HR) for CKD and SDMA were high (HR 2.93, interquartile range [IQR] 1.15-7.53; P = 0.02 and HR 6.80, IQR 2.09-22.2; P = 0.001, respectively) but, after mutual adjustment, only SDMA remained significantly associated with the primary end point (HR 5.73, IQR 1.55-21.2; P = 0.009). In NSTEMI patients, elevated SDMA plasma levels are associated with CKD and worse long-term prognosis.
    PLoS ONE 11/2012; 7(11):e48499. DOI:10.1371/journal.pone.0048499 · 3.53 Impact Factor
  • Giancarlo Marenzi, Angelo Cabiati, Emilio Assanelli
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    ABSTRACT: Chronic kidney disease (CKD) is associated with a high burden of coronary artery disease. In patients with acute coronary syndromes (ACS), CKD is highly prevalent and associated with poor short- and long-term outcomes. Management of patients with CKD presenting with ACS is more complex than in the general population because of the lack of well-designed randomized trials assessing therapeutic strategies in such patients. The almost uniform exclusion of patients with CKD from randomized studies evaluating new targeted therapies for ACS, coupled with concerns about further deterioration of renal function and therapy-related toxic effects, may explain the less frequent use of proven medical therapies in this subgroup of high-risk patients. However, these patients potentially have much to gain from conventional revascularization strategies used in the general population. The objective of this review is to summarize the current evidence regarding the epidemiology and the clinical and prognostic relevance of CKD in ACS patients, in particular with respect to unresolved issues and uncertainties regarding recommended medical therapies and coronary revascularization strategies.
    10/2012; 1(5):134-145. DOI:10.5527/wjn.v1.i5.134
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    ABSTRACT: Radiological procedures utilizing intravascular iodinated contrast media are being widely applied for both diagnostic and therapeutic purposes and represent one of the main causes of contrast-induced nephropathy (CIN) and hospital-acquired renal failure. Although the risk of CIN is low (0.6-2.3 %) in the general population, it may be very high (up to 50 %) in selected subsets, especially in patients with major risk factors such as advanced chronic kidney disease and diabetes mellitus, and in those undergoing emergency percutaneous coronary interventions (PCI). Due to the lack of any effective treatment, prevention of this iatrogenic disease, which is associated with significant in-hospital and long-term morbidity and mortality and increased costs, is the key strategy. However, prevention of CIN continues to elude clinicians and is a main concern during PCI, as patients undergoing these procedures often have multiple comorbidities. The purpose of this study is to examine the pathophysiology, risk factors and clinical course of CIN, as well as the most recent studies dealing with its prevention and potential therapeutic interventions, especially during PCI.
    Internal and Emergency Medicine 10/2012; 7 Suppl 3(S3):181-3. DOI:10.1007/s11739-012-0803-z · 2.41 Impact Factor
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    ABSTRACT: Local renal ischemia is regarded as an important factor in the development of contrast-induced nephropathy (CIN). Mannose-binding lectin (MBL) is involved in the tissue damage during experimental ischemia/reperfusion injury of the kidneys. The aim of the present study was to investigate the association of MBL deficiency with radiocontrast-induced renal dysfunction in a large prospective cohort. 246 patients with advanced non-dialysis-dependent renal dysfunction who underwent radiographic contrast procedures were included in the study. Baseline serum MBL levels were analyzed according to the occurrence of a creatinine-based (increase of ≥0.5 mg/dL or ≥25% within 48 hours) or cystatin C-based (increase of ≥10% within 24 hours) CIN. The incidence of creatinine-based and cystatin C-based CIN was 6.5% and 24%, respectively. MBL levels were not associated with the occurrence of creatinine-based CIN. However, patients that experienced a cystatin C increase of ≥10% showed significantly higher MBL levels than patients with a rise of <10% (median 2885 (IQR 1193-4471) vs. 1997 (IQR 439-3504)ng/mL, p = 0.01). In logistic regression analysis MBL deficiency (MBL levels≤500 ng/ml) was identified as an inverse predictor of a cystatin C increase ≥10% (OR 0.34, 95% CI 0.15-0.8, p = 0.01). MBL deficiency was associated with a reduced radiocontrast-induced renal dysfunction as reflected by the course of cystatin C. Our findings support a possible role of MBL in the pathogenesis of CIN.
    BMC Nephrology 09/2012; 13:99. DOI:10.1186/1471-2369-13-99 · 1.52 Impact Factor
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    ABSTRACT: Rationale: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very elevated circulating interleukin IL6(+)levels or very low IL6(-)levels. Objective: We compared these two groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response. Methods and Results: We compared 109 patients with STEMI in the top IL6 level (median 15.6 pg/ml; IL6(+)STEMI) with 96 in the bottom IL6 level (median 1.7 pg/ml; IL6(-)STEMI) and 103 matched controls extracted from the multi-ethnic First Acute Myocardial Infarction Study. We found minimal clinical differences between the IL6(+)STEMI and IL6(-)STEMI. We assessed the inflammatory profiles of the two STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL6(+)STEMI patients were characterized by the activation of two modules of interacting signals comprising (a)IL10, IL8, MIP1α and C-reactive protein and (b)MCP1, MIP1β and MIG. IL10 was increased both in IL6(+)STEMI and IL6(-)STEMI patients compared with controls. IL6(+)IL10(+)STEMI patients had an increased risk of systolic dysfunction at discharge and of death at six months in comparison with IL6(-)IL10(+)STEMI patients. We combined IL10 and MIG (derived from the two identified cytokine modules) with IL6 in a formula yielding a risk-index that outperformed any single cytokine in prediction of systolic dysfunction and death. Conclusions: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients that is not related to the extent of the myocardial damage. The simultaneous elevation of IL6 and IL10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and for immune-modulating therapies.
    Circulation Research 08/2012; 111(10). DOI:10.1161/CIRCRESAHA.111.262477 · 11.09 Impact Factor
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    ABSTRACT: Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases. The myeloperoxidase (MPO) content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS), 69 with chronic stable angina (CSA), 50 with inflammation due to either non-infectious (acute bone fracture), infectious (sepsis) or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis). Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization). One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI) patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via platelet-P selectin interactions. This paroxysmal activation could contribute to occlusive thrombosis.
    PLoS ONE 06/2012; 7(6):e39484. DOI:10.1371/journal.pone.0039484 · 3.53 Impact Factor

Publication Stats

3k Citations
741.11 Total Impact Points

Institutions

  • 1999–2015
    • Centro Cardiologico Monzino
      Milano, Lombardy, Italy
  • 1988–2015
    • University of Milan
      • Institute of Human Physiology II
      Milano, Lombardy, Italy
  • 1998
    • IRCCS Multimedica
      Milano, Lombardy, Italy
  • 1994–1998
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
    • INO - Istituto Nazionale di Ottica
      Florens, Tuscany, Italy
  • 1997
    • National Research Council
      Roma, Latium, Italy
  • 1996
    • Foundation of the Carlo Besta Neurological Institute
      Milano, Lombardy, Italy