Diabetes Mellitus and Acute Myocardial Infarction: Impact on Short and Long-Term Mortality.

Diabetes mellitus (DM) is an important risk factor for acute myocardial infarction (AMI) and a frequent co-morbidity in patients hospitalized with AMI, being present in about 30% of cases. Although current treatment of AMI has considerably improved survival in both patients with and without DM, the presence of DM still doubles the case fatality rate during both the acute phase of AMI and at long-term follow-up. This higher mortality risk of DM patients strongly indicates a particular need for better treatment options in these patients and suggests that intensive medical treatment, prolonged surveillance, and stringent control of other risk factors should be carefully pursued and maintained for as long as possible in them.In this review, we will focus on the close association between DM and in-hospital and long-term mortality in AMI patients. We will also aim at providing current evidence on the mechanisms underlying this association and on emerging therapeutic strategies, which may reduce the traditional mortality gap that still differentiates AMI patients with DM from those without.

Prognostic impact of admission high-sensitivity C-reactive protein in acute myocardial infarction patients with and without diabetes mellitus.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM. METHODS: We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint. RESULTS: Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients. CONCLUSIONS: This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.

Extended dual antiplatelet therapy after acute myocardial infarction. Current evidence and future perspectives.

Patients with acute myocardial infarction (AMI) are at increased risk of recurrent ischemic events after hospital discharge, despite optimal medical therapy. Current practice guidelines strongly encourage the early assessment of the residual ischemic risk in post-AMI patients, in order to identify those who may benefit from a prolonged dual antiplatelet therapy. To this end, some scoring systems have been proposed. However, most scores were developed for patients with stable coronary artery disease undergoing percutaneous coronary intervention. Moreover, nearly all failed to be implemented in everyday clinical practice, probably because of the perceived complexity due to the large number of incorporated variables. Therefore, the identification of the ideal AMI patient who can benefit from a prolonged (beyond 1 year after the index event) dual antiplatelet therapy remains to be clarified, especially when the bleeding risk associated with such therapy is considered. In this review, we summarize the current evidence on the prolonged use of dual antiplatelet therapy after AMI, with a special focus on recent advances regarding the identification of high-risk patients who may derive a favorable net clinical benefit from such a therapeutic strategy.

Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction.

RATIONALE: In contrast to cardiomyocyte necrosis, which can be quantified by cardiac troponin, functional cardiomyocyte impairment, including mitochondrial dysfunction, has escaped clinical recognition in acute myocardial infarction (AMI) patients. OBJECTIVE: To investigate the diagnostic accuracy for AMI and prognostic prediction of in-hospital mortality of cytochrome c. METHODS AND RESULTS: We prospectively assessed cytochrome c serum levels at hospital presentation in 2 cohorts: a diagnostic cohort of patients presenting with suspected AMI and a prognostic cohort of definite AMI patients. Diagnostic accuracy for AMI was the primary diagnostic end point, and prognostic prediction of in-hospital mortality was the primary prognostic end point. Serum cytochrome c had no diagnostic utility for AMI (area under the receiver-operating characteristics curve 0.51; 95% confidence intervals 0.44-0.58; P=0.76). Among 753 AMI patients in the prognostic cohort, cytochrome c was detectable in 280 (37%) patients. These patients had higher in-hospital mortality than patients with nondetectable cytochrome c (6% versus 1%; P<0.001). This result was mainly driven by the high mortality rate observed in ST-segment-elevation AMI patients with detectable cytochrome c, as compared with those with nondetectable cytochrome c (11% versus 1%; P<0.001). At multivariable analysis, cytochrome c remained a significant independent predictor of in-hospital mortality (odds ratio 3.0; 95% confidence interval 1.9-5.7; P<0.001), even after adjustment for major clinical confounders (odds ratio 4.01; 95% confidence interval 1.20-13.38; P=0.02). CONCLUSIONS: Cytochrome c serum concentrations do not have diagnostic but substantial prognostic utility in AMI.

Prognostic significance of serum creatinine and its change patterns in patients with acute coronary syndromes.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

B-type natriuretic peptide and risk of acute kidney injury in patients hospitalized with acute coronary syndromes*.

OBJECTIVES: To investigate whether admission B-type natriuretic peptide levels predict the development of acute kidney injury in acute coronary syndromes. DESIGN: Prospective study. SETTING: Single-center study, 13-bed intensive cardiac care unit at a University Cardiological Center. PATIENTS: Six-hundred thirty-nine acute coronary syndromes patients undergoing emergency and urgent percutaneous coronary intervention. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

Continuous ultrafiltration for congestive heart failure: the CUORE trial.

BACKGROUND: 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 and conventional therapy in patients hospitalized for HF and overt fluid overload. METHODS AND RESULTS: Fifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; n = 27). The primary end point of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 5.5 and 7.9 ± 9.0 kg, respectively; P = .75), a lower incidence of rehospitalizations 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 = .002). Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group (P = .33). CONCLUSIONS: In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.

Continuous ultrafiltration for congestive heart failure: the CUORE trial.

Background: 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 and conventional therapy in patients hospitalized for HF and overt fluid overload.Methods and Results: Fifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; = 27). The primary endpoint of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 4.5 and 7.9 ± 5.0 kg, respectively;P = .75), a lower incidence of rehospitalizations 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 = .002).Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group (P = .33).Conclusions: In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.

[Mild therapeutic hypothermia for the treatment of cardiac arrest and acute myocardial infarction]. / Ipotermia terapeutica moderata nel trattamento dell'arresto cardiocircolatorio e dell'infarto miocardico acuto.

Mild therapeutic hypothermia improves neurological outcomes after cardiac arrest by preserving brain function. It is currently under discussion the possibility that hypothermia may also provide a protective effect on cardiac function, in particular, by reducing the infarct size in patients with acute myocardial infarction complicated by cardiac arrest. Despite encouraging experimental and clinical data obtained so far may suggest a potential future indication in this population, routine use of therapeutic hypothermia in acute myocardial infarction patients needs further investigation and it is not currently recommended.

Vitamin D and cardiovascular diseases.

Vitamin D has an established role in calcium homeostasis but its deficiency is emerging also as a new risk factor for cardiovascular disease (CVD). In particular, several epidemiological and clinical studies have reported a close association between low vitamin D levels and several cardiovascular risk factors and major CVDs, such as coronary artery disease, heart failure, and cardiac arrhythmias. In all these clinical settings, vitamin D deficiency seems to predispose to increased morbidity, mortality, and recurrent cardiovascular events. Despite this growing evidence, interventional trials with supplementation of vitamin D in patients at risk of or with established CVD are still controversial. In this chapter, we summarize the currently available evidence on the links between vitamin D deficiency and major cardiovascular risk factors and CVD, in terms of both clinical relevance and potential therapeutic implications.

Impact of Prior Statin Therapy on In-Hospital Outcome of STEMI Patients Treated with Primary Percutaneous Coronary Intervention.

Background: Prior statin therapy has a cardioprotective effect in patients undergoing elective or urgent percutaneous coronary intervention (PCI). However, data on patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI are still controversial. We retrospectively evaluated the effect of prior statin therapy on in-hospital clinical outcomes in consecutive STEMI patients undergoing primary PCI. Methods: A total of 1790 patients (mean age 67 ± 11 years, 1354 men) were included. At admission, all patients were interrogated about prior (>6 months) statin therapy. The primary endpoint of the study was the composite of in-hospital mortality, acute pulmonary edema, and cardiogenic shock in patients with or without prior statin therapy. Results: A total of 427 patients (24%) were on prior statin therapy. The incidence of the primary endpoint was similar in patients with or without prior statin therapy (15% vs. 16%; p = 0.38). However, at multivariate analysis, prior statin therapy was associated with a lower risk of the primary endpoint, after adjustment for major prognostic predictors (odds ratio 0.61 [95% CI 0.39−0.96]; p = 0.03). Conclusions: This study demonstrated that prior statin therapy is associated with a better in-hospital clinical outcome in patients with STEMI undergoing primary PCI compared to those without prior statin therapy.

Vitamin D and Cardiovascular Disease: Current Evidence and Future Perspectives.

Vitamin D deficiency is a prevalent condition, occurring in about 30-50% of the population, observed across all ethnicities and among all age groups. Besides the established role of vitamin D in calcium homeostasis, its deficiency is emerging as a new risk factor for cardiovascular disease (CVD). In particular, several epidemiological and clinical studies have reported a close association between low vitamin D levels and major CVDs, such as coronary artery disease, heart failure, and atrial fibrillation. Moreover, in all these clinical settings, vitamin deficiency seems to predispose to increased morbidity, mortality, and recurrent cardiovascular events. Despite this growing evidence, interventional trials with supplementation of vitamin D in patients at risk of or with established CVD are still controversial. In this review, we aimed to summarize the currently available evidence supporting the link between vitamin D deficiency and major CVDs in terms of its prevalence, clinical relevance, prognostic impact, and potential therapeutic implications.

Mitochondrial Biomarkers in Patients with ST-Elevation Myocardial Infarction and Their Potential Prognostic Implications: A Prospective Observational Study.

BACKGROUND: Mitochondrial biomarkers have been investigated in different critical settings, including ST-elevation myocardial infarction (STEMI). Whether they provide prognostic information in STEMI, complementary to troponins, has not been fully elucidated. We prospectively explored the in-hospital and long-term prognostic implications of cytochrome c and cell-free mitochondrial DNA (mtDNA) in STEMI patients undergoing primary percutaneous coronary intervention. METHODS: We measured cytochrome c and mtDNA at admission in 466 patients. Patients were grouped according to mitochondrial biomarkers detection: group 1 (-/-; no biomarker detected; n = 28); group 2 (-/+; only one biomarker detected; n = 283); group 3 (+/+; both biomarkers detected; n = 155). A composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema was the primary endpoint. Four-year all-cause mortality was the secondary endpoint. RESULTS: Progressively lower left ventricular ejection fractions (52 ± 8%, 49 ± 8%, 47 ± 9%; p = 0.006) and higher troponin I peaks (54 ± 44, 73 ± 66, 106 ± 81 ng/mL; p = 0.001) were found across the groups. An increase in primary (4%, 14%, 19%; p = 0.03) and secondary (10%, 15%, 23%; p = 0.02) endpoint rate was observed going from group 1 to group 3. The adjusted odds ratio increment of the primary endpoint from one group to the next was 1.65 (95% CI 1.04-2.61; p = 0.03), while the adjusted hazard ratio increment of the secondary endpoint was 1.55 (95% CI 1.12-2.52; p = 0.03). The addition of study group allocation to admission troponin I reclassified 12% and 22% of patients for the primary and secondary endpoint, respectively. CONCLUSIONS: Detection of mitochondrial biomarkers is common in STEMI and seems to be associated with in-hospital and long-term outcome independently of troponin.

Characteristics, Management, and Outcomes of Acute Coronary Syndrome Patients with Cancer.

Patients with cancer are at increased risk of cardiovascular disease, with a reported prevalence of acute coronary syndrome (ACS) ranging from 3% to 17%. The increased risk of ACS in these patients seems to be due to the complex interaction of shared cardiovascular risk factors, cancer type and stage, and chemotherapeutic and radiotherapy regimens. The management of ACS in patients with cancer is a clinical challenge, particularly due to cancer's unique pathophysiology, which makes it difficult to balance thrombotic and bleeding risks in this specific patient population. In addition, patients with cancer have largely been excluded from ACS trials. Hence, an evidence-based treatment for ACS in this group of patients is unknown and only a limited proportion of them is treated with antiplatelets or invasive revascularization, despite initial reports suggesting their beneficial prognostic effects in cancer patients. Finally, cancer patients experiencing ACS are also at higher risk of in-hospital and long-term mortality as compared to non-cancer patients. In this review, we will provide an overview on the available evidence of the relationship between ACS and cancer, in terms of clinical manifestations, possible underlying mechanisms, and therapeutic and prognostic implications.

Whole blood transcriptome profile at hospital admission discriminates between patients with ST-segment elevation and non-ST-segment elevation acute myocardial infarction.

Whether ST-segment (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) should be regarded as distinct pathophysiological entities is a matter of debate. We tested the hypothesis that peripheral blood gene-expression profiles at presentation distinguish STEMI from NSTEMI. We performed a case-control study collecting whole-blood from 60 STEMI and 58 NSTEMI (defined according to the third universal definition of MI) consecutive patients on hospital admission. We used RNA-sequencing for the discovery phase, comparing 15 STEMI vs. 15 NSTEMI patients, matched for age, sex, and cardiovascular risk factors, and quantitative PCR in the remaining unmatched patients for validating top-significant genes. Gene-level differential expression analysis identified significant differences in the expression of 323 genes: 153 genes withstood correction for admission cardiac troponin I (cTnI), differentiating the two conditions independently of myocardial necrosis extent. Functional annotation analysis uncovered divergent modulation in leukocyte and platelet activation, cell migration, and mitochondrial respiratory processes. Linear regression analysis revealed gene expression patterns on admission predicting infarct size, as indexed by cTnI peak (R2 = 0.58-0.75). Our results unveil distinctive pathological traits for these two MI subtypes and provide insights into the early assessment of injury extent. This could translate into RNA-based disease-specific biomarkers for precision diagnosis and risk stratification.

Impact of Glomerular Filtration Rate on the Incidence and Prognosis of New-Onset Atrial Fibrillation in Acute Myocardial Infarction.

BACKGROUND: Atrial fibrillation (AF) is a frequent complication of acute myocardial infarction (AMI) and is associated with a worse prognosis. Patients with chronic kidney disease are more likely to develop AF. Whether the association between AF and glomerular filtration rate (GFR) is also true in AMI has never been investigated. METHODS: We prospectively enrolled 2445 AMI patients. New-onset AF was recorded during hospitalization. Estimated GFR was estimated at admission, and patients were grouped according to their GFR (group 1 (n = 1887): GFR >60; group 2 (n = 492): GFR 60-30; group 3 (n = 66): GFR <30 mL/min/1.73 m2). The primary endpoint was AF incidence. In-hospital and long-term (median 5 years) mortality were secondary endpoints. RESULTS: The AF incidence in the population was 10%, and it was 8%, 16%, 24% in groups 1, 2, 3, respectively (p < 0.0001). In the overall population, AF was associated with a higher in-hospital (5% vs. 1%; p < 0.0001) and long-term (34% vs. 13%; p < 0.0001) mortality. In each study group, in-hospital mortality was higher in AF patients (3.5% vs. 0.5%, 6.5% vs. 3.0%, 19% vs. 8%, respectively; p < 0.0001). A similar trend was observed for long-term mortality in three groups (20% vs. 9%, 51% vs. 24%, 81% vs. 50%; p < 0.0001). The higher risk of in-hospital and long-term mortality associated with AF in each group was confirmed after adjustment for major confounders. CONCLUSIONS: This study demonstrates that new-onset AF incidence during AMI, as well as the associated in-hospital and long-term mortality, increases in parallel with GFR reduction assessed at admission.

Iron deficiency in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Iron deficiency (ID) is a known co-morbidity and a potential therapeutic target in heart failure. Whether ID is frequent also in ST-segment elevation acute myocardial infarction (STEMI) patients and is associated with worse in-hospital outcomes has never been evaluated. METHODS: We defined ID as a serum ferritin < 100 µg/L or transferrin saturation < 20% at hospital admission. We assessed the association between ID and the primary endpoint (a composite of in-hospital mortality and Killip class ≥ 3). We explored the potential association between ID, circulating cell-free mitochondrial DNA (mtDNA), and cardiac magnetic resonance (CMR) parameters. RESULTS: Four-hundred-twenty STEMI patients undergoing primary percutaneous coronary intervention (pPCI) were included. Of them, 237 (56%) had ID. They had significantly higher admission high-sensitivity troponin and mtDNA levels as compared to non-ID patients (145 ±â€¯35 vs. 231 ±â€¯66 ng/L, P < 0.001; 917 [404-1748] vs. 1368 [908-4260] copies/µL; P < 0.003, respectively). A lower incidence of the primary endpoint (10% vs. 18%, P = 0.01) was observed in ID patients (adjusted OR 0.50 [95% CI 0.27-0.93]; P = 0.02). At CMR (n = 192), ID patients had a similar infarct size (21 ±â€¯18 vs. 21 ±â€¯19 g; P = 0.95), but a higher myocardial salvage index (0.56 ±â€¯0.30 vs. 0.43 ±â€¯0.27; P = 0.002), and a smaller microvascular obstruction extent (3.6 ±â€¯2.2 vs. 6.9 ±â€¯3.9 g; P < 0.001). CONCLUSIONS: Iron deficiency is frequent in STEMI patients, it is coupled with mitochondrial injury, and, paradoxically, with a better in-hospital outcome. This unexpected clinical result seems to be associated with a smaller myocardial reperfusion injury. The mechanisms underlying our findings and their potential clinical implications warrant further investigation.

A new score based on the PEGASUS-TIMI 54 criteria for risk stratification of patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) patients are at increased risk of death and recurrent ischemic events. We aimed to elaborate a risk score, based on the PEGASUS-TIMI 54 criteria, to predict mortality and non-fatal AMI in AMI patients. METHODS: We retrospectively analyzed two prospectively collected AMI cohorts. We calculated a cut-off for the developed score and investigated its 1-year prognostic power in the derivation cohort (n = 1257). We externally validated our score in 913 AMI patients with a longer follow-up. RESULTS: In the derivation cohort, the area under the curve of the score for the primary endpoint (1-year death and non-fatal AMI) was 0.70 (95% CI 0.65-0.76; P < 0.0001) and a cut-off of 6 was identified. The primary endpoint incidence in patients with a score above and below the cut-off was 12% and 3% (P < 0.001) in the derivation cohort and 16% and 6% in the validation cohort (P < 0.001). At multivariate analysis, the HR for the primary endpoint associated with a score ≥ 6 was 4.45 (P < 0.0001) in the derivation cohort and 2.86 (P < 0.0001) in the validation cohort. One-year major bleeding rate was low (<0.2% overall) and similar between risk groups. The prognostic performance of the score cut-off persisted beyond the first year after AMI in the validation cohort, maintaining a similar risk for death and non-fatal AMI (HR 3) at every following year. CONCLUSIONS: Our score, based on the PEGASUS-TIMI 54 criteria, may identify AMI patients at high risk of recurrent ischemic events, who might benefit from thorough preventive strategies.

High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study.

Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. Results. Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 ± 87 vs. 16 ± 41 mg/L; p < 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles (p for trend <0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23; p < 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 (p < 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. Conclusions. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome.

Reduced Cardio-Renal Function Accounts for Most of the In-Hospital Morbidity and Mortality Risk Among Patients With Type 2 Diabetes Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: ST-segment elevation myocardial infarction (STEMI) patients with type 2 diabetes mellitus (DM) have higher in-hospital mortality than those without. Since cardiac and renal functions are the main variables associated with outcome in STEMI, we hypothesized that this prognostic disparity may depend on a higher rate of cardiac and renal dysfunction in DM patients. RESEARCH DESIGN AND METHODS: We retrospectively analyzed 5,152 STEMI patients treated with primary angioplasty. Left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were evaluated at hospital admission. The primary end point was in-hospital mortality. A composite of in-hospital mortality, cardiogenic shock, and acute kidney injury was the secondary end point. RESULTS: There were 879 patients (17%) with DM. The incidence of LVEF ≤40% (30% vs. 22%), eGFR ≤60 mL/min/1.73 m2 (27% vs. 18%), or both (12% vs. 6%) was higher (P < 0.001 for all comparisons) in DM patients. In-hospital mortality was higher in DM patients than in non-DM patients (6.1% vs. 3.5%; P = 0.002), with an unadjusted odds ratio (OR) of 1.81 (95% CI 1.31-2.49; P < 0.001). However, DM was no longer associated with an increased mortality risk after adjustment for cardiac and renal function (OR 1.03, 95% CI 0.68-1.56; P = 0.89). A similar behavior was observed for the secondary end point, with an unadjusted OR for DM of 1.52 (95% CI 1.25-1.85; P < 0.001) and an OR after adjustment for cardiac and renal function of 1.07 (95% CI 0.85-1.36; P = 0.53). CONCLUSIONS: The study indicates that the increased in-hospital mortality and morbidity of DM patients with STEMI is mainly driven by their underlying cardio-renal dysfunction.