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)

Abstract

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")

Riassunto

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.

Prospective History of Long-Term Mortality and Modes of Death in Patients Discharged After Acute Coronary Syndrome: The ABC-2* Study on Acute Coronary Syndrome

Background: The aim of this study was to examine the prognostic value of several clinical characteristics on long-term mortality and causes of death after acute coronary syndrome.

Methods: The   ABC-2   study   is   a   prospective   investigation   comprising  557  patients  with  acute  coronary  syndrome.  During  hospitalization,   33   clinical   variables,   including   demographics,   cardiovascular  risk  factors,  in-hospital  characteristics,  and  blood  components, were examined. “Acute models” were survival models containing  the  variables  accrued  within  72  h  from  admission,  and  “sub-acute  models”  contained  data  accrued  over  a  7-day  period.  Cox regression models were used for the survival analysis.

Results: The  12-year  follow-up  study  revealed  that  51.2%  of  the  patients  died  (15.8%  of  the  patients  died  from  coronary  artery  disease  and/or  heart  failure,  12.6%  of  the  patients  experienced  sudden death, 8.3% of the patients died from other-cardiovascular diseases, and 14.5% of the patients died from non-cardiovascular causes. The following factors were independently associated with all-cause  mortality  in  both  the  acute  and  sub-acute  models:  age,  left ventricular ejection fraction (negative), body mass index (non-linear),  previous  myocardial  infarction,  diabetes  mellitus,  blood  glucose  (non-linear),  Killip  class>1,  albumin/creatinine  ratio,  and  pre-hospital  time  delay.  The  variables  associated  with  coronary  artery  disease  and/or  heart  failure  included  age,  left  ventricular  ejection fraction (negative), body mass index (non-linear), previous myocardial   infarction,   Killip   class>1,   albumin/creatinine   ratio,   and  pre-hospital  time  delay,  while  the  variables  associated  with  sudden  death  included  age,  hypertension  (negative),  uric  acid,  left  ventricular  ejection  fraction  (negative),  and  pre-hospital  time  delay,  and  those  associated  with  other-  cardiovascular  causes  included age, hypertension, and albumin/creatinine ratio. The only variable associated with non- cardiovascular mortality was age. The C-statistic of the predictive models was 0.86 for all-cause mortality, whereas the C-statistic ranged from 0.74 to 0.80 for cardiovascular causes.

Conclusions: The  ABC-2  study  revealed  clinical  predictors  of long-term  mortality  after  acute  coronary  syndrome  that  might  help  prognostication,  patient  education,  and  risk  modification. Furthermore,  the  results  showed  that  the  modes  of  death  are  independently associated with different baseline clinical features.

Keywords: Acute coronary syndrome;  Mortality; Risk   prediction; Survival analysis

Heart Failure in Women and Men During Acute Coronary Syndrome and Long-term Cardiovascular Mortality (the ABC-3* Study on Heart Disease) (*Adria, Bassano, Conegliano, and Padova Hospitals)

Aims: We investigated the gender-based differences in the association between heart failure (HF) during acutecoronary syndrome (ACS) and post-discharge, long-term cardiovascular (CV) mortality.

Methods and results: The present study included 557 patients enrolled in three intensive coronary care units anddischarged alive. HF during ACS was evaluated by Killip class and left ventricular ejection fraction (LVEF). Inter-action between gender and HF after 15 years of follow up was studied using Cox models including a formal inter-action term. Median age was 67 (interquartile range [IQR], 59–75) years, 29% were females, 37% had non-STelevation myocardial infarction and 32% Killip classN1, and median LVEF was 53% (IQR 46–61). All butfive pa-tients were followed up to 15 years, representing 5332 person-years. Of these, 40.2% died of CV-related causes.Crude CV mortality rate was higher among women (52.2%) than men (35.3%;Pb0.0001). At a univariablelevel, a negative interaction between female gender and Killip class for CV mortality was found [hazard ratio(HR) = 0.51 (0.34–0.77),P=0.002].Infive multivariable models after controlling for age, main CV risk factors,clinical features, post-discharge medical treatment, and mechanical coronary reperfusion, the interaction wassignificant across all models [HR = 0.63 (0.42–0.95),P= 0.02 in the fully adjusted model]. LVEF showed no sig-nificant hazard associated with female gender on univariable analysis [HR = 1.4 (0.9–0.2.0),P= 0.11] but did soin all adjusted models [HR = 1.7 (1.2–2.5),P= 0.005 in the fully adjusted model].

Conclusion: Gender is a consistent, independent effect modifier in the association between HF and long-term CVmortality after ACS.

Keywords: Gender, Heart failure, Killip class, LVEF, Acute coronary syndrome, Cardiovascular mortality, Surviving analysis