Microalbuminuria during acute coronary syndrome: Association with 22-year mortality and causes of death. The ABC-8 study on heart disease.

Background: Microalbuminuria is associated with adverse outcomes in acute coronary syndrome (ACS) patients.
Methods: To evaluate the very long-term association between Microalbuminuria and the overall mortality and causes of death in this clinical setting, we prospectively studied 579 unselected ACS patients admitted to three hospitals. The baseline albumin-to-creatinine ratio (ACR) was measured on days 1, 3, and 7 in 24-h urine samples. Patients were followed for 22 years or until death.
Results: Virtually all patients completed follow-up; 449(78%) had died: 41% due to non-sudden cardiac death (non-SCD), 19% sudden cardiac death (SCD), 40% due to non-cardiac (non-CD) death. Using unadjusted Cox regression analysis, ACR was a significant predictor of all-cause mortality (hazard ratio [HR] 1.26;95%confidence interval [CI] 1.22–1.31; p˂0.0001) and the three causes of death (HR 1.40;95%CI 1.32–1.48; p˂0.0001), (HR 1.22;95%CI 1.12–1.32; p˂0.0001) and (HR 1.16;95%CI 1.09–1.23; p˂0.0001) for non-SCD, SCD and non-CD respectively.
Using a fully adjusted model, ACR was a significant independent predictor of all-cause mortality
(HR 1.12; 95% CI 1.08–1.16; p˂0.0001) and only non-SCD (HR 1.21; 95%CI 1.14–1.29; p˂0.0001). There was a positive interaction between ACR level and history of AMI (HR 1.15; 95%CI 1.03– 1.29; p = 0.01) and the presence of heart failure at admission (HR 1.11; 95%CI 1.01–1.24; p =0.04), and negative interaction with higher than median LVEF (HR 0.89; 95%CI 0.80–0.99; p =0.03) for all-cause mortality at the multivariable level.
Conclusion: Based on the present analysis, baseline urinary albumin excretion during ACS is a strong independent predictor of the very long-term mortality risk, chiefly due to non-sudden cardiac death.

Differences in Cancer Death Risk Long After ACS Among Selected Urban and Rural Areas in North Italy: The ABC-7a Study on Heart Disease

Background: An increased risk of cancer death has been demonstrated for patients
diagnosed with acute coronary syndrome (ACS). We are investigating possible
geographic risk disparities.
Methods: This prospective study included 541 ACS patients who were admitted to
hospitals and discharged alive in three provinces of Italy’s Veneto region. The patients
were classified as residing in urban or rural areas in each province.
Results: With 3 exceptions, all patients completed the 22-year follow-up or were followed
until death. Urban (46%) and rural (54%) residents shared most of their baseline
demographic and clinical characteristics. Pre-existing malignancy was noted in 15
patients, whereas 106 patients developed cancer during the follow-up period, which
represented 6232 person-years. No difference in the cancer death risk was found
between the urban and rural areas or between southern and northern provinces
(hazard ratio [HR] 1.1; 95% confidence interval [CI] 0.7–1.7; p = 0.59 and HR 1.1; 95%
CI 0.9–1.4; p = 0.29, respectively) according to the unadjusted Cox regression analysis.
Geographic areas, however, showed a strong positive interaction, with risk increasing
from the urban to rural areas from southern to northern provinces (HR 1.9; 95% CI 1.1–
3.0; p = 0.01). The fully adjusted Cox regression and Fine-Gray competing risk regression
models provided similar results. Interestingly, these results persisted, and even
strengthened, after exclusion of the 22 patients who developed malignancy and
survived to the end of follow-up. We did not observe an urban/rural difference in nonneoplastic
death risk or a significant interaction between the geographic areas.
Conclusion: Our analysis reveals that the cancer death risk among unselected ACS
patients in Italy’s Veneto region significantly differs by geography. The northern rural area
has the highest risk. These results highlight the importance of implementing a preventive
policy based on area-specific knowledge.

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.

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

Risk of malignancy long after acute coronary syndrome in selected urban and rural areas and comparison with smoking risk: the ABC-7* study on Heart Disease

Background: Increased cancer risk has been reported in patients with acute coronary syndrome (ACS).
Objectives: To investigate geographic differences in risk malignancy long after ACS.
Methods: We enrolled 586 ACS patients admitted to hospitals in three provinces in the Veneto region of Italy in this prospective study. Patient’s residency was classified into three urban and three nearby rural areas.
Results: All (except for 3) patients completed the follow-up (22 years or death) and 54 % were living in rural areas. Sixteen patients had pre-existing malignancy, and 106 developed the disease during follow-up. Cancer prevalence was 17 % and 24 % (p = 0.05) and incidence of malignancy was 16 and 21/1000 person-years for urban and rural areas, respectively. In unadjusted logistic regression analysis, cancer risk increased from urban to rural areas (odds ratio [OR] 3.4;95 % confidence interval [CI] 1.7–7.1; p = 0.001), with little change from north to south provinces (OR 1.5;95 % CI 1.0-2.2; p = 0.06). Yet, we found a strong positive interaction between urban-rural areas and provinces (OR 2.1;95 % CI 1.2–3.5; p = 0.003). These results kept true in the fully adjusted model. Unadjusted Cox regression analysis revealed increasing hazards ratios (HRs) for malignancy onset from urban to rural areas (HR 3.0;95 % CI 1.5–6.2; p = 0.02), but not among provinces (HR 1.3;95 % CI 1.0–2.0; p = 0.14). Also, we found a strong positive interaction between geographic areas (HR 2.1;95 % CI 1.3–3.5; p = 0.002), even with a fully adjusted model.
Conclusions: The results in unselected real-world patients demonstrate a significant geographic difference in malignancy risk in ACS patients, with the highest risk in the north-rural area.
Keywords: Acute coronary syndrome, Malignancy risk, Urban-Rural.

Neoplastic Disease After Acute Coronary Syndrome: Incidence, Duration and Features. (The ABC-4* Study on Heart Disease)

Aim To investigate the clinical features and incidence ofmalignant neoplasia during 17 years of follow-up in anunselected sample of patients with acute coronarysyndrome (ACS).

Methods The Adria, Bassano, Conegliano, and PadovaHospital-4 Study on Heart Disease is an ongoing,prospective study of an unbiased population of patientswith ACS. Baseline clinical and laboratory data wereobtained during the first 7 days of hospitalization at threedifferent intensive coronary care units. The current study included data from 589 patients with ACS.

Results At enrollment, 19 patients had confirmed neoplasia.During follow-up, 99 additional patients developedmalignant neoplastic disease. The incidence rate was 17.8cases per 1000 person-years, which was about three timeshigher than that observed in the general population.Patients had a shorter duration of neoplasia when theydeveloped it after enrollment compared with those withpreexisting neoplasia [hazard ratioU2.0 (1.5–2.6),PU0.001]. Patients with neoplasia who died during follow-up had an earlier onset of neoplasia [hazard ratioU1.8(1.1–2.9),PU0.01] and shorter duration than survivors[hazard ratioU4.1 (2.4–7.0),P<0.0001]. The estimated time to diagnosis of neoplasia indicated elderly patientshad a significantly higher risk than younger people duringthe 17 years of follow-up. After the onset of neoplasia,survival time declined more sharply in the elderly thanyounger people.

Conclusion The long-term prospective study showed thatpatients with ACS have a higher incidence of malignancythan the general population. Those who develop neoplasmafter being diagnosed with ACS have a worse prognosisthan patients with a preexisting neoplasia.

Keywords: acute coronary syndrome, long-term follow-up, neoplasia,outcomes, survival analysis

L’escrezione urinaria di albumina aumenta durante infarto miocardico acuto soprattutto nei pazienti che sviluppano insufficienza cardiaca


AIM OF THE STUDY. To evaluate the profile of albumin excretion rate (AER) in the first days of acute myocardial infarction (AMI), its relationship with serum enzymes and the presence of heart failure, and the effect of thrombolytic therapy.

METHODS. Two hundred and thirtyone consecutive patients admitted to coronary care unit for suspected AMI were examined. Patients with diabetes mellitus, urinary tract infections or proteinuric diseases were excluded. In 135 patients (95 males, 40 females) AMI diagnosis was confirmed. The remaining 96 (56 males, 40 females) were considered as controls. AER was measured by radioimmunoassay in 24-hour urine samples at the first, third and seventh day after admission and expressed as mg/24h. Statistical analysis was performed after AER logarithmic transformation using repeated measure ANOVA.

RESULTS. Mean age was 66.9+12.2 years (range =35 -91) in the AMI group and 63.2+12.3 years (range = 33-91) in the controls (p= 0.023) Age-adjusted blood pressure was lower in the AMI group than in the controls (p<0.0001 for both systolic and diastolic), while no difference was found in heart rate. Plasma cholesterol, triglycerides, creatinine and uric acid were similar in the 2 groups. Mean AER was 43.4+ 64.8, 26.9+51.2 and 23.9+52.7 mg/24h at ist, 3rd and 7th day respectively in the AMI group and 24.9 +58.2, 13.7+ 25.8 and 17.9+ 44.1 mg/24h respectively in the controls (p= 0.014). In the AMI group, first day AER significantly and positively correlated with CPK (r=0.287, p=0.001), CPK-MB (r=0.239, p=0.007) and GOT (r= 0.300, p= 0.001). Within the patients with AMI, those who developed heart failure {n= 57), had higher AER (48.6 + 68.4, 29.7 +54.9 and 28.1 +55.8 mg/24h at 1st, 3rd and 7th day in patients with mild heart failure -2nd Killip Class- and 100.0+141.7, 50.3 + 66.4 and 64.2 + 74.4 mg/24h in those with severe heart failure -3rd and 4th Killip Class-) than those who did not (31.0+41.7, 19.6+45.6 and 16.5+45.7 mg/24h respectively) (p= 0.004). In a multiple linear regression model AER was significantly related to peak values of GOT (1st day) and CPK (3rd day) and to presence of heart failure (3rd and 7th day). Thrombolitic therapy (n= 48) did not influence AER.

CONCLUSIONS. The results of the present study show that AER increases following AMI, chiefly in the subjects who develop heart failure. AER correlates with serum enzymes peak levels at 1st and 3rd day and with presence of heart failure at 3rd and 7th day after admission, and is not influenced by thrombolitic therapy. These data suggest that in AMI the initial increase in AER is due to the inflammatory process which accompanies cardiac necrosis, while in a later phase its rise is mainly due to the increased intraglomerular capillary pressure consequent to heart failure.

G ItalCardiol, 1995, 25: 999-1009

Keywords : Albumin excretion rate, Acute myocardial infarction, Heart failure, Thrombolysis

Association Between Plasma Lipid Levels During Acute Coronary Syndrome and Long-term Malignancy Risk. The ABC-4* 5 Study on Heart Disease

Background: Emerging evidence suggests that patients with coronary artery disease carry an increased risk of developing malignancy, with deleterious effects on long-term prognosis. Our aim was to ascertain whether baseline plasma lipid levels during acute coronary syndrome (ACS) are associated with malignancy in long-term.

Methods: This study included 589 patients admitted with ACS to three centers and discharged alive. Plasma lipid levels were assessed on the first morning after admission. Patients were followed for 17 years or until death.

Results: Five hundred seventy-one patients were free from malignancy at enrollment, of them 99 (17.3%) developed the disease during follow-up and 75 (13.1%) died due to it. Compared to patients without malignancy, those with malignancy showed lower plasma levels of total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG). The groups showed similar statin use rates at any time in follow-up. The incidence rate of neoplasia and neoplastic mortality was higher in patients with baseline TC or LDL values ≤ median; they showed 85 and 72% increased incidence rate of developing malignancy and 133 and 122% increased incidence rate of neoplastic death respectively. No differences were observed relative to HDL and TG levels. In survival analysis using Cox regression with parsimonious models, patients with baseline TC or LDL values > median, respectively, showed risks of 0.6(95% CI 0.4–0.9; p = 0.01) and 0.6(95%CI 0.4–0.9; p = 0.02) for malignancy onset, and 0.5(95% CI 0.3–0.8; p = 0.005) and 0.5(95% CI 0.3–0.8; p = 0.004) for neoplastic death. Similar results were obtained using competitive risk analysis with parsimonious models.

Conclusions: This long-term prospective study of an unselected real-world patient sample showed that neoplasia onset and mortality are independently associated with low plasma TC and LDL levels at admission for ACS.

Keywords: Acute coronary syndrome, Coronary artery disease, Neoplasia, Plasma lipids, Long-term follow-up, Competitive risks