Acute-phase Inflammatory Markers During Myocardial Infarction: Association with Mortality and Modes of Death after 7 Years of Follow-up

Giuseppe Berton, Rosa Palmieri, Rocco Cordiano, Fiorella Cavuto, Sigismondo Pianca and Paolo Palatini

Background The relationship between acute-phase inflammatory markers in the setting of acute myocardial infarction (AMI) and long-term outcomes is largely unexplored.

Objectives The aim of the study was to investigate the predictive power of acute-phase inflammatory markers following AMI for short-term and long-term mortality separately and modes of death.

Methods In 220 unselected patients with AMI [median age 67 (interquartile range 60-74) years, women 26%], blood neutrophil granulocytes, erythrocyte sedimentation rate, C-reactive protein, and a1-acid glycoprotein were measured 1, 3 and 7 days after admission. All patients completed 7 years of follow-up. Endpoints were 1-year (short-term) and 2- to 7-vear (long-term) mortality and modes of death, classified as nonsudden cardiovascular, sudden, and noncardiovascular death.

Results The short-term mortality rate was 18%. The long- term mortality rate was 26%. The short-term mortality risk was higher in patients in whom the markers were in the upper tertile. Fully adjusted hazard ratios (and 95% confidence interval) were 3.2 (1.4-7.9), 3.5 (1.7-7.9), 3.5 (1.6-8.6), and 6.1 (2.3-19.1) for neutrophil granulocyte, erythrocyte sedimentation rate, C-reactive protein, and «i-acid glycoprotein, respectively. The excess mortality was chiefly due to nonsudden cardiovascular mortality

Conclusion The acute-phase inflammatory markers tested following AMI are independently and concordantly associated with short-term mortality and their prediction is associated only with nonsudden cardiovascular modes of death. These markers are not associated with long-term mortality.

Keywords C-reactive protein, inflammatory markers, long-term mortality, myocardial infarction, prognosis, short-term mortality

Comparison of C-reactive Protein and Albumin Excretion as Prognostic Markers for 10-Year Mortality After Myocardial Infarction

Giuseppe Berton, MD,FESC;Rocco Cordiano, MD;Rosa Palmieri, MD;Fiorella Cavuto, MD;Patrizio Buttazzi, PhD; Paolo Palatini, MD

Background: C-reactive protein (CRP) is an established prognostic marker in the setting of acute coronarysyndromes. Recently, albumin excretion rate also has been found to be associated with adverse outcomesin this clinical setting. Our aim was to compare the prognostic power of CRP and albumin excretion rate forlong-term mortality following acute myocardial infarction (AMI).

Hypothesis: To determine whether albumin excretion rate is a better predictor of long-term outcome than CRPin post-AMI patients.Methods:We prospectively studied 220 unselected patients with definite AMI (median [interquartile] age67 [60–74] y, female 26%, heart failure 39%). CRP and albumin-to-creatinine ratio (ACR) were measured onday 1, day 3, and day 7 after admission in 24-hour urine samples. Follow-up duration was 10 years for allpatients.

Results: At survival analysis, both CRP and ACR were associated with increased risk of 10-year all-causemortality, also after adjusting for age, hypertension, diabetes mellitus, prehospital time delay, creatinekinase-MB isoenzyme peak, heart failure, and creatinine clearance. CRP and ACR were associated withnonsudden cardiovascular(non-SCV) mortality but not with sudden death (SD) or noncardiovascular(non-CV)death. CRP was not associated with long-term mortality, while ACR was independently associated withoutcome both in short- and long-term analyses. At C-statistic analysis, CRP did not improve the baselineprediction model for all-cause mortality, while it did for short-term non-SCV mortality. ACR improved all-causeand non-SCV mortality prediction, both in the short and long term.

Conclusions: ACR was a better predictor of long-term mortality after AMI than CRP.

Albuminuria During Acute Myocardial Infarction and Prognosis: a Methodological Issue

To the Editor. In the recently published study by Lazzeri et al. [1], microalbuminuria and other clinical variables were evaluated in hypertensive, nondiabetic patients with ST elevation myocardial infarction [1]. "The authors concluded that microalbuminuria does not yield prognostic information about the inhospital mortality or complications and claimed an association between acute glucose dysmetabolism and outcomes. We believe that, in this study, the predictive power of microalbuminuria has been overlooked by the authors due to a series of methodological problems.

Predictors of Ten-Year Event-Free Survival in Patients With AcuteMyocardial Infarction (from the Adria, Bassano, Conegliano, andPadova Hospitals [ABC] Study on Myocardial Infarction)


The long-term event-free survival (EFS) after acute myocardial infarction (AMI) is largelyuninvestigated. We analyzed noninvasive clinical variables in association with long-termEFS after AMI. The present prospective study included 504 consecutive patients with AMIat 3 hospitals from 1995 to 1998 (Adria, Bassano, Conegliano, and Padova Hospitals [ABC]study).

Thirty-seven variables were examined, including demographics, cardiovascular riskfactors, in-hospital characteristics, and blood components. The end point was 10-year EFS.Logistic and Cox regression models were used to identify the predictive factors. Wecompared 3 predictive models according to the goodness of fit and C-statistic analyses. Atenrollment, the median age was 67 years (interquartile range 58 to 75), 29% were women,38% had Killip class>1, and the median left ventricular ejection fraction was 51%(interquartile range 43% to 60%).

The 10-year EFS rate was 19%. Both logistic and Coxanalyses identified independent predictors, including young age (hazard ratio 1.2, 95%confidence interval 1.1 to 1.3, p=0.0006), no history of angina (hazard ratio 1.4, 95%confidence interval 1.1 to 1.8, p=0.009), no previous myocardial infarction (hazard ratio1.4, 95% confidence interval 1.1 to 1.7, p0.01), high estimated glomerular filtration rate(hazard ratio 0.8, 95% confidence interval 0.7 to 0.9, p=0.001), low albumin/creatinineexcretion ratio (hazard ratio 1.2, 95% confidence interval 1.1 to 1.3, p<0.0001), andhighleft ventricular ejection fraction (hazard ratio 0.8, 95% confidence interval 0.7 to 0.9, p=0.006).These variables had greater predictive power and improved the predictive power of 2 othermodels, including Framingham cardiovascular risk factors and the recognized predictors ofacute heart damage. In conclusion, 10-year EFS was strongly associated with 4 factors (ABCmodel) typically neglected in studies of AMI survival, including estimated glomerular filtrationrate, albumin/creatinine excretion ratio, a history of angina, and previous myocardial infarc-tion. This model had greater predictive power and improved the power of 2 other models usingtraditional cardiovascular risk factors and indicators of heart damage during AMI. 

Traduzione dall’originale: Rosanna Sedran, RN, Giuseppe Berton, MD.

Predittori clinici della sopravvivenza libera da eventi per 10 anni dopo infarto miocardico acuto (da: “the Adria, Bassano, Conegliano, and Padova Hospitals [ABC] Study on Myocardial Infarction")


La sopravvivenza a lungo termine libera da eventi (EFS) dopo infarto miocardico acuto (AMI) è poco conosciuta.
Abbiamo analizzato variabili cliniche non invasive in associazione con EFS per un lungo periodo dopo un infarto miocardico acuto. Questo studio prospettico ha riguardato 504 pazienti con infarto miocardico acuto, non selezionati, arruolati consecutivamente in 3 ospedali generali dal 1995 al 1998 (the ABC study). Trentasette variabili cliniche sono state esaminate, compresi fattori demografici, fattori di rischio cardiovascolare, caratteristiche ospedaliere e componenti ematochimici.
L’obbiettivo dello studio è stato verificare l'EFS per 10 anni dopo l’AMI. Per l’analisi statistica sono stati usati modelli di regressione logistica e di Cox per identificare i fattori associati con EFS. Abbiamo confrontato 3 modelli predittivi usando analisi basate su “goodness of fit” e “C-­‐ statistic”. All'inizio dello studio l'età mediana dei pazienti era di 67 anni (interquartili 58-­‐75), il 29% donne, il 38% in classe di Killip > 1, e la mediana della frazione di eiezione ventricolare sinistra è stata del 51% (interquartili 43-­‐60%). L’EFS a 10 anni è stato del 19%. All’analisi logistica e di
Cox sono stati identificati i seguenti fattori predittivi indipendenti: giovane età (hazard ratio 1,2, intervallo di confidenza 95%, 1.1-­‐1.3, p=0,0006), non-­‐storia di angina (hazard ratio 1,4, 95% intervallo di confidenza 1,1-­‐1,8, p = 0,009), non-­‐precedente infarto miocardico (hazard ratio 1,4,  intervallo  di  confidenza  95%  1,1-­‐1,7,  p  =  0,01), elevata velocità di filtrazione glomerulare stimata (hazard ratio 0.8, intervallo di confidenza 95% 0,7-­‐0,9, p = 0.001), basso livello di escrezione di albumina/creatinina (hazard ratio 1.2, intervallo di confidenza 95% 1,1-­‐1,3, p <0,0001) ed elevata frazione di eiezione ventricolare sinistra (hazard ratio 0.8, intervallo di confidenza 95% 0,7-­‐0,9, p = 0.006). Queste variabili hanno mostrato maggiore potere predittivo di altri 2 modelli, che includono fattori di rischio cardiovascolare di Framingham e predittori di danno cardiaco acuto. In conclusione l'EFS per 10 anni dopo AMI è risultato fortemente associato a 4 fattori (the ABC model) sinora poco considerati negli studi di sopravvivenza dopo AMI, tra cui filtrazione glomerulare stimata, rapporto albumina/creatinina, storia di angina e precedente infarto miocardico. Questo modello ha maggiore capacità predittiva e risulta migliorativo rispetto ad altri due modelli tradizionali basati sui fattori di rischio cardiovascolare ed indicatori di danno cardiaco durante AMI.