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

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

GIUSEPPE BERTON, TIZIANA CITRO, ROCCO CORDIANO, ROSA PALMIERI, RENZO DE TONI, FRANCESCO CUCCHINI, PAOLO PALATINI

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

Baseline Plasma Lipid Levels in Patients with Acute Coronary Syndrome: Association with 20-year Mortality. The ABC-5a* Study on Heart Disease

Background: The relationship between baseline plasma lipid levels during acute coronary syndrome and the outcome has clinical relevance.
Methods: To evaluate their long-term prognostic value, we examined 589 patients admitted with acute coronary syndrome at three hospitals. Baseline plasma lipids were assessed on days 1 and 7. Patients were followed for 20 years or until death.
Results: Virtually, all patients completed follow-up; 437 (74%) had died: 24% from coronary artery disease/heart failure (CAD/HF), 21% sudden cardiac death (SCD), 16% from other cardiovascular causes and 39% had non-cardiac death. The incidence rate (IR) of all-cause mortality was not different among patients with baseline plasma lipids less or greater than the median value. The IR of CAD/HF mortality was not significantly higher among patients with greater than median low-density lipoprotein (LDL) cholesterol and triglyceride (TG) levels. The IR of non-cardiac death tended to
be lower among patients with greater than median total cholesterol (TC) and LDL levels. Using three levels of adjusted Cox survival models, baseline plasma lipids had no consistent independent or inverse association with all-cause mortality, even after excluding patients who received statins. Competitive risk survival models for each cause of death revealed that the only hazard of non-cardiac death was consistently higher among patients with less than or equal to median TC and LDL levels.
Conclusion: In the present prospective long-term study, after acute coronary syndrome, baseline plasma lipid levels seem not to be associated with long-term global
mortality. Only an independent inverse association between TC and LDL and noncardiac death has been observed.

Plasma Lipid Levels During ACS: Association with 20-year Mortality: The ABC-5* Study on Heart Disease

Baseline plasma total cholesterol, LDL, HDL and triglyceride levels at the time of ACS were not associated with long-term global mortality.
Only an independent inverse association between TC and LDL levels and non-cardiac death was observed.
The associations seem to be mostly independent of anti-lipid treatment, suggesting that the core prognostic issue lies on the lipid levels per se.

Albumin Excretion in Acute Myocardial Infarction: a Guide for Long-term Prognosis

Giuseppe Berton, MD, FESC, Rocco Cordiano, MD, Stefano Mazzuco, PhD, Ethan Katz, MD, Renzo De Toni, PhD, and Paolo Palatini, MD Conegliano, Adria, and Padova, Italy; and Cleveland, OH

Background Albumin excretion rate has been found to be associated with increased risk of mortality in several clinicalsettings. We assessed the relationship between urinary albumin and 7-year mortality in a cohort of patients with acutemyocardial infarction (AMI).

Methods In this prospective study, we examined 505 white patients admitted with AMI to the intensive care unit of3 hospitals. Main end points were nonearly all-cause and cardiovascular (CV) mortality. Albumin-to-creatinine ratio (ACR) was measured by radioimmunoassay on the first, third, and seventh days after admission. Risk estimates were made using Coxproportional-hazard model and relative odds. Forty patients (7.9%) died early inhospital, and 175 (34.7%) died during therest of the follow-up (nonearly mortality).

Results The ACR measured on the third day predicted the occurrence of 7-year nonearly all-cause and CV mortality.Hazard ratios for ACR≥0.97 mg/mmol were 3.0 (95% confidence limit 2.2-4.1),P< .0001, for nonearly all-cause mortalityand 3.5 (95% confidence limit 2.5-5.0),P< .0001, for CV mortality. Correspondent fully adjusted hazard ratios were1.9 (95% CI 1.4-2.6),P< .0001, and 2.2 (95% CI 1.5-3.2),P< .0001, respectively. By adding ACR to the 18-variablepredictive model, ACR improved significantly both the goodness of fitting of the model for nonearly all-cause (P< .0001) andCV mortality (P< .0001) and the C-statistic value (P< .0001 andP= .002 for nonearly all-cause and CV mortality,respectively). Similar results were obtained for ACR measured on the first day or the seventh day.

Conclusions An early increase of urinary albumin in AMI is a strong independent predictor of long-term adverse clinicaloutcome. The ACR improved clinical prediction over and above baseline traditional multivariable risk models.

(Am Heart J2008;156:760-8.)

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.

Atrial Fibrillation during Acute Myocardial Infarction: Association with All-cause Mortality and Sudden Death after 7-year of Follow-up

G. Berton, R. Cordiano, F. Cucchini, F. Cavuto, M. Pellegrinet, P. Palatini

Aims: Atrial fibrillation⁄flutter (AF⁄FL) is a common complication of acute myocar-dial infarction (AMI). Indeed, the determinants of AF⁄FL in AMI-patients and theassociation of AF⁄FL with mortality are not well-known. The purpose of the pres-ent study was to investigate the relationship between presence of AF⁄FL and mor-tality in patients with AMI and to report on predictors of AF⁄FL.

Methods: We studied 505 patients enrolled in three intensive care units with definite AMI andfollowed up for 7 years. No patient was lost to follow-up. Patients with AF⁄FLduring the 1st week of hospitalisation were compared with those with steady sinusrhythm. End-points were all-cause mortality and modes of death.

Results: At multivariable logistic regression analysis, elderly, body mass index, congestive heartfailure (CHF), history of hypertension and plasma cholesterol (in a negative fashion)were independently associated with the presence of AF⁄FL. At survival analysis,after full adjustment, AF⁄FL was not associated with in-hospital mortality. After7 years of follow-up, AF⁄FL was found to be associated with all-cause mortality[adjusted odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.2–2.3], togetherwith age, diabetes mellitus, creatine kinase-MB isoenzyme (CK-MB) peak, CHF,estimated glomerular filtration rate and thrombolysis. At adjusted logistic polyno-mial regression analysis, AF⁄FL was found to be associated with an excess of mor-tality for reasons of sudden death (SD) (adjusted OR = 2.7; 95% CI = 1.2–6.4).No interaction was observed between AF⁄FL and medications on in-hospitalmortality. For 7-year mortality, angiotensin-converting enzyme (ACE)-inhibitors anddigitalis showed an independent negative (protective) interaction chiefly on SD(adjusted OR = 0.06; 95% CI = 0.01–0.74, and RR = 0.10; 95% CI = 0.02–0.58, respectively).

Conclusions: Patients with AMI and AF⁄FL portend a poorprognosis in the long-term chiefly because of an excess of SD. Treatment withACE-inhibitors and digitalis may have long-term beneficial effects on SD.