Background Adverse cardiovascular events often recur after acute coronary syndrome (ACS), despite secondary prevention measures. Residual risk involves various inflammatory, metabolic and renal factors as well as lipid and thrombotic processes. This cohort study investigates the relationship between four risk biomarkers at 1 month after ACS and all-cause death within 3 years in patients treated with early invasive strategy and high-intensity statins from admission. Methods Levels of residual risk for the biomarkers were: low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dl; high-sensitivity C reactive protein (hs-CRP) ≥ 2 mg/l; glycosylated hemoglobin (HbA1c) ≥ 7% in diabetic and ≥ 5.7% in non-diabetic patients; decrease in estimated glomerular filtration rate (eGFR) ≥ 25% compared to baseline. The association between the four biomarkers and all-cause death within 3 years was evaluated with Cox proportional analysis. Results This study included 1099 patients (68±12 years; 70.3% males). At 1 month the majority of patients had levels of LDL-C, hs-CRP and/or HbA1c above the risk cut-points, and only 7% of cases presented reduced eGFR. Reduced eGFR and hs-CRP ≥ 2 mg/l at 1 month were the sole independent biomarker predictors of 3-year mortality (adjusted hazard ratios 3.03 and 2.66, respectively). Conclusions In this population on high-intensity statin therapy only hsCRP and eGFR were independently associated with medium-term mortality. Diversification of secondary preventive measures based on routine evaluations of inflammation and kidney function markers, not only LDL-C, could lead to better targeted reduction of residual risk after ACS.

Abstract Background Previous studies showed that incidence of antiplatelet therapy resistance is higher in elderly patients. There is a paucity of data about the response to antiplatelet therapy in patients with atrial fibrillation (AF). The purpose of this study is to analyze platelet reactivity during dual antiplatelet therapy (DAPT) in elderly patients (≥ 75 years) with acute coronary syndrome (ACS), stratifying them by the presence or absence of AF. Methods From the PRATO–ACS registry we selected 160 patients (81±5 years; 45% female) treated with DAPT (Aspirin 100 mg daily and Clopidogrel 75 mg daily). At discharge they were tested with the VerifyNow assay to measure platelet reactivity in aspirin (aspirin–reaction unit – ARU) and in clopidogrel (P2Y12–reaction unit – PRU). Low response to aspirin was defined as ARU ≥550; low response to clopidogrel was defined as PRU ≥ 208; high response was defined as PRU values ≤ 85. Results The ARU and PRU values for patients divided according to the presence of AF are shown in the Figure 1. Conclusions In this series of elderly ACS patients, AF was associated with higher residual platelet reactivity under both clopidogrel and aspirin. AF patients were significantly more clopidogrel low responders than non–AF, while non–AF patients were significantly more high responders. No difference was found for aspirin low responders between AF and no AF patients.

Abstract Background Stress hyperglycemia is strongly associated with adverse prognosis in patients with acute coronary syndrome (ACS). Recently, the stress hyperglycemia ratio (SHR- relationship between acute/chronic glycemic values) has been proposed as a better measurement of stress hyperglycemia. Studies on SHR and long-term clinical outcome in ACS are limited. This study aimed to clarify the association between SHR and 3-year adverse clinical events in patients with ACS. Methods We analyzed data of 795 patients admitted to our center for ACS who were enrolled in the PRATO-ACS Registry (ClinicalTrials.gov ID: NCT04087200) and underwent laboratory analyses 1 month after the index event. All patients had undergone early invasive strategy and received high intensity statins during hospitalization and at discharge. Patients were stratified in baseline SHR tertiles: < 0.95, ≥ 0.95 to < 1.17 and ≥ 1.17. The primary end point was 3-year all cause death; secondary end points were major adverse clinical events (MACE) including all-cause death, myocardial infarction or congestive heart failure. The association between SHR and outcome measures was evaluated with Cox proportional analysis expressed by hazard ratio (HR) and 95% confidence intervals (CI). Results With increasing SHR, there was a significant progressive increase in mortality (4.2, 8.3, and 11.7% in the 1st, 2nd, and 3rd tertile, respectively, p= 0.006) and MACE (10.6, 14, and 20.8% in the 1st, 2nd, and 3rd tertile, respectively, p=0.004). Multivariable analysis shows that SHR was an independent predictor of 3-year all-cause death (HR 1.65, 95% CI 1.12-2.4; p= 0.012). Subgroup analysis evidenced that the relationship between SHR and mortality was statistically significant only for patients with poor glycemic control at 1 month follow up (HR 3.4, 95% CI 1.14-10.9, p= 0.02 in the 2nd tertile and HR 3.9, 95% CI 1.3-11.8, p= 0.015 in the 3rd tertile). Conclusion Baseline SHR is significantly associated with 3-year all-cause death and MACE in patients with ACS. However, its prognostic impact is much stronger in patients who do not achieve desired glycemic targets at 1 month after the index event. Therefore, insistent attention to glycemic values is mandatory in ACS patients even after discharge.

Background: prior statin treatment has been shown to have favourable effects on short- and long-term prognosis in patients with acute coronary syndrome (ACS). There are limited data in older patients. The aim of this study was to investigate the association of previous statin therapy and presentation characteristics, infarct size and clinical outcome in older patients, with or without atherosclerotic cardiovascular disease (ASCVD), included in the Elderly-ACS 2 trial. Methods: data on statin use pre-admission were available for 1,192 of the 1,443 patients enrolled in the original trial. Of these, 531 (44.5%) were already taking statins. Patients were stratified based on established ASCVD and statin therapy. ACS was classified as non-ST elevation or ST elevation myocardial infarction (STEMI). Infarct size was measured by peak creatine kinase MB (CK-MB). All-cause death in-hospital and within 1 year were the major end points. Results: there was a significantly lower frequency of STEMI in statin patients, in both ASCVD and No-ASCVD groups. Peak CK-MB levels were lower in statin users (10 versus 25 ng/ml, P < 0.0001). There was lower all-cause death in-hospital and within 1 year for subjects with ASCVD already on statins independent of other baseline variables. There were no differences in all-cause death for No-ASCVD patients whether or not on statins. Conclusions: statin pretreatment was associated with more favourable ACS presentation and lower myocardial damage in older ACS patients both ASCVD and No-ASCVD. The incidence of all-cause death (in-hospital and within 1 year) was significantly lower in the statin treated ASCVD patients.

Aims The aim of the colchicine on-admission to reduce inflammation in acute coronary syndrome (COLOR-ACS) study is to evaluate the effects of the addition of short-term, low-dose colchicine to high-dose atorvastatin in limiting levels of inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). Methods The COLOR-ACS study is a multicenter, randomized, open-label, two-arm trial. Statin-naive patients with NSTE-ACS, scheduled for an early invasive strategy, are randomized on admission to receive standard treatment of atorvastatin 80 mg or standard treatment plus colchicine (1 mg loading dose followed by 0.5 mg/day until discharge). The main exclusion criteria are prior statin and/or colchicine treatment, current treatment with potent inhibitors of CYP3A4, P-glycoprotein or immunosuppressive drugs, known active malignancy, severe kidney, cardiac, liver disease. There is clinical and biochemical follow-up at 30 days after discharge and telephone interview at 6 months. The primary end point is the change in hs-CRP from admission to discharge. Secondary end points include: incidence of acute kidney injury; MB fraction of creatine kinase peak value; glomerular filtration rate change from baseline to 30 days; persistence of hs-CRP ≥2 mg/dl at 30 days; adverse clinical events within 30 days; tolerance to colchicine. Conclusion The COLOR-ACS study will provide evidence on the efficacy of early short-term treatment with colchicine in addition to high-dose atorvastatin compared to atorvastatin alone in ACS patients. The potential anti-inflammatory action of colchicine plus atorvastatin is expected to limit hs-CRP increase with resultant clinical benefits. Trial registration ClinicalTrials.gov; NCT05250596.

Abstract Background Recent randomized clinical trials have shown that an anti–inflammatory treatment may reduce the recurrence of cardiovascular events in association with traditional secondary prevention measures. Aim: The aim of this observational retrospective study based on patients with acute coronary syndrome (ACS), treated with high intensity statins and undergoing an early invasive strategy, was to evaluate the incidence of residual inflammatory risk after 1 month, its possible determinants and its association with the medium–long term prognosis. Methods We selected patients with ACS without ST segment elevation (ACS–NSTEMI) admitted to our hospital from June 2015 to June 2018 who had a complete biochemical examination at 1 month after the acute event. All these patients were included in the PRATO–ACS Registry (ClinicalTrials.gov ID: NCT04087200). All–cause mortality was analyzed within 3 years. Residual inflammatory risk (RIR) was defined as 1–month high sensitivity C reactive protein (hs–CRP) value > 2 mg/l. The association between 1–month hs–CRP and 3–year all–cause mortality was expressed by hazard ratio (HR) and 95% confidence interval (CI). Results The study group consisted of 739 patients (mean age 68 ± 12 years, male 68.3%, mean hospital stay 5 ± 2 days) all treated with high intensity statins (rosuvastatin 20–40 mg or atorvastatin 40–80 mg) immediately upon admission and scheduled for early invasive strategy (74.5% underwent PCI). At baseline 525 patients (71%) had hs–CRP values ≥ 2 mg/l and 568 (77%) LDL cholesterol levels > 100 mg/dl. The incidence of RIR was 58.7%, with no significant differences between patients with LDL 70 mg/dl. Lipid profile (LDL > 100 mg/dl, HDL < 40mg/dl in man and < 50mg/dl in woman), hs–CRP > 2 mg/l, the left ventricular ejection fraction < 40% and glomerular filtration rate <60 ml/min/m2 were independently associated with RIR. Multivariate analysis showed that RIR was an independent predictor of 3–year all–cause mortality (HR = 2.15 (95% CI 1.06–4.33; p = 0.03)) while LDL cholesterol > 70 mg/dl did not (HR = 0.98 95% (CI 0.50–1.91; p = 0.9)). Conclusions In a population of ACS patients treated with high intensity statins and an early invasive therapeutic strategy, the incidence of RIR (hs–CRP ≥ 2 mg/l) at 1 month after ACS is high (58.7%). The RIR is associated with a higher baseline clinical risk profile and was an independent predictor of 3 year all–cause mortality regardless of achieved LDL values.

Abstract Background Despite administration of current evidence-based therapies, substantial residual risk for cardiovascular events persists, particularly after acute coronary syndrome (ACS). It is well known that different inflammatory, metabolic, renal factors concur in defining the residual risk, beyond lipids, platelets and coagulation. Purpose The purpose of this study is to analyze the prevalence of various residual risk factors in patients at 1 month after ACS and their association with all-cause death within 3 years. Methods Of the 1585 patients admitted to our center for ACS and included in the PRATO-ACS Registry we selected the 1099 patients (69±12 yrs; 30% female; 26.7% with diabetes; 73% NSTE-ACS and 27% STEMI) who underwent laboratory analyses 1 month after the index event. All patients had undergone early invasive strategy and received high intensity statins during hospitalization and at discharge. The frequency of 5 specific risk factors was evaluated: LDL cholesterol ≥70 mg/dl; high sensitivity C reactive protein (hs-CRP) ≥2 mg/l; triglycerides ≥135 mg/dl; high glycosylated hemoglobin (HbA1c) ≥6.5% in diabetic and ≥5.7% in non-diabetic patients; decrease in estimated glomerular filtration rate (eGFR) ≥25% compared to baseline. Patients were followed up for three years. The association between the individual risk factors and all-cause death within 3 years was evaluated with Cox proportional analysis expressed by hazard ratio (HR) and 95% confidence intervals (CI). Results The Table lists the prevalence of the five residual risk factors at 1 month and the mortality HR (95% CI) within 3 years for each risk factor. Conclusions After ACS, despite the secondary prevention therapy (high intensity statins), residual risk factors, all measured at 1 month, are persistently elevated in the majority of patients. Their association with all-cause death at 3 years is significantly high for inflammatory and metabolic parameters as well as renal function deterioration. These findings should prod us to develop new strategies that target all residual risk factors, not only lipid profile. Funding Acknowledgement Type of funding sources: None.

Different pharmacologic agents have been tested in the effort to prevent contrast-induced acute kidney injury (AKI) in the last two decades. To date, however, no individual drug has received unanimous approval for this aim. Since 2014 statins have been included as preventive treatment in the European guidelines for revascularization procedures in cardiac patients. The present update presents the latest findings in this field focusing on the changing paradigms in the definition and consequently the approach to nephroprotection that considers clinical prognosis as the major issue. We note the current shift from attention to contrast-induced AKI to contrast-associated AKI.

Background/Aims: Both high-dose atorvastatin and rosuvastatin have been shown to reduce contrast-induced acute kidney injury (AKI) occurrence and improve clinical outcomes in high-risk coronary patients undergoing angiographic procedures. However, there is a lack of head-to-head comparative studies on the effects of atorvastatin or rosuvastatin administered upon hospital admission in statin-naive patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS). Methods: In this open-label, noninferiority study, we compared changes in renal function in 709 NSTE-ACS patients randomized to atorvastatin (80 mg upon admission followed by 40 mg/day) or rosuvastatin (40 mg upon admission followed by 20 mg/day). The primary end point was AKI (increase in serum creatinine ≥0.5 mg/dL or ≥25% above baseline within 72 h). Worsening renal function (WRF) (decrease of ≥25% in the glomerular filtration rate from baseline to 30 days), 30-day major adverse cardiovascular events, and 12-month myocardial infarction (MI) or death were also evaluated. Results: The AKI incidence was similar in the 2 groups (i.e., 8.2% with rosuvastatin and 7.6% with atorvastatin; absolute risk difference = 0.54; 90% CI –3.9 to 2.8), satisfying the noninferiority criteria. WRF occurred in 53 (7.5%) patients, 19 (34%) of whom had developed AKI. The rates of WRF and adverse events at 30 days and at 12 months did not differ significantly between the 2 groups. Both AKI and WRF were found to be closely associated with the 12-month cardiovascular outcome irrespectively of statin choice. Conclusions: High-dose rosuvastatin or atorvastatin started upon hospital admission led to similar rates of AKI, 30-day renal function changes, and 12-month death or MI in NSTE-ACS patients who underwent an early invasive strategy (clinical trial registration: https://www.clinicaltrials.gov; unique identifier: NCT01870804).

aCardiology Division of Prato Hospital, Prato bDepartment of Cardiovascular, Multimedica IRCCS, Milano, Italy Correspondence to Anna Toso, MD, Division of Cardiology, Santo Stefano Hospital, Via Suor Niccolina Infermiera, 22 Prato, Italy Tel: +39 0574 803733; fax: +39 0574 803732; e-mail: [email protected] Received 24 November, 2018 Accepted 26 November, 2018

Journal Article ACUTE MYOCARDIAL INFARCTION AND ANGINA 4 Get access European Heart Journal Supplements, Volume 21, Issue Supplement_E, May 2019, Pages E218–E219, https://doi.org/10.1093/eurheartj/suz139 Published: 16 May 2019

BACKGROUND Intravascular volume expansion plays a major role in the prevention of contrast-induced acute kidney injury (CI-AKI). Recommended standard amounts of fluid infusion before procedures do not produce homogeneous responses in subjects with different initial hydration status. OBJECTIVES The goal of this study was to compare the effect of standard and double intravenous (IV) infusion volumes in patients with low body fluid level, assessed by using bioimpedance vector analysis (BIVA), on the incidence of CIAKI after elective coronary angiographic procedures. METHODS A total of 303 patients with low BIVA level on admission were randomized to receive standard volume saline (1 ml/kg/h for 12 h before and after the procedure) or double volume saline (2 ml/kg/h). Patients (n = 715) with an optimal BIVA level received standard volume saline and were included in a prospective registry. The saline infusion was halved in all patients with an ejection fraction < 40%. BIVA was repeated immediately before the angiographic procedure in all patients. CI-AKI was defined as an increase in levels of cystatin C >= 10% above baseline at 24 h after contrast administration. RESULTS The incidence of CI-AKI was significantly lower (11.5% vs. 22.3%; p = 0.015) in patients receiving double volume saline than in those receiving standard volume saline, respectively. Before the angiographic procedure, 50% of the double volume patients achieved the optimal BIVA level compared with only 27.7% in the standard group (p = 0.0001). The findings were consistent in all the pre-specified subgroups excluding patients with a left ventricular ejection fraction < 40% (p for interaction = 0.01). CONCLUSIONS Evaluation of BIVA levels on admission in patients with stable coronary artery disease allows adjustment of intravascular volume expansion, resulting in lower CI-AKI occurrence after angiographic procedures. (C) 2018 by the American College of Cardiology Foundation.

To investigate changes in sympathetic activity, perfusion, and left ventricular (LV) functionality in takotsubo cardiomyopathy (TTC) patients from onset (T0) to post-onset conditions at 1 month (T1), 1-2 years (T2, T3).

Introduction: The PRATO-ACS trial showed that early on-admission high-dose rosuvastatin reduced contrast induced-acute kidney injury (CI-AKI) occurrence and improved clinical outcome in statin-naiv...

Statin use is associated with enhanced pharmacodynamic response to clopidogrel in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). However, the impact of statin therapy on clopidogrel response profiles in patients with acute coronary syndrome (ACS) undergoing PCI has not been established and represents the objective of this investigation. On-treatment P2Y12 platelet reactivity was measured using the vasodilator stimulated phosphoprotein (VASP) phosphorylation assay before PCI, at hospital discharge, and at 1 month after PCI in ACS patients enrolled in the multicenter, prospective GEne polymorphisms, Platelet Reactivity, and Syntax Score (GEPRESS) study (n = 962). High platelet reactivity (HPR) was defined as platelet reactivity index ≥50%. Statins were prescribed at hospital discharge in 87% (n = 835) of patients. All patients were followed for 1 year. The 1-month HPR rate was lower in statin than in non-statin treated patients (39.6 vs 52%, respectively, p = 0.009). This finding was confirmed also among statin-treated patients with high Syntax score (≥15). After adjustment for differences in baseline characteristics, statin use at discharge was independently associated with 1-month HPR rate (odds ratio, 0.58, 95% confidence interval, 0.38–0.89; p = 0.015). In ACS patients undergoing PCI treated with clopidogrel the use of statins at discharge was associated with significantly lower 1-month HPR rates compared with patients not treated with statins.

Background: Age is a major predictor of contrast-induced acute kidney injury (CI-AKI). Few studies have focused on CI-AKI in elderly patients with acute coronary syndrome (ACS). Methods: We compare the incidence of CI-AKI in patients <75 and ≥75 years enrolled in the Protective effect of Rosuvastatin and Antiplatelet Therapy On contrast-induced acute kidney injury and myocardial damage in patients with ACS (PRATO-ACS) study and explore the impact of high-dose rosuvastatin on CI-AKI and clinical outcomes in the 2 age-groups. Statin-naive patients with non-ST-segment elevation ACS scheduled for early invasive strategy (total 504) were randomized to rosuvastatin (40 mg on admission followed by 20 mg/day) or no statin treatment. Contrast-induced acute kidney injury was defined as creatinine increase ≥0.5 mg/dL or ≥25% above baseline within 72 hours after contrast administration. All patients were stratified in tertiles according to baseline high-sensitivity C-reactive protein (hs-CRP). Results: Rate of CI-AKI was significantly higher in patients ≥75 years (15.9% vs 8.7%, odds ratio: 2.001; 95% confidence interval: 1.14-3.53, P = .015). No significant interaction was observed between age and statin treatment ( P = .17). Pretreatment with rosuvastatin was associated with 65% relative reduction in CI-AKI rate (22/170 [12.9%] vs 8/177 [4.5%], P = .007) in younger patients and 38% (16/82 [19.5%] vs 9/75 [12%], P = .20) in the elderly individuals. The greatest protective effect of statin treatment was achieved in patients with the highest hs-CRP values in both age-groups. Conclusion: Patients ≥75 years with ACS had a higher risk of developing CI-AKI. Early high-dose rosuvastatin is efficacious in reducing kidney injury in all patients, especially those with the highest baseline hs-CRP values.